Carcinoma of the Vulva Epidemiology

1. Carcinoma of the VulvaEpidemiology • 4% of gynecologic malignancy • The median age of patients with invasive vulvar cancer at diagnosis is about 65 to 70 years • median age of women with VIN at diagnosis is 45 to 50 years

2. The relatively stable incidence of invasive cancer despite a steady increase in patients diagnosed with VIN could suggest • etiologic factors are different • Dx improved • effective treatment of VIN has prevented a significant increase in the incidence of invasive disease.

3. HPV • 89 percent of VIN lesions • 40% of invasive vulvar carcinomas • HPV vaccination

4. Invasive SCC • associated with HPV infection • notassociated with HPV infection

5. HPV-positive tumors • Basaloid or warty carcinomas with little keratin formation • often associated with VIN • frequently multifocal • in younger women (35 to 55 years) • more likely to have CIN • to have risk factors typically associated with cervical cancer

6. HPV-negative tumors • In older women (55 to 85 years) • often associated with vulvar inflammation or lichen sclerosis (but rarely with VIN) • Unifocal • well differentiated • Higher incidence of p53 mutations

7. Natural History and Pattern of Spread

8. female external genitalia • mons pubis, • labia majora, labia minora • clitoris, • vestibular bulb, • vestibular glands (including Bartholin's glands • vestibule of the vagina.

9. gynecologic perineum • The region between the posterior commissure of the labia and the anus is termed the gynecologic perineum.

10. lymphatics Even minimally invasive • superficial inguinal lymph nodes(lateralized lesions) • deeper femoral lymph nodes (secondarily ) • pelvic lymph nodes (then) • medial femoral lymph nodes(more medial lesions) • obturator nodes(clitoris)

11. Despite the extensive anastomosis of lymphatics in the region, metastasis of vulvar carcinoma to contralateral lymph nodes is uncommon in patients with well-lateralized T1 lesions.

12. The lungs are the most common sites of hematogenous metastasis

13. Pathology Nonneoplastic epithelial disorders of the vulva • lichen sclerosis • squamous hyperplasia • dermatoses

14. About 10% of these lesions have cellular atypia and are termed vulvar intraepithelial neoplasia • VIN lesions are assigned a grade from 1 to 3 according to their degree of maturation

15. Paget's disease of the vulva • a rare intraepithelial lesion located in the epidermis and skin adnexa, accounts for 1% to 5% of vulvar neoplasms. • negative for HPV • in postmenopausal women

16. SCC(More than 90% ) Most squamous carcinomas are well differentiated, About 5% of vulvar cancers are anaplastic carcinomas

17. Verrucous carcinoma • Rare • very well-differentiated • in the fifth or sixth decade • a large, locally invasive lesion. • Even with extensive local invasion, lymph node metastasis from verrucous carcinoma is very rare.

18. primary mammary adenocarcinoma • basal cell carcinomas • sebaceous carcinomas • Malignant melanomas • Vulvar sarcomas

19. Diagnosis, Clinical Evaluation, and Staging Patients with VIN may complain of : • vulvar pruritus • irritation, • a mass • 50% are asymptomatic • bleeding • tender

20. new vulvar lesion • biopsy • Once the diagnosis of high-grade VIN has been established, the entire vulva, cervix, and vagina should be carefully examined because patients often have multifocal or multicentric involvement.

21. Colposcopic examination • wedge biopsy • Excisional biopsy is preferred for lesions smaller than 1 cm in diameter.

22. a careful physical examination • chest radiography • biochemical profile • Cystoscopy and proctoscopy • skeletal radiography • CT or MRI scans • PET (poor sensitivity but high specificity in the prediction of lymph node metastases)

23. (FIGO) Staging of Carcinoma of the Vulva • I Lesions 2 cm or less in size confined to the vulva or perineum. (T1) (N0) • IA Lesions 2 cm or less in size confined to the vulva or perineum and with stromal invasion no greater than 1.0 mm (No) • IB Lesions 2 cm or less in size confined to the vulva or perineum and with stromal invasion greater than 1.0 mm (No)

24. II Tumor confined to the vulva and/or perineum or more than 2 cm in the greatest dimension. (T2) (N0) • III Tumor of any size with:Adjacent spread to the lower urethra and/or the vagina, or the anus (T3) and/or Unilateral regional node metastasis (N1)

25. IVA Tumor invades any of the following: upper urethra, bladder mucosa, rectal mucosa, pelvic bone (T4) and/or Bilateral regional node metastasis. (N2) • IVB Any distant metastasis including pelvic lymph nodes. (M1)

26. Px • Clinical tumor diameter • depth of invasion • tumor thickness • presence or absence of LVSI • tumor grade? • More than 75% of patients with LVSI have positive inguinal nodes.

27. Prognostic Factors • amount of keratin • the mitotic rate • the tumor growth pattern • Aneuploid tumors (not be an independent predictor of outcome) • HPV DNA ( a poorer prognosis) • age ?

28. LN • presence and number of inguinal node metastases • bilateral node involvement • pelvic node metastases (as stage IV) • extracapsular extension

29. surgical margins and tumor recurrence 1 cm or <8mm

30. Treatment • Radical en bloc resection of the vulva, and inguinofemoral nodes until the early 1980s. • 5-year survival rates of 60% to 70%, • the surgery caused significant physical and psychological complications, • patients with multiple positive nodes continued to have a poor prognosis.

31. operating through separate vulvar and groin incisions • cure rates similar to vulvectomy. • role of radiotherapy in the curative management of locoregionally advanced disease.

32. Preinvasive Disease (VIN)- • treatment of high-grade VIN (VIN 3) should be as conservative as possible • Focal lesions can be simply excised. • Multiple lesions can be excised separately or, if confluent, with a larger single excision. • This approach is generally well tolerated and provides material for histologic assessment. • more extensive high-grade VIN, with a CO2 laser.

33. Extensive, diffuse VIN 3 • a wider excision, particularly if the lesion involves the perianal skin. • a partial vulvectomy of the superficial skin (skinning vulvectomy‌)

34. VIN 3 often recurs • VIN 3 can recur within the donor skin from split-thickness grafts

35. T1 and T2 Tumors • Invasive vulvar tumors can usually be treated effectively without en bloc radical vulvectomy and inguinal node dissection. • Today, most gynecologic oncologists advocate an individualized approach to early invasive vulvar carcinomas.

36. Overall 5-year disease-specific survival rates for stage I (T1N0M0) and stage II (T2N0M0) disease are approximately 98% and 85%, respectively.

37. T1 and selected T2 lesions • radical local excision. • A wide and deep excision of the lesion is performed, with the incision extended down to the inferior fascia of the urogenital diaphragm. • An effort should be made to remove the lesion with a 1-cm margin of normal tissue in all directions unless this would require compromise of the anus or urethra.

38. Small T1 lesions that invade 1 mm or less can be managed with local resection alone because the risk of regional spread is very small.

39. Larger T2 lesions : modified radical or radical vulvectomy • separate vulvar and groin incisions.

40. Acute complication • Wound seroma (15% ) • urinary tract infection • wound cellulitis • temporary anterior thigh anesthesia from femoral nerve injury • thrombophlebitis • pulmonary embolus.

41. Chronic complication • leg edema • genital prolapse • urinary stress incontinence • temporary weakness of the quadriceps muscle • introital stenosis. • pubic osteomyelitis, • femoral hernia, • rectoperineal fistula

42. T3 and T4 Tumors • T3 tumors S +_RT • the vulva may be treated with opposed anterior and posterior photon fields (if the inguinal regions also require treatment) or with an appositional perineal electron beam. The vulva should receive a total dose of 50 to 65 Gy, depending on the proximity of disease to the surgical margin.

43. preoperative chemoradiation in some patients with T3 and T4 • These reports indicated that modest doses of radiation (45 to 55 Gy) produced dramatic tumor responses in some patients with T3 and T4 disease, permitting organ-sparing surgery without sacrifice of tumor control. • Investigators have emphasized the use of concurrent chemoradiation in this setting.

44. Chemoradiation in Locally Advanced Disease • Most studies have used combinations of cisplatin ,5-FU, and mitomycin-C, • Treatment schedules usually include a 4- to 5-day infusion of 5-FU combined with one of the other two drugs, with this course repeated every 3 to 4 weeks

45. CHRT • Impressive responses • Cisplatin

46. neoadjuvant chemotherapy in the treatment of locally advanced vulvar cancer. • two to three cycles of cisplatin, bleomycin, and methotrexate followed by radical surgery. • Caution is warranted Elderly (concurrent medical problems)

47. Tx: • Small T1 lesions : local resection alone • T1 and selected T2 lesions: radical local excision • Larger T2 lesions: modified radical or radical vulvectomy • Locally Advanced Disease: CHRT +S T3 : S+_RT T4 Tumors:RT+_S+_CHT

48. Treatment of Regional Disease • patients who suffer inguinal recurrences are rarely curable • primary tumors that invade more than 1 mm must have their inguinal nodes treated

49. compared pelvic lymphadenectomy with inguinal and pelvic irradiation in patients with inguinal node metastases from carcinoma of the vulva: a survival advantage for the radiotherapy arm

50. postoperative radiotherapy became standard for most patients with inguinal node metastases.