27 Vulval Carcinoma

1. GROSS DESCRIPTION

Specimen — biopsy/partial/simple/radical vulvectomy/uni-/bilateral inguinal lym- phadenectomy/pelvic exenteration. — size (cm) and weight (g). — vulval cancer forms 5% of gynaecological malignancies and occurs mainly in women aged 60–75 years. It can present as itch in an area of pallor or redness (/VIN) on a background of atrophic or hypertrophic lichen sclerosus. A nodular, verruciform or ulcerat- ing mass may be present and a diagnostic wedge or punch biopsy taken with the former more likely to establish the presence of any invasive disease and the latter sufficient for abnormalities in a flat epithelium such as VIN. CT and MRI scan can be used to detect and stage inguinal lymphadenopathy, which may also be amenable to FNA cytology. Because of the strong HPV association, concurrent cervico- vaginal disease is excluded. Surgical treatment is geared to the patient’s age, fitness, tumour site and stage with wide local excision for “early” stage IA disease. Central and lateral stage IB lesions may be treated by partial vulvectomy and bilateral or ipsilateral groin node dissection, respectively. Stage II cancers and above need radical vul- vectomy, which includes removal of the perianal skin and bilateral inguinal lymphadenectomy. Pre-operative radiotherapy may be given for tumours with extensive local invasion or involved nodes in an attempt to downstage, facilitate surgery and avoid pelvic exenteration.

Tumour

Site — anterior/posterior. — lateral (right/left). — labia majora/labia minora/. — labia majora is the commonest site, then labia minora and clitoris. — bilateral (25%).

Size — length × width × depth (cm) or maximum dimension (cm). 27. VULVAL CARCINOMA 287

Appearance — polypoid/verrucous/ulcerated/necrotic/satellite lesions/pigmented. — 50% are ulcerated, 30% exophytic.

Edge — circumscribed/irregular.

2. HISTOLOGICAL TYPE Vulval carcinomas show the full range of cutaneous cancers.

Squamous cell carcinoma — 80–90% of malignant vulval neoplasms. — keratinizing or non-keratinizing and of two main types. a. 60% of cases are in older women, not related to HPV and a kera- tinizing squamous cell carcinoma with adjacent epidermal hyper- plasia/hyperkeratosis/differentiated VIN, or, b. 30% of cases are in younger women, HPV 16/18 positive, of basa- loid or warty histology and with adjacent VIN of undifferentiated or classic type (see 8. Other pathology for discussion). variants: — basaloid: 28% of cases at a younger age (<60 years) and association with HPV, cervical and vaginal lesions. Nests of basaloid cells with peripheral palisading, central focal keratinization and mitoses. — warty: association with HPV and koilocytosis. Prognosis intermediate between usual squamous carcinoma and verrucous carcinoma. Dis- tinguish from pseudoepitheliomatous hyperplasia overlying lichen sclerosus, Crohn’s disease or granular cell tumour. — adenoid: pseudoglandular/acantholytic. — verrucous: exophytic with pushing deep margin of cytologically bland bulbous processes. Local recurrence after incomplete excision or radiotherapy. — spindle cell: cytokeratin positive sarcomatoid carcinoma.

Basal cell carcinoma — 20% local recurrence rate and metastases are rare. Distinguish from basaloid squamous carcinoma, Merkel cell tumour and secondary small cell carcinoma.

Adenocarcinoma — rare. — appendage origin/Bartholin’s gland/mesonephric duct remnants, or metastatic.

Paget’s disease — 2% of vulval malignancy. — intraepithelial cells probably arising from basal layer multipotential cells differentiating along sweat gland lines. In 288 HISTOPATHOLOGY REPORTING

10–20% there is a locoregional or extragenital malignancy, e.g. vulval appendage tumour or bladder carcinoma, cervical or endometrial carcinoma, anorectal carcinoma, breast carcinoma. Immunohisto- chemistry may help to indicate a possible bladder (uroplakin III/CK7/20 positive) or anorectal (CK20 positive) origin. GCDFP-15 can be positive in vulval Paget’s disease and metastatic breast cancer. — multifocal: check margins histologically as there is a 40% recurrence rate. Mucin stains and immunohistochemistry (EMA, CEA, CAM5.2, cytokeratin 7 positive) may be necessary to distinguish from Bowenoid VIN (AE1/AE3 positive, CAM5.2/CEA/CK7 negative) and superficial spreading malignant melanoma (S100, HMB-45, melan-A positive). Paget’s disease without an associated neoplasm has a very good prog- nosis but it may also, per se, progress to invasive carcinoma and nodal metastases if beyond the microinvasive stage.

Merkel cell carcinoma — exclude secondary small cell carcinoma from lung. — aggressive neuroendocrine carcinoma. — CAM5.2 (paranuclear dot), cytokeratin 20, chromogranin/ synapophysin/CD56 positive. Lung small cell carcinoma is cytokeratin 20 negative/TTF-1 positive.

Malignant melanoma — 3–10% of malignant vulval neoplasms. — usually mucosal and cutaneous involvement with Breslow depth and clinical stage the main prognostic indicators.

Metastatic carcinoma — 5% of malignant vulval neoplasms. — direct spread: (50% of cases), , , urethra, bladder, anorectum. — distant spread: ovary, kidney, breast, lung, malignant melanoma, choriocarcinoma. Secondary urethral tumours are squamous cell carcinoma, transitional cell carcinoma or malignant melanoma.

3. DIFFERENTIATION Well/moderate/poor/undifferentiated, or Grade 1/2/3/4. — well >50%; moderate 20–40% of cases. — there is no specific recommended grading system for vulval tumours other than the above which should broadly reflect that of non- melanocytic cutaneous carcinomas. Grade 4 (undifferentiated) tumours show no squamous or glandular differentiation.

4. EXTENT OF LOCAL TUMOUR SPREAD Border: pushing/infiltrative. An irregular infiltrative margin has a higher incidence of nodal metastases. 27. VULVAL CARCINOMA 289

Tumour invades any of: lower urethra, vagina, anus

FIGURE 27.1. Vulval carcinoma. W

Lymphocytic reaction: prominent/sparse. Microinvasion ≤3mm: use of this nomenclature should be avoided as some of these carcinomas will have nodal metastases and invasive lesions >1mm in depth should probably have radical surgery. Superficially inva- sive squamous cell carcinoma is defined as a single lesion measuring ≤2cm diameter and with a depth of invasion ≤1mm, i.e. pT1a. Distance (mm) to the nearest painted surgical margin (lateral cuta- neous, medial mucosal, deep subcutaneous). Involvement of vagina, urethra, perineum, anus. FIGO is based on surgical staging, TNM on clinical and/or pathologi- cal classification. The TNM classification applies to primary carcinomas of the vulva only. pTis carcinoma in situ pT1 tumour confined to vulva/perineum ≤2cm in greatest dimension a. stromal invasion ≤1mm* b. stromal invasion >1mm pT2 tumour confined to vulva/perineum >2cm in greatest dimension pT3 tumour of any size and invades any of: lower urethra/vagina/anus pT4 tumour invades any of: bladder mucosa/rectal mucosa/upper urethra or is fixed to pubic bone. Invasion of bladder or rectal wall is pT3 and mucosal involvement pT4. Upper urethra (pT4) is proximal, lower urethra (pT3) is distal. Invasion of urethral wall (only) is pT3. Spread is direct to the vagina, urethra, anus, inferior pubic and ischial rami and ischiorectal fossae.

*From the epithelial–stromal junction of the adjacent most superficial dermal papilla. Thickness is from the surface, or if there is keratinization, from the deep aspect of the granular layer to the deepest point of invasion. 290 HISTOPATHOLOGY REPORTING

Tumour invades any of: bladder or rectal mucosa, upper urethral mucosa; or is fixed to bone

FIGURE 27.2. Vulval carcinoma. W

5. LYMPHOVASCULAR INVASION Present/absent. Intra-/extratumoral. Carcinomas invading > 1mm have a higher incidence of lymphovascular invasion and lymph node metastases and the vulval subepithelial con- nective tissues have a particularly rich vascular network.

6. LYMPH NODES Site/number/size/number involved/extracapsular spread. Regional nodes: femoral and inguinal. A regional lymphadenectomy will ordinarily include a minimum of six lymph nodes. pN0 no regional lymph node metastasis pN1 unilateral regional lymph node metastasis pN2 bilateral regional lymph node metastasis. Labial tumours go initially to inguinal nodes whereas clitoral lesions may go directly to deep nodes. Ulcerated tumours can produce reactive regional lymphadenopathy mimicking metastatic disease and this can be further investigated by FNA cytology.

7. EXCISION MARGINS Distances (mm) of tumour and VIN to the nearest painted cutaneous and subcutaneous excision margins and anal, vaginal, urethral limits.

8. OTHER PATHOLOGY

Lichen sclerosus — atrophic, or hyperplastic with hyperkeratosis (mixed dystrophy). — associated with (5–25% of cases) but low risk (5%) of progression to carcinoma. — overexpresses p53 and sometimes shows basal layer atypia. 27. VULVAL CARCINOMA 291

Condyloma — warty (condyloma accuminatum) or flat and caused by HPV 6/11 with koilocytosis.

Bowenoid papulosis — brown perineal patches in young women. — HPV induced. — histology of VIN III. — negligible risk of progression to carcinoma.

Vulval intraepithelial neoplasia (VIN) grades I/II/III — typically multifocal and present in the adjacent epithelium of 60–70% of cases of squamous carcinoma. — progression to carcinoma is in the order of 10–20%. — classic, or, variant types.

Classic or undifferentiated: includes Bowenoid/warty type (young, HPV, associated cervical and anal disease) and basaloid type (old, de novo, resembles CIN III). Variant: simplex or differentiated VIN with maturation, hyperplasia, hyperkeratosis, variable parabasal atypia and overexpression of p53.

Prognosis Nearly 30% of vulval squamous carcinomas have metastasized to inguinal or pelvic nodes at presentation. Prognosis relates to tumour size, an infil- trative tumour margin, depth of invasion, vascular involvement and, in particular, nodal disease. Stage I lesions have a 5-year survival of 85%, stage II 60%, stage III 40%, stage IV 20% and overall 50–75%. Treatment is by vulvectomy with uni-/bilateral inguinal lymph node dissection. A limited local excision with wide (1cm) surgical margins may be used in early-stage (well-differentiated superficially invasive) disease or medically unfit patients. VIN III may be treated by topical therapy, laser, electroco- agulation, wide local excision, partial/total or skinning vulvectomy. Pelvic exenteration is reserved for locally extensive disease. Prognosis of malig- nant melanoma relates to tumour thickness and depth of invasion at the time of presentation, with average 5-year survival of 30–35%.

9. OTHER MALIGNANCY

Lymphoma/leukaemia — secondary to systemic disease usually diffuse large B cell in type.

Adnexal/Bartholin’s gland carcinomas — rare and arising from eccrine or apocrine glands, when distinction from metastatic ductal carcinoma of the breast can be problematic.

Bartholin’s gland carcinoma forms 1–5% of vulval neoplasms and shows a range of differentiation: squamous cell, adenocarcinoma, mixed 292 HISTOPATHOLOGY REPORTING adenoid cystic/mucoepidermoid carcinoma. Ideally an origin from adjacent Bartholin’s gland structures should be demonstrable. Five-year survival rates vary from 40% to 80% depending on the stage at presentation.

Aggressive angiomyxoma — myxoid stroma, prominent vessels and spindle cells. A locally infil- trative vulvovaginal tumour in young women, the edges of which are difficult to define surgically and therefore problematic to resect with ischiorectal and retroperitoneal recurrence a likelihood. Vimentin, actin positive ± desmin. They are also ER and progesterone receptor positive, raising a possible role for hormonal therapy.

Sarcomas — leiomyo-/rhabdo-/liposarcoma. — leiomyosarcoma: >5cm diameter, infiltrating margins, >5–10 mitoses/10hpfs, cellular atypia. — rhabdomyosarcoma occurs in childhood and young adults with vaginal disease being embryonal in type and vulval alveolar; desmin/ myo D1/myogenin positive. — liposarcoma: well-differentiated adipocytic/atypical lipoma in type.

Others — dermatofibrosarcoma protuberans, epithelioid sarcoma, malignant rhabdoid tumour.