Benign vascular tumor: Difference between revisions

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Latest revision as of 19:33, 25 October 2018

For information about classification of vascular tumors, click here.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Hannan Javed, M.D.[2]

Overview

Benign vascular tumors, are benign growths formed from blood vessels; such as, hemangioma, hemangioendothelioma, Kaposi sarcoma. They exhibit a wide range of clinical manifestations, and may occur as isolated lesions or may occur as manifestation of multi-system syndromes and diseases. Their diagnosis and management depends on their clinical manifestations and coexistent anomalies. International Society for the Study of Vascular Anomalies (ISSVA) has classified these lesions into benign vascular tumors and related lesions.

Benign Vascular Tumors

Infantile hemangioma / Hemangioma of infancy


Pattern	Different types
Focal Multifocal Segmental Indeterminate	Superficial Deep Mixed (superficial + deep) Reticular / abortive / minimal growth Others
Adapted from International Society for the Study of Vascular Anomalies^[1]


Association with other lesions
PHACE association / syndrome	Posterior fossa malformations, Hemangioma, Arterial anomalies, Cardiovascular anomalies, Eye anomalies , sternal clefting and ⁄ or supraumbilical raphe
LUMBAR (SACRAL, PELVIS) association / syndrome
LUMBAR (SACRAL, PELVIS) association / syndrome	Lower body hemangioma, Urogenital anomalies, Ulceration, Myelopathy, Bony deformities, Anorectal malformations, Arterial anomalies, and Renal anomalies
Adapted from International Society for the Study of Vascular Anomalies^[1]

Most common tumor of infancy. Usually appearing after birth, infantile hemangiomas undergo a period of proliferation in few weeks after birth followed by regression and involution in first year of life. Superficial lesions appear as red or “strawberry” colored nodules, papules, or plaques while deeper hemangiomas are typically bluish or skin colored. Mixed tumors, involving both epidermis and deeper structures, may display characteristics of both. They may also be classified as focal, that appear in a specific anatomical area, and segmental that shows varied pattern of growth following developmental growth regions. Segmental type is often associated with other developmental abnormalities.^[2]^[3]^[4]
Rarely, infantile hemangioms can cause life-threatening complications such as congestive cardiac failure, respiratory difficulty and respiratory compromise, and loss of vision. There may also be long-term sequela including permanent disfigurement and scarring. If lesions are multiple, there is an increased risk of visceral involvement. There may be an association with certain syndromes such as PHACE syndrome.^[2]^[5]
Some studies have indicated autosomal-dominant and maternal patterns of inheritance. Some studies suggest that environmental factors play the key role. Some risk factors that have been identified in association with infantile hemangioma include female gender, preterm birth, low weight at birth, increasing maternal age at birth, placenta previa, pre-eclampsia, progesterone use by mother, and Caucasian race.^[6]^[2]^[7]^[8]
The diagnosis is made clinically and a thorough investigation should be carried out for visceral hemangiomas and other associative abnormalities if suspicion arises. Majority of these lesions do not require any treatment but treatment is indicated if there is risk for complications such as visual or respiratory involvement. Elective treatment is also offered to prevent disfigurement or scarring. Recently there have been an increased usage of oral beta-blockers such as timolol over systemic glucocorticoids because of higher efficacy. Vincristine and interferon alpha have been used in some high risk hemangiomas but carry the risk of severe complications. Visceral hemangioms may require embolization or surgery if they do not respond to systemic therapy. Laser therapy especially PDL is another modality used in cases of hemangiomas unresponsive to medication.^[2]^[9]^[10]^[11]^[12]^[13]^[14]^[15]^[16]

Congenital hemangioma

Rare tumor that arises in utero and presents as fully developed lesion at birth. Following birth they can regress completely, partially or not at all. So they can be classified as rapidly involuting (RICH), non-involuting (NICH), partially involuting (PICH).^[17]^[18]
1. Rapidly involuting (RICH)
  - This fast flow tumor can be detected in utero and appears as raised gray single lesions with dilated veins, telangiectasias and a halo at birth.
  - This tumor may be complicated by thrombocytopenia and congestive cardiac failure due to its high-flow nature.
  - Tumor typically regresses spontaneously in 1 to 2 years of life. Sometimes it can occur in [liver]] where it follows the same pattern of involution as that of skin.^[18]^[19]
2. Non-involuting (NICH)
  - Fast flow tumor that presents as well defined, plaque like lesion with pink to purple color, telangiectasias and pale borders.
  - Typically remains stable but there have been some reports of growth and expansion.^[18]
3. Partially involuting (PICH)
  - These lesions start involution as RICH but become stable over time and persist as NICH.^[20]
Somatic mutations in GNAQ/GNA11 are thought to cause the congenital hemangioma. GNAQ and its paralogue GNA11 function in intracellular signaling pathways as Gq alpha subunit.^[18]^[21]
Diagnosis is usually clinical but imaging techniques such as MRI, CT scan, contrast-enhanced ultrasound and later biopsy can be considered if required. Surgical excision should be considered in case of complications, NICH and PICH.^[22]^[23]

Tufted angioma

Benign tumor that is characterized by dense clumps of endothelial cells and capillaries located in dermis. Most lesions appear in adolescence but some can manifest at birth or late in adulthood. Clinical presentation varies but majority of lesions appear as solitary stained area or elevation that later forms red-purple or dusky red plaque while some lesions appear as firm nodules. Lesions are usually solitary, asymptomatic but tender with occasional painful episodes and located on trunk and neck in majority of the cases. Some cases of multi-focal tufted angiomas have also been reported.^[24]^[25]^[26]^[27]
Tufted angioma can be associated with Kasabach-Merritt phenomenon.^[27]^[17]^[24]
Somatic activating GNA14 c.614A>T (p.Gln205Leu) mutations have been found in some tufted angiomas. These mutations may cause the cell growth to be growth-factor independent by up-regulating the MAPK pathway.^[28]^[29]
Imaging such as MRI and ultrasound can add into clinical diagnosis to differentiate tufted angioma from similar lesions such as Kaposi sarcoma, kaposiform hemangioendothelioma and infantile hemangioma. Biopsy and histopathological studies are sometimes required for accurate diagnosis.
Surgical excision is the treatment modality but some recommend to only observe the lesions due to its slow growth and possible remission. Other therapies include radiation beam therapy, cryosurgery, corticosteroids, and pulsed laser therapy. Vincristine and embolization has been used with success in angiomas associated with Kasabach-Merritt phenomenon.^[27]^[30]^[31]^[32]^[33]^[34]^[35]

For more information on tufted angioma, click here

Spindle-cell hemangioma

Rare benign tumor that manifests as solitary or multiple nodules confined to dermis and subcutaneous tissues in almost all of the cases. Histopathologically, it appears as solid areas that are cellular and consist of spindle cells seen attached to vessel walls, and cavernous spaces that can be thrombosed. Size may increase over time and patient usually complains of swelling and pain. The nodules or masses can be mobile and elastic or can be firm and immobile.^[36]^[37]^[38]
Somatic mutations in IDH1 and IDH2 have been found to be present in 70% of spindle-cell hemangiomas. IDH1 and IDH2 are important enzymes in cell energy cycles (α-ketoglutarate and NADPH generation).^[39]^[40]
Diagnosis often requires biopsy and imaging studies such as MRI to ascertain the extent of the tumor. Local excision is the treatment modality of choice with excellent prognosis in majority of the cases although recurrence is very common.^[36]^[37]^[38]^[41]^[42]

Epithelioid hemangioma

Rare benign tumor that typically presents as solitary painful nodule on head and neck. Penis is an atypical location. They can involve skin, bone and soft tissues. Histopathologically, these lesions are characterized by presence of endothelial cells that resemble epithelial cells with evidence of proliferation such as large nuclei and prominent nucleoli, and often inflammatory infiltrates. Vessels are typically well-formed. Nuclear atypia is absent.^[43]^[44]^[45]
FOS gene rearrangements such as ZFP36-FOSB fusions are found to be present in one third of epithelioid hemangioma in a study. It encodes a transcription factors that causes over-expression of vascular endothelial growth factor-D (VEGF-D).^[46]^[47]^[48]^[49]
Diagnosis requires biopsy to determine characteristic histopathological features. Imaging techniques such as MRI can useful. Bone tumors often require surgery for accurate diagnosis. Surgical excision has been used in majority of cases. Other treatment modalities include radiotherapy and embolization. Recently chemoembolization and microwave ablation in combination have been used with success.^[43]^[44]^[50]

For more information on epithelioid hemangioma, click here

Pyogenic granuloma

Also called as lobular capillary hemangioma, this common vascular lesion typically manifests as single, localized nodules on gingiva with sessile base but large lesions often present as lobulated or pedinculated. Majority of the lesions are <2 cm in diameter and color of the lesion depending on vascularity varies from pink to purple. It can found anywhere on skin and mucous membranes such as lips, tongues, palate, and on atypical locations such asperiungual or gastrointestinal tract but gingiva is the typical location. Majority of the patients present with profuse bleeding. Others complain of painless mass, swelling, obstructive or interference related symptoms.^[51]^[52]^[53]^[54]
Trauma or chronic irritation have been cited as the most common causes but it can arise due to multiple other factors such as medications, viral infections such as herpes virus type 1, Orf virus and/or human papilloma virus type 2, and BRAF mutations or use of BRAF inhibitors that can cause multiple, disseminated lesions. Medications that have been implicated in development of this lesion include oral contraceptives, retinoids, gefitinib, cabecitabine, and afatinib, BRAF inhibitors such as vemurafenib or encorafenib, and rituximab. Mutations in BRAF/RAS/GNA14 have all been associated with pyogenic granuloma, BRAF c.1799T>A has been recently described as one of the major mutations associated.^[52]^[53]^[54]^[55]^[56]^[57]^[58]
The diagnosis is made by clinical features and then confirmed by histopatholgical features. Current standard of care is surgical excision. Other treatment modalities include curettage, electrocautery, radiosurgery, cryosurgery, sclerotherapy, or laser treatment. Topical or oral beta-blockers timolol or propranolol and topical imiquimod have also been successful.^[52]^[53]^[59]^[60]^[61]^[62]

For more information on Pyogenic granuloma, click here.

Hobnail hemangioma

Benign tumor that typically presents as solitary growth with often, but not always, tagetoid appearance of a central papule and peripheral brown ring that may or may not disappear over time. Characteristic histopathological feature include plump endothelial cells in superficial dermis that line ectatic and irregular vessels, and project into lumina like hobnails. Deeper dermis shows vessels dissecting collagen fibers. Majority of the lesions are fund on trunk and extremities with head and neck, and oral cavity as uncommon locations. Patient may present with pain, or an asymptomatic growing lesion.^[63]^[64]^[65]
Etiology is not well understood but trauma may play a key role in pathogenesis. Some studies have found congenital etiology in some lesions.^[63]^[64]^[66]^[67]
Diagnosis is based on clinical features and histopathological studies. Treatment is usually by excision. Other modalities of treatment include intermittent triamcinolone intralesional injections and pulsed dye laser treatment.^[63]^[64]

Microvenular hemangioma

Rare lesion that most often manifests as single asymptomatic nodule, plaque or papule with color varying from red to bluish-red. Majority of the lesions are located on trunk and limbs. Histologically, the tumor consists of irregular and branching venous structures with inconspicuous lumina. Endothelial cells display absence of atypia and mitotic figures. Some lesions may be painful and/or tender.^[68]^[69]^[70]^[71]
Etiology and pathogenesis have not been well-understood but a recent study may associate progesterone with microvenular hemangioma.^[72]
Diagnosis requires biopsy because of rarity of this tumor. Treatment is through surgical excision.^[68]^[69]^[70]^[71]

Anastomosing hemangioma

Rare tumor characterized by presence of anastomosing capillary-sized vessels with irregular fenestration, lined by endothelial cells with absence of atypia and occasional hobnailing. Majority of the lesions are found in kidneys and genitourinary tract with some being located in liver, adrenal glands and gastrointestinal tract. These tumors are typically incidental findings on radiology but some may present with back and/or flank pain with/without radiation to lower limbs.^[73]^[74]^[75]^[76]^[77]
Etiology is not well-known but a recent study suggests mutations in GNAQ genes that encodes members of G protein family.^[78]
The diagnosis is very challenging because radiological findings of anastomosing hemangioma are similar to that of malignant tumors such as renal cell carcinoma, hepatocellular carcinoma and low grade angiosarcoma. So excision and biopsy are often suggested. There is no current guidelines for treatment but excision and local ablation are the options.^[73]^[76]^[75]^[79]^[80]

Glomeruloid hemangioma

Characterized by red blood cells filled clumps of capillaries inside dilated vascular spaces. These collections of capillaries, lined by swollen endothelial cells, resemble renal glomeruli and stain positive for periodic acid-Schiff (PAS)-positive, diastase-resistant eosinophilic globules. Clinical presentation varies and are not discernible from other cutaneous lesions. Majority of the lesions manifest as multiple, asymptomatic pauples or nodules..^[81]^[82]
Glomeruloid hemangioma is associated with POEMS syndrome in majority of the cases and rarely with Castleman's disease. Very few isolated cases of glomeruloid hemangioma have been reported.^[81]^[82]
- POEMS stands for peripheral neuropathy (P), organomegaly (O), endocrinopathy (E) monoclonal plasma-cells proliferative disorder (M) and skin changes (S) although diagnosis does not require presence of all of these symptoms. Other manifestations of POEMS syndrome may include sclerotic bone lesions, papilledema, edema, ascites, effusions, pulmonary hypertension, Castleman’s disease (CD), thrombocytosis and erythrocytosis, and increased serum VEGF.^[83]
- Castleman's disease is characterized as lymphoproliferative disorder with inflammatory response involving multiple systems. Clinical presentation ranges from asymptomatic lymphadenopathy to severe systemic manifestations such as weight loss, fever and organomegaly.^[84]
Etiology is not well-understood but some theories suggest role of vascular endothelial growth factor (VEGF), increased estrogen levels, human herpesvirus-8 and increased cytokines in its pathogenesis.^[81]^[82]
Diagnosis relies on characteristic histology. Patients who present with glomeruloid hemangioma should undergo evaluation for POEMS syndrome and should be kept under follow-up because these lesions can precede full-blown POEMS syndrome in some cases.^[81]^[82]

Papillary hemangioma

Rare tumor characterized by presence of papillary growths within dilated vascular channels, that contain cores of pericytes around normal capillaries.
The tumor typically manifests as solitary papules in head and neck region, without any systemic manifestations.^[85]^[86]
Diagnosis may require biopsy. Treatment options include excision and photodynamic therapy.^[87]

Intravascular papillary endothelial hyperplasia

Also called as Masson's tumor, this benign lesions is characterized by presence of intravascular papillary structures that are enveloped by proliferating endothelial cells. It is considered to be a reactive lesion associated with an organizing thrombus. Clinically it manifests as solitary painless mass in head-neck and the extremities especially the hand, that may grow rapidly in size and become painful and/or tender. Some lesions have been found intra-abdominallly such as in the liver that can bleed and present with anemia.^[88]^[89]^[90]^[91]
This lesions appears to be associated with vascular trauma, and thrombus that may lead to chronic irritation and increased levels of fibroblast growth factor (FGF), hypoxia-inducible factor-1 (HIF-1α), and vascular endothelial growth factor (VEGF) stimulating endothelial cells proliferation.^[89]^[90]^[92]
Histopathological studies are generally required for diagnosis and may also require immunohistochemical confirmation. Treatment is surgery with uncommon recurrence.^[92]^[93]

Cutaneous epithelioid angiomatous nodule

This recently diagnosed lesion is characterized histologically as proliferating, swollen epithelioid cells and thin walled vascular channels lined by swollen endothelial cells that resemble the epithelioid cells. These cells typically contain pale pink cytoplasm, intracytoplasmic vacuoles, and vesicular nuclei. Clinically these lesions manifest as solitary nodules or papules that may grow rapidly. Rarely multiple lesions have also been reported.^[94]^[95]^[96]
Thought to be a reactive process but no trigger has been identified yet. Immunosuppression has been proposed to be associated with this benign vascular proliferation.^[94]^[95]
Diagnosis requires careful clinical and histopathological evaluation. Surgery has been the treatment used in majority of the lesions although cryotherapy has also been used. Steroids are found to be ineffective.^[94]^[96]

Acquired elastotic hemangioma

First described in 2002, this rare lesion typically manifests as solitary, asymptomatic, red to purple, patches and plaques on areas damaged by sun exposure such as hands and forearms. Some patients may complain of pain or growth of the lesion. Histologically, its exhibits solar elastosis and band like proliferation of capillaries in superficial dermis. These proliferating channels are arranged parallel to epidermis and endothelial cells typically display absence of atypia but may show hobnail pattern.^[97]^[98]
This lesion has slight preference for females. Damage due to sun exposure such as free radical production are thought to be associated with pathogenesis. Some case reports showed use of progesterone associated with appearance of lesions in peri-menopausal women.^[97]^[98]^[99]^[100]
Diagnosis requires biopsy to rule out basal cell carcinoma and other similar appearing lesions. Treatment options include observation, discontinuance of progesterone, laser therapy and excision. Recurrence was not observed in any of the cases observed or treated.^[98]^[100]^[97]^[100]^[101]

Littoral cell hemangioma of the spleen

Benign tumor that originates from cells that line the red pup sinuses. Majority of the patients are asymptomatic but some present with symptoms related to splenic enlargement such as abdominal distension, hypersplenism such as persistent anemia and thrombocytopenia, and constitutional symptoms such as weight loss, fever, and fatigue. Histopathological features include anastomosing vascular channels lined by cuboidal cells, with somewhat rarer presence of papillary structures.^[102]^[103]^[104]^[105]
Although not well-established, few case reports have demonstrated malignant histology and features in this neoplasm. This tumor can be related to visceral malignancies such as non-Hodgkin's lymphoma, tumors of the liver and brain, epithelial ovarian cancer, non-small cell lung cancer, plasmablastic B-cell lymphoma, villous lymphocyte leukemia and neoplasm of colon, kidney and pancreas. Association with Crohn's disease and Gaucher's disease has also been described leading to hypothesis of immune dysfunction as a possible cause of littoral cell hemangioma of spleen.^[103]^[104]^[105]^[106]^[107]^[108]^[109]^[110]^[111]^[112]
Preferred diagnostic modality is biopsy often following splenectomy. Fine needle aspiration can also be used. Imaging studies such as MRI and CT scan are inconclusive. All patients with this neoplasm should undergo evaluation for other associated neoplasms especially visceral neoplasms. Splenectomy is the treatment.^[102]^[104]^[113]^[114]^[115]

Related lesions

Eccrine angiomatous hamartoma

Benign non-neoplastic proliferation of eccrine and capillary structures leading to increased sweat glands and dilated vascular channels in the middle and deep dermis, and subcutaneous structures. Clinical presentations vary remarkably but majority of the lesions are asymptomatic and appear as red to violaceous to brown single nodule or plaque on the extremities but macules, patches, multiple lesions and uncommon sites for the lesion have been reported. Many patients complain of pain, tenderness, increased sweating and excessive hair over the lesion.^[116]^[117]^[118]^[119]^[120]
Etiology for this benign lesion has not been established. Diagnosis requires biopsy although imaging studies such as MRI and CT scan can be used to define the extent of the lesion. Asymptomatic lesion do not require treatment. Surgical excision is the treatment of choice if treatment is indicated. Alternative therapies include use of botulinum toxin to treat hyperhidrosis and use of intralesional sclerosants.^[116]^[121]^[122]^[123]^[124]^[125]^[126]

Reactive angioendotheliomatosis

Characterized by hyperplasia of endothelial cells within lumina of vascular channels that leads to formation of thrombi. These secondary thrombi may obstruct lumen of vascular channels. Clinically majority of the lesions manifests as multiple reddish to violaceous macules, papules, or plaques that can be found almost anywhere on the body but tend to involve limbs. Patients may complain of pain and ulceration in the lesion or may report with non-specific symptoms such as fever and weigh loss.^[127]^[128]^[129]
Etiology and pathogenesis is unknown but immune system is hypothesized to play a role in pathogenesis. Majority of the patients have coexistent systemic diseases such as cryoglobulinemia, antiphospholipid syndrome, renal disease, valvular cardiac disease, alcoholic cirrhosis, glioblastoma multiforme, and rheumatoid arthritis/polymyalgia rheumatica. Iatrogenic immunosuppression have also been associated. Based on these associations some consider this lesion as the marker of an underlying systemic disease.^[127]^[130]^[131]
Diagnosis requires biopsy. There is no standard management guideline. Treatment of coexistent systemic disease may cause resolution of reactive angioendotheliomatosis. Management options include observation, antibiotics, corticosteroids, laser therapy, and excision.^[127]^[130]

Bacillary angiomatosis

Bacillary angiomatosis is characterized by the proliferation of blood vessels, resulting in them forming tumor-like masses in the skin and other organs. Symptoms vary depending on which parts of the body are affected; for example, those whose livers are affected may have an enlarged liver and fever, while those with osseous BA will experience intense pain in the affected area. These lesions may take several forms such as papules or nodules and plaque.
Bacillary angiomatosis (BA) is a bacterial infection caused by either Bartonella henselae or Bartonella quintana.
BA responds dramatically to several antibiotics. Usually, erythromycin will cause the skin lesions to gradually fade away in the next four weeks, resulting in complete recovery. Doxycycline may also be used. However, if the infection does not respond to either of these, the medication is usually changed to tetracycline.

For more information on bacillary angiomatosis, click here.

References

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@@ Line 1: / Line 1: @@
 __NOTOC__
 '''For information about classification of vascular tumors, [[Vascular tumor#Vascular tumor|click here]].'''
 {{Vascular tumor}}
@@ Line 8: / Line 9: @@
 ==Overview==
 ''' [[Benign]] [[vascular]] [[tumors]]''', are [[benign]] growths formed from [[blood vessel]]s; such as, [[hemangioma]], [[hemangioendothelioma]], [[Kaposi sarcoma]]. They exhibit a wide range of clinical manifestations, and may occur as isolated [[lesions]] or may occur as manifestation of multi-system [[syndromes]] and [[diseases]]. Their [[diagnosis]] and management depends on their clinical manifestations and coexistent [[anomalies]]. '''International Society for the Study of Vascular Anomalies (ISSVA)''' has classified these [[lesions]] into [[benign vascular tumors]] and related [[lesions]].
 ==Benign Vascular Tumors==
@@ Line 14: / Line 14: @@
 {| class="wikitable" style="width:40%; height:100px" border="1"
 |+
-!style="background:#4479BA; color: #FFFFFF;" align="center" + |Pattern
+! style="background:#4479BA; color: #FFFFFF;" align="center" + |Pattern
-!style="background:#4479BA; color: #FFFFFF;" align="center" + |Different types
+! style="background:#4479BA; color: #FFFFFF;" align="center" + |Different types
 |-
 |
-* focal
+* Focal
-* multifocal
+* Multifocal
-* segmental
+* Segmental
-* indeterminate
+* Indeterminate
 |
-* superficial
+* Superficial
-* deep
+* Deep
-* mixed (superficial + deep)
+* Mixed (superficial + deep)
-* reticular / abortive / minimal growth
+* Reticular / abortive / minimal growth
-* others
+* Others
 |-
 | colspan="2" style="background:#7d7d7d; color: #FFFFFF;" + |<small>'''Adapted from International Society for the Study of Vascular Anomalies'''<ref name="urlClassification | International Society for the Study of Vascular Anomalies">{{cite web |url=http://www.issva.org/classification |title=Classification &#124; International Society for the Study of Vascular Anomalies |format= |work= |accessdate=}}</ref></small>
@@ Line 40: / Line 40: @@
 {| class="wikitable" style="width:40%; height:100px" border="1"
 |+
-! colspan="2" style="background:#4479BA; color: #FFFFFF;" align="center" +|Association with other lesions
+! colspan="2" style="background:#4479BA; color: #FFFFFF;" align="center" + |Association with other lesions
 |-
-|style="background:#DCDCDC;" align="center" + |PHACE association /
+| style="background:#DCDCDC;" align="center" + |PHACE association /
 syndrome
 |Posterior fossa malformations, Hemangioma, Arterial
@@ Line 49: / Line 49: @@
 sternal clefting and ⁄ or supraumbilical raphe
 |-
-| rowspan="2" style="background:#DCDCDC;" align="center" +|LUMBAR (SACRAL,
+| rowspan="2" style="background:#DCDCDC;" align="center" + |LUMBAR (SACRAL,
 PELVIS) association /
@@ Line 61: / Line 61: @@
 | colspan="2" style="background:#7d7d7d; color: #FFFFFF;" + |<small>'''Adapted from International Society for the Study of Vascular Anomalies'''<ref name="urlClassification | International Society for the Study of Vascular Anomalies">{{cite web |url=http://www.issva.org/classification |title=Classification &#124; International Society for the Study of Vascular Anomalies |format= |work= |accessdate=}}</ref></small>
 |}
-* Most common [[tumor]] of [[infancy]]. Usually appearing after [[birth]], [[infantile hemangiomas]] undergo a period of proliferation in few weeks after [[birth]] followed by regression and involution in first year of life. Superficial [[lesions]] appear as red or “strawberry” colored nodules, papules, or plaques while deeper [[hemangiomas]] are typically bluish or skin colored. Mixed [[tumors]], involving both [[epidermis]] and deeper structures, may display characteristics of both. They may also be classified as focal, that appear in a specific [[anatomical]] area, and segmental that shows varied pattern of growth following developmental growth regions. Segmental type is often associated with other developmental abnormalities.<ref name="pmid28402073">{{cite journal |vauthors=Smith CJF, Friedlander SF, Guma M, Kavanaugh A, Chambers CD |title=Infantile Hemangiomas: An Updated Review on Risk Factors, Pathogenesis, and Treatment |journal=Birth Defects Res |volume=109 |issue=11 |pages=809–815 |date=July 2017 |pmid=28402073 |pmc=5839165 |doi=10.1002/bdr2.1023 |url=}}</ref><ref name="pmid12472344">{{cite journal |vauthors=Chiller KG, Passaro D, Frieden IJ |title=Hemangiomas of infancy: clinical characteristics, morphologic subtypes, and their relationship to race, ethnicity, and sex |journal=Arch Dermatol |volume=138 |issue=12 |pages=1567–76 |date=December 2002 |pmid=12472344 |doi= |url=}}</ref><ref name="pmid22229118">{{cite journal |vauthors=Greenberger S, Bischoff J |title=Infantile hemangioma-mechanism(s) of drug action on a vascular tumor |journal=Cold Spring Harb Perspect Med |volume=1 |issue=1 |pages=a006460 |date=September 2011 |pmid=22229118 |pmc=3234458 |doi=10.1101/cshperspect.a006460 |url=}}</ref>
+* Most common [[tumor]] of [[infancy]]. Usually appearing after [[birth]], infantile hemangiomas undergo a period of proliferation in few weeks after [[birth]] followed by regression and involution in first year of life. Superficial [[lesions]] appear as red or “strawberry” colored nodules, papules, or plaques while deeper [[hemangiomas]] are typically bluish or skin colored. Mixed [[tumors]], involving both [[epidermis]] and deeper structures, may display characteristics of both. They may also be classified as focal, that appear in a specific [[anatomical]] area, and segmental that shows varied pattern of growth following developmental growth regions. Segmental type is often associated with other developmental abnormalities.<ref name="pmid28402073">{{cite journal |vauthors=Smith CJF, Friedlander SF, Guma M, Kavanaugh A, Chambers CD |title=Infantile Hemangiomas: An Updated Review on Risk Factors, Pathogenesis, and Treatment |journal=Birth Defects Res |volume=109 |issue=11 |pages=809–815 |date=July 2017 |pmid=28402073 |pmc=5839165 |doi=10.1002/bdr2.1023 |url=}}</ref><ref name="pmid12472344">{{cite journal |vauthors=Chiller KG, Passaro D, Frieden IJ |title=Hemangiomas of infancy: clinical characteristics, morphologic subtypes, and their relationship to race, ethnicity, and sex |journal=Arch Dermatol |volume=138 |issue=12 |pages=1567–76 |date=December 2002 |pmid=12472344 |doi= |url=}}</ref><ref name="pmid22229118">{{cite journal |vauthors=Greenberger S, Bischoff J |title=Infantile hemangioma-mechanism(s) of drug action on a vascular tumor |journal=Cold Spring Harb Perspect Med |volume=1 |issue=1 |pages=a006460 |date=September 2011 |pmid=22229118 |pmc=3234458 |doi=10.1101/cshperspect.a006460 |url=}}</ref>
-* Rarely, [[infantile hemangioms]] can cause life-threatening [[complications]] such as [[congestive cardiac failure]], respiratory difficulty and [[respiratory]] compromise, and loss of [[vision]]. There may also be long-term sequela including permanent disfigurement and [[scarring]]. If [[lesions]] are multiple, there is an increased risk of visceral involvement. There may be an association with certain syndromes such as [[PHACE syndrome]].<ref name="pmid28402073">{{cite journal |vauthors=Smith CJF, Friedlander SF, Guma M, Kavanaugh A, Chambers CD |title=Infantile Hemangiomas: An Updated Review on Risk Factors, Pathogenesis, and Treatment |journal=Birth Defects Res |volume=109 |issue=11 |pages=809–815 |date=July 2017 |pmid=28402073 |pmc=5839165 |doi=10.1002/bdr2.1023 |url=}}</ref><ref name="pmid29924216">{{cite journal |vauthors=Rotter A, Samorano LP, Rivitti-Machado MC, Oliveira ZNP, Gontijo B |title=PHACE syndrome: clinical manifestations, diagnostic criteria, and management |journal=An Bras Dermatol |volume=93 |issue=3 |pages=405–411 |date=June 2018 |pmid=29924216 |pmc=6001075 |doi=10.1590/abd1806-4841.20187693 |url=}}</ref>
+* Rarely, [[infantile hemangioms]] can cause life-threatening [[complications]] such as [[congestive cardiac failure]], respiratory difficulty and [[respiratory]] compromise, and loss of [[vision]]. There may also be long-term sequela including permanent disfigurement and [[scarring]]. If [[lesions]] are multiple, there is an increased risk of visceral involvement. There may be an association with certain syndromes such as PHACE syndrome.<ref name="pmid28402073">{{cite journal |vauthors=Smith CJF, Friedlander SF, Guma M, Kavanaugh A, Chambers CD |title=Infantile Hemangiomas: An Updated Review on Risk Factors, Pathogenesis, and Treatment |journal=Birth Defects Res |volume=109 |issue=11 |pages=809–815 |date=July 2017 |pmid=28402073 |pmc=5839165 |doi=10.1002/bdr2.1023 |url=}}</ref><ref name="pmid29924216">{{cite journal |vauthors=Rotter A, Samorano LP, Rivitti-Machado MC, Oliveira ZNP, Gontijo B |title=PHACE syndrome: clinical manifestations, diagnostic criteria, and management |journal=An Bras Dermatol |volume=93 |issue=3 |pages=405–411 |date=June 2018 |pmid=29924216 |pmc=6001075 |doi=10.1590/abd1806-4841.20187693 |url=}}</ref>
-* Some studies have indicated autosomal-dominant and maternal patterns of [[inheritance]]. Some studies suggest that environmental factors play the key role. Some [[risk factors]] that have been identified in association with [[infantile hemangioma]] include [[female]] [[gender]], [[preterm birth]], low weight at [[birth]], increasing maternal age at [[birth]], [[placenta previa]], [[pre-eclampsia]], [[progesterone]] use by mother, and Caucasian race.<ref name="pmid27940781">{{cite journal |vauthors=Castrén E, Salminen P, Vikkula M, Pitkäranta A, Klockars T |title=Inheritance Patterns of Infantile Hemangioma |journal=Pediatrics |volume=138 |issue=5 |pages= |date=November 2016 |pmid=27940781 |doi=10.1542/peds.2016-1623 |url=}}</ref><ref name="pmid28402073">{{cite journal |vauthors=Smith CJF, Friedlander SF, Guma M, Kavanaugh A, Chambers CD |title=Infantile Hemangiomas: An Updated Review on Risk Factors, Pathogenesis, and Treatment |journal=Birth Defects Res |volume=109 |issue=11 |pages=809–815 |date=July 2017 |pmid=28402073 |pmc=5839165 |doi=10.1002/bdr2.1023 |url=}}</ref><ref name="pmid17307549">{{cite journal |vauthors=Haggstrom AN, Drolet BA, Baselga E, Chamlin SL, Garzon MC, Horii KA, Lucky AW, Mancini AJ, Metry DW, Newell B, Nopper AJ, Frieden IJ |title=Prospective study of infantile hemangiomas: demographic, prenatal, and perinatal characteristics |journal=J. Pediatr. |volume=150 |issue=3 |pages=291–4 |date=March 2007 |pmid=17307549 |doi=10.1016/j.jpeds.2006.12.003 |url=}}</ref><ref name="pmid18940356">{{cite journal |vauthors=Drolet BA, Swanson EA, Frieden IJ |title=Infantile hemangiomas: an emerging health issue linked to an increased rate of low birth weight infants |journal=J. Pediatr. |volume=153 |issue=5 |pages=712–5, 715.e1 |date=November 2008 |pmid=18940356 |doi=10.1016/j.jpeds.2008.05.043 |url=}}</ref>
+* Some studies have indicated [[Autosomal dominant|autosomal-dominant]] and maternal patterns of [[inheritance]]. Some studies suggest that environmental factors play the key role. Some [[risk factors]] that have been identified in association with [[infantile hemangioma]] include [[female]] [[gender]], [[preterm birth]], low weight at [[birth]], increasing maternal age at [[birth]], [[placenta previa]], [[pre-eclampsia]], [[progesterone]] use by mother, and Caucasian race.<ref name="pmid27940781">{{cite journal |vauthors=Castrén E, Salminen P, Vikkula M, Pitkäranta A, Klockars T |title=Inheritance Patterns of Infantile Hemangioma |journal=Pediatrics |volume=138 |issue=5 |pages= |date=November 2016 |pmid=27940781 |doi=10.1542/peds.2016-1623 |url=}}</ref><ref name="pmid28402073">{{cite journal |vauthors=Smith CJF, Friedlander SF, Guma M, Kavanaugh A, Chambers CD |title=Infantile Hemangiomas: An Updated Review on Risk Factors, Pathogenesis, and Treatment |journal=Birth Defects Res |volume=109 |issue=11 |pages=809–815 |date=July 2017 |pmid=28402073 |pmc=5839165 |doi=10.1002/bdr2.1023 |url=}}</ref><ref name="pmid17307549">{{cite journal |vauthors=Haggstrom AN, Drolet BA, Baselga E, Chamlin SL, Garzon MC, Horii KA, Lucky AW, Mancini AJ, Metry DW, Newell B, Nopper AJ, Frieden IJ |title=Prospective study of infantile hemangiomas: demographic, prenatal, and perinatal characteristics |journal=J. Pediatr. |volume=150 |issue=3 |pages=291–4 |date=March 2007 |pmid=17307549 |doi=10.1016/j.jpeds.2006.12.003 |url=}}</ref><ref name="pmid18940356">{{cite journal |vauthors=Drolet BA, Swanson EA, Frieden IJ |title=Infantile hemangiomas: an emerging health issue linked to an increased rate of low birth weight infants |journal=J. Pediatr. |volume=153 |issue=5 |pages=712–5, 715.e1 |date=November 2008 |pmid=18940356 |doi=10.1016/j.jpeds.2008.05.043 |url=}}</ref>
 * The [[diagnosis]] is made clinically and a thorough investigation should be carried out for visceral [[hemangiomas]] and other associative abnormalities if suspicion arises. Majority of these [[lesions]] do not require any treatment but treatment is indicated if there is risk for [[complications]] such as visual or respiratory involvement. Elective treatment is also offered to prevent disfigurement or [[scarring]]. Recently there have been an increased usage of oral [[beta-blockers]] such as [[timolol]] over systemic [[glucocorticoids]] because of higher efficacy.  [[Vincristine]] and [[interferon alpha]] have been used in some high risk [[hemangiomas]] but carry the risk of severe [[complications]]. Visceral hemangioms may require [[embolization]] or [[surgery]] if they do not respond to systemic therapy. [[Laser]] therapy especially PDL is another modality used in cases of [[hemangiomas]] unresponsive to [[medication]].<ref name="pmid28402073">{{cite journal |vauthors=Smith CJF, Friedlander SF, Guma M, Kavanaugh A, Chambers CD |title=Infantile Hemangiomas: An Updated Review on Risk Factors, Pathogenesis, and Treatment |journal=Birth Defects Res |volume=109 |issue=11 |pages=809–815 |date=July 2017 |pmid=28402073 |pmc=5839165 |doi=10.1002/bdr2.1023 |url=}}</ref><ref name="pmid26416928">{{cite journal |vauthors=Darrow DH, Greene AK, Mancini AJ, Nopper AJ |title=Diagnosis and Management of Infantile Hemangioma: Executive Summary |journal=Pediatrics |volume=136 |issue=4 |pages=786–91 |date=October 2015 |pmid=26416928 |doi=10.1542/peds.2015-2482 |url=}}</ref><ref name="pmid14871317">{{cite journal |vauthors=Ceisler EJ, Santos L, Blei F |title=Periocular hemangiomas: what every physician should know |journal=Pediatr Dermatol |volume=21 |issue=1 |pages=1–9 |date=2004 |pmid=14871317 |doi= |url=}}</ref><ref name="pmid26859502">{{cite journal |vauthors=Tal R, Dotan M, Lorber A |title=Approach to haemangiomatosis causing congestive heart failure |journal=Acta Paediatr. |volume=105 |issue=6 |pages=600–4 |date=June 2016 |pmid=26859502 |doi=10.1111/apa.13359 |url=}}</ref><ref name="pmid21788220">{{cite journal |vauthors=Hogeling M, Adams S, Wargon O |title=A randomized controlled trial of propranolol for infantile hemangiomas |journal=Pediatrics |volume=128 |issue=2 |pages=e259–66 |date=August 2011 |pmid=21788220 |doi=10.1542/peds.2010-0029 |url=}}</ref><ref name="pmid11559219">{{cite journal |vauthors=Bennett ML, Fleischer AB, Chamlin SL, Frieden IJ |title=Oral corticosteroid use is effective for cutaneous hemangiomas: an evidence-based evaluation |journal=Arch Dermatol |volume=137 |issue=9 |pages=1208–13 |date=September 2001 |pmid=11559219 |doi= |url=}}</ref><ref name="pmid12102167">{{cite journal |vauthors=Perez J, Pardo J, Gomez C |title=Vincristine--an effective treatment of corticoid-resistant life-threatening infantile hemangiomas |journal=Acta Oncol |volume=41 |issue=2 |pages=197–9 |date=2002 |pmid=12102167 |doi= |url=}}</ref><ref name="pmid20936416">{{cite journal |vauthors=Schiestl C, Neuhaus K, Zoller S, Subotic U, Forster-Kuebler I, Michels R, Balmer C, Weibel L |title=Efficacy and safety of propranolol as first-line treatment for infantile hemangiomas |journal=Eur. J. Pediatr. |volume=170 |issue=4 |pages=493–501 |date=April 2011 |pmid=20936416 |doi=10.1007/s00431-010-1324-2 |url=}}</ref><ref name="pmid26711436">{{cite journal |vauthors=Chinnadurai S, Sathe NA, Surawicz T |title=Laser treatment of infantile hemangioma: A systematic review |journal=Lasers Surg Med |volume=48 |issue=3 |pages=221–33 |date=March 2016 |pmid=26711436 |doi=10.1002/lsm.22455 |url=}}</ref>
 ===Congenital hemangioma===
-* Rare [[tumor]] that arises in utero and presents as fully developed [[lesion]] at [[birth]]. Following [[birth]] they can regress completely, partially or not at all. So they can be classified as Rapidly involuting (RICH), Non-involuting (NICH), Partially involuting (PICH).<ref name="urlwww.issva.org">{{cite web |url=http://www.issva.org/UserFiles/file/ISSVA-Classification-2018.pdf |title=www.issva.org |format= |work= |accessdate=}}</ref><ref name="pmid27058448">{{cite journal |vauthors=Ayturk UM, Couto JA, Hann S, Mulliken JB, Williams KL, Huang AY, Fishman SJ, Boyd TK, Kozakewich HP, Bischoff J, Greene AK, Warman ML |title=Somatic Activating Mutations in GNAQ and GNA11 Are Associated with Congenital Hemangioma |journal=Am. J. Hum. Genet. |volume=98 |issue=4 |pages=789–95 |date=April 2016 |pmid=27058448 |pmc=4833432 |doi=10.1016/j.ajhg.2016.03.009 |url=}}</ref>
+* Rare [[tumor]] that arises in utero and presents as fully developed [[lesion]] at [[birth]]. Following [[birth]] they can regress completely, partially or not at all. So they can be classified as rapidly involuting (RICH), non-involuting (NICH), partially involuting (PICH).<ref name="urlwww.issva.org">{{cite web |url=http://www.issva.org/UserFiles/file/ISSVA-Classification-2018.pdf |title=www.issva.org |format= |work= |accessdate=}}</ref><ref name="pmid27058448">{{cite journal |vauthors=Ayturk UM, Couto JA, Hann S, Mulliken JB, Williams KL, Huang AY, Fishman SJ, Boyd TK, Kozakewich HP, Bischoff J, Greene AK, Warman ML |title=Somatic Activating Mutations in GNAQ and GNA11 Are Associated with Congenital Hemangioma |journal=Am. J. Hum. Genet. |volume=98 |issue=4 |pages=789–95 |date=April 2016 |pmid=27058448 |pmc=4833432 |doi=10.1016/j.ajhg.2016.03.009 |url=}}</ref>
 *# '''Rapidly involuting (RICH)'''
-*#* This fast flow [[tumor]] can be detected in utero and appears as raised gray single [[lesions]] with dilated [[veins]], [[telangiectasias]] and a halo at birth. This tumor may be complicated by [[thrombocytopenia]] and [[congestive cardiac failure]] due to its high-flow nature. [[Tumor]] typically regresses spontaneously in 1 to 2 years of life. Sometimes it can occur in [liver]] where it follows the same pattern of involution as that of skin.<ref name="pmid27058448">{{cite journal |vauthors=Ayturk UM, Couto JA, Hann S, Mulliken JB, Williams KL, Huang AY, Fishman SJ, Boyd TK, Kozakewich HP, Bischoff J, Greene AK, Warman ML |title=Somatic Activating Mutations in GNAQ and GNA11 Are Associated with Congenital Hemangioma |journal=Am. J. Hum. Genet. |volume=98 |issue=4 |pages=789–95 |date=April 2016 |pmid=27058448 |pmc=4833432 |doi=10.1016/j.ajhg.2016.03.009 |url=}}</ref><ref name="pmid15018449">{{cite journal |vauthors=Berenguer B, Mulliken JB, Enjolras O, Boon LM, Wassef M, Josset P, Burrows PE, Perez-Atayde AR, Kozakewich HP |title=Rapidly involuting congenital hemangioma: clinical and histopathologic features |journal=Pediatr. Dev. Pathol. |volume=6 |issue=6 |pages=495–510 |date=2003 |pmid=15018449 |doi= |url=}}</ref>
+*#* This fast flow [[tumor]] can be detected in utero and appears as raised gray single [[lesions]] with dilated [[veins]], [[telangiectasias]] and a halo at birth.
+*#* This tumor may be complicated by [[thrombocytopenia]] and [[congestive cardiac failure]] due to its high-flow nature.
+*#* [[Tumor]] typically regresses spontaneously in 1 to 2 years of life. Sometimes it can occur in [liver]] where it follows the same pattern of involution as that of skin.<ref name="pmid27058448">{{cite journal |vauthors=Ayturk UM, Couto JA, Hann S, Mulliken JB, Williams KL, Huang AY, Fishman SJ, Boyd TK, Kozakewich HP, Bischoff J, Greene AK, Warman ML |title=Somatic Activating Mutations in GNAQ and GNA11 Are Associated with Congenital Hemangioma |journal=Am. J. Hum. Genet. |volume=98 |issue=4 |pages=789–95 |date=April 2016 |pmid=27058448 |pmc=4833432 |doi=10.1016/j.ajhg.2016.03.009 |url=}}</ref><ref name="pmid15018449">{{cite journal |vauthors=Berenguer B, Mulliken JB, Enjolras O, Boon LM, Wassef M, Josset P, Burrows PE, Perez-Atayde AR, Kozakewich HP |title=Rapidly involuting congenital hemangioma: clinical and histopathologic features |journal=Pediatr. Dev. Pathol. |volume=6 |issue=6 |pages=495–510 |date=2003 |pmid=15018449 |doi= |url=}}</ref>
 *# '''Non-involuting (NICH)'''
-*#* Fast flow [[tumor]] that presents as well defined, [[plaque]] like [[lesion]] with pink to purple color, [[telangiectasias]] and pale borders. Typically remains stable but there have been some reports of growth and expansion.<ref name="pmid27058448">{{cite journal |vauthors=Ayturk UM, Couto JA, Hann S, Mulliken JB, Williams KL, Huang AY, Fishman SJ, Boyd TK, Kozakewich HP, Bischoff J, Greene AK, Warman ML |title=Somatic Activating Mutations in GNAQ and GNA11 Are Associated with Congenital Hemangioma |journal=Am. J. Hum. Genet. |volume=98 |issue=4 |pages=789–95 |date=April 2016 |pmid=27058448 |pmc=4833432 |doi=10.1016/j.ajhg.2016.03.009 |url=}}</ref>
+*#* Fast flow [[tumor]] that presents as well defined, [[plaque]] like [[lesion]] with pink to purple color, [[telangiectasias]] and pale borders.
+*#* Typically remains stable but there have been some reports of growth and expansion.<ref name="pmid27058448">{{cite journal |vauthors=Ayturk UM, Couto JA, Hann S, Mulliken JB, Williams KL, Huang AY, Fishman SJ, Boyd TK, Kozakewich HP, Bischoff J, Greene AK, Warman ML |title=Somatic Activating Mutations in GNAQ and GNA11 Are Associated with Congenital Hemangioma |journal=Am. J. Hum. Genet. |volume=98 |issue=4 |pages=789–95 |date=April 2016 |pmid=27058448 |pmc=4833432 |doi=10.1016/j.ajhg.2016.03.009 |url=}}</ref>
 *# '''Partially involuting (PICH)'''
 *#* These lesions start involution as RICH but become stable over time and persist as NICH.<ref name="pmid24176519">{{cite journal |vauthors=Nasseri E, Piram M, McCuaig CC, Kokta V, Dubois J, Powell J |title=Partially involuting congenital hemangiomas: a report of 8 cases and review of the literature |journal=J. Am. Acad. Dermatol. |volume=70 |issue=1 |pages=75–9 |date=January 2014 |pmid=24176519 |doi=10.1016/j.jaad.2013.09.018 |url=}}</ref>
-* [[Somatic]] [[mutations]] in GNAQ/GNA11 are thought to cause the congenital [[hemangioma]]. GNAQ and its paralogue GNA11 function in intracellular signaling pathways as Gq alpha subunit.<ref name="pmid27058448">{{cite journal |vauthors=Ayturk UM, Couto JA, Hann S, Mulliken JB, Williams KL, Huang AY, Fishman SJ, Boyd TK, Kozakewich HP, Bischoff J, Greene AK, Warman ML |title=Somatic Activating Mutations in GNAQ and GNA11 Are Associated with Congenital Hemangioma |journal=Am. J. Hum. Genet. |volume=98 |issue=4 |pages=789–95 |date=April 2016 |pmid=27058448 |pmc=4833432 |doi=10.1016/j.ajhg.2016.03.009 |url=}}</ref><ref name="urlError 403">{{cite web |url=https://www.omim.org/entry/139313 |title=Error 403 |format= |work= |accessdate=}}</ref>
+* [[Somatic]] [[mutations]] in GNAQ/GNA11 are thought to cause the congenital [[hemangioma]]. GNAQ and its paralogue GNA11 function in [[intracellular]] signaling pathways as Gq alpha subunit.<ref name="pmid27058448">{{cite journal |vauthors=Ayturk UM, Couto JA, Hann S, Mulliken JB, Williams KL, Huang AY, Fishman SJ, Boyd TK, Kozakewich HP, Bischoff J, Greene AK, Warman ML |title=Somatic Activating Mutations in GNAQ and GNA11 Are Associated with Congenital Hemangioma |journal=Am. J. Hum. Genet. |volume=98 |issue=4 |pages=789–95 |date=April 2016 |pmid=27058448 |pmc=4833432 |doi=10.1016/j.ajhg.2016.03.009 |url=}}</ref><ref name="urlError 403">{{cite web |url=https://www.omim.org/entry/139313 |title=Error 403 |format= |work= |accessdate=}}</ref>
 * [[Diagnosis]] is usually clinical but [[imaging]] techniques such as [[MRI]], [[CT scan]], [[contrast-enhanced ultrasound]] and later [[biopsy]] can be considered if required. [[Surgical excision]] should be considered in case of complications, NICH and PICH.<ref name="pmid29922526">{{cite journal |vauthors=Ramphul K, Mejias SG, Ramphul-Sicharam Y, Sonaye R |title=Congenital Hemangioma: A Case Report of a Finding Every Physician Should Know |journal=Cureus |volume=10 |issue=4 |pages=e2485 |date=April 2018 |pmid=29922526 |pmc=6003795 |doi=10.7759/cureus.2485 |url=}}</ref><ref name="pmid29971555">{{cite journal |vauthors=Thimm MA, Rhee D, Takemoto CM, Karnsakul W, Cuffari C, Guerrerio AL, Garcia A, Gearhart J, Huisman TAGM, Hwang M |title=Diagnosis of congenital and acquired focal lesions in the neck, abdomen, and pelvis with contrast-enhanced ultrasound: a pictorial essay |journal=Eur. J. Pediatr. |volume=177 |issue=10 |pages=1459–1470 |date=October 2018 |pmid=29971555 |doi=10.1007/s00431-018-3197-8 |url=}}</ref>
 ===Tufted angioma===
 * [[Benign]] [[tumor]] that is characterized by dense clumps of [[endothelial]] [[cells]] and [[capillaries]] located in dermis. Most [[lesions]] appear in adolescence but some can manifest at birth or late in [[adulthood]]. Clinical presentation varies but majority of [[lesions]] appear as solitary stained area or elevation that later forms red-purple or dusky red plaque while some [[lesions]] appear as firm nodules. [[Lesions]] are usually solitary, asymptomatic but tender with occasional painful episodes and located on [[trunk]] and [[neck]] in majority of the cases. Some cases of multi-focal tufted angiomas have also been reported.<ref name="pmid26225332">{{cite journal |vauthors=Prasuna A, Rao PN |title=A tufted angioma |journal=Indian Dermatol Online J |volume=6 |issue=4 |pages=266–8 |date=2015 |pmid=26225332 |pmc=4513407 |doi=10.4103/2229-5178.160259 |url=}}</ref><ref name="pmid2644316">{{cite journal |vauthors=Jones EW, Orkin M |title=Tufted angioma (angioblastoma). A benign progressive angioma, not to be confused with Kaposi's sarcoma or low-grade angiosarcoma |journal=J. Am. Acad. Dermatol. |volume=20 |issue=2 Pt 1 |pages=214–25 |date=February 1989 |pmid=2644316 |doi= |url=}}</ref><ref name="pmid26312663">{{cite journal |vauthors=Pesapane F, Nazzaro G, Alberti-Violetti S, Gianotti R |title=A case of acquired tufted angioma in adulthood |journal=An Bras Dermatol |volume=90 |issue=3 Suppl 1 |pages=16–8 |date=2015 |pmid=26312663 |pmc=4540497 |doi=10.1590/abd1806-4841.20153733 |url=}}</ref><ref name="pmid26288441">{{cite journal |vauthors=Bandyopadhyay D, Saha A |title=Multifocal Annular Tufted Angioma: An Uncommon Clinical Entity |journal=Indian J Dermatol |volume=60 |issue=4 |pages=422 |date=2015 |pmid=26288441 |pmc=4533571 |doi=10.4103/0019-5154.160528 |url=}}</ref>
 * [[Tufted angioma]] can be associated with [[Kasabach-Merritt phenomenon]].<ref name="pmid26288441">{{cite journal |vauthors=Bandyopadhyay D, Saha A |title=Multifocal Annular Tufted Angioma: An Uncommon Clinical Entity |journal=Indian J Dermatol |volume=60 |issue=4 |pages=422 |date=2015 |pmid=26288441 |pmc=4533571 |doi=10.4103/0019-5154.160528 |url=}}</ref><ref name="urlwww.issva.org">{{cite web |url=http://www.issva.org/UserFiles/file/ISSVA-Classification-2018.pdf |title=www.issva.org |format= |work= |accessdate=}}</ref><ref name="pmid26225332">{{cite journal |vauthors=Prasuna A, Rao PN |title=A tufted angioma |journal=Indian Dermatol Online J |volume=6 |issue=4 |pages=266–8 |date=2015 |pmid=26225332 |pmc=4513407 |doi=10.4103/2229-5178.160259 |url=}}</ref>
-* Somatic activating GNA14 c.614A>T (p.Gln205Leu) mutations have been found in some tufted angiomas. These mutations may cause the cell growth to be growth-factor independent by up-regulating the MAPK pathway.<ref name="pmid27476652">{{cite journal |vauthors=Lim YH, Bacchiocchi A, Qiu J, Straub R, Bruckner A, Bercovitch L, Narayan D, McNiff J, Ko C, Robinson-Bostom L, Antaya R, Halaban R, Choate KA |title=GNA14 Somatic Mutation Causes Congenital and Sporadic Vascular Tumors by MAPK Activation |journal=Am. J. Hum. Genet. |volume=99 |issue=2 |pages=443–50 |date=August 2016 |pmid=27476652 |pmc=4974082 |doi=10.1016/j.ajhg.2016.06.010 |url=}}</ref><ref name="urlGNA14 G protein subunit alpha 14 [Homo sapiens (human)] - Gene - NCBI">{{cite web |url=https://www.ncbi.nlm.nih.gov/gene/9630 |title=GNA14 G protein subunit alpha 14 [Homo sapiens (human)] - Gene - NCBI |format= |work= |accessdate=}}</ref>
+* Somatic activating GNA14 c.614A>T (p.Gln205Leu) mutations have been found in some tufted angiomas. These [[mutations]] may cause the [[cell growth]] to be growth-factor independent by up-regulating the MAPK pathway.<ref name="pmid27476652">{{cite journal |vauthors=Lim YH, Bacchiocchi A, Qiu J, Straub R, Bruckner A, Bercovitch L, Narayan D, McNiff J, Ko C, Robinson-Bostom L, Antaya R, Halaban R, Choate KA |title=GNA14 Somatic Mutation Causes Congenital and Sporadic Vascular Tumors by MAPK Activation |journal=Am. J. Hum. Genet. |volume=99 |issue=2 |pages=443–50 |date=August 2016 |pmid=27476652 |pmc=4974082 |doi=10.1016/j.ajhg.2016.06.010 |url=}}</ref><ref name="urlGNA14 G protein subunit alpha 14 [Homo sapiens (human)] - Gene - NCBI">{{cite web |url=https://www.ncbi.nlm.nih.gov/gene/9630 |title=GNA14 G protein subunit alpha 14 [Homo sapiens (human)] - Gene - NCBI |format= |work= |accessdate=}}</ref>
-* [[Imaging]] such as [[MRI]] and [[ultrasound]] can add into clinical [[diagnosis]] to differentiate tufted angioma from similar [[lesions]] such as [[Kaposi sarcoma]], [[kaposiform hemangioendothelioma]] and [[infantile hemangioma]]. [[Biopsy]] and histopathological studies are sometimes required for accurate [[diagnosis]]. [[Surgical excision]] is the treatment modality but some recommend to only observe the [[lesions]] due to its slow growth and possible remission. Other therapies include [[radiation]] beam therapy, [[cryosurgery]], [[corticosteroids]] and [[pulsed laser therapy]]. [[Vincristine]] and [[embolization]] has been used with success in angiomas associated with [[Kasabach-Merritt phenomenon]].<ref name="pmid26288441">{{cite journal |vauthors=Bandyopadhyay D, Saha A |title=Multifocal Annular Tufted Angioma: An Uncommon Clinical Entity |journal=Indian J Dermatol |volume=60 |issue=4 |pages=422 |date=2015 |pmid=26288441 |pmc=4533571 |doi=10.4103/0019-5154.160528 |url=}}</ref><ref name="pmid21965850">{{cite journal |vauthors=Ghosh SK, Bandyopadhyay D, Ghosh A, Biswas SK, Barma KD |title=Acquired multifocal tufted angiomas in an immunocompetent young adult |journal=Indian J Dermatol |volume=56 |issue=4 |pages=412–4 |date=July 2011 |pmid=21965850 |pmc=3179005 |doi=10.4103/0019-5154.84741 |url=}}</ref><ref name="pmid20644037">{{cite journal |vauthors=Osio A, Fraitag S, Hadj-Rabia S, Bodemer C, de Prost Y, Hamel-Teillac D |title=Clinical spectrum of tufted angiomas in childhood: a report of 13 cases and a review of the literature |journal=Arch Dermatol |volume=146 |issue=7 |pages=758–63 |date=July 2010 |pmid=20644037 |doi=10.1001/archdermatol.2010.135 |url=}}</ref><ref name="pmid17520468">{{cite journal |vauthors=Chiu CS, Yang LC, Hong HS, Kuan YZ |title=Treatment of a tufted angioma with intense pulsed light |journal=J Dermatolog Treat |volume=18 |issue=2 |pages=109–11 |date=2007 |pmid=17520468 |doi=10.1080/09546630601028752 |url=}}</ref><ref name="pmid18301012">{{cite journal |vauthors=Yesudian PD, Parslew R, Klafowski J, Gould D, Pizer B |title=Tufted angioma-associated Kasabach-Merritt syndrome treated with embolization and vincristine |journal=Plast. Reconstr. Surg. |volume=121 |issue=2 |pages=692–3 |date=February 2008 |pmid=18301012 |doi=10.1097/01.prs.0000298541.92722.5d |url=}}</ref><ref name="pmid29166525">{{cite journal |vauthors=Silva CMD, Schettini APM, Santos M, Chirano CAR |title=Tufted angioma |journal=An Bras Dermatol |volume=92 |issue=5 |pages=742–743 |date=2017 |pmid=29166525 |pmc=5674719 |doi=10.1590/abd1806-4841.20175896 |url=}}</ref><ref name="pmid28623854">{{cite journal |vauthors=Kimura R, Yoshida Y, Wakumoto K, Yamada N, Yamamoto O |title=Successful treatment of tufted angioma with low-dose electron beam radiation therapy: Report of two cases |journal=J. Dermatol. |volume=44 |issue=10 |pages=e262–e263 |date=October 2017 |pmid=28623854 |doi=10.1111/1346-8138.13936 |url=}}</ref>
+* [[Imaging]] such as [[MRI]] and [[ultrasound]] can add into clinical [[diagnosis]] to differentiate [[tufted angioma]] from similar [[lesions]] such as [[Kaposi sarcoma]], [[kaposiform hemangioendothelioma]] and [[infantile hemangioma]]. [[Biopsy]] and histopathological studies are sometimes required for accurate [[diagnosis]].
-For more information on Tufted angioma, [[Tufted angioma#Tufted angioma|click here]]
+* [[Surgical excision]] is the treatment modality but some recommend to only observe the [[lesions]] due to its slow growth and possible remission. Other therapies include [[radiation]] beam therapy, [[cryosurgery]], [[corticosteroids]], and [[pulsed laser therapy]]. [[Vincristine]] and [[embolization]] has been used with success in angiomas associated with [[Kasabach-Merritt phenomenon]].<ref name="pmid26288441">{{cite journal |vauthors=Bandyopadhyay D, Saha A |title=Multifocal Annular Tufted Angioma: An Uncommon Clinical Entity |journal=Indian J Dermatol |volume=60 |issue=4 |pages=422 |date=2015 |pmid=26288441 |pmc=4533571 |doi=10.4103/0019-5154.160528 |url=}}</ref><ref name="pmid21965850">{{cite journal |vauthors=Ghosh SK, Bandyopadhyay D, Ghosh A, Biswas SK, Barma KD |title=Acquired multifocal tufted angiomas in an immunocompetent young adult |journal=Indian J Dermatol |volume=56 |issue=4 |pages=412–4 |date=July 2011 |pmid=21965850 |pmc=3179005 |doi=10.4103/0019-5154.84741 |url=}}</ref><ref name="pmid20644037">{{cite journal |vauthors=Osio A, Fraitag S, Hadj-Rabia S, Bodemer C, de Prost Y, Hamel-Teillac D |title=Clinical spectrum of tufted angiomas in childhood: a report of 13 cases and a review of the literature |journal=Arch Dermatol |volume=146 |issue=7 |pages=758–63 |date=July 2010 |pmid=20644037 |doi=10.1001/archdermatol.2010.135 |url=}}</ref><ref name="pmid17520468">{{cite journal |vauthors=Chiu CS, Yang LC, Hong HS, Kuan YZ |title=Treatment of a tufted angioma with intense pulsed light |journal=J Dermatolog Treat |volume=18 |issue=2 |pages=109–11 |date=2007 |pmid=17520468 |doi=10.1080/09546630601028752 |url=}}</ref><ref name="pmid18301012">{{cite journal |vauthors=Yesudian PD, Parslew R, Klafowski J, Gould D, Pizer B |title=Tufted angioma-associated Kasabach-Merritt syndrome treated with embolization and vincristine |journal=Plast. Reconstr. Surg. |volume=121 |issue=2 |pages=692–3 |date=February 2008 |pmid=18301012 |doi=10.1097/01.prs.0000298541.92722.5d |url=}}</ref><ref name="pmid29166525">{{cite journal |vauthors=Silva CMD, Schettini APM, Santos M, Chirano CAR |title=Tufted angioma |journal=An Bras Dermatol |volume=92 |issue=5 |pages=742–743 |date=2017 |pmid=29166525 |pmc=5674719 |doi=10.1590/abd1806-4841.20175896 |url=}}</ref><ref name="pmid28623854">{{cite journal |vauthors=Kimura R, Yoshida Y, Wakumoto K, Yamada N, Yamamoto O |title=Successful treatment of tufted angioma with low-dose electron beam radiation therapy: Report of two cases |journal=J. Dermatol. |volume=44 |issue=10 |pages=e262–e263 |date=October 2017 |pmid=28623854 |doi=10.1111/1346-8138.13936 |url=}}</ref>
+For more information on [[tufted angioma]], [[Tufted angioma#Tufted angioma|click here]]
 ===Spindle-cell hemangioma===
-* Rare [[benign]] [[tumor]] that manifests as solitary or multiple nodules confined to [[dermis]] and [[subcutaneous tissues]] in almost all of the cases. Histopathologically it appears as solid areas that are cellular and consist of spindle cells seen attached to [[vessel]] walls, and cavernous spaces that can be thrombosed. Size may increase over time and patient usually complains of [[swelling]] and pain. The nodules or masses can be mobile and elastic or can be firm and immobile.<ref name="pmid29780644">{{cite journal |vauthors=Murakami K, Yamamoto K, Sugiura T, Kirita T |title=Spindle Cell Hemangioma in the Mucosa of the Upper Lip: A Case Report and Review of the Literature |journal=Case Rep Dent |volume=2018 |issue= |pages=1370701 |date=2018 |pmid=29780644 |pmc=5892276 |doi=10.1155/2018/1370701 |url=}}</ref><ref name="pmid26266229">{{cite journal |vauthors=Chavva S, Priya MH, Garlapati K, Reddy GS, Gannepalli A |title=Rare Case of Spindle Cell Haemangioma |journal=J Clin Diagn Res |volume=9 |issue=6 |pages=ZD19–21 |date=June 2015 |pmid=26266229 |pmc=4525619 |doi=10.7860/JCDR/2015/11998.6080 |url=}}</ref><ref name="pmid22606579">{{cite journal |vauthors=Minagawa T, Yamao T, Shioya R |title=Spindle cell hemangioendothelioma of the temporal muscle resected with zygomatic osteotomy: a case report of an unusual intramuscular lesion mimicking sarcoma |journal=Case Rep Surg |volume=2011 |issue= |pages=481654 |date=2011 |pmid=22606579 |pmc=3350060 |doi=10.1155/2011/481654 |url=}}</ref>
+* Rare [[benign]] [[tumor]] that manifests as solitary or multiple nodules confined to [[dermis]] and [[subcutaneous tissues]] in almost all of the cases. Histopathologically, it appears as solid areas that are cellular and consist of [[spindle cells]] seen attached to [[vessel]] walls, and cavernous spaces that can be [[thrombosed]]. Size may increase over time and patient usually complains of [[swelling]] and pain. The nodules or masses can be mobile and elastic or can be firm and immobile.<ref name="pmid29780644">{{cite journal |vauthors=Murakami K, Yamamoto K, Sugiura T, Kirita T |title=Spindle Cell Hemangioma in the Mucosa of the Upper Lip: A Case Report and Review of the Literature |journal=Case Rep Dent |volume=2018 |issue= |pages=1370701 |date=2018 |pmid=29780644 |pmc=5892276 |doi=10.1155/2018/1370701 |url=}}</ref><ref name="pmid26266229">{{cite journal |vauthors=Chavva S, Priya MH, Garlapati K, Reddy GS, Gannepalli A |title=Rare Case of Spindle Cell Haemangioma |journal=J Clin Diagn Res |volume=9 |issue=6 |pages=ZD19–21 |date=June 2015 |pmid=26266229 |pmc=4525619 |doi=10.7860/JCDR/2015/11998.6080 |url=}}</ref><ref name="pmid22606579">{{cite journal |vauthors=Minagawa T, Yamao T, Shioya R |title=Spindle cell hemangioendothelioma of the temporal muscle resected with zygomatic osteotomy: a case report of an unusual intramuscular lesion mimicking sarcoma |journal=Case Rep Surg |volume=2011 |issue= |pages=481654 |date=2011 |pmid=22606579 |pmc=3350060 |doi=10.1155/2011/481654 |url=}}</ref>
-* Somatic [[mutations]] in IDH1 and IDH2 have been found to be present in 70% of spindle-cell hemangiomas. IDH1 and IDH2 are important [[enzymes]] in cell energy cycles (α-ketoglutarate and NADPH generation).<ref name="pmid22057234">{{cite journal |vauthors=Pansuriya TC, van Eijk R, d'Adamo P, van Ruler MA, Kuijjer ML, Oosting J, Cleton-Jansen AM, van Oosterwijk JG, Verbeke SL, Meijer D, van Wezel T, Nord KH, Sangiorgi L, Toker B, Liegl-Atzwanger B, San-Julian M, Sciot R, Limaye N, Kindblom LG, Daugaard S, Godfraind C, Boon LM, Vikkula M, Kurek KC, Szuhai K, French PJ, Bovée JV |title=Somatic mosaic IDH1 and IDH2 mutations are associated with enchondroma and spindle cell hemangioma in Ollier disease and Maffucci syndrome |journal=Nat. Genet. |volume=43 |issue=12 |pages=1256–61 |date=November 2011 |pmid=22057234 |pmc=3427908 |doi=10.1038/ng.1004 |url=}}</ref><ref name="pmid22343901">{{cite journal |vauthors=Lu C, Ward PS, Kapoor GS, Rohle D, Turcan S, Abdel-Wahab O, Edwards CR, Khanin R, Figueroa ME, Melnick A, Wellen KE, O'Rourke DM, Berger SL, Chan TA, Levine RL, Mellinghoff IK, Thompson CB |title=IDH mutation impairs histone demethylation and results in a block to cell differentiation |journal=Nature |volume=483 |issue=7390 |pages=474–8 |date=February 2012 |pmid=22343901 |pmc=3478770 |doi=10.1038/nature10860 |url=}}</ref>
+* Somatic [[mutations]] in IDH1 and IDH2 have been found to be present in 70% of spindle-cell hemangiomas. IDH1 and IDH2 are important [[enzymes]] in cell energy cycles (α-ketoglutarate and [[Nicotinamide adenine dinucleotide phosphate|NADPH]] generation).<ref name="pmid22057234">{{cite journal |vauthors=Pansuriya TC, van Eijk R, d'Adamo P, van Ruler MA, Kuijjer ML, Oosting J, Cleton-Jansen AM, van Oosterwijk JG, Verbeke SL, Meijer D, van Wezel T, Nord KH, Sangiorgi L, Toker B, Liegl-Atzwanger B, San-Julian M, Sciot R, Limaye N, Kindblom LG, Daugaard S, Godfraind C, Boon LM, Vikkula M, Kurek KC, Szuhai K, French PJ, Bovée JV |title=Somatic mosaic IDH1 and IDH2 mutations are associated with enchondroma and spindle cell hemangioma in Ollier disease and Maffucci syndrome |journal=Nat. Genet. |volume=43 |issue=12 |pages=1256–61 |date=November 2011 |pmid=22057234 |pmc=3427908 |doi=10.1038/ng.1004 |url=}}</ref><ref name="pmid22343901">{{cite journal |vauthors=Lu C, Ward PS, Kapoor GS, Rohle D, Turcan S, Abdel-Wahab O, Edwards CR, Khanin R, Figueroa ME, Melnick A, Wellen KE, O'Rourke DM, Berger SL, Chan TA, Levine RL, Mellinghoff IK, Thompson CB |title=IDH mutation impairs histone demethylation and results in a block to cell differentiation |journal=Nature |volume=483 |issue=7390 |pages=474–8 |date=February 2012 |pmid=22343901 |pmc=3478770 |doi=10.1038/nature10860 |url=}}</ref>
 * [[Diagnosis]] often requires [[biopsy]] and [[imaging]] studies such as [[MRI]] to ascertain the extent of the [[tumor]]. Local excision is the treatment modality of choice with excellent [[prognosis]] in majority of the cases although [[recurrence]] is very common.<ref name="pmid29780644">{{cite journal |vauthors=Murakami K, Yamamoto K, Sugiura T, Kirita T |title=Spindle Cell Hemangioma in the Mucosa of the Upper Lip: A Case Report and Review of the Literature |journal=Case Rep Dent |volume=2018 |issue= |pages=1370701 |date=2018 |pmid=29780644 |pmc=5892276 |doi=10.1155/2018/1370701 |url=}}</ref><ref name="pmid26266229">{{cite journal |vauthors=Chavva S, Priya MH, Garlapati K, Reddy GS, Gannepalli A |title=Rare Case of Spindle Cell Haemangioma |journal=J Clin Diagn Res |volume=9 |issue=6 |pages=ZD19–21 |date=June 2015 |pmid=26266229 |pmc=4525619 |doi=10.7860/JCDR/2015/11998.6080 |url=}}</ref><ref name="pmid22606579">{{cite journal |vauthors=Minagawa T, Yamao T, Shioya R |title=Spindle cell hemangioendothelioma of the temporal muscle resected with zygomatic osteotomy: a case report of an unusual intramuscular lesion mimicking sarcoma |journal=Case Rep Surg |volume=2011 |issue= |pages=481654 |date=2011 |pmid=22606579 |pmc=3350060 |doi=10.1155/2011/481654 |url=}}</ref><ref name="pmid23730241">{{cite journal |vauthors=Gray SS, Eltorky MA, Riascos RF, Montilla RD |title=Spindle cell hemangioma reoccurrence in the hand: case report |journal=Hand (N Y) |volume=7 |issue=2 |pages=194–9 |date=June 2012 |pmid=23730241 |pmc=3351523 |doi=10.1007/s11552-012-9397-1 |url=}}</ref><ref name="pmid8827025">{{cite journal |vauthors=Perkins P, Weiss SW |title=Spindle cell hemangioendothelioma. An analysis of 78 cases with reassessment of its pathogenesis and biologic behavior |journal=Am. J. Surg. Pathol. |volume=20 |issue=10 |pages=1196–204 |date=October 1996 |pmid=8827025 |doi= |url=}}</ref>
 ===Epithelioid hemangioma===
-* Rare [[benign]] [[tumor]] that typically presents as solitary painful nodule on [[head]] and [[neck]]. [[Penis]] is an atypical location. They can involve [[skin]], [[bone]] and [[soft tissues]]. Histopathologically these [[lesions]] are characterized by presence of [[endothelial cells]] that resemble [[epithelial cells]] with evidence of proliferation such as large [[nuclei]] and prominent [[nucleoli]], and often inflammatory infiltrates. [[Vessels]] are typically well-formed. Nuclear atypia is absent.<ref name="pmid25295139">{{cite journal |vauthors=Barber E, Domes T |title=Painful erections secondary to rare epithelioid hemangioma of the penis |journal=Can Urol Assoc J |volume=8 |issue=9-10 |pages=E647–9 |date=September 2014 |pmid=25295139 |pmc=4164556 |doi=10.5489/cuaj.1833 |url=}}</ref><ref name="pmid28159479">{{cite journal |vauthors=Tsikopoulos K, Perdikakis E, Georgiannos D, Bisbinas I |title=Epithelioid hemangioma of the scapula treated with chemoembolization and microwave ablation: Α case report |journal=Acta Orthop Traumatol Turc |volume=52 |issue=2 |pages=157–161 |date=March 2018 |pmid=28159479 |pmc=6136344 |doi=10.1016/j.aott.2017.01.003 |url=}}</ref><ref name="pmid24314244">{{cite journal |vauthors=Gong QX, Fan QH, Xie J, Su ZL, Zhang MH, Zhang ZH |title=[Epithelioid hemangioma: a clinicopathologic analysis of 7 cases] |language=Chinese |journal=Zhonghua Bing Li Xue Za Zhi |volume=42 |issue=9 |pages=593–8 |date=September 2013 |pmid=24314244 |doi= |url=}}</ref>
+* Rare [[benign]] [[tumor]] that typically presents as solitary painful nodule on [[head]] and [[neck]]. [[Penis]] is an atypical location. They can involve [[skin]], [[bone]] and [[soft tissues]]. Histopathologically, these [[lesions]] are characterized by presence of [[endothelial cells]] that resemble [[epithelial cells]] with evidence of [[proliferation]] such as large [[nuclei]] and prominent [[nucleoli]], and often inflammatory infiltrates. [[Vessels]] are typically well-formed. Nuclear atypia is absent.<ref name="pmid25295139">{{cite journal |vauthors=Barber E, Domes T |title=Painful erections secondary to rare epithelioid hemangioma of the penis |journal=Can Urol Assoc J |volume=8 |issue=9-10 |pages=E647–9 |date=September 2014 |pmid=25295139 |pmc=4164556 |doi=10.5489/cuaj.1833 |url=}}</ref><ref name="pmid28159479">{{cite journal |vauthors=Tsikopoulos K, Perdikakis E, Georgiannos D, Bisbinas I |title=Epithelioid hemangioma of the scapula treated with chemoembolization and microwave ablation: Α case report |journal=Acta Orthop Traumatol Turc |volume=52 |issue=2 |pages=157–161 |date=March 2018 |pmid=28159479 |pmc=6136344 |doi=10.1016/j.aott.2017.01.003 |url=}}</ref><ref name="pmid24314244">{{cite journal |vauthors=Gong QX, Fan QH, Xie J, Su ZL, Zhang MH, Zhang ZH |title=[Epithelioid hemangioma: a clinicopathologic analysis of 7 cases] |language=Chinese |journal=Zhonghua Bing Li Xue Za Zhi |volume=42 |issue=9 |pages=593–8 |date=September 2013 |pmid=24314244 |doi= |url=}}</ref>
 * FOS [[gene]] rearrangements such as  ZFP36-FOSB fusions are found to be present in one third of epithelioid [[hemangioma]] in a study. It encodes a [[transcription factors]] that causes over-expression of vascular endothelial growth factor-D (VEGF-D).<ref name="pmid16199154">{{cite journal |vauthors=Milde-Langosch K |title=The Fos family of transcription factors and their role in tumourigenesis |journal=Eur. J. Cancer |volume=41 |issue=16 |pages=2449–61 |date=November 2005 |pmid=16199154 |doi=10.1016/j.ejca.2005.08.008 |url=}}</ref><ref name="pmid19760594">{{cite journal |vauthors=Durchdewald M, Angel P, Hess J |title=The transcription factor Fos: a Janus-type regulator in health and disease |journal=Histol. Histopathol. |volume=24 |issue=11 |pages=1451–61 |date=November 2009 |pmid=19760594 |doi=10.14670/HH-24.1451 |url=}}</ref><ref name="pmid10449752">{{cite journal |vauthors=Marconcini L, Marchio S, Morbidelli L, Cartocci E, Albini A, Ziche M, Bussolino F, Oliviero S |title=c-fos-induced growth factor/vascular endothelial growth factor D induces angiogenesis in vivo and in vitro |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=96 |issue=17 |pages=9671–6 |date=August 1999 |pmid=10449752 |pmc=22268 |doi= |url=}}</ref><ref name="pmid26135557">{{cite journal |vauthors=Huang SC, Zhang L, Sung YS, Chen CL, Krausz T, Dickson BC, Kao YC, Agaram NP, Fletcher CD, Antonescu CR |title=Frequent FOS Gene Rearrangements in Epithelioid Hemangioma: A Molecular Study of 58 Cases With Morphologic Reappraisal |journal=Am. J. Surg. Pathol. |volume=39 |issue=10 |pages=1313–21 |date=October 2015 |pmid=26135557 |pmc=4567921 |doi=10.1097/PAS.0000000000000469 |url=}}</ref>
 * [[Diagnosis]] requires [[biopsy]] to determine characteristic histopathological features. [[Imaging]] techniques such as [[MRI]] can useful. [[Bone]] [[tumors]] often require [[surgery]] for accurate [[diagnosis]]. [[Surgical]] excision has been used in majority of cases. Other treatment modalities include [[radiotherapy]] and [[embolization]]. Recently [[chemoembolization]] and [[microwave ablation]] in combination have been used with success.<ref name="pmid25295139">{{cite journal |vauthors=Barber E, Domes T |title=Painful erections secondary to rare epithelioid hemangioma of the penis |journal=Can Urol Assoc J |volume=8 |issue=9-10 |pages=E647–9 |date=September 2014 |pmid=25295139 |pmc=4164556 |doi=10.5489/cuaj.1833 |url=}}</ref><ref name="pmid28159479">{{cite journal |vauthors=Tsikopoulos K, Perdikakis E, Georgiannos D, Bisbinas I |title=Epithelioid hemangioma of the scapula treated with chemoembolization and microwave ablation: Α case report |journal=Acta Orthop Traumatol Turc |volume=52 |issue=2 |pages=157–161 |date=March 2018 |pmid=28159479 |pmc=6136344 |doi=10.1016/j.aott.2017.01.003 |url=}}</ref><ref name="pmid26054166">{{cite journal |vauthors=Gérard V, Tomasella M, Kurth W, Brands G, Lognard M |title=[Epithelioid hemangioma, a rare bone tumor] |language=French |journal=Rev Med Liege |volume=70 |issue=4 |pages=169–71 |date=April 2015 |pmid=26054166 |doi= |url=}}</ref>
-For more information on [[Epithelioid hemangioma]], [[Angiolymphoid hyperplasia with eosinophilia#Angiolymphoid hyperplasia with eosinophilia|click here]]
+For more information on [[epithelioid hemangioma]], [[Angiolymphoid hyperplasia with eosinophilia#Angiolymphoid hyperplasia with eosinophilia|click here]]
 ===Pyogenic granuloma===
-* Also called as [[lobular capillary hemangioma]], this common vascular [[lesion]] typically manifests as single, localized nodules on [[gingiva]] with sessile base but large [[lesions]] often present as lobulated or pedinculated. Majority of the [[lesions]] are <2 cm in diameter and color of the [[lesion]] depending on vascularity varies from pink to purple. It can found anywhere on [[skin]] and [[mucous membranes]] such as lips, tongues, palate, and on atypical locations such asperiungual or [[gastrointestinal tract]] but gingiva is the typical location. Majority of the patients present with profuse bleeding. Others complain of painless mass, swelling, obstructive or interference related symptoms.<ref name="pmid27382492">{{cite journal |vauthors=Marla V, Shrestha A, Goel K, Shrestha S |title=The Histopathological Spectrum of Pyogenic Granuloma: A Case Series |journal=Case Rep Dent |volume=2016 |issue= |pages=1323798 |date=2016 |pmid=27382492 |pmc=4921146 |doi=10.1155/2016/1323798 |url=}}</ref><ref name="pmid24859551">{{cite journal |vauthors=Thada SR, Pai KM, Agarwal P |title=A huge oral pyogenic granuloma with extensive alveolar bone loss and 'sun-ray' appearance mimicking a malignant tumour |journal=BMJ Case Rep |volume=2014 |issue= |pages= |date=May 2014 |pmid=24859551 |pmc=4039851 |doi=10.1136/bcr-2013-202367 |url=}}</ref><ref name="pmid28785323">{{cite journal |vauthors=Wollina U, Langner D, França K, Gianfaldoni S, Lotti T, Tchernev G |title=Pyogenic Granuloma - A Common Benign Vascular Tumor with Variable Clinical Presentation: New Findings and Treatment Options |journal=Open Access Maced J Med Sci |volume=5 |issue=4 |pages=423–426 |date=July 2017 |pmid=28785323 |pmc=5535648 |doi=10.3889/oamjms.2017.111 |url=}}</ref><ref name="pmid22434943">{{cite journal |vauthors=Kamal R, Dahiya P, Puri A |title=Oral pyogenic granuloma: Various concepts of etiopathogenesis |journal=J Oral Maxillofac Pathol |volume=16 |issue=1 |pages=79–82 |date=January 2012 |pmid=22434943 |pmc=3303528 |doi=10.4103/0973-029X.92978 |url=}}</ref>
+* Also called as [[lobular capillary hemangioma]], this common vascular [[lesion]] typically manifests as single, localized nodules on [[gingiva]] with sessile base but large [[lesions]] often present as lobulated or pedinculated. Majority of the [[lesions]] are <2 cm in diameter and color of the [[lesion]] depending on [[vascularity]] varies from pink to purple. It can found anywhere on [[skin]] and [[mucous membranes]] such as lips, tongues, palate, and on atypical locations such asperiungual or [[gastrointestinal tract]] but gingiva is the typical location. Majority of the patients present with profuse bleeding. Others complain of painless mass, swelling, obstructive or interference related symptoms.<ref name="pmid27382492">{{cite journal |vauthors=Marla V, Shrestha A, Goel K, Shrestha S |title=The Histopathological Spectrum of Pyogenic Granuloma: A Case Series |journal=Case Rep Dent |volume=2016 |issue= |pages=1323798 |date=2016 |pmid=27382492 |pmc=4921146 |doi=10.1155/2016/1323798 |url=}}</ref><ref name="pmid24859551">{{cite journal |vauthors=Thada SR, Pai KM, Agarwal P |title=A huge oral pyogenic granuloma with extensive alveolar bone loss and 'sun-ray' appearance mimicking a malignant tumour |journal=BMJ Case Rep |volume=2014 |issue= |pages= |date=May 2014 |pmid=24859551 |pmc=4039851 |doi=10.1136/bcr-2013-202367 |url=}}</ref><ref name="pmid28785323">{{cite journal |vauthors=Wollina U, Langner D, França K, Gianfaldoni S, Lotti T, Tchernev G |title=Pyogenic Granuloma - A Common Benign Vascular Tumor with Variable Clinical Presentation: New Findings and Treatment Options |journal=Open Access Maced J Med Sci |volume=5 |issue=4 |pages=423–426 |date=July 2017 |pmid=28785323 |pmc=5535648 |doi=10.3889/oamjms.2017.111 |url=}}</ref><ref name="pmid22434943">{{cite journal |vauthors=Kamal R, Dahiya P, Puri A |title=Oral pyogenic granuloma: Various concepts of etiopathogenesis |journal=J Oral Maxillofac Pathol |volume=16 |issue=1 |pages=79–82 |date=January 2012 |pmid=22434943 |pmc=3303528 |doi=10.4103/0973-029X.92978 |url=}}</ref>
-* Trauma or chronic irritation have been cited as the most common causes but it can arise due to multiple other factors such as [[medications]], [[viral infections]] such as [[herpes virus type 1]], Orf virus and/or [[human papilloma virus type 2]], and BRAF mutations or use of BRAF inhibitors that can cause multiple, disseminated lesions. [[Medications]] that have been implicated in development of this [[lesion]] include oral contraceptives, retinoids, gefitinib, cabecitabine, and afatinib, BRAF inhibitors such as vemurafenib or encorafenib, and rituximab. Mutations in BRAF/RAS/GNA14 have all been associated with pyogenic granuloma, BRAF c.1799T>A has been recently described as one of the major mutations associated.<ref name="pmid24859551">{{cite journal |vauthors=Thada SR, Pai KM, Agarwal P |title=A huge oral pyogenic granuloma with extensive alveolar bone loss and 'sun-ray' appearance mimicking a malignant tumour |journal=BMJ Case Rep |volume=2014 |issue= |pages= |date=May 2014 |pmid=24859551 |pmc=4039851 |doi=10.1136/bcr-2013-202367 |url=}}</ref><ref name="pmid28785323">{{cite journal |vauthors=Wollina U, Langner D, França K, Gianfaldoni S, Lotti T, Tchernev G |title=Pyogenic Granuloma - A Common Benign Vascular Tumor with Variable Clinical Presentation: New Findings and Treatment Options |journal=Open Access Maced J Med Sci |volume=5 |issue=4 |pages=423–426 |date=July 2017 |pmid=28785323 |pmc=5535648 |doi=10.3889/oamjms.2017.111 |url=}}</ref><ref name="pmid22434943">{{cite journal |vauthors=Kamal R, Dahiya P, Puri A |title=Oral pyogenic granuloma: Various concepts of etiopathogenesis |journal=J Oral Maxillofac Pathol |volume=16 |issue=1 |pages=79–82 |date=January 2012 |pmid=22434943 |pmc=3303528 |doi=10.4103/0973-029X.92978 |url=}}</ref><ref name="pmid27885661">{{cite journal |vauthors=Simmons BJ, Chen L, Hu S |title=Pyogenic granuloma association with isotretinoin treatment for acne |journal=Australas. J. Dermatol. |volume=57 |issue=4 |pages=e144–e145 |date=November 2016 |pmid=27885661 |doi=10.1111/ajd.12418 |url=}}</ref><ref name="pmid26603180">{{cite journal |vauthors=Inoue A, Sawada Y, Nishio D, Nakamura M |title=Pyogenic granuloma caused by afatinib: Case report and review of the literature |journal=Australas. J. Dermatol. |volume=58 |issue=1 |pages=61–62 |date=February 2017 |pmid=26603180 |doi=10.1111/ajd.12423 |url=}}</ref><ref name="pmid27116335">{{cite journal |vauthors=Henning B, Stieger P, Kamarachev J, Dummer R, Goldinger SM |title=Pyogenic granuloma in patients treated with selective BRAF inhibitors: another manifestation of paradoxical pathway activation |journal=Melanoma Res. |volume=26 |issue=3 |pages=304–7 |date=June 2016 |pmid=27116335 |doi=10.1097/CMR.0000000000000248 |url=}}</ref><ref name="pmid26802240">{{cite journal |vauthors=Groesser L, Peterhof E, Evert M, Landthaler M, Berneburg M, Hafner C |title=BRAF and RAS Mutations in Sporadic and Secondary Pyogenic Granuloma |journal=J. Invest. Dermatol. |volume=136 |issue=2 |pages=481–6 |date=February 2016 |pmid=26802240 |doi=10.1038/JID.2015.376 |url=}}</ref>
+* Trauma or chronic irritation have been cited as the most common causes but it can arise due to multiple other factors such as [[medications]], [[viral infections]] such as [[Herpes virus|herpes virus type 1]], Orf virus and/or [[Human papilloma virus|human papilloma virus type 2]], and BRAF mutations or use of BRAF inhibitors that can cause multiple, disseminated lesions. [[Medications]] that have been implicated in development of this [[lesion]] include oral contraceptives, [[retinoids]], [[gefitinib]], cabecitabine, and [[afatinib]], BRAF inhibitors such as [[vemurafenib]] or [[encorafenib]], and [[rituximab]]. Mutations in BRAF/RAS/GNA14 have all been associated with [[pyogenic granuloma]], BRAF c.1799T>A has been recently described as one of the major mutations associated.<ref name="pmid24859551">{{cite journal |vauthors=Thada SR, Pai KM, Agarwal P |title=A huge oral pyogenic granuloma with extensive alveolar bone loss and 'sun-ray' appearance mimicking a malignant tumour |journal=BMJ Case Rep |volume=2014 |issue= |pages= |date=May 2014 |pmid=24859551 |pmc=4039851 |doi=10.1136/bcr-2013-202367 |url=}}</ref><ref name="pmid28785323">{{cite journal |vauthors=Wollina U, Langner D, França K, Gianfaldoni S, Lotti T, Tchernev G |title=Pyogenic Granuloma - A Common Benign Vascular Tumor with Variable Clinical Presentation: New Findings and Treatment Options |journal=Open Access Maced J Med Sci |volume=5 |issue=4 |pages=423–426 |date=July 2017 |pmid=28785323 |pmc=5535648 |doi=10.3889/oamjms.2017.111 |url=}}</ref><ref name="pmid22434943">{{cite journal |vauthors=Kamal R, Dahiya P, Puri A |title=Oral pyogenic granuloma: Various concepts of etiopathogenesis |journal=J Oral Maxillofac Pathol |volume=16 |issue=1 |pages=79–82 |date=January 2012 |pmid=22434943 |pmc=3303528 |doi=10.4103/0973-029X.92978 |url=}}</ref><ref name="pmid27885661">{{cite journal |vauthors=Simmons BJ, Chen L, Hu S |title=Pyogenic granuloma association with isotretinoin treatment for acne |journal=Australas. J. Dermatol. |volume=57 |issue=4 |pages=e144–e145 |date=November 2016 |pmid=27885661 |doi=10.1111/ajd.12418 |url=}}</ref><ref name="pmid26603180">{{cite journal |vauthors=Inoue A, Sawada Y, Nishio D, Nakamura M |title=Pyogenic granuloma caused by afatinib: Case report and review of the literature |journal=Australas. J. Dermatol. |volume=58 |issue=1 |pages=61–62 |date=February 2017 |pmid=26603180 |doi=10.1111/ajd.12423 |url=}}</ref><ref name="pmid27116335">{{cite journal |vauthors=Henning B, Stieger P, Kamarachev J, Dummer R, Goldinger SM |title=Pyogenic granuloma in patients treated with selective BRAF inhibitors: another manifestation of paradoxical pathway activation |journal=Melanoma Res. |volume=26 |issue=3 |pages=304–7 |date=June 2016 |pmid=27116335 |doi=10.1097/CMR.0000000000000248 |url=}}</ref><ref name="pmid26802240">{{cite journal |vauthors=Groesser L, Peterhof E, Evert M, Landthaler M, Berneburg M, Hafner C |title=BRAF and RAS Mutations in Sporadic and Secondary Pyogenic Granuloma |journal=J. Invest. Dermatol. |volume=136 |issue=2 |pages=481–6 |date=February 2016 |pmid=26802240 |doi=10.1038/JID.2015.376 |url=}}</ref>
 * The [[diagnosis]] is made by clinical features and then confirmed by histopatholgical features. Current standard of care is [[surgical excision]]. Other treatment modalities include [[curettage]], [[electrocautery]], [[radiosurgery]], [[cryosurgery]], [[sclerotherapy]], or [[laser]] treatment. Topical or oral [[beta-blockers]] [[timolol]] or [[propranolol]] and topical imiquimod have also been successful.<ref name="pmid24859551">{{cite journal |vauthors=Thada SR, Pai KM, Agarwal P |title=A huge oral pyogenic granuloma with extensive alveolar bone loss and 'sun-ray' appearance mimicking a malignant tumour |journal=BMJ Case Rep |volume=2014 |issue= |pages= |date=May 2014 |pmid=24859551 |pmc=4039851 |doi=10.1136/bcr-2013-202367 |url=}}</ref><ref name="pmid28785323">{{cite journal |vauthors=Wollina U, Langner D, França K, Gianfaldoni S, Lotti T, Tchernev G |title=Pyogenic Granuloma - A Common Benign Vascular Tumor with Variable Clinical Presentation: New Findings and Treatment Options |journal=Open Access Maced J Med Sci |volume=5 |issue=4 |pages=423–426 |date=July 2017 |pmid=28785323 |pmc=5535648 |doi=10.3889/oamjms.2017.111 |url=}}</ref><ref name="pmid17478135">{{cite journal |vauthors=Giblin AV, Clover AJ, Athanassopoulos A, Budny PG |title=Pyogenic granuloma - the quest for optimum treatment: audit of treatment of 408 cases |journal=J Plast Reconstr Aesthet Surg |volume=60 |issue=9 |pages=1030–5 |date=2007 |pmid=17478135 |doi=10.1016/j.bjps.2006.10.018 |url=}}</ref><ref name="pmid27874157">{{cite journal |vauthors=Al-Mohaya MA, Al-Malik AM |title=Excision of oral pyogenic granuloma in a diabetic patient with 940nm diode laser |journal=Saudi Med J |volume=37 |issue=12 |pages=1395–1400 |date=December 2016 |pmid=27874157 |pmc=5303780 |doi=10.15537/smj.2016.12.15941 |url=}}</ref><ref name="pmid24836966">{{cite journal |vauthors=Malik M, Murphy R |title=A pyogenic granuloma treated with topical timolol |journal=Br. J. Dermatol. |volume=171 |issue=6 |pages=1537–8 |date=December 2014 |pmid=24836966 |doi=10.1111/bjd.13116 |url=}}</ref><ref name="pmid24656264">{{cite journal |vauthors=Millsop JW, Trinh N, Winterfield L, Berrios R, Hutchens KA, Tung R |title=Resolution of recalcitrant pyogenic granuloma with laser, corticosteroid, and timolol therapy |journal=Dermatol. Online J. |volume=20 |issue=3 |pages= |date=March 2014 |pmid=24656264 |doi= |url=}}</ref>
 For more information on [[Pyogenic granuloma]], [[Pyogenic granuloma#Pyogenic granuloma|click here]].
 ===Hobnail hemangioma===
-* [[Benign]] [[tumor]] that typically presents as solitary growth with often, but not always, tagetoid appearance of a central papule and peripheral brown ring that may or may not disappear over time. Characteristic histopathological feature include plump [[endothelial cells]] in superficial [[dermis]] that line ectatic and irregular [[vessels]], and project into lumina like hobnails. Deeper [[dermis]] shows [[vessels]] dissecting collagen fibers. Majority of the [[lesions]] are fund on trunk and extremities with [[head and neck]], and oral cavity as uncommon locations. Patient may present with pain, or an asymptomatic growing [[lesion]].<ref name="pmid23808782">{{cite journal |vauthors=Hiremath SK, Charantimath S, Byakodi S, Bijjal S, Byakodi R, Sapra G |title=Oral hobnail hemangioma: a case report |journal=Arch Iran Med |volume=16 |issue=7 |pages=428–30 |date=July 2013 |pmid=23808782 |doi=013167/AIM.0013 |url=}}</ref><ref name="pmid22148030">{{cite journal |vauthors=Yoon SY, Kwon HH, Jeon HC, Lee JH, Cho S |title=Congenital and multiple hobnail hemangiomas |journal=Ann Dermatol |volume=23 |issue=4 |pages=539–43 |date=November 2011 |pmid=22148030 |pmc=3229956 |doi=10.5021/ad.2011.23.4.539 |url=}}</ref><ref name="pmid26156669">{{cite journal |vauthors=Takayama R, Ueno T, Futagami A, Ansai S, Fukumoto T, Saeki H |title=Hobnail Hemangioma: A Case Report |journal=J Nippon Med Sch |volume=82 |issue=3 |pages=151–5 |date=2015 |pmid=26156669 |doi=10.1272/jnms.82.151 |url=}}</ref>
+* [[Benign]] [[tumor]] that typically presents as solitary growth with often, but not always, tagetoid appearance of a central [[papule]] and peripheral brown ring that may or may not disappear over time. Characteristic histopathological feature include plump [[endothelial cells]] in superficial [[dermis]] that line ectatic and irregular [[vessels]], and project into lumina like hobnails. Deeper [[dermis]] shows [[vessels]] dissecting collagen fibers. Majority of the [[lesions]] are fund on trunk and extremities with [[head and neck]], and oral cavity as uncommon locations. Patient may present with pain, or an asymptomatic growing [[lesion]].<ref name="pmid23808782">{{cite journal |vauthors=Hiremath SK, Charantimath S, Byakodi S, Bijjal S, Byakodi R, Sapra G |title=Oral hobnail hemangioma: a case report |journal=Arch Iran Med |volume=16 |issue=7 |pages=428–30 |date=July 2013 |pmid=23808782 |doi=013167/AIM.0013 |url=}}</ref><ref name="pmid22148030">{{cite journal |vauthors=Yoon SY, Kwon HH, Jeon HC, Lee JH, Cho S |title=Congenital and multiple hobnail hemangiomas |journal=Ann Dermatol |volume=23 |issue=4 |pages=539–43 |date=November 2011 |pmid=22148030 |pmc=3229956 |doi=10.5021/ad.2011.23.4.539 |url=}}</ref><ref name="pmid26156669">{{cite journal |vauthors=Takayama R, Ueno T, Futagami A, Ansai S, Fukumoto T, Saeki H |title=Hobnail Hemangioma: A Case Report |journal=J Nippon Med Sch |volume=82 |issue=3 |pages=151–5 |date=2015 |pmid=26156669 |doi=10.1272/jnms.82.151 |url=}}</ref>
 * [[Etiology]] is not well understood but trauma may play a key role in [[pathogenesis]]. Some studies have found [[congenital]] [[etiology]] in some [[lesions]].<ref name="pmid23808782">{{cite journal |vauthors=Hiremath SK, Charantimath S, Byakodi S, Bijjal S, Byakodi R, Sapra G |title=Oral hobnail hemangioma: a case report |journal=Arch Iran Med |volume=16 |issue=7 |pages=428–30 |date=July 2013 |pmid=23808782 |doi=013167/AIM.0013 |url=}}</ref><ref name="pmid22148030">{{cite journal |vauthors=Yoon SY, Kwon HH, Jeon HC, Lee JH, Cho S |title=Congenital and multiple hobnail hemangiomas |journal=Ann Dermatol |volume=23 |issue=4 |pages=539–43 |date=November 2011 |pmid=22148030 |pmc=3229956 |doi=10.5021/ad.2011.23.4.539 |url=}}</ref><ref name="pmid7829718">{{cite journal |vauthors=Morganroth GS, Tigelaar RE, Longley BJ, Luck LE, Leffell DJ |title=Targetoid hemangioma associated with pregnancy and the menstrual cycle |journal=J. Am. Acad. Dermatol. |volume=32 |issue=2 Pt 1 |pages=282–4 |date=February 1995 |pmid=7829718 |doi= |url=}}</ref><ref name="pmid11391103">{{cite journal |vauthors=Christenson LJ, Stone MS |title=Trauma-induced simulator of targetoid hemosiderotic hemangioma |journal=Am J Dermatopathol |volume=23 |issue=3 |pages=221–3 |date=June 2001 |pmid=11391103 |doi= |url=}}</ref>
-* [[Diagnosis]] is based on clinical features and histopathological studies. Treatment is usually by [[excision]]. Other modalities of treatment include intermittent triamcinolone intralesional injections and [[pulsed dye laser]] treatment.<ref name="pmid23808782">{{cite journal |vauthors=Hiremath SK, Charantimath S, Byakodi S, Bijjal S, Byakodi R, Sapra G |title=Oral hobnail hemangioma: a case report |journal=Arch Iran Med |volume=16 |issue=7 |pages=428–30 |date=July 2013 |pmid=23808782 |doi=013167/AIM.0013 |url=}}</ref><ref name="pmid22148030">{{cite journal |vauthors=Yoon SY, Kwon HH, Jeon HC, Lee JH, Cho S |title=Congenital and multiple hobnail hemangiomas |journal=Ann Dermatol |volume=23 |issue=4 |pages=539–43 |date=November 2011 |pmid=22148030 |pmc=3229956 |doi=10.5021/ad.2011.23.4.539 |url=}}</ref>
+* [[Diagnosis]] is based on clinical features and histopathological studies. Treatment is usually by [[excision]]. Other modalities of treatment include intermittent [[triamcinolone]] intralesional injections and [[pulsed dye laser]] treatment.<ref name="pmid23808782">{{cite journal |vauthors=Hiremath SK, Charantimath S, Byakodi S, Bijjal S, Byakodi R, Sapra G |title=Oral hobnail hemangioma: a case report |journal=Arch Iran Med |volume=16 |issue=7 |pages=428–30 |date=July 2013 |pmid=23808782 |doi=013167/AIM.0013 |url=}}</ref><ref name="pmid22148030">{{cite journal |vauthors=Yoon SY, Kwon HH, Jeon HC, Lee JH, Cho S |title=Congenital and multiple hobnail hemangiomas |journal=Ann Dermatol |volume=23 |issue=4 |pages=539–43 |date=November 2011 |pmid=22148030 |pmc=3229956 |doi=10.5021/ad.2011.23.4.539 |url=}}</ref>
 ===Microvenular hemangioma===
-* Rare [[lesion]] that most often manifests as single asymptomatic nodule, plaque or papule with color varying from red to bluish-red. Majority of the [[lesions]] are located on trunk and limbs. Histologically, the [[tumor]] consists of irregular and branching [[venous]] structures with inconspicuous lumina. Endothelial cells display absence of atypia and [[mitotic]] figures. Some [[lesions]] may be painful and/or tender.<ref name="pmid29445567">{{cite journal |vauthors=Mansur AT, Demirci GT, Ozbal Koc EA, Yildiz S |title=An unusual lesion on the nose: microvenular hemangioma |journal=Dermatol Pract Concept |volume=8 |issue=1 |pages=7–11 |date=January 2018 |pmid=29445567 |pmc=5808364 |doi=10.5826/dpc.0801a02 |url=}}</ref><ref name="pmid9418757">{{cite journal |vauthors=Requena L, Sangueza OP |title=Cutaneous vascular proliferation. Part II. Hyperplasias and benign neoplasms |journal=J. Am. Acad. Dermatol. |volume=37 |issue=6 |pages=887–919; quiz 920–2 |date=December 1997 |pmid=9418757 |doi= |url=}}</ref><ref name="pmid25138781">{{cite journal |vauthors=Koch PS, Goerdt S, Peitsch WK |title=Solitary red-purple plaque on the chest of a 7-year-old boy: a quiz. Microvenular haemangioma |journal=Acta Derm. Venereol. |volume=95 |issue=3 |pages=378–82 |date=March 2015 |pmid=25138781 |doi=10.2340/00015555-1953 |url=}}</ref><ref name="pmid12592086">{{cite journal |vauthors=Kim YC, Park HJ, Cinn YW |title=Microvenular hemangioma |journal=Dermatology (Basel) |volume=206 |issue=2 |pages=161–4 |date=2003 |pmid=12592086 |doi=10.1159/000068453 |url=}}</ref>
+* Rare [[lesion]] that most often manifests as single asymptomatic nodule, plaque or papule with color varying from red to bluish-red. Majority of the [[lesions]] are located on trunk and limbs. Histologically, the [[tumor]] consists of irregular and branching [[venous]] structures with inconspicuous lumina. Endothelial cells display absence of atypia and [[mitotic]] figures. Some [[lesions]] may be [[Pain|painful]] and/or [[tender]].<ref name="pmid29445567">{{cite journal |vauthors=Mansur AT, Demirci GT, Ozbal Koc EA, Yildiz S |title=An unusual lesion on the nose: microvenular hemangioma |journal=Dermatol Pract Concept |volume=8 |issue=1 |pages=7–11 |date=January 2018 |pmid=29445567 |pmc=5808364 |doi=10.5826/dpc.0801a02 |url=}}</ref><ref name="pmid9418757">{{cite journal |vauthors=Requena L, Sangueza OP |title=Cutaneous vascular proliferation. Part II. Hyperplasias and benign neoplasms |journal=J. Am. Acad. Dermatol. |volume=37 |issue=6 |pages=887–919; quiz 920–2 |date=December 1997 |pmid=9418757 |doi= |url=}}</ref><ref name="pmid25138781">{{cite journal |vauthors=Koch PS, Goerdt S, Peitsch WK |title=Solitary red-purple plaque on the chest of a 7-year-old boy: a quiz. Microvenular haemangioma |journal=Acta Derm. Venereol. |volume=95 |issue=3 |pages=378–82 |date=March 2015 |pmid=25138781 |doi=10.2340/00015555-1953 |url=}}</ref><ref name="pmid12592086">{{cite journal |vauthors=Kim YC, Park HJ, Cinn YW |title=Microvenular hemangioma |journal=Dermatology (Basel) |volume=206 |issue=2 |pages=161–4 |date=2003 |pmid=12592086 |doi=10.1159/000068453 |url=}}</ref>
-* Etiology and pathogenesis have not been well-understood but a recent study may associate progesterone with microvenular hemangioma.<ref name="pmid30019384">{{cite journal |vauthors=Juan YC, Chen CJ, Hsiao CH, Chiu TM |title=A microvenular hemangioma with a rare expression of progesterone receptor immunocreativity and a review of the literature |journal=J. Cutan. Pathol. |volume= |issue= |pages= |date=July 2018 |pmid=30019384 |doi=10.1111/cup.13322 |url=}}</ref>
+* Etiology and pathogenesis have not been well-understood but a recent study may associate [[progesterone]] with microvenular hemangioma.<ref name="pmid30019384">{{cite journal |vauthors=Juan YC, Chen CJ, Hsiao CH, Chiu TM |title=A microvenular hemangioma with a rare expression of progesterone receptor immunocreativity and a review of the literature |journal=J. Cutan. Pathol. |volume= |issue= |pages= |date=July 2018 |pmid=30019384 |doi=10.1111/cup.13322 |url=}}</ref>
-* [[Diagnosis]] requires [[biopsy]] because of rarity of this [[tumor]]. Treatment is through [[surgical excision]].<ref name="pmid29445567">{{cite journal |vauthors=Mansur AT, Demirci GT, Ozbal Koc EA, Yildiz S |title=An unusual lesion on the nose: microvenular hemangioma |journal=Dermatol Pract Concept |volume=8 |issue=1 |pages=7–11 |date=January 2018 |pmid=29445567 |pmc=5808364 |doi=10.5826/dpc.0801a02 |url=}}</ref><ref name="pmid9418757">{{cite journal |vauthors=Requena L, Sangueza OP |title=Cutaneous vascular proliferation. Part II. Hyperplasias and benign neoplasms |journal=J. Am. Acad. Dermatol. |volume=37 |issue=6 |pages=887–919; quiz 920–2 |date=December 1997 |pmid=9418757 |doi= |url=}}</ref><ref name="pmid25138781">{{cite journal |vauthors=Koch PS, Goerdt S, Peitsch WK |title=Solitary red-purple plaque on the chest of a 7-year-old boy: a quiz. Microvenular haemangioma |journal=Acta Derm. Venereol. |volume=95 |issue=3 |pages=378–82 |date=March 2015 |pmid=25138781 |doi=10.2340/00015555-1953 |url=}}</ref><ref name="pmid12592086">{{cite journal |vauthors=Kim YC, Park HJ, Cinn YW |title=Microvenular hemangioma |journal=Dermatology (Basel) |volume=206 |issue=2 |pages=161–4 |date=2003 |pmid=12592086 |doi=10.1159/000068453 |url=}}</ref>
+* [[Diagnosis]] requires [[biopsy]] because of rarity of this [[tumor]]. Treatment is through surgical excision.<ref name="pmid29445567">{{cite journal |vauthors=Mansur AT, Demirci GT, Ozbal Koc EA, Yildiz S |title=An unusual lesion on the nose: microvenular hemangioma |journal=Dermatol Pract Concept |volume=8 |issue=1 |pages=7–11 |date=January 2018 |pmid=29445567 |pmc=5808364 |doi=10.5826/dpc.0801a02 |url=}}</ref><ref name="pmid9418757">{{cite journal |vauthors=Requena L, Sangueza OP |title=Cutaneous vascular proliferation. Part II. Hyperplasias and benign neoplasms |journal=J. Am. Acad. Dermatol. |volume=37 |issue=6 |pages=887–919; quiz 920–2 |date=December 1997 |pmid=9418757 |doi= |url=}}</ref><ref name="pmid25138781">{{cite journal |vauthors=Koch PS, Goerdt S, Peitsch WK |title=Solitary red-purple plaque on the chest of a 7-year-old boy: a quiz. Microvenular haemangioma |journal=Acta Derm. Venereol. |volume=95 |issue=3 |pages=378–82 |date=March 2015 |pmid=25138781 |doi=10.2340/00015555-1953 |url=}}</ref><ref name="pmid12592086">{{cite journal |vauthors=Kim YC, Park HJ, Cinn YW |title=Microvenular hemangioma |journal=Dermatology (Basel) |volume=206 |issue=2 |pages=161–4 |date=2003 |pmid=12592086 |doi=10.1159/000068453 |url=}}</ref>
 ===Anastomosing hemangioma===
-* Rare [[tumor]] characterized by presence of anastomosing [[capillary]]-sized vessels with irregular fenestration, lined by [[endothelial cells]] with absence of atypia and occasional hobnailing. Majority of the [[lesions]] are found in [[kidneys]] and [[genitourinary tract]] with some being located in [[liver]], [[adrenal glands]] and [[gastrointestinal tract]]. These [[tumors]] are typically incidental findings on [[radiology]] but some may present with back and/or flank pain with/without radiation to [[lower limbs]].<ref name="pmid26893881">{{cite journal |vauthors=Jin LU, Liu J, Li Y, Sun S, Mao X, Yang S, Lai Y |title=Anastomosing hemangioma: The first case report in the bladder |journal=Mol Clin Oncol |volume=4 |issue=2 |pages=310–312 |date=February 2016 |pmid=26893881 |pmc=4734195 |doi=10.3892/mco.2015.699 |url=}}</ref><ref name="pmid22840861">{{cite journal |vauthors=Ross M, Polcari A, Picken M, Sankary H, Milner J |title=Anastomosing hemangioma arising from the adrenal gland |journal=Urology |volume=80 |issue=3 |pages=e27–8 |date=September 2012 |pmid=22840861 |doi=10.1016/j.urology.2012.05.032 |url=}}</ref><ref name="pmid23887160">{{cite journal |vauthors=Lin J, Bigge J, Ulbright TM, Montgomery E |title=Anastomosing hemangioma of the liver and gastrointestinal tract: an unusual variant histologically mimicking angiosarcoma |journal=Am. J. Surg. Pathol. |volume=37 |issue=11 |pages=1761–5 |date=November 2013 |pmid=23887160 |doi=10.1097/PAS.0b013e3182967e6c |url=}}</ref><ref name="pmid29962849">{{cite journal |vauthors=Cheon PM, Rebello R, Naqvi A, Popovic S, Bonert M, Kapoor A |title=Anastomosing hemangioma of the kidney: radiologic and pathologic distinctions of a kidney cancer mimic |journal=Curr Oncol |volume=25 |issue=3 |pages=e220–e223 |date=June 2018 |pmid=29962849 |pmc=6023565 |doi=10.3747/co.25.3927 |url=}}</ref><ref name="pmid28118845">{{cite journal |vauthors=Perdiki M, Datseri G, Liapis G, Chondros N, Anastasiou I, Tzardi M, Delladetsima JK, Drakos E |title=Anastomosing hemangioma: report of two renal cases and analysis of the literature |journal=Diagn Pathol |volume=12 |issue=1 |pages=14 |date=January 2017 |pmid=28118845 |pmc=5260082 |doi=10.1186/s13000-017-0597-4 |url=}}</ref>
+* Rare [[tumor]] characterized by presence of anastomosing [[capillary]]-sized vessels with irregular fenestration, lined by [[endothelial cells]] with absence of atypia and occasional hobnailing. Majority of the [[lesions]] are found in [[kidneys]] and [[genitourinary tract]] with some being located in [[liver]], [[adrenal glands]] and [[gastrointestinal tract]]. These [[tumors]] are typically incidental findings on [[radiology]] but some may present with back and/or [[flank pain]] with/without [[radiation]] to [[lower limbs]].<ref name="pmid26893881">{{cite journal |vauthors=Jin LU, Liu J, Li Y, Sun S, Mao X, Yang S, Lai Y |title=Anastomosing hemangioma: The first case report in the bladder |journal=Mol Clin Oncol |volume=4 |issue=2 |pages=310–312 |date=February 2016 |pmid=26893881 |pmc=4734195 |doi=10.3892/mco.2015.699 |url=}}</ref><ref name="pmid22840861">{{cite journal |vauthors=Ross M, Polcari A, Picken M, Sankary H, Milner J |title=Anastomosing hemangioma arising from the adrenal gland |journal=Urology |volume=80 |issue=3 |pages=e27–8 |date=September 2012 |pmid=22840861 |doi=10.1016/j.urology.2012.05.032 |url=}}</ref><ref name="pmid23887160">{{cite journal |vauthors=Lin J, Bigge J, Ulbright TM, Montgomery E |title=Anastomosing hemangioma of the liver and gastrointestinal tract: an unusual variant histologically mimicking angiosarcoma |journal=Am. J. Surg. Pathol. |volume=37 |issue=11 |pages=1761–5 |date=November 2013 |pmid=23887160 |doi=10.1097/PAS.0b013e3182967e6c |url=}}</ref><ref name="pmid29962849">{{cite journal |vauthors=Cheon PM, Rebello R, Naqvi A, Popovic S, Bonert M, Kapoor A |title=Anastomosing hemangioma of the kidney: radiologic and pathologic distinctions of a kidney cancer mimic |journal=Curr Oncol |volume=25 |issue=3 |pages=e220–e223 |date=June 2018 |pmid=29962849 |pmc=6023565 |doi=10.3747/co.25.3927 |url=}}</ref><ref name="pmid28118845">{{cite journal |vauthors=Perdiki M, Datseri G, Liapis G, Chondros N, Anastasiou I, Tzardi M, Delladetsima JK, Drakos E |title=Anastomosing hemangioma: report of two renal cases and analysis of the literature |journal=Diagn Pathol |volume=12 |issue=1 |pages=14 |date=January 2017 |pmid=28118845 |pmc=5260082 |doi=10.1186/s13000-017-0597-4 |url=}}</ref>
-* [[Etiology]] is not well-known but a recent study suggests [[muations]] in GNAQ [[genes]] that encodes members of [[G protein]] family.<ref name="pmid28084343">{{cite journal |vauthors=Bean GR, Joseph NM, Gill RM, Folpe AL, Horvai AE, Umetsu SE |title=Recurrent GNAQ mutations in anastomosing hemangiomas |journal=Mod. Pathol. |volume=30 |issue=5 |pages=722–727 |date=May 2017 |pmid=28084343 |doi=10.1038/modpathol.2016.234 |url=}}</ref>
+* [[Etiology]] is not well-known but a recent study suggests [[mutations]] in GNAQ [[genes]] that encodes members of [[G protein]] family.<ref name="pmid28084343">{{cite journal |vauthors=Bean GR, Joseph NM, Gill RM, Folpe AL, Horvai AE, Umetsu SE |title=Recurrent GNAQ mutations in anastomosing hemangiomas |journal=Mod. Pathol. |volume=30 |issue=5 |pages=722–727 |date=May 2017 |pmid=28084343 |doi=10.1038/modpathol.2016.234 |url=}}</ref>
-* The [[diagnosis]] is very challenging because radiological findings of anastomosing hemangioma are similar to that of [[malignant tumors]] such as [[renal cell carcinoma]], [[hepatocellular carcinoma]] and low grade [[angiosarcoma]]. So [[excision]] and [[biopsy]] are often suggested. There is no current guidelines for treatment but [[excision]] and [[local ablation]] are the options.<ref name="pmid26893881">{{cite journal |vauthors=Jin LU, Liu J, Li Y, Sun S, Mao X, Yang S, Lai Y |title=Anastomosing hemangioma: The first case report in the bladder |journal=Mol Clin Oncol |volume=4 |issue=2 |pages=310–312 |date=February 2016 |pmid=26893881 |pmc=4734195 |doi=10.3892/mco.2015.699 |url=}}</ref><ref name="pmid29962849">{{cite journal |vauthors=Cheon PM, Rebello R, Naqvi A, Popovic S, Bonert M, Kapoor A |title=Anastomosing hemangioma of the kidney: radiologic and pathologic distinctions of a kidney cancer mimic |journal=Curr Oncol |volume=25 |issue=3 |pages=e220–e223 |date=June 2018 |pmid=29962849 |pmc=6023565 |doi=10.3747/co.25.3927 |url=}}</ref><ref name="pmid23887160">{{cite journal |vauthors=Lin J, Bigge J, Ulbright TM, Montgomery E |title=Anastomosing hemangioma of the liver and gastrointestinal tract: an unusual variant histologically mimicking angiosarcoma |journal=Am. J. Surg. Pathol. |volume=37 |issue=11 |pages=1761–5 |date=November 2013 |pmid=23887160 |doi=10.1097/PAS.0b013e3182967e6c |url=}}</ref><ref name="pmid29279869">{{cite journal |vauthors=Abboudi H, Tschobotko B, Carr C, DasGupta R |title=Bilateral Renal Anastomosing Hemangiomas: A Tale of Two Kidneys |journal=J Endourol Case Rep |volume=3 |issue=1 |pages=176–178 |date=2017 |pmid=29279869 |pmc=5734139 |doi=10.1089/cren.2017.0018 |url=}}</ref><ref name="pmid28808574">{{cite journal |vauthors=Peng X, Li J, Liang Z |title=Anastomosing haemangioma of liver: A case report |journal=Mol Clin Oncol |volume=7 |issue=3 |pages=507–509 |date=September 2017 |pmid=28808574 |pmc=5543263 |doi=10.3892/mco.2017.1341 |url=}}</ref>
+* The [[diagnosis]] is very challenging because [[radiological]] findings of anastomosing hemangioma are similar to that of [[malignant tumors]] such as [[renal cell carcinoma]], [[hepatocellular carcinoma]] and low grade [[angiosarcoma]]. So [[excision]] and [[biopsy]] are often suggested. There is no current guidelines for treatment but [[excision]] and local [[ablation]] are the options.<ref name="pmid26893881">{{cite journal |vauthors=Jin LU, Liu J, Li Y, Sun S, Mao X, Yang S, Lai Y |title=Anastomosing hemangioma: The first case report in the bladder |journal=Mol Clin Oncol |volume=4 |issue=2 |pages=310–312 |date=February 2016 |pmid=26893881 |pmc=4734195 |doi=10.3892/mco.2015.699 |url=}}</ref><ref name="pmid29962849">{{cite journal |vauthors=Cheon PM, Rebello R, Naqvi A, Popovic S, Bonert M, Kapoor A |title=Anastomosing hemangioma of the kidney: radiologic and pathologic distinctions of a kidney cancer mimic |journal=Curr Oncol |volume=25 |issue=3 |pages=e220–e223 |date=June 2018 |pmid=29962849 |pmc=6023565 |doi=10.3747/co.25.3927 |url=}}</ref><ref name="pmid23887160">{{cite journal |vauthors=Lin J, Bigge J, Ulbright TM, Montgomery E |title=Anastomosing hemangioma of the liver and gastrointestinal tract: an unusual variant histologically mimicking angiosarcoma |journal=Am. J. Surg. Pathol. |volume=37 |issue=11 |pages=1761–5 |date=November 2013 |pmid=23887160 |doi=10.1097/PAS.0b013e3182967e6c |url=}}</ref><ref name="pmid29279869">{{cite journal |vauthors=Abboudi H, Tschobotko B, Carr C, DasGupta R |title=Bilateral Renal Anastomosing Hemangiomas: A Tale of Two Kidneys |journal=J Endourol Case Rep |volume=3 |issue=1 |pages=176–178 |date=2017 |pmid=29279869 |pmc=5734139 |doi=10.1089/cren.2017.0018 |url=}}</ref><ref name="pmid28808574">{{cite journal |vauthors=Peng X, Li J, Liang Z |title=Anastomosing haemangioma of liver: A case report |journal=Mol Clin Oncol |volume=7 |issue=3 |pages=507–509 |date=September 2017 |pmid=28808574 |pmc=5543263 |doi=10.3892/mco.2017.1341 |url=}}</ref>
 ===Glomeruloid hemangioma===
-* Characterized by [[red blood cells]] filled clumps of [[capillaries]] inside dilated [[vascular]] spaces. These collections of [[capillaries]], lined by swollen endothelial cells, resemble renal [[glomeruli]] and stain positive for periodic acid-Schiff (PAS)-positive, diastase-resistant eosinophilic globules. Clinical presentation varies and are not discernible from other [[cutaneous]] [[lesions]]. Majority of the [[lesions]] manifest as multiple, asymptomatic pauples or nodules..<ref name="pmid23716835">{{cite journal |vauthors=Gupta J, Kandhari R, Ramesh V, Singh A |title=Glomeruloid hemangioma in normal individuals |journal=Indian J Dermatol |volume=58 |issue=2 |pages=160 |date=March 2013 |pmid=23716835 |pmc=3657245 |doi=10.4103/0019-5154.108088 |url=}}</ref><ref name="pmid27279314">{{cite journal |vauthors=Gupta V, Rai A, Mridha AR, Sharma VK |title=Multiple glomeruloid hemangiomas without POEMS syndrome |journal=Indian J Dermatol Venereol Leprol |volume=82 |issue=4 |pages=442–4 |date=2016 |pmid=27279314 |doi=10.4103/0378-6323.181461 |url=}}</ref>
+* Characterized by [[red blood cells]] filled clumps of [[capillaries]] inside dilated [[vascular]] spaces. These collections of [[capillaries]], lined by swollen [[endothelial]] cells, resemble renal [[glomeruli]] and stain positive for [[periodic acid-Schiff]] (PAS)-positive, diastase-resistant [[eosinophilic]] globules. Clinical presentation varies and are not discernible from other [[cutaneous]] [[lesions]]. Majority of the [[lesions]] manifest as multiple, asymptomatic pauples or nodules..<ref name="pmid23716835">{{cite journal |vauthors=Gupta J, Kandhari R, Ramesh V, Singh A |title=Glomeruloid hemangioma in normal individuals |journal=Indian J Dermatol |volume=58 |issue=2 |pages=160 |date=March 2013 |pmid=23716835 |pmc=3657245 |doi=10.4103/0019-5154.108088 |url=}}</ref><ref name="pmid27279314">{{cite journal |vauthors=Gupta V, Rai A, Mridha AR, Sharma VK |title=Multiple glomeruloid hemangiomas without POEMS syndrome |journal=Indian J Dermatol Venereol Leprol |volume=82 |issue=4 |pages=442–4 |date=2016 |pmid=27279314 |doi=10.4103/0378-6323.181461 |url=}}</ref>
 * Glomeruloid hemangioma is associated with [[POEMS syndrome]] in majority of the cases and rarely with [[Castleman's disease]]. Very few isolated cases of glomeruloid hemangioma have been reported.<ref name="pmid23716835">{{cite journal |vauthors=Gupta J, Kandhari R, Ramesh V, Singh A |title=Glomeruloid hemangioma in normal individuals |journal=Indian J Dermatol |volume=58 |issue=2 |pages=160 |date=March 2013 |pmid=23716835 |pmc=3657245 |doi=10.4103/0019-5154.108088 |url=}}</ref><ref name="pmid27279314">{{cite journal |vauthors=Gupta V, Rai A, Mridha AR, Sharma VK |title=Multiple glomeruloid hemangiomas without POEMS syndrome |journal=Indian J Dermatol Venereol Leprol |volume=82 |issue=4 |pages=442–4 |date=2016 |pmid=27279314 |doi=10.4103/0378-6323.181461 |url=}}</ref>
-** POEMS stands for peripheral neuropathy (P), organomegaly (O), endocrinopathy (E) monoclonal plasma-cells proliferative disorder (M) and skin changes (S) although [[diagnosis]] does not require presence of all of these symptoms. Other manifestations of POEMS syndrome may include sclerotic bone lesions, [[papilledema]], [[edema]], [[ascites]], effusions, [[pulmonary hypertension]], [[Castleman’ disease (CD)]], thrombocytosis and erythrocytosis, and increased serum VEGF.<ref name="pmid28894560">{{cite journal |vauthors=Nozza A |title=POEMS SYNDROME: an Update |journal=Mediterr J Hematol Infect Dis |volume=9 |issue=1 |pages=e2017051 |date=2017 |pmid=28894560 |pmc=5584767 |doi=10.4084/MJHID.2017.051 |url=}}</ref>
+** [[POEMS syndrome|POEMS]] stands for [[peripheral neuropathy]] (P), [[organomegaly]] (O), [[endocrinopathy]] (E) [[Plasma cell disorder|monoclonal plasma-cells proliferative disorder]] (M) and skin changes (S) although [[diagnosis]] does not require presence of all of these symptoms. Other manifestations of POEMS syndrome may include sclerotic bone lesions, [[papilledema]], [[edema]], [[ascites]], effusions, [[pulmonary hypertension]], [[Castleman's disease|Castleman’s disease]] (CD), [[thrombocytosis]] and [[erythrocytosis]], and increased serum [[VEGF]].<ref name="pmid28894560">{{cite journal |vauthors=Nozza A |title=POEMS SYNDROME: an Update |journal=Mediterr J Hematol Infect Dis |volume=9 |issue=1 |pages=e2017051 |date=2017 |pmid=28894560 |pmc=5584767 |doi=10.4084/MJHID.2017.051 |url=}}</ref>
-** [[Castleman's disease]] is characterized as lymphoproliferative disorder with inflammatory response involving multiple systems. Clinical presentation ranges from [[asymptomatic]] lymphadenopathy to severe systemic manifestations such as weight loss, [[fever]] and organomegaly.<ref name="pmid21499466">{{cite journal |vauthors=Kahn F, Fagerström A, Segelmark M, Bakoush O |title=Irreversible Kidney Damage due to Multicentric Castleman's Disease |journal=Libyan J Med |volume=3 |issue=2 |pages=101–3 |date=June 2008 |pmid=21499466 |pmc=3074288 |doi=10.4176/080108 |url=}}</ref>
+** [[Castleman's disease]] is characterized as lymphoproliferative disorder with inflammatory response involving multiple systems. Clinical presentation ranges from [[asymptomatic]] [[lymphadenopathy]] to severe systemic manifestations such as [[weight loss]], [[fever]] and [[organomegaly]].<ref name="pmid21499466">{{cite journal |vauthors=Kahn F, Fagerström A, Segelmark M, Bakoush O |title=Irreversible Kidney Damage due to Multicentric Castleman's Disease |journal=Libyan J Med |volume=3 |issue=2 |pages=101–3 |date=June 2008 |pmid=21499466 |pmc=3074288 |doi=10.4176/080108 |url=}}</ref>
-* Etiology is not well-understood but some theories suggest role of vascular endothelial growth factor (VEGF), increased estrogen levels, human herpesvirus-8 and increased cytokines in its pathogenesis.<ref name="pmid23716835">{{cite journal |vauthors=Gupta J, Kandhari R, Ramesh V, Singh A |title=Glomeruloid hemangioma in normal individuals |journal=Indian J Dermatol |volume=58 |issue=2 |pages=160 |date=March 2013 |pmid=23716835 |pmc=3657245 |doi=10.4103/0019-5154.108088 |url=}}</ref><ref name="pmid27279314">{{cite journal |vauthors=Gupta V, Rai A, Mridha AR, Sharma VK |title=Multiple glomeruloid hemangiomas without POEMS syndrome |journal=Indian J Dermatol Venereol Leprol |volume=82 |issue=4 |pages=442–4 |date=2016 |pmid=27279314 |doi=10.4103/0378-6323.181461 |url=}}</ref>
+* Etiology is not well-understood but some theories suggest role of [[vascular endothelial growth factor]] ([[VEGF]]), increased [[estrogen]] levels, [[human herpesvirus-8]] and increased [[cytokines]] in its [[pathogenesis]].<ref name="pmid23716835">{{cite journal |vauthors=Gupta J, Kandhari R, Ramesh V, Singh A |title=Glomeruloid hemangioma in normal individuals |journal=Indian J Dermatol |volume=58 |issue=2 |pages=160 |date=March 2013 |pmid=23716835 |pmc=3657245 |doi=10.4103/0019-5154.108088 |url=}}</ref><ref name="pmid27279314">{{cite journal |vauthors=Gupta V, Rai A, Mridha AR, Sharma VK |title=Multiple glomeruloid hemangiomas without POEMS syndrome |journal=Indian J Dermatol Venereol Leprol |volume=82 |issue=4 |pages=442–4 |date=2016 |pmid=27279314 |doi=10.4103/0378-6323.181461 |url=}}</ref>
 * [[Diagnosis]] relies on characteristic histology. Patients who present with glomeruloid hemangioma should undergo evaluation for [[POEMS syndrome]] and should be kept under follow-up because these [[lesions]] can precede full-blown [[POEMS syndrome]] in some cases.<ref name="pmid23716835">{{cite journal |vauthors=Gupta J, Kandhari R, Ramesh V, Singh A |title=Glomeruloid hemangioma in normal individuals |journal=Indian J Dermatol |volume=58 |issue=2 |pages=160 |date=March 2013 |pmid=23716835 |pmc=3657245 |doi=10.4103/0019-5154.108088 |url=}}</ref><ref name="pmid27279314">{{cite journal |vauthors=Gupta V, Rai A, Mridha AR, Sharma VK |title=Multiple glomeruloid hemangiomas without POEMS syndrome |journal=Indian J Dermatol Venereol Leprol |volume=82 |issue=4 |pages=442–4 |date=2016 |pmid=27279314 |doi=10.4103/0378-6323.181461 |url=}}</ref>
 ===Papillary hemangioma===
-* Rare [[tumor]] characterized by presence of papillary growths within dilated [[vascular]] channels, that contain cores of pericytes around normal [[capillaries]]. The [[tumor]] typically manifests as solitary papules in head and neck region, without any systemic manifestations.<ref name="pmid18805868">{{cite journal |vauthors=Suurmeijer AJ |title=Papillary hemangiomas and glomeruloid hemangiomas are distinct clinicopathological entities |journal=Int. J. Surg. Pathol. |volume=18 |issue=1 |pages=48–54 |date=February 2010 |pmid=18805868 |doi=10.1177/1066896908323504 |url=}}</ref><ref name="pmid17927585">{{cite journal |vauthors=Suurmeijer AJ, Fletcher CD |title=Papillary haemangioma. A distinctive cutaneous haemangioma of the head and neck area containing eosinophilic hyaline globules |journal=Histopathology |volume=51 |issue=5 |pages=638–48 |date=November 2007 |pmid=17927585 |doi=10.1111/j.1365-2559.2007.02847.x |url=}}</ref>
+* Rare [[tumor]] characterized by presence of papillary growths within dilated [[vascular]] channels, that contain cores of [[pericytes]] around normal [[capillaries]].
+* The [[tumor]] typically manifests as solitary [[papules]] in head and neck region, without any systemic manifestations.<ref name="pmid18805868">{{cite journal |vauthors=Suurmeijer AJ |title=Papillary hemangiomas and glomeruloid hemangiomas are distinct clinicopathological entities |journal=Int. J. Surg. Pathol. |volume=18 |issue=1 |pages=48–54 |date=February 2010 |pmid=18805868 |doi=10.1177/1066896908323504 |url=}}</ref><ref name="pmid17927585">{{cite journal |vauthors=Suurmeijer AJ, Fletcher CD |title=Papillary haemangioma. A distinctive cutaneous haemangioma of the head and neck area containing eosinophilic hyaline globules |journal=Histopathology |volume=51 |issue=5 |pages=638–48 |date=November 2007 |pmid=17927585 |doi=10.1111/j.1365-2559.2007.02847.x |url=}}</ref>
 * [[Diagnosis]] may require [[biopsy]]. Treatment options include [[excision]] and [[photodynamic therapy]].<ref name="pmid12093647">{{cite journal |vauthors=Schmidt-Erfurth UM, Kusserow C, Barbazetto IA, Laqua H |title=Benefits and complications of photodynamic therapy of papillary capillary hemangiomas |journal=Ophthalmology |volume=109 |issue=7 |pages=1256–66 |date=July 2002 |pmid=12093647 |doi= |url=}}</ref>
 ===Intravascular papillary endothelial hyperplasia===
-* Also called as [[Masson's tumor]], this [[benign]] [[lesions]] is characterized by presence of intravascular [[papillary]] structures that are enveloped by proliferating [[endothelial cells]]. It is considered to be a reactive [[lesion]] associated with an organizing thrombus. Clinically it manifests as solitary painless mass in head-neck and the extremities especially the hand, that may grow rapidly in size and become painful and/or tender. Some [[lesions]] have been found intra-abdominallly such as in the [[liver]] that can bleed and present with [[anemia]].<ref name="pmid24125024">{{cite journal |vauthors=Akdur NC, Donmez M, Gozel S, Ustun H, Hucumenoglu S |title=Intravascular papillary endothelial hyperplasia: histomorphological and immunohistochemical features |journal=Diagn Pathol |volume=8 |issue= |pages=167 |date=October 2013 |pmid=24125024 |pmc=4016006 |doi=10.1186/1746-1596-8-167 |url=}}</ref><ref name="pmid24294378">{{cite journal |vauthors=Kim S, Jun JH, Kim J, Kim DW, Jang YH, Lee WJ, Chung HY, Lee SJ |title=HIF-1α and VEGF expression correlates with thrombus remodeling in cases of intravascular papillary endothelial hyperplasia |journal=Int J Clin Exp Pathol |volume=6 |issue=12 |pages=2912–8 |date=2013 |pmid=24294378 |pmc=3843272 |doi= |url=}}</ref><ref name="pmid24891960">{{cite journal |vauthors=Guledgud MV, Patil K, Saikrishna D, Madhavan A, Yelamali T |title=Intravascular papillary endothelial hyperplasia: diagnostic sequence and literature review of an orofacial lesion |journal=Case Rep Dent |volume=2014 |issue= |pages=934593 |date=2014 |pmid=24891960 |pmc=4033548 |doi=10.1155/2014/934593 |url=}}</ref><ref name="pmid15082910">{{cite journal |vauthors=Hong SG, Cho HM, Chin HM, Park IY, Yoo JY, Hwang SS, Kim JG, Park WB, Chun CS |title=Intravascular papillary endothelial hyperplasia (Masson's hemangioma) of the liver: a new hepatic lesion |journal=J. Korean Med. Sci. |volume=19 |issue=2 |pages=305–8 |date=April 2004 |pmid=15082910 |pmc=2822318 |doi=10.3346/jkms.2004.19.2.305 |url=}}</ref>
+* Also called as [[Masson's tumor]], this [[benign]] [[lesions]] is characterized by presence of [[intravascular]] [[papillary]] structures that are enveloped by proliferating [[endothelial cells]]. It is considered to be a reactive [[lesion]] associated with an organizing thrombus. Clinically it manifests as solitary painless mass in head-neck and the extremities especially the hand, that may grow rapidly in size and become [[painful]] and/or tender. Some [[lesions]] have been found intra-abdominallly such as in the [[liver]] that can bleed and present with [[anemia]].<ref name="pmid24125024">{{cite journal |vauthors=Akdur NC, Donmez M, Gozel S, Ustun H, Hucumenoglu S |title=Intravascular papillary endothelial hyperplasia: histomorphological and immunohistochemical features |journal=Diagn Pathol |volume=8 |issue= |pages=167 |date=October 2013 |pmid=24125024 |pmc=4016006 |doi=10.1186/1746-1596-8-167 |url=}}</ref><ref name="pmid24294378">{{cite journal |vauthors=Kim S, Jun JH, Kim J, Kim DW, Jang YH, Lee WJ, Chung HY, Lee SJ |title=HIF-1α and VEGF expression correlates with thrombus remodeling in cases of intravascular papillary endothelial hyperplasia |journal=Int J Clin Exp Pathol |volume=6 |issue=12 |pages=2912–8 |date=2013 |pmid=24294378 |pmc=3843272 |doi= |url=}}</ref><ref name="pmid24891960">{{cite journal |vauthors=Guledgud MV, Patil K, Saikrishna D, Madhavan A, Yelamali T |title=Intravascular papillary endothelial hyperplasia: diagnostic sequence and literature review of an orofacial lesion |journal=Case Rep Dent |volume=2014 |issue= |pages=934593 |date=2014 |pmid=24891960 |pmc=4033548 |doi=10.1155/2014/934593 |url=}}</ref><ref name="pmid15082910">{{cite journal |vauthors=Hong SG, Cho HM, Chin HM, Park IY, Yoo JY, Hwang SS, Kim JG, Park WB, Chun CS |title=Intravascular papillary endothelial hyperplasia (Masson's hemangioma) of the liver: a new hepatic lesion |journal=J. Korean Med. Sci. |volume=19 |issue=2 |pages=305–8 |date=April 2004 |pmid=15082910 |pmc=2822318 |doi=10.3346/jkms.2004.19.2.305 |url=}}</ref>
-* This [[lesions]] appears to be associated with [[vascular]] trauma, and thrombus that may lead to chronic irritation and increased levels of fibroblast growth factor (FGF), hypoxia-inducible factor-1 (HIF-1α), and vascular endothelial growth factor (VEGF) stimulating [[endothelial cells]] proliferation.<ref name="pmid24294378" /><ref name="pmid24891960" /><ref name="pmid26225335">{{cite journal |vauthors=Mahapatra QS, Sahai K, Malik A, Mani NS |title=Intravascular papillary endothelial hyperplasia: An unusual histopathological entity |journal=Indian Dermatol Online J |volume=6 |issue=4 |pages=277–9 |date=2015 |pmid=26225335 |pmc=4513410 |doi=10.4103/2229-5178.160269 |url=}}</ref>
+* This [[lesions]] appears to be associated with [[vascular]] trauma, and thrombus that may lead to chronic irritation and increased levels of [[fibroblast growth factor]] (FGF), hypoxia-inducible factor-1 (HIF-1α), and [[vascular endothelial growth factor]] (VEGF) stimulating [[endothelial cells]] proliferation.<ref name="pmid24294378" /><ref name="pmid24891960" /><ref name="pmid26225335">{{cite journal |vauthors=Mahapatra QS, Sahai K, Malik A, Mani NS |title=Intravascular papillary endothelial hyperplasia: An unusual histopathological entity |journal=Indian Dermatol Online J |volume=6 |issue=4 |pages=277–9 |date=2015 |pmid=26225335 |pmc=4513410 |doi=10.4103/2229-5178.160269 |url=}}</ref>
 * Histopathological studies are generally required for [[diagnosis]] and may also require [[immunohistochemical]] confirmation. Treatment is [[surgery]] with uncommon recurrence.<ref name="pmid26225335" /><ref name="pmid21103239">{{cite journal |vauthors=Meadows MC, Sun X, Dardik M, Tarantino DR, Chamberlain RS |title=Intraabdominal Intravascular Papillary Endothelial Hyperplasia (Masson's Tumor): A Rare and Novel Cause of Gastrointestinal Bleeding |journal=Case Rep Gastroenterol |volume=4 |issue=1 |pages=124–132 |date=March 2010 |pmid=21103239 |pmc=2988909 |doi=10.1159/000294148 |url=}}</ref>
 ===Cutaneous epithelioid angiomatous nodule===
@@ Line 131: / Line 136: @@
 * [[Diagnosis]] requires careful clinical and histopathological evaluation. [[Surgery]] has been the treatment used in majority of the [[lesions]] although [[cryotherapy]] has also been used. [[Steroids]] are found to be ineffective.<ref name="pmid27981217" /><ref name="pmid23551998">{{cite journal |vauthors=Dastgheib L, Aslani FS, Sepaskhah M, Saki N, Motevalli D |title=A young woman with multiple cutaneous epithelioid angiomatous nodules (CEAN) on her forearm: a case report and follow-up of therapeutic intervention |journal=Dermatol. Online J. |volume=19 |issue=3 |pages=1 |date=March 2013 |pmid=23551998 |doi= |url=}}</ref>
 ===Acquired elastotic hemangioma===
-* First described in 2002, this rare [[lesion]] typically manifests as solitary, [[asymptomatic]], red to purple, patches and plaques on areas damaged by sun exposure such as hands and forearms. Some [[patients]] may complain of pain or growth of the [[lesion]]. Histologically its exhibits solar elastosis and band like proliferation of [[capillaries]] in superficial [[dermis]]. These proliferating channels are arranged parallel to [[epidermis]] and [[endothelial cells]] typically display absence of atypia but may show hobnail pattern.<ref name="pmid27867745">{{cite journal |vauthors=Hicks T, Katz I |title=First description of the dermatoscopic features of acquired elastotic hemangioma-a case report |journal=Dermatol Pract Concept |volume=6 |issue=4 |pages=35–37 |date=October 2016 |pmid=27867745 |pmc=5108644 |doi=10.5826/dpc.0604a08 |url=}}</ref><ref name="pmid29507844">{{cite journal |vauthors=Cohen PR, Hinds BR |title=Acquired Elastotic Hemangioma: Case Series and Comprehensive Literature Review |journal=Cureus |volume=9 |issue=12 |pages=e1994 |date=December 2017 |pmid=29507844 |pmc=5832390 |doi=10.7759/cureus.1994 |url=}}</ref>
+* First described in 2002, this rare [[lesion]] typically manifests as solitary, [[asymptomatic]], red to purple, patches and plaques on areas damaged by sun exposure such as hands and forearms. Some [[patients]] may complain of pain or growth of the [[lesion]]. Histologically, its exhibits solar elastosis and band like proliferation of [[capillaries]] in superficial [[dermis]]. These proliferating channels are arranged parallel to [[epidermis]] and [[endothelial cells]] typically display absence of atypia but may show hobnail pattern.<ref name="pmid27867745">{{cite journal |vauthors=Hicks T, Katz I |title=First description of the dermatoscopic features of acquired elastotic hemangioma-a case report |journal=Dermatol Pract Concept |volume=6 |issue=4 |pages=35–37 |date=October 2016 |pmid=27867745 |pmc=5108644 |doi=10.5826/dpc.0604a08 |url=}}</ref><ref name="pmid29507844">{{cite journal |vauthors=Cohen PR, Hinds BR |title=Acquired Elastotic Hemangioma: Case Series and Comprehensive Literature Review |journal=Cureus |volume=9 |issue=12 |pages=e1994 |date=December 2017 |pmid=29507844 |pmc=5832390 |doi=10.7759/cureus.1994 |url=}}</ref>
-* This lesion has slight preference for [[females]]. Damage due to sun exposure such as free radical production are thought to be associated with [[pathogenesis]]. Some case reports showed use of [[progesterone]] associated with appearance of [[lesions]] in perimenopausal women.<ref name="pmid27867745" /><ref name="pmid29507844" /><ref name="pmid12196746">{{cite journal |vauthors=Requena L, Kutzner H, Mentzel T |title=Acquired elastotic hemangioma: A clinicopathologic variant of hemangioma |journal=J. Am. Acad. Dermatol. |volume=47 |issue=3 |pages=371–6 |date=September 2002 |pmid=12196746 |doi= |url=}}</ref><ref name="pmid20950363">{{cite journal |vauthors=Tong PL, Beer TW |title=Acquired elastotic hemangioma: ten cases with immunohistochemistry refuting a lymphatic origin in most lesions |journal=J. Cutan. Pathol. |volume=37 |issue=12 |pages=1259–60 |date=December 2010 |pmid=20950363 |doi=10.1111/j.1600-0560.2010.01610.x |url=}}</ref>
+* This lesion has slight preference for [[females]]. Damage due to sun exposure such as free radical production are thought to be associated with [[pathogenesis]]. Some case reports showed use of [[progesterone]] associated with appearance of [[lesions]] in peri-menopausal women.<ref name="pmid27867745" /><ref name="pmid29507844" /><ref name="pmid12196746">{{cite journal |vauthors=Requena L, Kutzner H, Mentzel T |title=Acquired elastotic hemangioma: A clinicopathologic variant of hemangioma |journal=J. Am. Acad. Dermatol. |volume=47 |issue=3 |pages=371–6 |date=September 2002 |pmid=12196746 |doi= |url=}}</ref><ref name="pmid20950363">{{cite journal |vauthors=Tong PL, Beer TW |title=Acquired elastotic hemangioma: ten cases with immunohistochemistry refuting a lymphatic origin in most lesions |journal=J. Cutan. Pathol. |volume=37 |issue=12 |pages=1259–60 |date=December 2010 |pmid=20950363 |doi=10.1111/j.1600-0560.2010.01610.x |url=}}</ref>
 * [[Diagnosis]] requires [[biopsy]] to rule out [[basal cell carcinoma]] and other similar appearing [[lesions]]. Treatment options include observation, discontinuance of [[progesterone]], [[laser therapy]] and [[excision]]. [[Recurrence]] was not observed in any of the cases observed or treated.<ref name="pmid29507844" /><ref name="pmid20950363" /><ref name="pmid27867745" /><ref name="pmid20950363">{{cite journal |vauthors=Tong PL, Beer TW |title=Acquired elastotic hemangioma: ten cases with immunohistochemistry refuting a lymphatic origin in most lesions |journal=J. Cutan. Pathol. |volume=37 |issue=12 |pages=1259–60 |date=December 2010 |pmid=20950363 |doi=10.1111/j.1600-0560.2010.01610.x |url=}}</ref><ref name="pmid28296791">{{cite journal |vauthors=Mendieta-Eckert M, Díaz-Ramón JL, Gardeazabal-García J |title=Response of an Acquired Elastotic Hemangioma to Vascular Laser |journal=Dermatol Surg |volume=44 |issue=1 |pages=136–137 |date=January 2018 |pmid=28296791 |doi=10.1097/DSS.0000000000001105 |url=}}</ref>
 ===Littoral cell hemangioma of the spleen===
-* [[Benign]] [[tumor]] that originates from cells that line the red pup sinuses. Majority of the patients are [[asymptomatic]] but some present with symptoms related to splenic enlargement such as abdominal distension, [[hypersplenism]] such as persistent [[anemia]] and [[thrombocytopenia]], and constitutional symptoms such as weight loss, fever, and fatigue. Histopathological features include anastomosing [[vascular]] channels lined by cuboidal cells, with somewhat rarer presence of [[papillary]] structures.<ref name="pmid22172167">{{cite journal |vauthors=Hu ZQ, A YJ, Sun QM, Li W, Li L |title=The splenic Littoral cell angioma in China: a case report and review |journal=World J Surg Oncol |volume=9 |issue= |pages=168 |date=December 2011 |pmid=22172167 |pmc=3271992 |doi=10.1186/1477-7819-9-168 |url=}}</ref><ref name="pmid26604237">{{cite journal |vauthors=de Ridder GG, Galeotti J, Carney J, Wang E |title=Persistent thrombocytopaenia in a young man with splenomegaly, rebound thrombocytosis after splenectomy and subsequent pulmonary embolism: splenic littoral cell angioma and associated events |journal=BMJ Case Rep |volume=2015 |issue= |pages= |date=November 2015 |pmid=26604237 |pmc=4680245 |doi=10.1136/bcr-2015-212882 |url=}}</ref><ref name="pmid18713469">{{cite journal |vauthors=Tee M, Vos P, Zetler P, Wiseman SM |title=Incidental littoral cell angioma of the spleen |journal=World J Surg Oncol |volume=6 |issue= |pages=87 |date=August 2008 |pmid=18713469 |pmc=2527567 |doi=10.1186/1477-7819-6-87 |url=}}</ref><ref name="pmid18161935">{{cite journal |vauthors=Cosme A, Tejada A, Bujanda L, Vaquero M, Elorza JL, Ojeda E, Goikoetxea U |title=Littoral-cell angioma of the spleen: a case report |journal=World J. Gastroenterol. |volume=13 |issue=48 |pages=6603–4 |date=December 2007 |pmid=18161935 |pmc=4611304 |doi= |url=}}</ref>
+* [[Benign]] [[tumor]] that originates from cells that line the red pup sinuses. Majority of the patients are [[asymptomatic]] but some present with symptoms related to [[Splenomegaly|splenic enlargement]] such as [[abdominal distension]], [[hypersplenism]] such as persistent [[anemia]] and [[thrombocytopenia]], and constitutional symptoms such as [[weight loss]], [[fever]], and [[fatigue]]. Histopathological features include anastomosing [[vascular]] channels lined by cuboidal cells, with somewhat rarer presence of [[papillary]] structures.<ref name="pmid22172167">{{cite journal |vauthors=Hu ZQ, A YJ, Sun QM, Li W, Li L |title=The splenic Littoral cell angioma in China: a case report and review |journal=World J Surg Oncol |volume=9 |issue= |pages=168 |date=December 2011 |pmid=22172167 |pmc=3271992 |doi=10.1186/1477-7819-9-168 |url=}}</ref><ref name="pmid26604237">{{cite journal |vauthors=de Ridder GG, Galeotti J, Carney J, Wang E |title=Persistent thrombocytopaenia in a young man with splenomegaly, rebound thrombocytosis after splenectomy and subsequent pulmonary embolism: splenic littoral cell angioma and associated events |journal=BMJ Case Rep |volume=2015 |issue= |pages= |date=November 2015 |pmid=26604237 |pmc=4680245 |doi=10.1136/bcr-2015-212882 |url=}}</ref><ref name="pmid18713469">{{cite journal |vauthors=Tee M, Vos P, Zetler P, Wiseman SM |title=Incidental littoral cell angioma of the spleen |journal=World J Surg Oncol |volume=6 |issue= |pages=87 |date=August 2008 |pmid=18713469 |pmc=2527567 |doi=10.1186/1477-7819-6-87 |url=}}</ref><ref name="pmid18161935">{{cite journal |vauthors=Cosme A, Tejada A, Bujanda L, Vaquero M, Elorza JL, Ojeda E, Goikoetxea U |title=Littoral-cell angioma of the spleen: a case report |journal=World J. Gastroenterol. |volume=13 |issue=48 |pages=6603–4 |date=December 2007 |pmid=18161935 |pmc=4611304 |doi= |url=}}</ref>
-* Although not well-established, few case reports have demonstrated [[malignant]] histology and features in this [[neoplasm]]. This [[tumor]] can be related to visceral [[malignancies]] such as [[non-Hodgkin's lymphoma]], [[tumors]] of the [[liver]] and [[brain]], [[epithelial ovarian cancer]], [[non-small cell lung cancer]], [[plasmablastic B-cell lymphoma]], villous lymphocyte leukaemia and [[neoplasm]] of [[colon]], [[kidney]] and [[pancreas]]. Association with [[Crohn's disease]] and [[Gaucher's disease]] has also been described leading to [[hypothesis]] of [[immune dysfunction]] as a possible cause of littoral cell hemangioma of splen.<ref name="pmid26604237" /><ref name="pmid18713469" /><ref name="pmid18161935" /><ref name="pmid16971207">{{cite journal |vauthors=Harmon RL, Cerruto CA, Scheckner A |title=Littoral cell angioma: a case report and review |journal=Curr Surg |volume=63 |issue=5 |pages=345–50 |date=2006 |pmid=16971207 |doi=10.1016/j.cursur.2006.06.011 |url=}}</ref><ref name="pmid22098375">{{cite journal |vauthors=Melzer N, Barth PJ, Müller KM, Foss HD, Krug U, Schilling M, Marziniak M, Grauer OM, Wiendl H |title=Rapidly progressive B-cell dominated inflammatory neuropathy and littoral cell angioma of the spleen associated with plasmablastic B-cell lymphoma |journal=Leuk. Lymphoma |volume=53 |issue=6 |pages=1242–4 |date=June 2012 |pmid=22098375 |doi=10.3109/10428194.2011.640677 |url=}}</ref><ref name="pmid12405918">{{cite journal |vauthors=Chatelain D, Bonte H, Guillevin L, Balladur P, Flejou JF |title=Small solitary littoral cell angioma associated with splenic marginal zone lymphoma and villous lymphocyte leukaemia in a patient with hepatitis C infection |journal=Histopathology |volume=41 |issue=5 |pages=473–5 |date=November 2002 |pmid=12405918 |doi= |url=}}</ref><ref name="pmid9862523">{{cite journal |vauthors=Bisceglia M, Sickel JZ, Giangaspero F, Gomes V, Amini M, Michal M |title=Littoral cell angioma of the spleen: an additional report of four cases with emphasis on the association with visceral organ cancers |journal=Tumori |volume=84 |issue=5 |pages=595–9 |date=1998 |pmid=9862523 |doi= |url=}}</ref><ref name="pmid25705528">{{cite journal |vauthors=Johansson J, Björnsson B, Ignatova S, Sandström P, Ekstedt M |title=Littoral cell angioma in a patient with Crohn's disease |journal=Case Rep Gastrointest Med |volume=2015 |issue= |pages=474969 |date=2015 |pmid=25705528 |pmc=4326338 |doi=10.1155/2015/474969 |url=}}</ref><ref name="pmid11559940">{{cite journal |vauthors=Gupta MK, Levin M, Aguilera NS, Pastores GM |title=Littoral cell angioma of the spleen in a patient with Gaucher disease |journal=Am. J. Hematol. |volume=68 |issue=1 |pages=61–2 |date=September 2001 |pmid=11559940 |doi= |url=}}</ref><ref name="pmid7573679">{{cite journal |vauthors=Rosso R, Paulli M, Gianelli U, Boveri E, Stella G, Magrini U |title=Littoral cell angiosarcoma of the spleen. Case report with immunohistochemical and ultrastructural analysis |journal=Am. J. Surg. Pathol. |volume=19 |issue=10 |pages=1203–8 |date=October 1995 |pmid=7573679 |doi= |url=}}</ref>
+* Although not well-established, few case reports have demonstrated [[malignant]] histology and features in this [[neoplasm]]. This [[tumor]] can be related to visceral [[malignancies]] such as [[non-Hodgkin's lymphoma]], [[tumors]] of the [[liver]] and [[brain]], epithelial ovarian cancer, [[non-small cell lung cancer]], plasmablastic B-cell lymphoma, villous lymphocyte leukemia and [[neoplasm]] of [[colon]], [[kidney]] and [[pancreas]]. Association with [[Crohn's disease]] and [[Gaucher's disease]] has also been described leading to [[hypothesis]] of [[immune dysfunction]] as a possible cause of littoral cell [[hemangioma]] of [[spleen]].<ref name="pmid26604237" /><ref name="pmid18713469" /><ref name="pmid18161935" /><ref name="pmid16971207">{{cite journal |vauthors=Harmon RL, Cerruto CA, Scheckner A |title=Littoral cell angioma: a case report and review |journal=Curr Surg |volume=63 |issue=5 |pages=345–50 |date=2006 |pmid=16971207 |doi=10.1016/j.cursur.2006.06.011 |url=}}</ref><ref name="pmid22098375">{{cite journal |vauthors=Melzer N, Barth PJ, Müller KM, Foss HD, Krug U, Schilling M, Marziniak M, Grauer OM, Wiendl H |title=Rapidly progressive B-cell dominated inflammatory neuropathy and littoral cell angioma of the spleen associated with plasmablastic B-cell lymphoma |journal=Leuk. Lymphoma |volume=53 |issue=6 |pages=1242–4 |date=June 2012 |pmid=22098375 |doi=10.3109/10428194.2011.640677 |url=}}</ref><ref name="pmid12405918">{{cite journal |vauthors=Chatelain D, Bonte H, Guillevin L, Balladur P, Flejou JF |title=Small solitary littoral cell angioma associated with splenic marginal zone lymphoma and villous lymphocyte leukaemia in a patient with hepatitis C infection |journal=Histopathology |volume=41 |issue=5 |pages=473–5 |date=November 2002 |pmid=12405918 |doi= |url=}}</ref><ref name="pmid9862523">{{cite journal |vauthors=Bisceglia M, Sickel JZ, Giangaspero F, Gomes V, Amini M, Michal M |title=Littoral cell angioma of the spleen: an additional report of four cases with emphasis on the association with visceral organ cancers |journal=Tumori |volume=84 |issue=5 |pages=595–9 |date=1998 |pmid=9862523 |doi= |url=}}</ref><ref name="pmid25705528">{{cite journal |vauthors=Johansson J, Björnsson B, Ignatova S, Sandström P, Ekstedt M |title=Littoral cell angioma in a patient with Crohn's disease |journal=Case Rep Gastrointest Med |volume=2015 |issue= |pages=474969 |date=2015 |pmid=25705528 |pmc=4326338 |doi=10.1155/2015/474969 |url=}}</ref><ref name="pmid11559940">{{cite journal |vauthors=Gupta MK, Levin M, Aguilera NS, Pastores GM |title=Littoral cell angioma of the spleen in a patient with Gaucher disease |journal=Am. J. Hematol. |volume=68 |issue=1 |pages=61–2 |date=September 2001 |pmid=11559940 |doi= |url=}}</ref><ref name="pmid7573679">{{cite journal |vauthors=Rosso R, Paulli M, Gianelli U, Boveri E, Stella G, Magrini U |title=Littoral cell angiosarcoma of the spleen. Case report with immunohistochemical and ultrastructural analysis |journal=Am. J. Surg. Pathol. |volume=19 |issue=10 |pages=1203–8 |date=October 1995 |pmid=7573679 |doi= |url=}}</ref>
-* Preferred [[diagnostic]] modality is [[biopsy]] often following [[splenectomy]]. ]]Fina needle aspiration]] can also be used. [[Imaging]] studies such as [[MRI]] and [[CT scan]] are inconclusive. All [[patients]] with this [[neoplasm]] should undergo evaluation for other associated [[neoplasms]] especially visceral [[neoplasms]]. [[Splenectomy]] is the treatment.<ref name="pmid22172167" /><ref name="pmid18713469" /><ref name="pmid17449783">{{cite journal |vauthors=Bhatt S, Huang J, Dogra V |title=Littoral cell angioma of the spleen |journal=AJR Am J Roentgenol |volume=188 |issue=5 |pages=1365–6 |date=May 2007 |pmid=17449783 |doi=10.2214/AJR.06.1157 |url=}}</ref><ref name="pmid25820845">{{cite journal |vauthors=Vancauwenberghe T, Snoeckx A, Vanbeckevoort D, Dymarkowski S, Vanhoenacker FM |title=Imaging of the spleen: what the clinician needs to know |journal=Singapore Med J |volume=56 |issue=3 |pages=133–44 |date=March 2015 |pmid=25820845 |pmc=4371192 |doi= |url=}}</ref><ref name="pmid28607812">{{cite journal |vauthors=Liu D, Chen Z, Wang T, Zhang B, Zhou H, Li Q |title=Littoral-cell angioma of the spleen: a case report |journal=Cancer Biol Med |volume=14 |issue=2 |pages=194–195 |date=May 2017 |pmid=28607812 |pmc=5444933 |doi=10.20892/j.issn.2095-3941.2016.0094 |url=}}</ref>
+* Preferred [[diagnostic]] modality is [[biopsy]] often following [[splenectomy]]. [[Fine needle aspiration]] can also be used. [[Imaging]] studies such as [[MRI]] and [[CT scan]] are inconclusive. All [[patients]] with this [[neoplasm]] should undergo evaluation for other associated [[neoplasms]] especially visceral [[neoplasms]]. [[Splenectomy]] is the treatment.<ref name="pmid22172167" /><ref name="pmid18713469" /><ref name="pmid17449783">{{cite journal |vauthors=Bhatt S, Huang J, Dogra V |title=Littoral cell angioma of the spleen |journal=AJR Am J Roentgenol |volume=188 |issue=5 |pages=1365–6 |date=May 2007 |pmid=17449783 |doi=10.2214/AJR.06.1157 |url=}}</ref><ref name="pmid25820845">{{cite journal |vauthors=Vancauwenberghe T, Snoeckx A, Vanbeckevoort D, Dymarkowski S, Vanhoenacker FM |title=Imaging of the spleen: what the clinician needs to know |journal=Singapore Med J |volume=56 |issue=3 |pages=133–44 |date=March 2015 |pmid=25820845 |pmc=4371192 |doi= |url=}}</ref><ref name="pmid28607812">{{cite journal |vauthors=Liu D, Chen Z, Wang T, Zhang B, Zhou H, Li Q |title=Littoral-cell angioma of the spleen: a case report |journal=Cancer Biol Med |volume=14 |issue=2 |pages=194–195 |date=May 2017 |pmid=28607812 |pmc=5444933 |doi=10.20892/j.issn.2095-3941.2016.0094 |url=}}</ref>
 ==Related lesions==
 ===Eccrine angiomatous hamartoma===
-* [[Benign]] non-neoplastic proliferation of [[eccrine]] and [[capillary]] structures leading to increased [[sweat glands]] and dilated [[vascular]] channels in the middle and deep [[dermis]], and subcutaneous structures. Clinical presentations vary remarkably but majority of the [[lesions]] are [[asymptomatic]] and appear as red to violaceous to brown single nodule or plaque on the extremities but macules, patches, multiple [[lesions]] and uncommon sites for the [[lesion]] have been reported. Many [[patients]] complain of pain, tenderness, [[increased sweating]] and [[excessive hair]] over the lesion.<ref name="pmid23717013">{{cite journal |vauthors=Shin J, Jang YH, Kim SC, Kim YC |title=Eccrine angiomatous hamartoma: a review of ten cases |journal=Ann Dermatol |volume=25 |issue=2 |pages=208–12 |date=May 2013 |pmid=23717013 |pmc=3662915 |doi=10.5021/ad.2013.25.2.208 |url=}}</ref><ref name="pmid16776719">{{cite journal |vauthors=Chien AJ, Asgari M, Argenyi ZB |title=Eccrine angiomatous hamartoma with elements of an arterio-venous malformation: a newly recognized variant |journal=J. Cutan. Pathol. |volume=33 |issue=6 |pages=433–6 |date=June 2006 |pmid=16776719 |pmc=4113075 |doi=10.1111/j.0303-6987.2006.00272.x |url=}}</ref><ref name="pmid">{{cite journal |vauthors=Nygaard U, Dalager S, Spaun E, Hedelund L |title=Large eccrine angiomatous hamartoma: a novel clinical presentation of disease |journal=J Dermatol Case Rep |volume=9 |issue=3 |pages=58–61 |date=September 2015 |pmid= |pmc=4619160 |doi=10.3315/jdcr.2015.1211 |url=}}</ref><ref name="pmid22148055">{{cite journal |vauthors=Lee Y, Jung YJ, Lee WS |title=Late-onset eccrine angiomatous hamartoma associated with a ganglion cyst on the sole of the foot |journal=Ann Dermatol |volume=23 |issue=Suppl 2 |pages=S218–21 |date=October 2011 |pmid=22148055 |pmc=3229070 |doi=10.5021/ad.2011.23.S2.S218 |url=}}</ref><ref name="pmid22028582">{{cite journal |vauthors=Yun JH, Kang HK, Na SY, Roh JY, Lee JR |title=Eccrine angiomatous hamartoma mimicking a traumatic hemorrhage |journal=Ann Dermatol |volume=23 Suppl 1 |issue= |pages=S84–7 |date=September 2011 |pmid=22028582 |pmc=3199432 |doi=10.5021/ad.2011.23.S1.S84 |url=}}</ref>
+* [[Benign]] non-neoplastic proliferation of eccrine and [[capillary]] structures leading to increased [[sweat glands]] and dilated [[vascular]] channels in the middle and deep [[dermis]], and subcutaneous structures. Clinical presentations vary remarkably but majority of the [[lesions]] are [[asymptomatic]] and appear as red to violaceous to brown single nodule or plaque on the extremities but [[macules]], patches, multiple [[lesions]] and uncommon sites for the [[lesion]] have been reported. Many [[patients]] complain of [[pain]], [[tenderness]], [[increased sweating]] and excessive hair over the lesion.<ref name="pmid23717013">{{cite journal |vauthors=Shin J, Jang YH, Kim SC, Kim YC |title=Eccrine angiomatous hamartoma: a review of ten cases |journal=Ann Dermatol |volume=25 |issue=2 |pages=208–12 |date=May 2013 |pmid=23717013 |pmc=3662915 |doi=10.5021/ad.2013.25.2.208 |url=}}</ref><ref name="pmid16776719">{{cite journal |vauthors=Chien AJ, Asgari M, Argenyi ZB |title=Eccrine angiomatous hamartoma with elements of an arterio-venous malformation: a newly recognized variant |journal=J. Cutan. Pathol. |volume=33 |issue=6 |pages=433–6 |date=June 2006 |pmid=16776719 |pmc=4113075 |doi=10.1111/j.0303-6987.2006.00272.x |url=}}</ref><ref name="pmid">{{cite journal |vauthors=Nygaard U, Dalager S, Spaun E, Hedelund L |title=Large eccrine angiomatous hamartoma: a novel clinical presentation of disease |journal=J Dermatol Case Rep |volume=9 |issue=3 |pages=58–61 |date=September 2015 |pmid= |pmc=4619160 |doi=10.3315/jdcr.2015.1211 |url=}}</ref><ref name="pmid22148055">{{cite journal |vauthors=Lee Y, Jung YJ, Lee WS |title=Late-onset eccrine angiomatous hamartoma associated with a ganglion cyst on the sole of the foot |journal=Ann Dermatol |volume=23 |issue=Suppl 2 |pages=S218–21 |date=October 2011 |pmid=22148055 |pmc=3229070 |doi=10.5021/ad.2011.23.S2.S218 |url=}}</ref><ref name="pmid22028582">{{cite journal |vauthors=Yun JH, Kang HK, Na SY, Roh JY, Lee JR |title=Eccrine angiomatous hamartoma mimicking a traumatic hemorrhage |journal=Ann Dermatol |volume=23 Suppl 1 |issue= |pages=S84–7 |date=September 2011 |pmid=22028582 |pmc=3199432 |doi=10.5021/ad.2011.23.S1.S84 |url=}}</ref>
-* [[Etiology]] for this [[benign]] [[lesion]] has not been established. [[Diagnosis]] requires [[biopsy]] although [[imaging]] studies such as [[MRI]] and [[CT scan]] can be used to define the extent of the [[lesion]]. [[Asymptomatic]] [[lesion]] do not require treatment. [[Surgical excision]] is the treatment of choice if treatment is indicated. Alternative therapies include use of [[botulinum toxin]] to treat [[hyperhidrosis]] and use of intralesional sclerosants.<ref name="pmid23717013" /><ref name="pmid26512300">{{cite journal |vauthors=Nygaard U, Dalager S, Spaun E, Hedelund L |title=Large eccrine angiomatous hamartoma: a novel clinical presentation of disease |journal=J Dermatol Case Rep |volume=9 |issue=3 |pages=58–61 |date=September 2015 |pmid=26512300 |pmc=4619160 |doi=10.3315/jdcr.2015.1211 |url=}}</ref><ref name="pmid22707779">{{cite journal |vauthors=Kar S, Krishnan A, Gangane N |title=Eccrine angiomatous hamartoma: a rare skin lesion with diverse histological features |journal=Indian J Dermatol |volume=57 |issue=3 |pages=225–7 |date=May 2012 |pmid=22707779 |pmc=3371531 |doi=10.4103/0019-5154.96206 |url=}}</ref><ref name="pmid19289750">{{cite journal |vauthors=Barco D, Baselga E, Alegre M, Curell R, Alomar A |title=Successful treatment of eccrine angiomatous hamartoma with botulinum toxin |journal=Arch Dermatol |volume=145 |issue=3 |pages=241–3 |date=March 2009 |pmid=19289750 |doi=10.1001/archdermatol.2008.575 |url=}}</ref><ref name="pmid22837574">{{cite journal |vauthors=Sen S, Chatterjee G, Mitra PK, Gangopadhyay A |title=Eccrine angiomatous naevus revisited |journal=Indian J Dermatol |volume=57 |issue=4 |pages=313–5 |date=July 2012 |pmid=22837574 |pmc=3401855 |doi=10.4103/0019-5154.97682 |url=}}</ref><ref name="pmid23559910">{{cite journal |vauthors=Fathaddin AA, Alhumidi AA |title=Eccrine angiomatous hamartoma, with verrocous hemangioma-like features: A case report |journal=Int J Health Sci (Qassim) |volume=7 |issue=1 |pages=103–6 |date=January 2013 |pmid=23559910 |pmc=3612410 |doi= |url=}}</ref><ref name="pmid26500534">{{cite journal |vauthors=Tantanasrigul P, Kootiratrakarn T, Wessagowit V, Kattipathanapong P, Sudtikoonaseth P |title=Eccrine Angiomatous Hamartoma in an Adolescent |journal=Case Rep Dermatol |volume=7 |issue=3 |pages=233–6 |date=2015 |pmid=26500534 |pmc=4608655 |doi=10.1159/000439399 |url=}}</ref>
+* [[Etiology]] for this [[benign]] [[lesion]] has not been established. [[Diagnosis]] requires [[biopsy]] although [[imaging]] studies such as [[MRI]] and [[CT scan]] can be used to define the extent of the [[lesion]]. [[Asymptomatic]] [[lesion]] do not require treatment. Surgical excision is the treatment of choice if treatment is indicated. Alternative therapies include use of [[botulinum toxin]] to treat [[hyperhidrosis]] and use of intralesional sclerosants.<ref name="pmid23717013" /><ref name="pmid26512300">{{cite journal |vauthors=Nygaard U, Dalager S, Spaun E, Hedelund L |title=Large eccrine angiomatous hamartoma: a novel clinical presentation of disease |journal=J Dermatol Case Rep |volume=9 |issue=3 |pages=58–61 |date=September 2015 |pmid=26512300 |pmc=4619160 |doi=10.3315/jdcr.2015.1211 |url=}}</ref><ref name="pmid22707779">{{cite journal |vauthors=Kar S, Krishnan A, Gangane N |title=Eccrine angiomatous hamartoma: a rare skin lesion with diverse histological features |journal=Indian J Dermatol |volume=57 |issue=3 |pages=225–7 |date=May 2012 |pmid=22707779 |pmc=3371531 |doi=10.4103/0019-5154.96206 |url=}}</ref><ref name="pmid19289750">{{cite journal |vauthors=Barco D, Baselga E, Alegre M, Curell R, Alomar A |title=Successful treatment of eccrine angiomatous hamartoma with botulinum toxin |journal=Arch Dermatol |volume=145 |issue=3 |pages=241–3 |date=March 2009 |pmid=19289750 |doi=10.1001/archdermatol.2008.575 |url=}}</ref><ref name="pmid22837574">{{cite journal |vauthors=Sen S, Chatterjee G, Mitra PK, Gangopadhyay A |title=Eccrine angiomatous naevus revisited |journal=Indian J Dermatol |volume=57 |issue=4 |pages=313–5 |date=July 2012 |pmid=22837574 |pmc=3401855 |doi=10.4103/0019-5154.97682 |url=}}</ref><ref name="pmid23559910">{{cite journal |vauthors=Fathaddin AA, Alhumidi AA |title=Eccrine angiomatous hamartoma, with verrocous hemangioma-like features: A case report |journal=Int J Health Sci (Qassim) |volume=7 |issue=1 |pages=103–6 |date=January 2013 |pmid=23559910 |pmc=3612410 |doi= |url=}}</ref><ref name="pmid26500534">{{cite journal |vauthors=Tantanasrigul P, Kootiratrakarn T, Wessagowit V, Kattipathanapong P, Sudtikoonaseth P |title=Eccrine Angiomatous Hamartoma in an Adolescent |journal=Case Rep Dermatol |volume=7 |issue=3 |pages=233–6 |date=2015 |pmid=26500534 |pmc=4608655 |doi=10.1159/000439399 |url=}}</ref>
 ===Reactive angioendotheliomatosis===
-* Characterized by [[hyperplasia]] of e[[endothelial cells]] within lumina of [[vascular]] channels that leads to formation of thrombi. These secondary thrombi may obstruct lumen of [[vascular]] channels. Clinically majority of the [[lesions]] manifests as multiple reddish to violaceous  macules, papules, or plaques that can be found almost anywhere on the [[body]] but tend to involve [[limbs]]. [[Patients]] may complain of pain and ulceration in the [[lesion]] or may report with non-specific [[symptoms]] such as fever and weigh loss.<ref name="pmid24314779">{{cite journal |vauthors=Boyapati A, Khan S, Mar A, Sheridan A |title=Reactive angioendotheliomatosis associated with cyroglobulinemia in a marathon runner |journal=Dermatol. Online J. |volume=19 |issue=11 |pages=20404 |date=November 2013 |pmid=24314779 |doi= |url=}}</ref><ref name="pmid8721593">{{cite journal |vauthors=Lazova R, Slater C, Scott G |title=Reactive angioendotheliomatosis. Case report and review of the literature |journal=Am J Dermatopathol |volume=18 |issue=1 |pages=63–9 |date=February 1996 |pmid=8721593 |doi= |url=}}</ref><ref name="pmid17004988">{{cite journal |vauthors=Kirke S, Angus B, Kesteven PJ, Calonje E, Simpson N |title=Localized reactive angioendotheliomatosis |journal=Clin. Exp. Dermatol. |volume=32 |issue=1 |pages=45–7 |date=January 2007 |pmid=17004988 |doi=10.1111/j.1365-2230.2006.02254.x |url=}}</ref>
+* Characterized by [[hyperplasia]] of [[endothelial cells]] within lumina of [[vascular]] channels that leads to formation of [[thrombi]]. These secondary [[thrombi]] may obstruct lumen of [[vascular]] channels. Clinically majority of the [[lesions]] manifests as multiple reddish to violaceous  [[macules]], [[papules]], or [[plaques]] that can be found almost anywhere on the [[body]] but tend to involve [[limbs]]. [[Patients]] may complain of pain and ulceration in the [[lesion]] or may report with non-specific [[symptoms]] such as fever and weigh loss.<ref name="pmid24314779">{{cite journal |vauthors=Boyapati A, Khan S, Mar A, Sheridan A |title=Reactive angioendotheliomatosis associated with cyroglobulinemia in a marathon runner |journal=Dermatol. Online J. |volume=19 |issue=11 |pages=20404 |date=November 2013 |pmid=24314779 |doi= |url=}}</ref><ref name="pmid8721593">{{cite journal |vauthors=Lazova R, Slater C, Scott G |title=Reactive angioendotheliomatosis. Case report and review of the literature |journal=Am J Dermatopathol |volume=18 |issue=1 |pages=63–9 |date=February 1996 |pmid=8721593 |doi= |url=}}</ref><ref name="pmid17004988">{{cite journal |vauthors=Kirke S, Angus B, Kesteven PJ, Calonje E, Simpson N |title=Localized reactive angioendotheliomatosis |journal=Clin. Exp. Dermatol. |volume=32 |issue=1 |pages=45–7 |date=January 2007 |pmid=17004988 |doi=10.1111/j.1365-2230.2006.02254.x |url=}}</ref>
-* [[Etiology]] and [[pathogenesis]] is unknown but [[immune system]] is hypothesized to play a role in [[pathogenesis]]. Majority of the [[patients]] have coexistent systemic diseases such as [[cyroglobulinemia]], [[antiphospholipid syndrome]], [[renal]] disease, [[valvular cardiac disease]], [[alcoholic cirrhosis]], [[glioblastoma multiforme]], and [[rheumatoid arthritis]]/[[polymyalgia rheumatica]]. Iatrogenic [[immunosuppression]]  have also been associated. Based on these associations some consider this [[lesion]] as the marker of an underlying systemic disease.<ref name="pmid24314779" /><ref name="pmid12752193">{{cite journal |vauthors=Thai KE, Barrett W, Kossard S |title=Reactive angioendotheliomatosis in the setting of antiphospholipid syndrome |journal=Australas. J. Dermatol. |volume=44 |issue=2 |pages=151–5 |date=May 2003 |pmid=12752193 |doi= |url=}}</ref><ref name="pmid12023572">{{cite journal |vauthors=McMenamin ME, Fletcher CD |title=Reactive angioendotheliomatosis: a study of 15 cases demonstrating a wide clinicopathologic spectrum |journal=Am. J. Surg. Pathol. |volume=26 |issue=6 |pages=685–97 |date=June 2002 |pmid=12023572 |doi= |url=}}</ref>
+* [[Etiology]] and [[pathogenesis]] is unknown but [[immune system]] is hypothesized to play a role in [[pathogenesis]]. Majority of the [[patients]] have coexistent systemic diseases such as [[cryoglobulinemia]], [[antiphospholipid syndrome]], [[renal]] disease, valvular cardiac disease, [[alcoholic cirrhosis]], [[glioblastoma multiforme]], and [[rheumatoid arthritis]]/[[polymyalgia rheumatica]]. Iatrogenic [[immunosuppression]] have also been associated. Based on these associations some consider this [[lesion]] as the marker of an underlying systemic disease.<ref name="pmid24314779" /><ref name="pmid12752193">{{cite journal |vauthors=Thai KE, Barrett W, Kossard S |title=Reactive angioendotheliomatosis in the setting of antiphospholipid syndrome |journal=Australas. J. Dermatol. |volume=44 |issue=2 |pages=151–5 |date=May 2003 |pmid=12752193 |doi= |url=}}</ref><ref name="pmid12023572">{{cite journal |vauthors=McMenamin ME, Fletcher CD |title=Reactive angioendotheliomatosis: a study of 15 cases demonstrating a wide clinicopathologic spectrum |journal=Am. J. Surg. Pathol. |volume=26 |issue=6 |pages=685–97 |date=June 2002 |pmid=12023572 |doi= |url=}}</ref>
-* [[Diagnosis]] requires [[biopsy]]. There is no standard management guideline. Treatment of coexistent systemic disease may cause resolution of reactive angioendotheliomatosis. Management options include observation, [[antibiotics]], [[corticosteroids]], [[laser therapy]] and [[excision]].<ref name="pmid24314779" /><ref name="pmid12752193" />
+* [[Diagnosis]] requires [[biopsy]]. There is no standard management guideline. Treatment of coexistent systemic disease may cause resolution of reactive angioendotheliomatosis. Management options include observation, [[antibiotics]], [[corticosteroids]], [[laser therapy]], and [[excision]].<ref name="pmid24314779" /><ref name="pmid12752193" />
 ===Bacillary angiomatosis===
-* [[Bacillary angiomatosis]] is characterized by the proliferation of [[blood vessels]], resulting in them forming [[tumor]]-like masses in the [[skin]] and other organs. [[Symptoms]] vary depending on which parts of the [[body]] are affected; for example, those whose [[livers]] are affected may have an enlarged [[liver]] and fever, while those with osseous BA will experience intense pain in the affected area. These [[lesions]] may take several forms such as papules or nodules and  plaque.
+* [[Bacillary angiomatosis]] is characterized by the proliferation of [[blood vessels]], resulting in them forming [[tumor]]-like masses in the [[skin]] and other organs. [[Symptoms]] vary depending on which parts of the [[body]] are affected; for example, those whose [[Liver|livers]] are affected may have an enlarged [[liver]] and [[fever]], while those with osseous BA will experience intense pain in the affected area. These [[lesions]] may take several forms such as papules or nodules and  plaque.
-* [[Bacillary angiomatosis]] (BA) is a bacterial infection caused by either [[Bartonella henselae]] or [[Bartonella quintana]].
+* [[Bacillary angiomatosis]] (BA) is a [[bacterial infection]] caused by either [[Bartonella henselae]] or [[Bartonella quintana]].
-* BA responds dramatically to several [[antibiotics]]. Usually, erythromycin will cause the skin lesions to gradually fade away in the next four weeks, resulting in complete recovery. Doxycycline may also be used. However, if the infection does not respond to either of these, the medication is usually changed to tetracycline.
+* BA responds dramatically to several [[antibiotics]]. Usually, [[erythromycin]] will cause the skin lesions to gradually fade away in the next four weeks, resulting in complete recovery. [[Doxycycline]] may also be used. However, if the [[infection]] does not respond to either of these, the medication is usually changed to [[tetracycline]].
 For more information on [[bacillary angiomatosis]], [[Bacillary angiomatosis#Bacillary angiomatosis|click here]].
 ==References==
 {{Reflist|2}}