Pathology Outlines

Vagina
Malignant tumors
Melanoma

Reviewer: Shweta Gera, M.D. (see Authors page)
Editor: Arzu Buyuk, M.D.

Revised: 3 May 2016, last major update August 2014

Copyright: (c) 2002-2016, PathologyOutlines.com, Inc.

PubMed Search: Melanoma [title] vagina

Table of Contents

Definition / General

Melanoma originating in vaginal wall without involvement of vulva, uterine cervix or other surrounding structures (Gynecol Obstet 3:183)

Terminology

Also called primary malignant melanoma of vagina

Epidemiology

Melanomas arising from female urogenital tract occur primarily in vulva (95%) and vagina (3%)

Primary melanoma of vagina is extremely rare and aggressive

Constitutes less than 3% of vaginal cancers and only 0.3-0.8% of all melanomas in women (Gynecol Obstet 3:183)

Occurs mainly in postmenopausal women, sixth and seventh decades of life (J Chin Med Assoc 2011;74:376)

Rare cases in young patients (Int J Pathol 2009;7:102)

Sites

More commonly in the lower third of vagina and on anterior vaginal wall (Gynecol Obstet 3:183, J Chin Med Assoc 2011;74:376)

Etiology

Appears to originate from melanocytes present in vaginal mucosa (Gynecol Obstet 3:183)

Clinical Features

Vaginal bleeding or discharge (J Chin Med Assoc 2011;74:376)

Diagnosis

Based on biopsy/resection specimen with clinical history and imaging

Radiology Description

Small tumors can be difficult to assess on CT scan

The use of fluorodeoxyglucose (FDG) as a glycolytic indicator in tumor-altered metabolism in PET/CT study can aid in early diagnosis and staging

Prognostic Factors

Common sites of recurrence of vaginal melanoma are vagina, vulva, groin

Prognosis poorer than cutaneous melanomas

Five year survival rate of 13-19% is poor compared to vulvar and cutaneous melanomas

Fifty percent have positive lymph nodes, and nearly 20 percent have distant metastases at presentation

Mean survival is 8.5 months after recurrence (Gynecol Obstet 3:183)

Case Reports

31 year old woman with primary amelanotic melanoma (Onkologie 2008;31:474)

Melanoma of vagina (Indian J Pathol Microbiol 2003;46:71)

Primary amelanotic melanoma (Int J Gynaecol Obstet 1989;29:159)

Treatment

Many different treatment modalities have been tested, but there is no standard therapeutic approach

Surgery provides local control; procedures include wide local excision, radical surgery (total vaginectomy with or without vulvectomy), pelvic extenteration

Sentinel lymph node biopsy (SLNB) provides important prognostic and staging data with minimal morbidity

Routine lymph node dissection is not recommended because morbidity is high, and prophylactic lymphadenectomy has not been shown to improve survival (J Chin Med Assoc 2011;74:376)

It is difficult to get negative surgical margins without pelvic exenteration due to multifocality and anatomic constraints

Surgery may be combined with radiotherapy or chemotherapy

Cytotoxic chemotherapy, IFNα, IL2, ipilimumab, and vemurafenib have been used in some cases (Gynecol Obstet 3:183)

IFN is used as adjuvant therapy in patients without disease but at high risk of systemic recurrence (J Chin Med Assoc 2011;74:376)

Clinical Images

Images hosted on other servers:

Diffuse black pigmentation

Colposcopic findings

Mass in posterior wall

Gross Description

Can have raised, ulcerated and irregular appearance (Gynecol Obstet 3:183)

Can present as polypoid lesion or a nodule

Usually pigmented with black to brown gross appearance, but 40% cases are amelanotic

Gross Images

Images hosted on other servers:

Nodular mass

Micro Description

Diffuse infiltration of large, pleomorphic, epithelioid and spindle shaped tumor cells in vaginal mucosa

Cells have eosinophilic cytoplasm, large oval or pleomorphic hyperchromatic nuclei, may have multiple nuclei with distinct nucleoli (J Clin Pathol 2004;57:986)

Amelanotic melanomas can be difficult to diagnose on histology

Junctional activity, if present. raises suspicion for melanoma (Int J Pathol 2009;7:102)

Immunohistochemical stains are helpful if no melanin pigment or junctional activity (Gynecol Obstet 3:183)

Micro Images

Images hosted on PathOut server:

Contributed by Dr. Mayank Gupta, Christian Medical College, Vellore (India)
60 year old woman with nodular growth on left lateral vaginal wall

10x

20x

40x

Cytokeratin (10x)

HMB45 (10x)

Melan-A (10x)

Images hosted on other servers:

Atypical tumor cells

Melanin granules

H&E, S100, HMB45

HMB45+

Cytology Description

Loose aggregates of large, pleomorphic, polygonal to spindle shaped tumor cells with ill-defined cytoplasmic borders, granular hyperchromatic nuclei and conspicuous nucleoli

Multinucleated tumor cells and mitoses can be seen (J Clin Pathol 2004;57:986)

Cytology Images

Images hosted on PathOut server:

Loose aggregates of
pleomorphic tumor cells

Positive Stains

S100, HMB45, vimentin

Melanin pigment can be demonstrated with Fontana-Masson silver staining (J Clin Pathol 2004;57:986)

MelanA, tyrosinase, MiTF

Negative Stains

Cytokeratin, epithelial membrane antigen (EMA), desmin, myoglobin, smooth muscle actin, CD34, CD68

Amelanotic melanomas are negative for melanin pigment (J Clin Pathol 2004;57:986)

Molecular / Cytogenetics Description

NRAS mutations and KIT amplifications occur in both vaginal and vulvar melanomas

KIT mutations appear to be more specific for vulvar melanoma

BRAF mutations are absent in both vaginal and vulvar melanomas originating from the vulva or vagina (Mod Pathol 2014 Mar 7 [Epub ahead of print])

Differential Diagnosis

Hemangioendothelioma

Malignant fibrous histiocytoma (MFH)

Malignant peripheral nerve sheath tumor

Sarcoma (Gynecol Obstet 3:183)

Undifferentiated carcinoma

Additional References

Int J Gynecol Cancer 2014;24:149, J Gynecol Oncol 2013;24:330, Int J Gynecol Cancer 2013;23:1484, Melanoma Res 2013;23:138