Vulva, vagina & female urethra
Melanocytic lesions
Melanoma
Author: Priya Nagarajan, M.D., Ph.D.
Topic Completed: 1 February 2015
Minor changes: 19 October 2020
Copyright: 2002-2021, PathologyOutlines.com, Inc.
PubMed Search: Melanoma vulva "loattrfree full text"[sb]
Table of Contents
Definition / general | Epidemiology | Sites | Clinical features | Diagnosis | Laboratory | Radiology description | Radiology images | Prognostic factors | Case reports | Treatment | Clinical images | Gross description | Microscopic (histologic) description | Microscopic (histologic) images | Positive stains | Negative stains | Molecular / cytogenetics description | Differential diagnosisCite this page: Nagarajan P. Melanoma. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/vulvamelanoma.html. Accessed January 24th, 2021.
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
Contributed by Priya Nagarajan, M.D., Ph.D.
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
SOX10
Images hosted on other servers:
Pleomorphic spindled to epitheloid cells
Cells in sheets
HMB45+
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)
