1、Carcinoma of Vulva,Prof. Surendra Nath Panda, M.S. Department of Obstetrics and Gynecology M.K.C.G.Medical College Berhampur, Orissa, India,17th Sept. 2002,Carcinoma of Vulva - Prof.S.N.Panda,2,INTRODUCTION,Diseases of the vulva in the aggregate constitute only a small fraction of gynaecologic pract
2、ice of which tumours are the most important lesions. Vulva contains a variety of tissues and hence all types of tumours can occur in the vulva. Many types have been recorded, both benign and malignant. Vulval malignancies account for about 4% - 5% of all genital malignancies,17th Sept. 2002,Carcinom
3、a of Vulva - Prof.S.N.Panda,3,MALIGNANT TUMOURS OF VULVA,I. Epithelial neoplasms of skin and mucosa A. Invasive Squamous cell carcinoma 1. Keratinizing 2. Non-keratinizing 3. Basaloid carcinoma 4. Verrucous Carcinoma 5. Warty carcinoma condylomatous B. Basal cell carcinoma C. Adenocarcinoma,Histolog
4、ical Classification: -,(Jo Ann Benda and Richard Zaino),17th Sept. 2002,Carcinoma of Vulva - Prof.S.N.Panda,4,MALIGNANT TUMOURS OF VULVA,II.Bartholin gland carcinomas A. Squamous cell carcinoma B. Adenocarcinoma C. Adenoid cystic carcinoma D. Adenosquamous carcinoma E. Transitional cell carcinoma F.
5、 Undifferentiated III.Carcinoma and Sarcoma of ectopic breast tissue IV. Carcinoma of sweat gland origin,Histological Classification: -,(Jo Ann Benda and Richard Zaino),17th Sept. 2002,Carcinoma of Vulva - Prof.S.N.Panda,5,MALIGNANT TUMOURS OF VULVA,Embryonal rhabdomyosarcoma (sarcoma botryoides) Le
6、iomyosarcoma Malignant fibrous histiocytoma Epithelioid sarcoma Aggressive angiomyxoma Dermatofibrosarcoma protuberans Epithelioid sarcoma,Histological Classification: -,Malignant rhabdoid tumor Malignant nerve sheath tumor Angiosarcoma Kaposi sarcoma Hemangiopericytoma Liposarcoma Alveolar soft par
7、t sarcoma Other sarcomas(Enzinger & Weiss or WHO),V. Soft tissue sarcomas,(Jo Ann Benda and Richard Zaino),17th Sept. 2002,Carcinoma of Vulva - Prof.S.N.Panda,6,MALIGNANT TUMOURS OF VULVA,VI. Other malignant tumours A. Malignant melanoma B. Endodermal sinus tumor (yolk sac tumour) C. Neuroectodermal
8、 tumours (Merkel cell) D. Lymphomas E. Others VII. Secondary and Metastatic tumors VIII. Unclassified tumors,Histological Classification: -,(Jo Ann Benda and Richard Zaino),17th Sept. 2002,Carcinoma of Vulva - Prof.S.N.Panda,7,MALIGNANT TUMOURS OF VULVA,Most of these forms are uncommon and moreover
9、are histologically analogous to similar tumours occurring elsewhere in the body. However epithelial malignant tumours (Carcinomas) arising from the skin, mucosa or rarely bartholin gland are by far the commonest malignant tumours seen, representing about 3% of all genital cancers in the female. Vulv
10、al carcinomas are classified basing on their degree of differentiation and histopathological grading.,17th Sept. 2002,Carcinoma of Vulva - Prof.S.N.Panda,8,CARCINOMAS OF THE VULVA,Differentiated carcinoma: begins at the surface and presents a pattern of broad buds with rounded borders composed of we
11、ll-differentiated tumour cells that contain abundant cytoplasm, keratin, keratohyaline granules, and intercellular bridges. Poorly differentiated carcinoma: is generally found at the epithelial stromal junction. It is characterized by small tumor cells with scant cytoplasm showing little or no diffe
12、rentiation that infiltrates the stroma either in elongated streaks or small clusters (spray pattern).,HISTOPATHOLOGIC GRADING: -,17th Sept. 2002,Carcinoma of Vulva - Prof.S.N.Panda,9,CARCINOMAS OF THE VULVA,Grade 1: No poorly differentiated component. Grade 2: Poorly differentiated component occupie
13、s less than or equal to 25% of the total area of the tumor. Grade 3: Poorly differentiated component occupies greater than 25%, but less than or equal to 50% of the total area of the tumour. Grade 4: Poorly differentiated component occupies greater than 50% of the tumour area.,HISTOPATHOLOGIC GRADIN
14、G: -,17th Sept. 2002,Carcinoma of Vulva - Prof.S.N.Panda,10,CARCINOMAS OF THE VULVA,Vulvar Intraepithelial Neoplasia, grade I (VIN I) - GX: Grade cannot be assessed VIN II G1: Well differentiated. VIN, III, (squamous cell carcinoma in situ) - G2: Moderately differentiated. Squamous Cell Carcinoma -
15、G3: Poorly differentiated. Verrucous carcinoma - G4: Undifferentiated Padgets disease of the vulva Basal cell carcinoma, NOS - Exceptionally rare Adenocarcinoma, NOS - Exceptionally rare Bartholins gland carcinomas - Exceptionally rare,HISTOPATHOLOGIC GRADING: -,17th Sept. 2002,Carcinoma of Vulva -
16、Prof.S.N.Panda,11,CARCINOMAS OF THE VULVA,Ninety per cent of these epithelial malignant tumours are squamous cell carcinomas, the remainder being basal cell carcinomas, melanomas, or adenocarcinomas Cases should be classified as carcinoma of the vulva when the primary site of the growth is in the vu
17、lva. Tumours present in the vulva as secondary growth from either a genital or extra-genital site should be excluded. Malignant melanoma should be reported separately. A carcinoma of the vulva that has extended to the vagina should be considered as a carcinoma of the vulva.,17th Sept. 2002,Carcinoma
18、 of Vulva - Prof.S.N.Panda,12,CARCINOMAS OF THE VULVA,Clinical Staging, TNM Classification FIGO - 1988 *: - Stage 0 TIS - Carcinoma in-situ, intraepithelial carcinoma (VIN III).Stage I - T1 N0 M0 - Tumour confined to the vulva and/or perineum - 2 cm or less in greatest dimension, nodes are not palpa
19、ble. Stage II - T2 N0 M0 - Tumour confined to the vulva and/or perineum - more than 2 cm in greatest dimension, nodes are not palpable.,*See notes page for details of T N M,17th Sept. 2002,Carcinoma of Vulva - Prof.S.N.Panda,13,CARCINOMAS OF THE VULVA,Clinical Staging, TNM Classification FIGO - 1988
20、 *: - Stage III - T3 N0 M0, T3 N1 M0, T1 N1 M0, T2 N1 M0 - Tumor of any size with: Adjacent spread to the lower urethra and/or the vagina, or the anus, and/or Unilateral regional lymph node metastasis,17th Sept. 2002,Carcinoma of Vulva - Prof.S.N.Panda,14,CARCINOMAS OF THE VULVA,Clinical Staging, TN
21、M Classification FIGO - 1988 *: - Stage IVa - T1 N0 M0 - T2 N2 M0 - T3 N2 M0 - T4 Any N M0, Tumor invades any of the following: Upper urethra, bladder mucosa, rectal mucosa, pelvic bone and/or bilateral regional node metastasis. Stage IVb - Any T, N & M - Any distant metastasis including pelvic lymp
22、h nodes.,17th Sept. 2002,Carcinoma of Vulva - Prof.S.N.Panda,15,Squamous Cell Carcinoma in Situ,This is a precancerous change also called Vulval intraepithelial neoplasia (VIN III) or Bowens disease. VIN is characterized by nuclear atypia in the epithelial cells, increased mitoses, and lack of surfa
23、ce differentiation. It is analogous to high-grade squamous intraepithelial lesions of the cervix . These lesions usually present as white or pigmented plaques on the vulva; identical lesions are encountered in the male. VIN is appearing with increasing frequency in women younger than 40 years.,17th
24、Sept. 2002,Carcinoma of Vulva - Prof.S.N.Panda,16,Squamous Cell Carcinoma in Situ,With or without associated invasive carcinoma, VIN is frequently multicentric, and 10% to 30% are associated with another primary squamous neoplasm in the vagina or cervix. This association indicates a common etiologic
25、 agent. Indeed, 90% of cases of VIN and many associated cancers contain HPV DNA, specifically types 16, 18, and other cancer-associated (high-risk) types. Spontaneous regression of VIN lesions has been reported; the risk of progression to invasive cancer increases in older (older than 45 years) or i
26、mmunosuppressed women. Wide local excision is the appropriate treatment.,17th Sept. 2002,Carcinoma of Vulva - Prof.S.N.Panda,17,Squamous Cell Carcinoma of Vulva,Vulvar squamous cell carcinomas begin as small areas of epithelial thickening that resemble leukoplakia but, in the course of time, progres
27、s to create firm, indurated, exophytic tumors or ulcerated, endophytic lesions. Although vulvar carcinomas are external tumors that are obviously apparent to the patient and the clinician, many are misinterpreted as dermatitis, eczema, or leukoplakia for long periods. The clinical manifestations evo
28、ked are chiefly those of pain, local discomfort, itching, and exudation because superficial secondary infection is common.,17th Sept. 2002,Carcinoma of Vulva - Prof.S.N.Panda,18,Squamous Cell Carcinoma of Vulva,The first group is associated with cancer-related (high-risk) HPV, may be multicentric, a
29、nd frequently coexists with or is preceded by a classic and easily recognized Vulval Intraepithelial Neoplasia (VIN). A variety of chromosome abnormalities are linked to invasive vulval cancer, some of which may be specific for HPV-positive tumours.,In terms of etiology, pathogenesis, and clinical p
30、resentation, vulvar squamous cell carcinomas may be divided into two general groups.,17th Sept. 2002,Carcinoma of Vulva - Prof.S.N.Panda,19,Squamous Cell Carcinoma of Vulva,The second group of squamous cell carcinomas are associated with squamous cell hyperplasia and lichen sclerosus. The etiology o
31、f this group of carcinomas is unclear, and they are infrequently associated with HPV. In one scenario, genetic alterations arise in lichen sclerosus or hyperplasia, leading directly to invasion, or Atypia develops within hyperplasia or lichen sclerosus (differentiated VIN). These tumours have also b
32、een associated with mutations in p53 and appear to have a significantly worse prognosis than HPV-positive tumours do.,17th Sept. 2002,Carcinoma of Vulva - Prof.S.N.Panda,20,Squamous Cell Carcinoma of Vulva,On histologic examination, tumours associated with HPV or VIN frequently exhibit cohesive inva
33、sive growth patterns that mimic intraepithelial neoplasia. These “intraepithelial-like“ patterns may be well (warty) or poorly differentiated (basaloid).HPV-negative tumours, which at times arise from lichen sclerosus or squamous hyperplasia, typically exhibit an invasive pattern with prominent kera
34、tinization.,17th Sept. 2002,Carcinoma of Vulva - Prof.S.N.Panda,21,Squamous Cell Carcinoma of Vulva,Risk of metastatic spread is linked to the size of tumour, depth of invasion, and involvement of lymphatic vessels. The inguinal, femoral, pelvic, iliac, and periaortic lymph nodes are most commonly i
35、nvolved. Ultimately, lymphohematogenous dissemination involves the lungs, liver, and other internal organs. Patients with lesions less than 2 cm in diameter have a 60% to 80% 5-year survival rate after treatment with one-stage vulvectomy and lymphadenectomy; larger lesions with lymph node involvemen
36、t yield a less than 10% 5-year survival rate.,17th Sept. 2002,Carcinoma of Vulva - Prof.S.N.Panda,22,Verrucous carcinoma of vulva,An uncommon variant of squamous cell carcinoma with low malignant potential. It may, however, grow very large. These lesions were originally described as occurring in the
37、 oral cavity but have also been described involving the vagina, cervix, and vulva. Clinically, these tumours are very slow growing and carry an excellent prognosis. The lesion grossly appears cauliflower-like in nature.,17th Sept. 2002,Carcinoma of Vulva - Prof.S.N.Panda,23,Verrucous carcinoma of vu
38、lva,This rare variant of squamous cell carcinoma may also resemble condyloma acuminatum and present as a large fungating tumor. Microscopically, the papillary fronds lack the connective tissue core that characterizes condyloma acuminata. These features are very similar to those of the giant condylom
39、ata of Buschke-Loewenstein, possibly representing successive stages of the same pathologic process.,17th Sept. 2002,Carcinoma of Vulva - Prof.S.N.Panda,24,Verrucous carcinoma of vulva,Local invasion confirms the malignant nature of the lesion, but it rarely metastasises and can be cured by wide exci
40、sion. If there are suspicious groin nodes, FNA or excisional biopsy should be carried out. Usually enlarged nodes are caused by inflammatory hypertrophy, but if they do contain metastases, radical vulvectomy and bilateral groin lymph node dissections are indicated. As metastasis to regional lymph no
41、des is rare, radical local excision is the standard treatment. However a course of radiotherapy after surgery is usually recommended.,17th Sept. 2002,Carcinoma of Vulva - Prof.S.N.Panda,25,Pagets Disease of Vulva,This curious and rare lesion of the vulva, and sometimes the perianal region, is simila
42、r in its skin manifestations to Paget disease of the breast. As a vulvar neoplasm, it manifests as a pruritic red, crusted, sharply demarcated, map like area, occurring usually on the labia majora. It may be accompanied by a palpable submucosal thickening or tumor.,17th Sept. 2002,Carcinoma of Vulva
43、 - Prof.S.N.Panda,26,Pagets Disease of Vulva,The diagnostic microscopic feature of this lesion is the presence of Paget cells, large tumor cells lying singly or in small clusters within the epidermis and its appendages. These cells are distinguished by a clear separation (“halo“) from the surroundin
44、g epithelial cells and a finely granular cytoplasm containing periodic acid-Schiff stain-, Alcian blue-, or mucicarmine-positive mucopolysaccharide. Ultrastructurally, Paget cells display apocrine, eccrine, and keratinocyte differentiation and presumably arise from primitive epithelial progenitor ce
45、lls.,17th Sept. 2002,Carcinoma of Vulva - Prof.S.N.Panda,27,Pagets Disease of Vulva,In contrast to Pagets disease of the nipple, in which 100% of patients show an underlying ductal breast carcinoma, vulvar lesions are most frequently confined to the epidermis of the skin and adjacent hair follicles
46、and sweat glands. The prognosis of Pagets disease is poor in the uncommon cases with associated carcinoma, but intraepidermal Pagets disease may persist for many years, even decades, without the development of invasion. However, because Pagets cells often extend into skin appendages and may extend b
47、eyond the confines of the grossly visible lesion, they are prone to recurrence. It is considered as nothing more than a variant of VIN,17th Sept. 2002,Carcinoma of Vulva - Prof.S.N.Panda,28,Malignant Melanoma,Melanomas of the vulva are rare, representing less than 5% of all vulvar cancers and 2% of
48、all melanomas in women. Their peak incidence is in the sixth or seventh decade; They tend to have the same biologic and histologic characteristics as melanomas occurring elsewhere and are capable of widespread metastatic dissemination. Because it is initially confined to the epithelium, melanoma may
49、 resemble Pagets disease, both grossly and histologically.,17th Sept. 2002,Carcinoma of Vulva - Prof.S.N.Panda,29,Malignant Melanoma,It can usually be differentiated by its uniform reactivity, with immunoperoxidase techniques, with antibodies to S100 protein, absence of reactivity with antibodies to
50、 carcinoembryonic antigen, and lack of mucopolysaccharides. Prognosis is linked principally to depth of invasion, with greater than 60% mortality for lesions invading deeper than 1 mm. Treatment is by wide excision or radical vulvectomy. The overall survival rate is less than 32%, presumably owing to delays in detection and a generally poor prognosis for mucosal melanomas.,
