Dysplastic nevus differential diagnosis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

Dysplastic nevus should be differentiated from common moles and melanoma.

Dysplastic nevus differential diagnosis

Dysplastic should be differentiated from:

• Common moles
• Melanoma

Biopsy is the only way to differentiate above mentioned conditions from dysplastic nevus.

Disease or Condition	Differentiating Signs and Symptoms	Differentiating Tests
Microcystic adnexal carcinoma	AKA sclerosing sweat duct carcinoma; simulate morpheaform variants of BCC; higher recurrence rate than BCC	Histopathology: there are more ductal structures lined by a cuticle of keratin, which are not prevalent in BCCs; it will occasionally be positive with cytokeratin 7 and CEA (usually negative in BCCs)
Trichoepithelioma/trichoblastoma	There is a formation of papillary-mesenchymal bodies (follicular units that simulate bulb of the hair follicle); a characteristic stroma-stroma split; a lower apoptotic and mitotic rate than seen in BCC	Histopathology: the characteristic stroma-epithelium split and increase in apoptotic bodies and mitotic figures is not seen; Immunohistochemical: a characteristic perinuclear dot-like pattern and high molecular weight cytokeratin cocktail
Merkel cell carcinoma	This is a highly malignant neoplasm derived from cutaneous neuroendocrine cells	Histopathology: opaque nuclei, no nucleoli, and increased nuclear/cytoplasmic ratio, peripheral palisading might be present
Squamous cell carcinoma (SCC)	It may impossible to distinguish between BCC and SCC	Histopathology: larger cells with prominent nucleoli, foci of keratinization and formation of squamous whorls where the neoplastic cells tightly wrap around each other

Oral melanoma must be differentiated from other mouth lesions such as oral candidiasis and aphthous ulcer

Disease	Presentation	Risk Factors	Diagnosis	Affected Organ Systems	Important features	Picture
Diseases predominantly affecting the oral cavity
Oral Candidiasis	Dysphagia or odynophagia White patches on the mouth and tongue	Newborn babies Denture users Poorly controlled diabetes As a side effect of medication, most commonly having taken antibiotics. Inhaled corticosteroids for the treatment of lung conditions (e.g, asthma or COPD) may also result in oral candidiasis which may be reduced by regularly rinsing the mouth with water after taking the medication. People with poor nutrition, specifically vitamin A, iron and folate deficiencies. People with an immune deficiency (e.g. as a result of AIDS/HIV or chemotherapy treatment). Women undergoing hormonal changes, like pregnancy or those on birth control pills. Organ transplantation patients	Clinical diagnosis Confirmatory tests rarely needed	Localized candidiasis Oral and esophageal candidasis Candida vulvovaginitis Chronic mucocutaneous candidiasis Invasive candidasis Candidaemia Candida endocarditis Candida osteoarticular disease	Oral candidiaisis is a benign self limiting disease unless accompanied by immunosuppression.	Tongue infected with oral candidiasis - By James Heilman, MD - Own work, CC BY-SA 3.0, httpscommons.wikimedia.orgwindex.phpcurid=11717223.jpg
Herpes simplex oral lesions	Fever Sore throat Painful ulcers	Stress Recent URTI Female sex	Physical examination Viral culture Tzanck smear	Orofacial Infection Anogenital Infection Ocular Infection Herpes Encephalitis Neonatal Herpes Herpetic Whitlow Herpes Gladiatorum	The symptoms of primary HSV infection generally resolve within two weeks	Oral herpes simplex infection - By James Heilman, MD - Own work, CC BY-SA 3.0, httpscommons.wikimedia.orgwindex.phpcurid=19051042.jpg
Aphthous ulcers	Painful, red spot or bump that develops into an open ulcer	Being a female Between the ages of 10-40 Family history of aphthous ulcers	Physical examination Diagnosis of exclusion	Oral cavity	Self-limiting , Pain decreases in 7 to 10 days, with complete healing in 1 to 3 weeks	By Ebarruda - Own work, CC BY-SA 3.0, httpscommons.wikimedia.orgwindex.phpcurid=7903358
Squamous cell carcinoma	Non healing ulcer, nodule, indurated plaque or mass May involve skin, lips, inside the mouth, throat or esophagus	Chronic sun or UV exposure Fair skin Elderly age (>45 yrs) Male sex Smoking	Physical exam Biopsy	Oral Cavity Floor of mouth Lateral tongue Throat Esophagus	Malignant Can spread to TMJ Some times associated with leukoplakia	Squamous cell carcinoma - By Luca Pastore, Maria Luisa Fiorella, Raffaele Fiorella, Lorenzo Lo Muzio - http://www.plosmedicine.org/article/showImageLarge.action?uri=info%3Adoi%2F10.1371%2Fjournal.pmed.0050212.g001, CC BY 2.5, https://commons.wikimedia.org/w/index.php?curid=15252632
Leukoplakia	White leathery spots on the mucous membranes of the tongue and inside of the mouth Lateral borders of tongue	Atypical Tobacco use Chronic irritation Immunodeficiency Bloodroot (sanguinaria)	Physical exam Diagnosis of exclusion Biopsy	Vulvar lesions occur independent of oral lesions	Associated with HIV Persistant white spots Benign but can progress to carcinoma after almost 10 years Oral proliferative verrucous leukoplakia is an aggressive sub type with multiple lesions and higher conversion to warts or carcinoma	Leukoplakia - By Aitor III - Own work, Public Domain, https://commons.wikimedia.org/w/index.php?curid=9873087
Melanoma	A lesion with ABCD Asymmetry Border irregularity Color variation Diameter changes Bleeding from the lesion	UV radiations Genetic predisposition Old age Male gender Family or personal history of melanoma Multiple benign or atypical nevi	ABCD characteristics Bleeding or ulceration may show malignancy Serum LDH may be elevated in case of malignancy Biopsy	Can metastasize All UV radiation or sun exposed areas can be effected independently 1-2 to hundreds of granules	Neural crest cell derivative Development begins with disruption of nevus growth control Progression involves MAPK/ERK pathway N-RAS or BRAF oncogene also involved	Oral melanoma - By Emmanouil K Symvoulakis, Dionysios E Kyrmizakis, Emmanouil I Drivas, Anastassios V Koutsopoulos, Stylianos G Malandrakis, Charalambos E Skoulakis and John G Bizakis - Symvoulakis et al. Head & Face Medicine 2006 2:7 doi:10.1186/1746-160X-2-7 (Open Access), [1], CC BY-SA 2.0, https://commons.wikimedia.org/w/index.php?curid=9839811
Fordyce spots	Rice-like granules or spots Small, painless, raised, pale, red or white 1 to 3 mm in diameter	Greasy skin types Some rheumatic disorders Hereditary nonpolyposis colorectal cancer Lower gingiva (gums) Vestibular mucosa	Physical exam Small keratin-filled pseudocysts May be seen on incidental mucosal biopsy Biopsy not done for them primarily	Oral cavity Vermilion border of the lips Oral mucosa of the upper lip Buccal mucosa in the commissural region often bilaterally Genitals	Benign neoplasms with sebaceous features Visible sebaceous glands No surrounding mucosal change Several adjacent glands may coalesce into a larger cauliflower-like cluster	Fordyce spots - Por Perene - Obra do próprio, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=19772899
Burning mouth syndrome	Burning or tingling on the lips, tongue, or entire mouth	Nutritional deficiencies Chronic anxiety or depression Diabetes type 2 Menopause Oral thrush or dry mouth, or damaged nerves transmitting taste Female gender Menopause	Presentation Physical exam	Oral cavity	Pain typically is low in the morning and builds up over the day Low dosages of benzodiazepines, tricyclic antidepressants or anticonvulsants may be effective
Torus palatinus	Bony growth on midline of the hard palate Nodular mass covered with normal mucosa	Genetic predisposition Autosomal dominant	Physical exam Types Flat tori Spindle tori Nodular tori Lobular tori	Hard palate	More common in Asian and Inuit populations Twice more common in females Repeated trauma can cause bleeding Surgery may be required in symptomatic	Torus palatinus - By Photo taken by dozenist, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=846591
Diseases involving oral cavity and other organ systems
Behcet's disease	Painful mouth sores Acne like skin lesions Headache, fever, poor balance, disorientation Abdominal pain, diarrhea or bleeding Uveitis Joint swelling and joint pain Genital sores wit pain and scaring Aneurysms	Over active immune system	Physical examination	Mouth Genitals GIT Eye Joints Skin Vascular system Brain	Outbreaks of exaggerated inflammation Affects smaller blood vessels	Behcet's disease - By Ahmet Altiner MD, Rajni Mandal MD - http://dermatology.cdlib.org/1611/articles/18_2009-10-20/2.jpg, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=17863021
Crohn's disease	Chronic, episodic diarrhea or constipation Abdominal pain Vomiting Weight loss or weight gain	Smoking Whites and European Jews Hormonal contraception Diets high in microparticles, sweet, fatty or refined foods Industrialized country	Typical history and symptoms Skip lesions on biopsy Anti-Saccharomyces cerevisiae antibodies (ASCA) Anti-neutrophil cytoplasmic antibodies (ANCA)	Eyes Joints Skin	May lead to Obstructions Abscesses Free perforation Hemorrhage
Agranulocytosis	Fever or chills Frequent infections Unusual redness, pain, or swelling around a wound Mouth ulcers Abdominal pain Burning sensation when urinating Sore throat	Medications Cytotoxic chemotherapy Hematologic malignancies Autoimmune disorders	Neutropenia <100 cells per micro litre Eosinopenia Basopenia	Oral cavity Skin GIT Urinary system Conjunctiva	Immunocompromization Types Drug-induced Malignant Autoimmune
Syphilis	Chancre Regional lymphadenopathy	Multiple sexual partners Illicit drug use Unprotected sex Men who have sex with men Residence in highly prevalent areas HIV infection Presence of other STIs Previous history of STIs Intravenous drug use	Darkfield microscopy Non treponemal tests like VDRL and RPR test) Treponemal testsFTA-ABS tests, (TP-PA) assay, enzyme immunoassays, and chemiluminescence immunoassays)	Oral cavity Penis Cervix Labia Anal canal Rectum CNS CVS	Primary syphilis Chancre Secondary syphilis Condylomata lata Latent syphilis Asymptomatic Tertiary syphilis Gummas Neurosyphilis	oral syphilis - By CDC/Susan Lindsley - http://phil.cdc.gov/phil_images/20021114/34/PHIL_2385_lores.jpg, Public Domain, https://commons.wikimedia.org/w/index.php?curid=2134349
Coxsackie virus	Fever Sores in the mouth Rash with blisters Aches	Pregnancy immunodeficiency	History and Physical exam Throat swabs Swabs from the lesion Tzanck test	Oral cavity Skin	Symptomatic treatment
Chicken pox	Conjunctival symptoms Catarrhal symptoms Characteristic spots on the trunk appearing in two or three waves Itching	Pregnancy Premature infants born to susceptible mothers All infants born at less than 28 weeks gestation or who weigh =1000 grams Immunocompromised	History and physical exam PCR to detect VZV in skin lesions (vesicles, scabs, maculopapular lesions)	Oral cavity Skin	Sodium bicarbonate in baths or antihistamines for itching Paracetamol (acetaminophen) for fever Prednisolone is contraindicated	Chickenpox - By James Heilman, MD - Own work, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=52872565
Measles	Fever Rash Cough Coryza (runny nose) Conjunctivitis (pink eye) Malaise Koplick spots in mouth	Unvaccinated individuals Crowded and/or unsanitary conditions Traveling to less developed and developing countries Immunocompromized Winter and spring seasons Born after 1956 and never fully vaccinated Health care workers	History and examination PCR for Measles-specific IgM antibody PCR for Measles RNA	Oral cavity Skin Respiratory tract Eyes Throat	Caused by Morbillivirus Primary site of infection is the respiratory epithelium of the nasopharynx Transmitted in respiratory secretions, via aerosol droplets containing virus particles	Koplick spots (Measles) - By CDC - http://phil.cdc.gov/PHIL_Images/20040908/4f54ee8f0e5f49f58aaa30c1bc6413ba/6111_lores.jpg, Public Domain, https://commons.wikimedia.org/w/index.php?curid=824483

Subtype	Frequency	Clinical Features
Common Subtypes
Superficial spreading melanoma	70%	Most common sub-type Usually affects sun exposed sites among both men and women aged 50-70 years Characterized by the presence of abundant junctional intra-epidermal spread of malignant melanocytes
Nodular melanoma	15-25%	Second most common subtype Usually affects sun exposed sites among both men and women aged 50-70 years Characterized by the absence of junctional intra-epidermal spread of malignant melanocytes
Acral lentiginous melanoma	5%	Not associated with chronic ultraviolet exposure Affects the extremities of individuals of all races Common among the elderly Caucasian and non-Caucasian individuals
Lentigo maligna melanoma	1-5%	Preceded by lentigo maligna Common among the elderly Caucasian patients Usually appears as a flat, non-palpable lesion that affects sun exposed sites, especially the head and neck (lesions on extremities are less common)
Non-cutaneous melanoma	5%	Melanoma that does not affect the skin Usually affects the eye (ocular melanoma) or the mucus membranes (mucosal melanoma)
Less Common Subtypes
Desmoplastic/Spindle cell melanoma	Rare	Lesion typically amelanotic and has a morphology similar to a scar tissue Appears indolent but is highly infiltrative Characterized by local recurrence and perineural spread Usually affects males aged 60-70 years in sun exposed sites May be de novo or can be associated with a pre-existing melanoma Has several subtypes: Pure: paucicellular Desmoplastic-neurotropic melanoma: characterized by neurotropism Pure neurotropic melanoma: no desmoplasia with spindle cell melanoma of neurotropic phenotype Mixed/Combined: epithelial and spindle cells
Nevoid melanoma	Rare	Lesion has features of both melanoma and melanocytic nevus on histopathological analysis Clinical features resemble those of a typical melanoma
Spitzoid melanocytic neoplasm	Rare	Lesion has features of both melanoma and Spitz (epithelioid) tumor Typically affects sun exposed sites among children and young adults, but adults with Spitz tumors are more often diagnosed with Spitzoid melanoma Compared to benign Spitz tumors, Spitzoid melanomas are usually large (>5 mm)
Angiotropic melanoma	Rare	Lesion characterized by angiotropism, whereby the melanoma grows in proximity (within 1-2 mm) to blood and/or lymphatic tissue but no tumor within the vascular lamina itself The tumor may originally be another sub-type of melanoma Clinical features similar to typical melanoma
Blue nevus-like melanoma	Rare	Melanoma that develops from a pre-existing blue nevus One of the rarest forms of melanoma Appears as a blue nevus that has recently been rapidly expanding with irregular contours Typically affects middle-aged men
Composite melanoma	Rare	Melanoma that develops in the proximity of other pre-existing epithelial malignancies (e.g. basal/squamous cell carcinoma) May be characterized by one of the following: Collision tumor: Collision of melanoma and another nearby malignant tumor Colonization: Colonization of melanocytes in a tumor Combined: Two distinct tumors appear to have mixed features of the melanoma and the other tumor Biphenotypic: One tumor that has features of melanoma and another epithelial malignancy