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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 muations 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’ 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 perimenopausal 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 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.^[103]^[104]^[105]^[106]^[107]^[108]^[109]^[110]^[111]^[112]
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.^[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 eendothelial 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 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.^[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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↑ "Error 403".
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@@ 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>