CARCINOMA VULVA Prof. M.C.Bansal MBBS,MS,MICOG,FICOG Professor OBGY Ex-Principal & Controller Jhalawar Medical College & Hospital Mahatma Gandhi Medical College, Jaipur.
Varieties of vulvalcarcinoma Cancer of vulva accounts for 1 to 5% of all genital cancers. Malignant tumours of vulva are groupe as follows--- 1.Preinvasive lesions— VIN I,II,III. Bowens disease Pagets disease } Intraepethelial ca. Micro invasive 2.Invasive Lesions – Sqamous cell carcinoma 90% most common Melanoma - 3-5% Adenocarcinoma - 1% Sarcoma - 2% Rodent ulcer or Basal cell carcinoma - 1% 3. Metastatic tumours In 5% cases the lesions are multifocal , and are seen in young women below 40 years.
Preinvasive Lesions Definition Intra epithelial vulval cancer is defined as Cellular abnormality limited to the epithelium of vulval skin excluding the keratinized layer. Presence of acanthosis, intraepithelial pearl formation and inflammatory reaction in dermis are the other characteristics of this lesion. Classification VIN I - cellular abnormality is mild , limited to the basal layer. VIN II- cellular abnormality is limited to lower 1/3rd of the vulval epithelium , basal & intermediate layers. VIN III- entire thickness is involved and shows cellular abnormality.
VIN Incidence Increasing because of increased awareness, early detection, increased age < 70yrs. Aetiology Chronic vulval irritation ,Immunosuppressive conditions ,HIV ,Human Papilloma virus infection , smoking STD , dystrophies , poor nutrition , poor hygiene and local moisture are also contributing factors. 50% VIN cases have sequential or concomitant neoplasia in the lower genital tract. VIN lesions are reported in young women <40 years. Obesity , Diabetes , Chronic puritus and dermatitis are often linked to this disease. HPV DNA detection combined with cytology improves the detection test to 95%.
Histology A loss of polarity and stratification , dystrophic changes are confined to epidermis ( epithelium only). Basement membrane remains intact. Clinical Features Asymptomatic for long time. Purities is common symptom usually being treated as fungal infection in early cases. Later on soreness , dysuria , dyspareunia develop. Pre existing leucoplakia , condyloma and dystrophy may show — white/red flat or papular lesions –single/multiple. Multiple wide spread lesions are more common in young women and occurs in5-25 % . Some develop Pigmentation. Purities -- Scratch /cuts – secondary infected. .
VULVAL INTRAEPITHELIAL NEOPLASIA
Investigations -Difficult to diagnose and differentiate from dystrophies – Biopsy . -Exfoliative cytology / colposcopy Are off no use because of poor exfoliation and keratinization. -5% acetic acid application , 1% Toludine blue stains abnormal areas . Excisional biopsy of a localized lesion picks up VIN.
Management Of VIN Purpose of Rx--- 1.To relieve symptoms of prurius and soreness. 2.To prevent development of invasive cancer. 3. To avoid mutilating surgery and sexual dysfunction in young woman . Redical vulvectomy causes disfigurement and dyspariunia.
VIN Rx Rx depends on age , sexual activity , site and extent of VIN and its grading. Conservative management in place of radical is giving 90- 94 % success. Modern Management VIN I &II with multiple lesion showing euploidy can be watched for 6 months to regress spontaneously in young woman having Immunocompromised state like pregnancy , following recent viral infection. With unifocal lesion local excision including 2cm healthy area all around . Closure of wound by stitching and approximating the margins. Local recurrence is to be watch for.
VIN Rx Persistent / recurrent lesions of early grades VIN II /VIN III need skinning vulvectomy with split thickness skin graft to avoid dyspareunia. Laser excision—Co2 Laser. Cryosurgery —up to depth of 2cm. Local application of Dinitrochlorobenzene , 5% testosteron e and corticosteroid cream . Flouracil (5Fu) 5% cream applied locally for 6-8 weeks . It causes sloughing and burning. Prophylactic -- HPV vaccination. Photodynamic therapy -- tumour photo sensitizer-5-amino- leuvinic acid application combinned with non thermal light of appropriate wave length causes nascent oxygen induced cell death. Elderly woman -- simple vulvectomy.
Follow up Reccurance around excised lesion or fresh lesion - 20-30 % cases. 5-10% progress to invasive cancer in 8-10 yrs. Regular follow up at 6-12 monthly interval.
Bowen’s Disease It is intra epithelial carcinoma of vulva. A slow growing hard excematous surface. Pruritus is the main symptom. It rarely metastastises. Biopsy reveals typical prickle cells invading the epidermis and presence of giant cells. The vagina & Cx both may be involved simultaneously. Simple vulvectomy is the treatment of choice.
Paget’s Disease A rare extra mammary disease. Apocrine sweat glands are involved. Slighted elevated , sharply demarcated , white indurated /excezmatous lesion found in postmenopausal woman c/o pruritis. Biopsy reveals typical large pale vacuolated cells in epidermis . These Paget’s cells are adeno carcinomatous mucus secreting round cells with vesicular nucleus and pale cytoplasm.
PAGET’S DISEASE HPE
Paget’s disease 20 % cases may have associated adenocarcinoma of Bartholin gland. 30% cases of perianal lesion may have cancer anus. Rx is vulvectomy if no underlying cancer is detected. Radiotherapy. Local and systemic 5Fu and Bleomycin is also tried. The tumour recurrence is 20%.
Paget’s Disease A rare extra mammary disease ,comperable to intraductal carcinoma of breast., apocrine sweat glands are involved. It occurs in postmenopausal women. It is a sharply demarcated and slightly elevated white indurated or eczematous lesion. Pruritus is presenting symptom. HPR –reveals large pale vacuolated cells in epidermis . Paget cells are adenocarcimatous, mucus secreting round cells with pale cytoplasm and vesicular nucleus. 20% cases may have underlying carcinoma of Bartholin glands Perianal lesion though rare ,but may have anal adenocarcinoma in 30% cases. Local excision or vulvectomy if no underlying cancer is present. With underlying lesion case is treated as invasive carcinoma Radiotherapy ,local or systemic 5 Fu and bleomycine are also tried. The tumor recurs in 20% cases.
Verrucous carcinomas Most commonly found in the oral cavity, but may be found on any moist membrane composed of squamous epithelium . They are a distinct entity, with no association with human papillomavirus infection, and a peculiar distribution pattern of cytokeratins AE1 and AE3 on immunohistochemical staining . Grossly, the tumors have a cauliflower-like appearance, and the diameter of reported lesions ranges from 1 to 15 cm . Microscopically, they contain multiple papillary fronds that lack the central connective tissue core that characterizes condylomata acuminata. The gross and microscopic features of a verrucous carcinoma are very similar to those of the giant condyloma of Buschke-Loewenstein, and they probably represent the same disease entity . Adequate biopsy from the base of the lesion is required to differentiate a verrucous carcinoma from a benign condyloma acuminatum or a squamous cell carcinoma with a verrucous growth pattern. .
Verrucous carcinomas (contd) Usually occur in postmenopausal women, and they are slowly growing but locally destructive lesions. Even bone may be invaded. Metastasis to regional lymph nodes is rare. Radical local excision is the basic treatment, palpably suspicious groin nodes, should be evaluated with fine-needle aspiration cytologic testing or excisional biopsy. If the nodes contain metastases, radical local excision and at least an ipsilateral inguinofemoral lymphadenectomy is indicated. Vulvar intraepithelial neoplasia or invasive squamous cell carcinoma may be seen in association with verrucous carcinoma. Radiation therapy is contraindicated as it may induce anaplastic transformation with subsequent regional and distant metastasis . 5-year survival rate of 94% treated with surgery alone, compared with 42% treated with surgery and radiation. If there is a recurrence, further surgical excision is the treatment of choice. This may occasionally necessitate some type of exenteration
VERRUCOUS VULVAL CARCINOMA
Microinvasive Cancer Microinvasive sqamous epithelioma is common, melanoma is very rare and detected hystologically. It is a single lesion measuring 2cm or less with a depth of invasion not more than 1cm. It is stage 1 A of figo staging . Multiple foci even depth < 1cm are not included in this classification. Simple excision with sentinel lymph node sampling is best mode of treatment. When lymph node is involved radical surgery is better than radiotherapy.
Invasive Carcinoma Of Vulva Epidemiology 1.Accounts for 2-4% of genital cancers. 2. Common in elderly women 6-7th decade(60%).Rest before 60yrs of age. 3.Now it is being reported in young patients- smoking,STD,HIVand HPV infection. 4. vulval cancer is associated with Ca Cx and ovarian cancer IN 20% cases., may be due to infection in forma and advancing age in later case. 5.Nulliparous and woman of low parity are more disposed to vulval cancer.
Invasive Cancer Of Vulva Aetiology - Causes are same as that of VIN. The lesion associated with VIN or dystrophy progress to invasive carcinoma of vulva. -However VIN always does not preceed invasive carcinoma as seen in cervical cancer.
Invasive Cancer Vulva 80% complain of pruritus ,lump ,swelling or ulcer. Lump may be raised papular area with pigmentation. Ulcer has everted margins and idurated base.Surronding skin may be fissured, cracked and inflamed. Leucoplakic or dystrophic area may also be present.,may be single or multiple foci . Labia major is commonly involved but clitoris,perineal area may also be involved. Anterior 2/3rd area is involved more. Ulcerative lesions bleed and offensively smell. Pain is late feature when nerve are infiltrated. Inguinal L.N. may be palpable. Urethral, rectal symptoms may be preset when cancer spread to them.
INVASIVE VULVAL CARCINOMA VULVECTOMY
Invasive carcinoma of Vulva Differential Diagnosis Tubercular ulcer. Syphilitic condiloma/ulcer Elephantiasis of vulva. Soft sore and Lymhogranuloma Excision biopsy will help .
Staging Of carcinomaVulva(FIGO) Stage 0--Intra epthelial,Bowe’s,Paget’s disease and dystrophy with atypia. Stage IA— single microinvasive cancer lesion <1cm invasion and no lymphatic infiltration. Stage IB– Lesion < 2cm with No suspicious lymph glands.(15% +ve lymph node) Stage II– Lesion > 2cm ,no suspicious lymph nodes(30%+ve lymph node)
Stages of Cancer Vulva(FIGO) Stage III– 1.lesion of any kind extending beyond vulva. 2.Unilateral lymph node ivolment Stage IV A---lesion ivading any of these structures-urethra, bladder,rectal mucosa, pelvic bone and/ Bilateral lymph nodes. Stage IV B—Distant metastesis , pelvic lymph nodes.
Spread of Vulvar Cancer 1. Direct spread to the adjacent organs. 2.By lymphatics. Blood born metastesis are rare. At first superficial inguinal LN are invaded by embolism. later lymphatic channel permeation occurs causing blockade and lymph edema of vulva & leg. Deep L N are involved via Cloquet -to the external iliac, internal iliac, obturator and common iliac deep pelvic LN. Centrally located lesion usually invade contra lateral nodes in 25%cases.
Spread of cancer of vulva---- Lymph Nodes not clinically suspicious may have +ve metastasis in 25% cases. Inguinal L N are involved in--- Stage I—10% Stage II– 30% Stage III—70% Stage IV– 100%
Investigations Diagnostic investigation includes--- Punch or excision biopsy. cystoscopy. PR, Anoscopy,Proctoscopy. X Ray Chest and log bones. CT and MRI for Lymph Node’s metastasis. Lymphangiography---superior to CT/MRI. Mapping is done by Intra operative intra dermal injection of blue dye around the lesion, detection rate –100% -Labeling tissue with radio active tracer and localization with handheld detector. - Lymphoscintigraphy—100% detection rate.
Treatment Of Cancer Vulva Stage I Lateral lesion <2cm can be delt by partial vulvectomy with the margins 3cm beyond the growth-or Unilateral vulvctomy, accompanied by ipsilateral lymphadenectomy.If frozen section reveals no metastasis ., nothing more is needed. if LN +ve for cancer cells contra lateral node dissection is must. Pelvic node dissection is required if cloquet LN is involved .,or pelvic gland’s radiotherapy may be given post operatively.
Rx of Ca vulva----- Stage IITumour between2-4cm will require total vulvectomy and Lymph node dissection/ pelvic radiotherapy. Tumour <4cm poorly diffrentiated /melanoma/ adenocarcinoma –nothing less than Radical vulvectomy ,bilateral inguinal LN and pelvic LN dissection is needed. Separate Incision for vulvectomy and inguinal dissection on either side are used ,so primary closure of wound is possible or ½ thickness skin graft is used.
Rx of Ca Vulva Stage III Mega voltage Radiotherapy 4000- 5000 rads over a period of 5 weeks. Shrunken lesion can locally excised. Local recurrence can be treated by chemotherapy. Stage IV It is treated by chemotherapy and/radiotherapy. Anal involvement is treated by infusion of 5-Fu and Mytomycin-C Followed by radiotherapy 300rads over 3 weeks. - 5Fu 750 mg / m 2 is given DAILY FOR 3-5 days and Mytomycin-C 10mg/m2 bolous given on 1st day.Cisplatinum is also given now a days with good out come. Chemotherapy and radiotherapy avoids exentration which carry high mortality and morbidity,. -Local excision of residual tumor may be required.
Results of treatment and 5 yearsurvival rates Figo Staging 5 years survival rate Stage I 90% Stage II 80% Stage III About 50% Stage IV About 15% Total About 60%
Way & Taussig’s Radicalvulvectomy 1935 Extensively wide incision for radical vulvectomy + bilateral inguinal and pelvic lymphadectomy--- has undergone radical modification in present era. Radical surgery can cause---wound infection,slouhging,haemohrrage.lymph loss, lymph edema, thromboembolism and High primary Mortality. Late sequels are lymph edema, scarring, disfigurement, dyspareunia,lymphoma, edema legs. Urinary incontinence.
Bartholin Gland’s tumor It is a rare unilateral tumor. It is commonly Adeno carcinoma Carries a poor prognosis. Redical vulvectomy is the treatment treatment. Chemotherapy and radiotherapy can also be added.
Vulval Sarcoma Rare tumor . Occurs in reatively young woman. Treatment is local excision. Distant metastasis are common. Chemotherapy is also helpful Prognosis is very poor.
Vulvar Sarcomas Sarcomas represent 1% to 2% of vulvar malignancies and comprise a heterogenous group of tumors. Leiomyosarcomas are the most common, and other histologic types include fibrosarcomas, neurofibrosarcomas, liposarcomas, rhabdomyosarcomas, angiosarcomas, epithelioid sarcomas, and malignant schwannomas . The primary treatment is wide surgical excision . Adjuvant radiation may be helpful for high-grade tumors and locally recurrent low-grade lesions . The overall survival rate is approximately 70%. Leiomyosarcomas usually appear as enlarging, often painful masses, usually in the labium majus. Recurrence was associated with three main determinants: diameter greater than 5 cm, infiltrating margins, and five or more mitotic figures per 10 high-power fields.. Vulvar smooth muscle tumor should be considered a sarcoma when three or all of the following four features were present: (i) over 5 cm in greatest dimension; (ii) infiltrate margins; (iii) 5 mitoses/10 HPF; and (iv) moderate to severe cytologic atypia . Lymphatic metastases are uncommon, and radical local excision is the usual treatment.
Vulvar Sarcomas + Epithelioid sarcomas characteristically develop in the soft tissues of the extremities of young adults but may rarely occur on the vulva epithelioid sarcomas behave more aggressively than their extragenital counterparts. Epithelioid sarcomas in general have a propensity for extensive local disease at presentation, local recurrence, lymph node metastasis, and distant metastasis . Treatment consists of radical excision of the tumor, and at least ipsilateral groin dissection. Systemic therapy is ineffective. + Rhabdomyosarcomas are the most common soft tissue sarcomas in childhood, and 20% involve the pelvis or genitourinary tract. A multimodality approach has evolved, principally as a result of four successful protocols organized by the Intergroup Rhabdomyosarcoma Study Group (IRSG), and survival rates have improved significantly, with a corresponding decrease in morbidity. Arndt et al. summarized the results of these four protocols in 2001. All were managed with chemotherapy (vincristine, dactinomycin ± cyclophosphamide ± doxorubicin), with or without radiation therapy. Wide local excision of the tumor, with or without inguinofemoral lymphadenectomy, was carried out before or after the chemotherapy. Patients with local and/or regional rhabdomyosarcoma of the female genital tract have an excellent prognosis, with an estimated 5-year overall survival of 87% .
Rodent ulcer This common lesion presents as ulcer which keeps invading deeper tissues. Biopsy reveals Basal carcinoma. It is locally malignant. It respond well to wide excision. Persistent cancer Persistent cancer is one which develop within 6 months of primary treatment.
Vulval MELANOMA Accounts for 3-5% of all cases of vulval tumors. Can occur in any age and may develop ina mole or de novo. It is pigmented nodule or superficial spreading tumor. Its margins are irregular and frequently ulcerate and bleed. Valvectomy and bilateral lymphadectomyis the treatment of choice. Post operative radiotherapy may be required. Prognosis is very poor.
Secondary growth of theVulva. It occurs following metastasis from chorio carcinoma, Endometrial and Ovarian cancer. Treated by radiotherapy and chemotherapy . 50% recurrent growths are seen after 2years of Rx of primary lesion. More common when primary lesion was large and Lymph Nodes were involved. RX– exenteration ,radiotherapy and chemotherapy. Recurrent growth occur due to incmplete excision.
Persistent Residual Cancer Persistent residual cancer is one which develops with in 6 months of primary treatment. Local excision with wide margin is required.
Prognostic factors Prognosis depends over size of tumor, grading, staging, how much excision is being done , inguinal and/ pelvic LN positivity. Immune status of woman Age and operability of patient. Hystolgical type of tumor.