Vulvar melanoma

Vulva, vagina & female urethra

Vulva & vagina

Other tumors

Vulvar melanoma

Author: Priya Nagarajan, M.D., Ph.D.

Topic Completed: 1 February 2015

Minor changes: 20 February 2020

Copyright: 2002-2020, PathologyOutlines.com, Inc.

PubMed Search: Melanoma vulva "loattrfree full text"[sb]

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Table of Contents

Cite this page: Nagarajan P. Vulvar melanoma. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/vulvamelanoma.html. Accessed August 8th, 2020.

Definition / general

See also topic to be merged
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 2015;22:1959)

Clinical features

May be discovered during routine gynecologic examinations
Usually present as pigmented and sometimes nonpigmented 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 description

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

Radiology images

Images hosted on other servers:

CT scan, enlarged lymph node

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 ≥ 1.0 mm is associated with better prognosis (Ann Surg Oncol 2015;22:1959)
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 c-kit 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

Images hosted on other servers:

Nodule and ulcer

Large friable, gray white growth

Vulvar melanoma

Gross description

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

Microscopic (histologic) 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 CAP: Cancer Protocol Templates [Accessed 9 October 2017]
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 nontumorigenic 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. nonbrisk)
- 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

Microscopic (histologic) images

Images hosted on other servers:

Pleomorphic spindled to epitheloid cells

Cells in sheets

HMB45+

Images contributed by Dr. Priya Nagarajan:

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

MelanA (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, nonspecific 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
BRAF V600E 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
Postinflammatory 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)