The epithelial changes associated with squamous cell carcinoma of the vulva: a review of the clinical, histological and viral findings in 78 women

Seventy-eight excised specimens of squamous cell carcinoma of the vulva were reviewed retrospectively for the presence of lichen sclerosus or vulvar intraepithelial neoplasia (VIN) at sites proximal to the tumour or more distant. Lichen sclerosus was evident in 61% and VIN alone in 31%. VIN III (differentiated) was associated with over 50% of the specimens with lichen sclerosus. HPV 16 was found in six of the 11 VIN lesions, investigated but in none of the six with lichen sclerosus.     

The relevance of various vulvar epithelial changes in the early detection of squamous cell carcinoma of the vulva

The objective of this study is to evaluate the possible relevance of vulvar epithelial changes as a risk factor for squamous cell carcinoma of the vulva. The data of 66 women surgically treated for squamous cell carcinoma of the vulva have been analyzed. More than 6500 slides from the resection specimens were revised with special emphasis on concurrent epithelial changes. Synchronous epithelial changes were seen in 63 patients. Thirty-nine patients had synchronous vulvar intra-epithelial neoplasia grade 1 (VIN I), 10 VIN II and 13 VIN III. Thirty-one patients had synchronous lichen sclerosus and 49 squamous cell hyperplasia. The difference between the percentage of patients with epithelial changes diagnosed preceding their carcinoma (30%) and the percentage of patients that had synchronous epithelial changes after reviewing the specimen (95%) was striking. It was concluded that more careful diagnosis, treatment and follow-up of these conditions might lead to an earlier recognition of squamous cell carcinoma of the vulva and therefore to a better prognosis.     

Chemotherapy of squamous cell carcinoma of the vulva: A review

A review of published experience with chemotherapy for the treatment of recurrent or metastatic squamous cell carcinoma of the vulva found data for nine different drugs used as single agents. Only 75 patients have been treated. Bleomycin produced responses in 19 out of 31 patients, adriamycin in 4 out of 6 patients, and methotrexate in 2 out of 5 patients. Seven patients with squamous cell carcinoma of the vulva were treated with five different combination chemotherapy regimens. Responses only occurred with regimens which contained bleomycin and methotrexate.     

Phase II trial of erlotinib in women with squamous cell carcinoma of the vulva

ObjectiveTo evaluate the efficacy and toxicity of erlotinib in the management of squamous cell carcinoma (SCC) of the vulva.MethodsPatients with vulvar lesions amenable to surgery or chemoradiation (cohort 1) or those with metastatic measurable disease (cohort 2) received erlotinib 150 mg daily. Patients were monitored for toxicity. Responses were determined by digital photography or RECIST 1.1. Cohort 1 underwent pre and post treatment biopsies. EGFR immunohistochemistry (IHC), fluorescence in-situ hybridization (FISH), and mutational analysis were performed.Results41 patients were enrolled: 17 in cohort 1 and 24 in cohort 2. Notable grade 3 or 4 toxicities included allergic reaction (1), diarrhea/electrolyte abnormalities (3), ischemic colitis (1), and renal failure (3) and electrolyte abnormalities (n = 2). Mean number of cycles for cohort 2 was 3.3. Overall clinical benefit rate was 67.5% with 11 (27.5%) partial responses (PR), 16 (40.0%) stable disease (SD), and 7 (17.5%) progressive disease. Responses were of short duration. All pre and post treatment biopsies exhibited 2–3 + EGFR staining. 5 of 14 patients (35%) were found to have EGFR amplification (n = 3) or high polysomy/trisomy (n = 2). These five patients had either a PR (n = 3) or SD (n = 2). Gain of function mutations were not been identified.ConclusionsThis is the first reported controlled trial evaluating erlotinib for the management of vulvar carcinoma. Toxicities were acceptable given the lack of treatment options for these patients. Given the observed clinical benefits erlotinib may represent one of the most active agents available to treat vulvar SCC.     

Microinvasive squamous cell carcinoma of the vulva

Six patients with microinvasive squamous cell carcinoma of the vulva were evaluated. None of the patients had carcinoma that invaded the stroma to the depth of more than 3 mm. One had positive lymph nodes and died as a result of nodal involvement. The management of patients with vulvar carcinoma is discussed.     

HPV changes and their significance in patients with invasive squamous cell carcinoma of the vulva: a clinicopathologic study.

Records of 28 patients with invasive squamous cell carcinoma of the vulva were analyzed with regard to age-specific incidence rate, associated human papillomavirus (HPV) changes, multifocal and unifocal distribution of the lesions, and incidence of nodal metastasis. The presence of HPV changes (koilocytosis and condyloma) around the neoplastic epithelium correlated with a mean age group younger than that of those without HPV changes (47 vs 77 years). All multifocal cancers were associated with HPV changes while only 35% of unifocal lesions were so associated. Patients with multifocal disease were found to have a mean age younger than that of those with unifocal disease (44 vs. 67). When patients with microinvasion were excluded, no patients with multifocal invasive cancer and HPV changes were found to have nodal metastases. In contrast, nodal metastases were present in 59% of patients with unifocal invasive cancer.     

The significance of histologic findings in predicting nodal metastases in invasive squamous cell carcinoma of the vulva

The significance of tumor differentiation, depth of stromal penetration, and vascular channel involvement in predicting nodal metastases was studied in 62 patients with invasive squamous cell carcinoma of the vulva treated with radical vulvectomy and bilateral inguinal and femoral lymphadenectomy. The pattern of arrangement of vulvar neoplastic cells at the interface with stroma was used as a criterion for histologic grading. Patients with less differentiated tumors had a higher incidence of nodal metastasis within each stage of disease. No nodal metastases were noted in patients with Grade III tumors who had Stage I disease. No well-differentiated tumor with less than 5 mm of stromal penetration was associated with nodal metastases. In this study, the degree of tumor differentiation and the depth of stromal penetration were important predictors of nodal metastases. It was concluded that a subgroup of patients with Stage I well-differentiated vulvar carcinoma invading less than 5 mm into the underlying stroma may benefit by less radical surgery without compromising cure.     

Necrotizing fasciitis: a complication of squamous cell carcinoma of the vulva

Necrotizing fasciitis is an often fatal, often initially unrecognized condition. Although it was first described over 60 years ago, occurrence in the vulva was only first recognized in 1972. The condition is most often associated with diabetes, prior injury, surgery, or irradiation. Aggressive surgical excision is required, early in the course of the disease, to salvage the patient. An association with vulvar carcinoma in a nondiabetic patient has not been previously reported. We report such a case, with a poor outcome, because surgical intervention was not possible until late in the course of the disease.     

Prognostic factors in squamous cell carcinoma of the vulva: a multivariate analysis

Based on 124 patients with squamous cell carcinoma of the vulva treated at the 1. Frauenklinik der Universit?t München from 1971 to 1980, the influence of pretreatment characteristics on survival was assessed. The patients underwent a simple vulvectomy with local and inguinal irradiation. All histologic specimens were worked up in the same manner, and all available specimens were reverified. Follow-up lasted from at least 2 up to 12 years post-treatment, with no dropouts. Using the Cox model of multivariate analysis, five pretreatment characteristics were found to most strongly influence survival: age, dissociated tumor growth, lymphatic spread, tumor thickness, and ulceration. These pretreatment characteristics were implemented in an algorithm for survival-oriented prognostic forecasting. Survival data as predicted from this algorithm correlated well with observed survival data. The validity of these prognostic factors needs to be examined in further studies using comparable patient populations and study designs.     

Inflammatory cell infiltration and survival in squamous cell carcinoma of the vulva

Summary. The prognostic significance of tumour infiltration by inflammatory cells in squamous cell carcinoma of the vulva was examined in a cohort of 34 patients surviving without recurrence for at least 5 years after radical surgery, and a comparative cohort of 35 patients who died of their diseases. Overall, heavy inflammatory infiltration correlated with a good prognosis and light infiltration with a poor one, independent of other indices such as differentiation, tumour size and nodal status. IgA-containing cell infiltration also correlated with a good prognosis but the presence of IgA-containing cells did not alone account for all the inflammation in the good prognosis group. An immunological response to the tumour may be influencing prognosis. At a practical level, the extent of inflammation appears, at least in this material, to be as useful a prognostic index as many more conventional ones.     

Cerebral metastasis in recurrent squamous cell carcinoma of the vulva: case report and review of the literature

Archives of Gynecology and Obstetrics - Distant metastases from squamous cell cancer of the vulva (VSCC) are encountered rarely and are associated with a poor prognosis. Cerebral metastases have...     

Inflammatory cell infiltration and survival in squamous cell carcinoma of the vulva

The prognostic significance of tumour infiltration by inflammatory cells in squamous cell carcinoma of the vulva was examined in a cohort of 34 patients surviving without recurrence for at least 5 years after radical surgery, and a comparative cohort of 35 patients who died of their diseases. Overall, heavy inflammatory infiltration correlated with a good prognosis and light infiltration with a poor one, independent of other indices such as differentiation, tumour size and nodal status. IgA-containing cell infiltration also correlated with a good prognosis but the presence of IgA-containing cells did not alone account for all the inflammation in the good prognosis group. An immunological response to the tumour may be influencing prognosis. At a practical level, the extent of inflammation appears, at least in this material, to be as useful a prognostic index as many more conventional ones.     

The surgical management of recurrent squamous cell carcinoma of the vulva

Thirty-four patients with recurrent/persistent squamous cell carcinoma of the vulva were treated at the University of Michigan Medical Center from 1975-1988. At follow-up, 19 patients (56%) were free of disease and 15 were dead of disease. Three patients developed a "bridge" recurrence, one patient each with original stages I, II, and IV. Two of these patients were free of disease and one patient died of disease. Ten patients had metastatic disease to the groin lymph nodes at the time of recurrence, and all of these patients are dead of disease. Therapy for the recurrence consisted of five radical vulvectomies (80% survival), four pelvic exenterations (25% survival), and 25 wide radical excisions (56% survival). The lymph node status was highly significant in predicting outcome, with zero of ten patients remaining free of disease when the lymph nodes were involved and 19 of 24 free of disease when the lymph nodes were uninvolved (P less than .0001). Factors that did not influence survival included the institution where the initial surgery was performed and the interval from initial therapy to recurrence. Twenty patients received their initial therapy at the University of Michigan and 12 (60%) were free of disease. Fourteen patients were referred from outside institutions for their recurrence and seven (50%) were free of disease. Nineteen patients had a recurrence within 2 years and nine were free of disease, ten patients recurred between 2-10 years of whom seven were free of disease, and five patients recurred after 10 years with three free of disease.(ABSTRACT TRUNCATED AT 250 WORDS)     

Regulation of apoptosis in squamous cell carcinoma of the vulva

OBJECTIVE: To analyze the expression of Bcl-2, Bax and ICH-1-L in squamous cell cancer of the vulva. STUDY DESIGN: Slides of 72 vulvar squamous cell carcinomas were stained immunohistologically for Bcl-2, Bax and ICH-1-L. They were analyzed for the percentage of positive tumor cells, staining intensity and pattern, and amount of Bcl-2-positive lymphocytes around the tumor. Results were analyzed for correlations with clinical and histologic characteristics. Disease-free and overall survival were evaluated by Kaplan-Meier curves with the log-rank test. RESULTS: Strong expression of Bcl-2 was present in 15% of tumors. Carcinomas with high Bcl-2 expression more frequently had lymph node metastasis (P = .03), without significant differences in other clinical or histologic parameters, disease-free and overall survival. Strong Bax expression was observed in 57%, without prognostic significance. Carcinomas showed high ICH-1-L expression in 35%. These tumors seemed to have longer disease-free survival, while overall survival was significantly longer (P = .02). A strong Bcl-2-positive inflammatory infiltrate was highly predictive of lymph node metastasis (P = .02) and disease-free survival (P = .03). CONCLUSION: In squamous cell carcinoma of the vulva, inhibition of apoptosis is associated with a more-aggressive phenotype, and a Bcl-2-positive inflammatory infiltrate is predictive of prognosis. A study with more patients should confirm the importance of apoptosis in vulvar carcinoma.     

Tumor proliferation in squamous cell carcinoma of the vulva.

Tumor proliferation is of important prognostic significance for several neoplasms. The very few previous studies on this parameter in vulvar carcinoma have shown contradictory results. The aim of this study was to determine the prognostic significance of tumor proliferation in vulvar carcinoma. Paraffin-embedded tissue of 74 squamous cell carcinomas of the vulva was immunostained for MIB-1, detecting Ki-67, and analyzed for staining patterns and the percentage of positive cells. There were three general staining patterns: a diffuse distribution (diffuse type), a localized staining at the infiltrating tumor border (infiltrating type), and a localized staining in basal parts of infiltrating tumor cell aggregates (basal type). The percentage of positive cells was not correlated with morphologic or clinical parameters, nor was it correlated with disease-free and overall survival. MIB-1 staining types were correlated with tumor type and grading. Tumors of diffuse and infiltrating type seemed to have more frequent lymph node metastasis (p = 0.053) and shorter disease-free survival (p = 0.076). In these tumors, overall survival time was reduced significantly (p = 0.02). In multivariate analysis, MIB-1 staining types were the most important factor for overall survival with an odds ratio of 4.73. In conclusion, distribution and not the percentage of proliferating cells is of prognostic significance in squamous cell carcinoma of the vulva.     

Prognostic factors for local recurrence of squamous cell carcinoma of the vulva: A systematic review

Background

In patients treated for early-stage squamous cell vulvar carcinoma local recurrence is reported in up to 40% after ten years. Knowledge on prognostic factors related to local recurrences should be helpful to select high risk patients and/or to develop strategies to prevent local recurrences.