General
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• Malignant tumors arising from the epithelial components of the vulva
• Since most of the common malignancies affecting the vulva are discussed separately, this section will focus on
  • The general aspects of vulvar carcinomas
  • Rare, unusual type of carcinomas that affect the vulva

Epidemiology
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• Rare tumors, accounting for 3-5% of female genital tract malignancies
• About 2/3rd of the cases affect older women (age > 70 years)
• Squamous cell carcinomas (SCC) are the most common type (~85%)
• Also basal cell, melanoma, adenocarcinoma

Sites
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• Labia majora and bartholin glands are most frequently affected

Etiopathogenesis
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• Most SCCs are related to HPV infection (90% are HPV 16, 18)
• Other causes include:
  • Lichen sclerosus
  • Chronic vulvar irritation (e.g. long-term use of diapers)
  • Exposure to ionizing radiation, arsenic
  • Immune deficiency
  • Presence of hamartomatous lesions

Clinical features
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• Most tumors are slow growing and are frequently painless, until the lesions ulcerate
• Other symptoms include itching, discomfort, bleeding, mass or swelling of the vulva or the groin

Diagnosis
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• Except for some of the well-differentiated, keratinizing and warty forms of SCC, most vulvar tumors look clinically similar to each other
• Histopathologic examination is essential for diagnosis

Laboratory
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• Except for non-specific findings such as anemia, mild leukocytosis, and rarely thrombocytopenia, routine laboratory investigations are not very useful in the diagnosis of vulvar tumors
• Serum tumoral markers such as AFP, CEA, CA125, CA15.3, and CA19.9 should be within normal limits

Radiology
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• MRI, CT-scan, PET and ultrasound are often used (AJR Am J Roentgenol 2013;201:W147)
  • To determine the extent of tumor involvement and presence of nodal metastases prior to therapy
  • To assess tumor response to chemotherapy, radiation or both, and
  • For post-treatment surveillance

Prognostic factors
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• Most of these prognostic factors are based on studies of vulvar SCCs
• Early diagnosis and complete tumor excision are favorable prognostic factors
• When diagnosed at an advanced stage (which happens in approximately 1/3rd of the patients), there is a high-risk for local recurrence and distant metastases (Int J Gynecol Pathol 1997;16:319)
• Tumor size (> 4 cm), depth of invasion (> 2 mm) are poor prognostic factors (Int J Gynecol Cancer 2014;24:766, World J Surg Oncol 2013;11:20)
• The histologic grade of the tumor is also an important prognostic factor (Eur J Gynaecol Oncol 2008;29:260)
• Women over 50 years are at a higher risk of vulvar cancer-specific mortality, which progressively increases with age (BJOG 2014;121:719)
• Older age adversely affects prognosis also due to comorbid health issues
• FIGO Staging - 2014 see: Int J Gynaecol Obstet 2014;125:97

Management
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• Management of primary tumor and nodal metastases may be independent
• For early lesions (primary tumor < 2 cm and no inguinal node involvement), wide local resection is the treatment of choice, aimed at achieving at least 1 cm of clear peripheral margins
• For primary lesions > 2 cm, radical local excision (to achieve 5 cm resection margin) may be necessary, with or without inguinofemoral lymphadenectomy
• If 2 or more inguinal lymph nodes are involved, or when there is extracapsular tumor spread, pelvic and groin radiation is frequently needed
• If radiologic imaging shows involvement of the retroperitoneal lymph nodes, surgical removal of enlarged lymph nodes is recommended, followed by radiotherapy
• Although chemotherapy is not commonly used to treat vulvar carcinoma, it is increasingly used in neo-adjuvant and palliative settings (Int J Gynaecol Obstet 2012;119:S90, Eur J Gynaecol Oncol 2011;32:505, J Gynecol Oncol 2014;25:22, Int J Gynecol Cancer 2012;22:865, Curr Oncol Rep 2013;15:573)

Histologic examination
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• The use of CAP synoptic reporting has become routine : Vulva Protocol
• The common histopathologic types include:
  • Squamous cell carcinoma, graded as
    • GX: Grade cannot be assessed
    • G1: Well differentiated
    • G2: Moderately differentiated
    • G3: Poorly or undifferentiated
  • Verrucous or warty carcinoma
  • Paget's disease of vulva
  • Adenocarcinoma, not otherwise specified (NOS)
  • Basal cell carcinoma, NOS
  • Bartholin's gland carcinoma
• Rare types of vulvar carcinomas:
  • Adenocarcinomas most often arise from the Bartholin’s glands, but may also originate in the cutaneous eccrine or apocrine glands, Skene's glands, minor vestibular glands, ectopic mammary tissue, or even endometriotic implants

Case reports (rare tumor types)
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• Intestinal-type adenocarcinoma or adenocarcinoma of cloacagenic origin
  • 2 women with "Intestinal-type" mucinous adenocarcinoma of the vulva (Eur J Gynaecol Oncol 2012;33:433)
  • 57 year old woman with unexpected complete remission of advanced intestinal-type vulvar adenocarcinoma (Case Rep Obstet Gynecol 2013;2013:427141)
• Adenocarcinoma of Ectopic Breast Tissue
  • 64 year old woman with primary breast carcinoma of the vulva (Gynecol Oncol 1999;73:155)
  • Mucinous adenocarcinoma of ectopic breast tissue of the vulva (Arch Pathol Lab Med 2002;126:1216)
  • Primary breast carcinoma of the vulva (Gynecol Oncol 1995;56:448)

Clinical images
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Before and after treatment

Before and after chemo

Micro description
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• Intestinal-type adenocarcinoma or adenocarcinoma of cloacagenic origin
  • The tumor is usually a moderately-differentiated adenocarcinoma with goblet cells and variable amounts of necrosis, reminiscent of colonic adenocarcinoma
• Adenocarcinoma of Ectopic Breast Tissue
  • The tumor is similar to the mammary counterparts
  • Could be in-situ, invasive or both

Micro images
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Adenocarcinoma, CK20

Mucinous adenocarcinoma: ER, BRST1

Positive stains
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• Intestinal-type adenocarcinoma or adenocarcinoma of cloacagenic origin
  • Strong positivity for cytokeratin 20, CEA, CDX2
  • Sometimes p16
  • Focal or weak cytokeratin 7
• Adenocarcinoma of Ectopic Breast Tissue
  • Estrogen receptor, BRST1

Negative stains
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• Intestinal-type adenocarcinoma or adenocarcinoma of cloacagenic origin
  • Vimentin, estrogen receptor
• Adenocarcinoma of Ectopic Breast Tissue
  • SMA, p63, calponin, CEA

Diagnostic criteria
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• Intestinal-type adenocarcinoma or adenocarcinoma of cloacagenic origin
  • Adenocarcinoma arising from the gastrointestinal tract must be ruled out
• Adenocarcinoma of Ectopic Breast Tissue
  • Presence of non-neoplastic mammary tissue adjacent to the adenocarcinoma
• Tumors with prominent keratinization are often confused with dermatitis or eczema

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