General
=========================================================================

• Melanoma constitutes about 4-10% of all vulvar malignancies (Int J Gynecol Cancer 2013;23:1118)
• Second most common malignant neoplasm after squamous cell carcinoma

Epidemiology
=========================================================================

• Incidence: ~ 0.2 per 100,000 women (Gynecol Oncol 2011;122:612, Obstet Gynecol 2007;110:296)
• Caucasian women are more commonly affected
• Age at diagnosis: 5th to 7th decade; median: 60.5 years

Sites
=========================================================================

• Labia (minora and majora) are the most commonly affected sites, followed by clitoris in some studies (Ann Surg Oncol 2014 Nov 11 [Epub ahead of print])

Clinical features
=========================================================================

• May be discovered during routine gynecologic examinations
• Usually present as pigmented and sometimes non-pigmented lesions (macules, patches, nodules)
• May be ulcerated
• May present with multiple lesions (satellitosis)

Diagnosis
=========================================================================

• Histologic examination is essential

Laboratory
=========================================================================

• Serum lactate dehydrogenase levels > 200 to 225 U/L are associated with poor survival

Radiology
=========================================================================

• CT/MRI for staging
• Lymphoscintigraphy for identification of sentinel nodes (Wien Klin Wochenschr 2006;118:286, Cancer 2002;94:486)

Prognostic factors
=========================================================================

• Age: Patients that are 68 years or younger at diagnosis have a better prognosis
• Histologic parameters:
  • Breslow depth (tumor thickness) and feasibility of complete resection with appropriate margins (J Am Acad Dermatol 2012;67:598)
  • Mitotic rate
  • Ulceration
  • Margin status: free margin of ≥ 1.0mm is associated with better prognosis (Ann Surg Oncol 2014 Nov 11 [Epub ahead of print])
• Stage:
  • Patients with localized disease (stage 0, I, II) have a better prognosis. (Obstet Gynecol 2007;110:296)
  • Higher number of positive lymph nodes is associated with worse prognosis
• Strong and diffuse cKit expression may be associated with a worse prognosis (Int J Mol Med 2014;33:784)

Case reports
=========================================================================

• 23 year old woman with primary amelanotic melanoma of vulva (Indian J Surg Oncol 2012;3:36)
• 35 year old pregnant woman with recurrent vulvar melanoma (J Low Genit Tract Dis 2013;17:223)
• 50 year old woman with nodular vulvar melanoma (J Obstet Gynaecol India 2012;62:87)

Treatment
=========================================================================

• Surgical resection with adequate margins is the principal management
• Radiation
• Chemotherapy
• Topical imiquimod therapy

Clinical images
=========================================================================

CT scan, enlarged lymph node

Nodule and ulcer

Large friable, grey white growth

Vulvar melanoma

Gross description
=========================================================================

• Preservation of specimen orientation is critical for thorough evaluation of peripheral and deep tissue margins

Micro description
=========================================================================

• Vulvar melanomas are evaluated and staged similar to cutaneous melanomas
• Most of the melanomas involving the cutaneous surface only are traditionally classified based on the histologic type (superficial spreading being the most common type at this site)
• However, when mucosal surfaces are involved, classifying them as mucosal lentiginous type would be most appropriate
• See Cancer Protocol Templates
• The following histologic parameters should be included in the report:
  • Histologic type
  • Clark (anatomic) level
  • Breslow thickness (primary tumor thickness, if completely mucosal)
  • Presence of radial or non-tumorigenic growth phase
  • Presence of vertical or tumorigenic growth phase
  • Mitotic rate per millimeter squared
  • Presence of ulceration (the microscopic size of ulceration is often included)
    • Must exercise caution in resection specimens as the ulceration might represent prior biopsy site
  • Presence of regression (mention percentage of regression, is associated with a poor prognosis if > 75%)
  • Presence of lymphovascular space invasion (the use of MART1 / MelanA plus D2-40 or CD34 immunostains is more sensitive)
  • Presence of perineural invasion (size of nerves involved should be mentioned)
  • Presence of microscopic satellitosis
  • Presence of tumor-infiltrating lymphocytes (presence or absence; brisk vs non-brisk)
  • Presence of associated melanocytic nevi
  • Predominant cytology of the tumor cells
  • Status of surgical margins (for in-situ and invasive melanoma)
• Sentinel lymph nodes:
  • Examination of several H&E sections cut at various depth into the paraffin block and the use of immunohistochemistry for melanocytic markers are routinely employed to detect single cell metastases

Micro images
=========================================================================

Pleomorphic spindled to epitheloid cells

Cells in sheets

HMB45+

   

Melanoma in situ

Melanoma in situ vs
atypical >melanocytic
hyperplasia

Mostly in-situ, minimal invasive component

Invasive and in situ melanoma

   

Polypoid melanoma: low to intermediate magnification

 

High magnification

Melanoma with ulceration

Heavily pigmented

 

Recurrence in subcutaneous fibroadipose tissue

Isolated nodal metastases

   

Melan A (three images)

SOX10

Positive stains
=========================================================================

• S100: cytoplasmic and nuclear
• MelanA/MART1, gp100/PMEL: cytoplasmic
• HMB45: cytoplasmic, patchy expression in epithelioid melanomas
• Tyrosinase: cytoplasmic
• MITF (microphthalmia-associated transcription factor): nuclear
• SOX10: nuclear
• p75 NGFR, nerve growth factor receptor: cytoplasmic (J Am Acad Dermatol 2010;63:852)
• NKI-C3 (CD63): cytoplasmic, not-specific and not commonly used
• NSE: cytoplasmic, not specific and not commonly used
• Vimentin, CD99: cytoplasmic, non specific, but CD99 may be the only positive stain in some poorly differentiated melanomas (Am J Dermatopathol 2007;29:169)
• Spindle cell melanomas, desmoplastic melanomas and poorly differentiated melanomas may not express MelanA/MART1, HMB45 or tyrosinase, but often express S100, SOX10 and p75 NGFR
• Melanomas, regardless of histology, may not express typical melanocytic markers (Hum Pathol 2005;36:1016, Dermatol Online J 2009;15:7)

Negative stains
=========================================================================

• Cytokeratins: usually negative; focal expression is not uncommon; should be interpreted with caution (Anticancer Res 2004;24:3203)
• Vascular / endothelial markers: CD34, D2-40
• Desmin

Molecular / cytogenetics description
=========================================================================

• KIT mutations and amplifications appear to be more common in vulvar melanomas (Mod Pathol 2014;27:1386); see also Molecular Pathology chapter
• NRAS mutations are also seen
• BRAFV600E mutations are rare (Biomed Res Int 2015;2015:303791); see also Molecular Pathology chapter
• May have copy number alterations 1q and 6p (Acta Oncol 2004;43:421)

Differential diagnosis
=========================================================================

• Dermatofibroma: epithelial induction with hyperpigmentation
• Other pigmented lesions including common or atypical vulvar nevi of the genital type: have architectural disorder, but lack cytologic atypia, dermal mitosis and other features of melanoma including ulceration
• Pigmented epidermal neoplasms including seborrheic keratosis, vulvar intraepithelial neoplasia, condyloma, basal cell carcinoma
• Post-inflammatory pigmentary alteration
• Vascular lesions such as angiokeratoma, Kaposi sarcoma
• Vulvar melanosis, mucosal melanotic macule (J Am Acad Dermatol 2014;71:1241, J Low Genit Tract Dis 2013;17:320)

This information is intended for physicians and related personnel, who understand that medical information is often imperfect, and must be interpreted in the context of a patient's clinical data using reasonable medical judgment. This website should not be used as a substitute for the advice of a licensed physician.

All information on this website is protected by copyright of PathologyOutlines.com, Inc. Information from third parties may also be protected by copyright. Please contact us at copyrightPathOut@gmail.com with any questions (click here for other contact information).