Vulva Premalignant Diseases
Non-neoplastic Epithelial Disorders
• The term vulvar dystrophy is used to describe non-neoplastic diseases of the vulvar epithelium. These non-neoplastic diseases have a low malignancy potential (< 5%).
Lichen Sclerosis
► It is the most common dystrophic disorder and the most common white lesion of the vulva. It is classically a disease of postmenopausal women and can be observed at any age. It is associated with squamous vulvar carcinoma in 5% of cases. Autoimmunity is questioned in the etiology.
► Patients have severe vulvar and perianal itching. Ecchymosis and ulcerations may occur due to intense scratching. The typical finding on examination is pale white plaque-like lesions. In advanced cases, the appearance of thinned parchment paper occurs. In advanced cases, labial recession and narrowing of the vaginal entrance are observed due to the decrease in subcutaneous adipose tissue, therefore dyspareunia is common and perianal stenosis may also be observed. It tends to be symmetrical and there is no vaginal involvement.
► Definitive diagnosis is made by biopsy. Ultrapotent topical steroids such as clobetasol or halobetasol are used for treatment.
Squamous Cell Hyperplasia
► Although it is frequently seen in postmenopausal women, it can also be encountered in reproductive ages. Although the exact cause is unknown, external irritants are blamed.
► The most common symptom is itching. The lesions are characterized by localized, well-circumscribed white epithelium that is raised from the skin and often thickened on the surface. Unlike lichen sclerosus, labia recession is not seen and tends to be single.
► Definitive diagnosis is made by biopsy. In the relief of symptoms, it is necessary to avoid vulvar allergens first. Medium patented corticosteroid pomades are used in the treatment.
Lichen Planus
► It progresses with oral and genital white ulcerations (vulvovaginal-gingival syndrome). Typically, desquamative vaginitis with erosion in the vestibule (plasma cell mucositis) dominates the picture. Easy bleeding of the vulva tissue and vaginal mucosa and erosive lesions in the vagina, synechia, and partial obliteration of the upper vagina may be observed
► Lichen planus can be diagnosed by punch biopsy taken from the vagina or vulva.
► Lichen planus may increase the risk of vulvar squamous cell carcinoma.
► Ultrapotent topical or systemic steroids are used in its treatment.
Vulvar Intraepithelial Neoplasms
Vulva Diseases Calcification (ISSVD= International Society for the Study of Vulvar Disease)
1- Non-neoplastic Epithelial Abnormalities (Skin or Mucosa)
A. Lichen sclerosus (formerly lichen sclerosus et atrophicus)
B. Squamous hyperplasia (formerly hyperplastic dystrophy)
C. Other dermatoses (eg psoriasis)
2- Vulvar intraepithelial neoplasia
A. Squamous intraepithelial Neoplasms (VIN)
1. Ordinary type VIN
a. Warty (condylomatous) type
b. basaloid type
c. Mixed (warty/basaloid) type
2. Differentiated (differentiated) type VIN
3. Unclassified type VIN
B. Non-squamous intraepithelial Neoplasia
1. Paget's disease
2. Non-invasive melanocytic tumors (Melanoma in situ)
3- Mixed Non-neoplastic and Neoplastic Epithelial disorders
4- Invasive Tumors
Squamous Vulvar Intraepithelial Neoplasms (VIN)
• Most of the VIN lesions are associated with HPV, the most common in HPV positive VIN cases.
(80%) HPV 16 is observed.
• VIN's progression to vulvar carcinoma is uncommon (5-10%).
• VINs fall into two categories:
► Ordinary type; It is more common. It is seen in young and premenopausal patients. HPV (most commonly HPV 16) is associated with smoking, sexually transmitted disease, and immunosuppression. It is usually multifocal and multicentric.
► Differentiated type; It is more rare. It is seen in elderly and postmenopausal patients. It is not associated with HPV, but is associated with lichen sclerosus and squamous hyperplasia. It is usually unifocal and localized. It is more likely to progress to squamous cell cancer.
• Local excision, laser ablation or superficial vulvectomy (performed in cases of VIN III with dissemination and recurrences) can be used for treatment. In pregnancy, it should be followed up as spontaneous resolution may occur in the postpartum period.
Non-squamous Intraepithelial Neoplasms (Paget's Disease)
► Paget's disease is an adenomatous intraepithelial neoplasia of the eccrine-apocrine glands and is believed to develop from undifferentiated basal cells. Some have an underlying adenocarcinoma (apocrine sweat glands, Bartholin gland, anorectum). In 4% of cases, a synchronous or metachronous primary cancer is also present (cervix, colon, bladder, gallbladder, breast and rectal).
► It often occurs in the postmenopausal period and its most prominent finding is itching. Macroscopically, the appearance of white crusts (areas of leukoplakia) over hyperemic areas is pathognomonic (cake cream appearance). It is an eczematoid and velvety lesion and begins in the hairy areas of the vulva.
► Diagnosis is made by biopsy. Histopathologically, characteristic intraepithelial paget cells (large cells with transparent granular cytoplasm) are observed in the epidermis and dense lymphocytic infiltration in the dermis. All forms of Paget's disease show positive staining with cytokeratin and epithelial membrane antigen.
To distinguish Paget's disease of the vulva from superficial spreading melanoma, staining with PAS and Mucicarmine is performed. While muscarmin is (+) in Paget, it is (-) in melanoma.
► Wide excision is made in the treatment. Since they extend beyond the gross lesion, positive surgical margins and frequent local recurrences can be seen. Sufficient dermis must be removed with surgery, so laser is insufficient for treatment.
Vulva Cancer
• It constitutes 5% of all gynecological cancers.
Histopathological classification
A) Vulvar Carcinomas
• Squamous cell (epidermoid) carcinoma; Most common vulvar cancer -------92%
• Basal cell carcinoma------2-3%
• Bartholin gland carcinoma-----1%
• Verrucous carcinoma-------<1%
• Adenocarcinoma----------<1%
• Merkel cell carcinoma
B) Malignant Melanoma; vulvar cancer with worst prognosis and second most common----------2-4%
C) Vulvar sarcoma; The most common vulvar sarcoma is leiomyosarcoma-----<1%
D) Metastatic vulvar cancers --------1%
E) Malignant germ cell tumors (yolk sac tumor etc.)----------<1%
Squamous Cell (Epidermoid) Carcinoma SCC
risk factors
• HPV infection; HPV 16 is the most common, followed by HPV 33 and HPV 18.
• Vulvar intraepithelial neoplasia (VIN)
• Cervical intraepithelial neoplasia (CIN)
• Lichen sclerosis
• Squamous hyperplasia
• Cigarette
• Alcohol
• Obesity
• Immunosuppression; Transplant patients, HIV infection
• History of previous cervical cancer
• Advanced age
• Being of Northern European descent
• HSV infection
etiology
► It is divided into 2 groups according to its etiology:
0 Basaloid or Wart (warty) type; It is a less common type (40%) and is observed in young patients. The risk factors are the same as for cervical cancer (HPV, smoking, immunosuppression). It is often associated with the usual (usual) VIN. It is usually multifocal.
0 Keratinized differentiated (differentiated) or simple (simplex) type; It is the more common type (60%) and is observed in elderly patients. It is not associated with HPV. Lichen sclerosis is associated with chronic inflammatory dermatoses and differentiated type VIN. It is usually unifocal.
The typical histological feature of invasive vulvar cancer is atypical keratinization.
Clinic
► It is usually the disease of postmenopausal women (65 years old).
► Many cases are asymptomatic at the time of diagnosis. The symptoms that occur are often vulvar itching, vulvar swelling or mass. On physical examination, the lesion appears as raised, ulcerated, leukoplakia or warts.
► In most cases, the lesion is located in the labium majus and minus (60%), but it can also originate from the clitoris (15%) and perineum (10%). 5% of cases are multifocal.
27% of squamous cell cancers of the vulva have a second primary malignancy associated with smoking or HPV.
Diagnosis
► Biopsy (punch or wedge) should be taken from any vulvar lesion. Vagina and cervix should be evaluated with colposcopy and cervical Pap smear should be taken in all cases due to the possibility of accompanying.
Spread
► Direct spread; vagina, anus, urethra
► Hematogenous spread; reaches the lungs, liver and bone.
► Lymphatic spread; It may occur in the early stage and the primary lymph group is the inguinal lymph nodes. Then the deep femoral lymph nodes and finally the iliac externa and other pelvic lymph nodes are involved.
0 posterior part of labium majus and labium minus ipsilateral; clitoris, anterior part of labium minus, urethra and perineum show bilateral lymphatic spread.
Vulvar structures with direct drainage to the pelvic lymph nodes; clitoris and Bartholin's gland.
0 Sentinel lymph nodes of vulvar cancers are Cloquet (Rosenmüller) lymph nodes located at the top level of the femoral lymph node group. The involvement of these lymph nodes indicates that the pelvic lymphatics are also involved. Therefore, pelvic lymphadenectomy should be performed in such cases.
Staging
► Vulvar cancers are surgically staged.
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FIGO Staging
(surgery) |
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Stage 1 |
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Tumor limited to vulva or perineum, lymph nodes
negative |
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1A |
T1aN0M0 |
Stromal invasion =< 1 mm, lesion diameter =<2
cm, lymph node negative (MICROINVASIVE STAGE) |
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1B |
T1bN0M0 |
Stromal invasion >1 mm or lesion diameter >2
cm, lymph node negative |
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Stage 2 |
T2N0M0 |
Tumor of any size, involvement of adjacent perineal
structures (1/3 lower urethra, 1/3 lower vagina or anus), but lent nodes are
negative |
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Stage 3 |
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Tumor of any size, with or without involvement of
adjacent perineal structures (1/3 lower urethra, 1/3 lower vagina or anus);
however, inguinofemoral lent nodes are positive |
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3A1 |
T1-2N1bM0 |
1 LN metastasis (>= 5 mm) |
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3A2 |
T1-2N1aM0 |
1-2 LN metastases ( < 5 mm) |
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3B1 |
T1-2N2bM0 |
N2bMo z 2 LN metastases (>=5 mm) |
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3B2 |
T1-2N2aM0 |
z 3 LN metastases (< 5 mm) |
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3C |
T1-2N2cM0 |
Lymph node involvement with extracapsular extension |
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Stage 4 |
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Tumor of any size with spread to other regional or
distant structures |
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4A1 |
T3N1-2-3M0 |
Involvement of upper 2/3 urethra, upper 2/3 vagina,
bladder mucosa, rectal mucosa or pelvic bone |
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4A2 |
T1-2-3N3 |
Fixed or ulcerated inguinofemoral lymph nodes (+) |
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4B |
T1-2-3N1-2-3M1 |
Distant metastases, including pelvic lymph nodes |
It is a gynecological malignancy in which pelvic lymph node involvement is distant metastasis (Stage 4B).
Bilateral lymph node involvement no longer has a place in staging and the presence of bilateral involvement is not decisive for survival.
Microinvasive Squamous Cell Carcinoma
They are tumors confined to the vulva or perineum with a lesion diameter of <= 2 cm and a stromal invasion of <=1 mm (Tla, Stage IA). The risk of inguinal lymph node metastasis in these tumors is very low. Therefore, the most appropriate treatment is wide local excision.
Prognosis and survival
► Among the factors affecting the prognosis; disease stage, lymph node metastasis, diameter of the lesion, depth of invasion, condition of the surgical margin, and lymphovascular space invasion.
► Among these, the single most important prognostic factor is the status of the lymph nodes and the number of positive lymph nodes. There is a strong negative correlation between the number of positive lymph nodes and survival. If three or more lymph nodes are involved, the prognosis is poor. The morphology of the involved lymph nodes is also determinant in the prognosis. There is a negative correlation between the diameter of nodal metastases, the amount of tumoral cells in the lymph node, and the presence of extracapsular spread and survival.
Treatment
► The main form of treatment is surgery. Surgical options include radical local excision, radical vulvectomy + bilateral lymph node dissection.
► Complete inguino femoral lymph node dissection should be performed in all stages except stage IA (microinvasive cancer Tla). If the primary lesion is unilateral (2 cm or more from the midline and if the ipsilateral lymph nodes are negative, bilateral inguinal lymph node dissection is not required. If 3 inguinal lymph nodes or more are positive, pelvic lymph node dissection should also be performed.
► The earliest complication after radical surgery and responsible for morbidity is inguinal wound infection and dehiscence. Another common complication in the early period is lymphocyst formation. The most important late postoperative complication is chronic leg edema (lymphedema).
recurrence
► Most recurrent vulvar cancers occur within the first 2 years following treatment, and inguinal recurrences occur earlier than vulvar recurrences.
► The recurrences show a significant correlation with the number of positive lymph nodes in the inguinal region. If >=3 lymph nodes are positive, the risk of local, regional or systemic recurrence increases. The most important determinant of the development of local recurrence in vulvar cancers is the condition of the surgical margin in the operation.
Malignant Melanoma
• It is the second most common vulvar cancer and the most common non-epidermoid vulvar cancer. It is most common in postmenopausal white women and in the labium minus, labium majus, or clitoris.
Staging
► Microstaging systems are used in staging, but FIGO staging system is not used. Breslow staging systems, which measure the depth of invasion, or Chung staging systems, which measure tumor thickness, are used. Clark staging system is not suitable because there is no papillary dermis in the vulva.
Prognosis
The most important prognostic factor is the depth of the lesion.
Treatment
Radical local excision is sufficient in cases with an invasion depth of less than 1 mm. Deeper invasions require removal of the primary tumor and all of the inguinal lymph nodes. Melanomas are resistant to radiotherapy
Since there are estrogen receptors in malignant melanomas, a response to tamoxifen is obtained in the treatment.
Bartholin Gland Carcinoma
• The most common location of vulvar adenocancers is Bartholin's gland and it is frequently seen in postmenopausal women.
Basal Cell Carcinoma BCC
• They are observed as rodent ulcers with rounded edges. It usually affects postmenopausal white women. These tumors are slow growing and locally invasive tumors. Lesions are usually smaller than 2 cm and are located in the anterior labium majus. It is associated with a high rate of second malignancies (pre-existing or concurrent).
• Treatment is radical local excision. Metastasis to regional lymph nodes is very rare.
Verrucous Carcinoma
• It is a variant of squamous cell carcinoma. It is associated with HPV 6 and 11. It has a cauliflower appearance as gross. Macroscopically and microscopically, it resembles a Buschke-Löwenstein giant condyloma.
• Usually occurs in postmenopausal women, they grow slowly but show local destruction (they may invade to the bone). Since they rarely metastasize, their prognosis is very good.
• In treatment; radical local excision is performed. If metastases are detected in lymph nodes, radical vulvectomy and bilateral inguinofemoral lymph node dissection should be performed.
Radiotherapy is strictly contraindicated as it causes anaplastic transformation and associated metastases.
Vulvar Sarcoma
• Leiomyosarcoma is the most common and often involves the labium majus.
• Rhabdomyosarcomas are the most common soft tissue sarcomas in childhood and involve 20% of the pelvis and genitourinary tract.
Metastatic Vulvar Cancers
• It most commonly metastasizes to the cervix, followed by the endometrium, kidney, urethra and vulva.
Rare Cancers
• Lymphoma: In the lower genital tract, the cervix is the most common, followed by the vulva and vagina. The cause is non-Hodgkin lymphoma in 3:4 of the cases.
• Endodermal sinus tumor; Endodermal sinus tumors constitute the majority of vulvar germ cell tumors.
• Merkel cell carcinoma; It is the primary small cell carcinoma of the skin.
pregnancy and vulvar cancer
• Pregnancy does not significantly affect the course of the disease. Appropriate treatment in the first and second trimesters is radical vulvectomy + bilateral inguinal lymphadenectomy. In the third trimester, wide local excision is made and full treatment is postponed to the end of delivery.