外阴癌细胞核DNA含量及面积的图像分析研究

应用图像分析技术定量测定了３３例外阴鳞癌细胞核的ＤＮＡ含量与面积，并结合随访结果分析了外阴癌的预后因素。结果表明，外阴鳞癌细胞核的ＤＮＡ含量与面积均明显高于正常外阴上皮的测定值，并随组织学分级的增高而增大，直径较大肿瘤的ＤＮＡ含量较高，外阴癌的临床分期与组织学分级相关。患者的预后与临床分期、淋巴结转移、肿瘤大小、组织学分级及ＤＮＡ含量相关，其中临床分期是影响外阴癌患者预后的最重要因素。     

Carcinoma in situ of the vulva: a review of 31 treated and five untreated cases

Thirty six patients with carcinoma in situ of the vulva have been followed from two to 23 years. Among 31 patients managed by surgical excision, there were four recurrences of vulvar carcinoma in situ and one patient developed a vulvar carcinoma 17 years later. Four middle-aged and elderly women managed only by biopsy all progressed to invasive vulvar carcinoma in two to eight years; one additional patient progressed to invasion after inadequate primary treatment. These last five cases all represented multifocal lower genital tract neoplasia. Untreated vulvar carcinoma in situ, when seen as part of a multifocal lower genital tract neoplastic process, in middle and later life is likely to progress to invasion.     

The presence of HPV 16, 18 and p53 immunohistochemical staining in tumor tissue of Israeli Jewish women with cervical and vulvar neoplasia

The incidence of cervical neoplasia in Israeli Jewish women is persistently lower, while that of vulvar carcinoma is comparable to that in other populations. The aim of the present investigation was to assess the prevalence of HPV and of immunohistochemically detected mutant p53 in Israeli Jewish women with cervical and vulvar neoplasia compared with other populations. Tissue sections from formalin-fixed paraffin-embedded blocks of ten patients with CIN III, 29 with invasive squamous cell carcinoma, three with adenocarcinoma and 14 with invasive vulvar carcinoma, were examined for the presence of HPV 16 and HPV 18 DNA by PCR amplification, and for mutant p53 protein by immunohistochemical staining. HPV negative cases were re-examined with a sensitive primer. HPV DNA was detected in eight patients with CIN III and in 23 patients with invasive squamous carcinoma. In the remaining cervical squamous neoplasia tissue analysis with the sensitive primer could not be done. HPV DNA was also detected in two patients with adenocarcinoma and in nine (64.2%) patients with vulvar carcinoma. Positive p53 immunohistochemical staining was found only in one CIN III patient, in six (20.7%) squamous carcinoma and in 11 (78.6%) vulvar carcinoma patients. Of the p53 immunohistochemical staining positive tissues, two with cervical carcinoma and six with vulvar carcinoma were also HPV-positive. The prevalence of HPV and of positive p53 immunohistochemical staining in our series of Israeli Jewish women with cervical and vulvar neoplasia is similar to that in other populations, suggesting that the etiological factors are probably also alike.     

Trends in the incidence of invasive and in situ vulvar carcinoma

OBJECTIVE: To characterize the incidence of vulvar carcinoma in situ and vulvar cancer over time. METHODS: We used the Surveillance Epidemiology and End Results database to assess trends in the incidence of vulvar cancer over a 28-year period (1973 through 2000) and determined whether there had been a change in incidence over time. Information collected included patient characteristics, primary tumor site, tumor grade, and follow-up for vital status. We calculated the incidence rates by decade of age, used chi(2) tests to compare demographic characteristics, and tested for trends in incidence over time. RESULTS: A total of 13,176 in situ and invasive vulvar carcinomas were identified; 57% of the women were diagnosed with in situ, 44% with invasive disease. Vulvar carcinoma in situ increased 411% from 1973 to 2000. Invasive vulvar cancer increased 20% during the same period. The incidence rates for in situ and invasive vulvar carcinomas are distributed differently across the age groups. In situ carcinoma incidence increases until the age of 40-49 years and then decreases, whereas invasive vulvar cancer risk increases as a woman ages, increasing more quickly after 50 years of age. CONCLUSION: The incidence of in situ vulvar carcinoma is increasing. The incidence of invasive vulvar cancer is also increasing but at a much lower rate.     

Expression of Ki-67 in vulvar carcinoma and vulvar intraepithelial neoplasia III: correlation with clinical prognostic factors

OBJECTIVES: In vulvar carcinoma, the expression of Ki-67 has been previously found to correlate with patient outcome. The objective of the study was to determine whether a specific pattern of expression was associated with occult vulvar cancer in patients with vulvar intraepithelial neoplasia (VIN) III and whether patterns of Ki-67 expression correlated with other clinical prognostic factors. METHODS: 19 women with only VIN III, 16 women with both vulvar cancer and VIN III, and 15 women with only vulvar cancer were identified. Immunostaining, using a monoclonal antibody for Ki-67, was then performed on representative tissue blocks and slides were assessed for diffuse or localized patterns of expression. For the patients with vulvar cancer, the type of staining was correlated with FIGO stage, tumor grade, lymph nodes status, and associated VIN III. RESULTS: All 35 patients with VIN III exhibited a diffuse staining pattern. In the 31 patients with vulvar carcinoma, 11 (35%) expressed a diffuse staining pattern while 20 (65%) showed a localized pattern. Poorly differentiated tumors were associated with a diffuse staining pattern (P = 0.013, RR 3.59, CI 1.59-7.60). For vulvar carcinoma, there were no statistically significant relationships between Ki-67 expression pattern and stage, associated VIN III, or lymph node involvement. CONCLUSION: VIN III, regardless of a concomitant vulvar cancer, always expressed a diffuse pattern; thus Ki-67 staining was not useful as a marker for occult cancer. In women with vulvar carcinoma, however, a diffuse Ki-67 expression was significantly associated with poorly differentiated tumors.     

Bone metastasis in vulvar carcinoma

Bone metastasis secondary to vulvar carcinoma, especially that involving distant bone, is an infrequent clinical entity. Three cases are reported in which the patients developed pathologic fractures within 8 months following radical surgery for advanced vulvar carcinoma. The incidence of bone metastasis secondary to vulvar carcinoma is reviewed.     

Multimodality therapy for advanced and recurrent vulvar squamous cell carcinoma. A pilot project

From 1985 to 1989 eight women with advanced or recurrent vulvar carcinoma were treated at the Women's Cancer Center of the University of Minnesota Hospital and Clinic. Each received a combination of 5-fluorouracil, mitomycin C and cisplatin during radiotherapy. Five of the eight women who underwent posttreatment radical vulvectomy had acceptable operative morbidity. Six patients experienced a complete clinical response. Of them, one had microscopic residual disease in the surgical specimen. One patient with recurrent vulvar carcinoma experienced progression of disease on therapy. One death was attributable to chemotherapy toxicity, and two patients died of intercurrent disease. The overall survival rate at 27 months was 33%. This multimodality approach to the treatment of advanced vulvar carcinoma should be considered when designing a therapeutic approach to treating extensive or resistant vulvar carcinoma.     

Occult lymph node metastases in early stage vulvar carcinoma patients

OBJECTIVE: In early stage vulvar carcinoma patients, there is at trend towards individualized treatment in order to reduce morbidity and sequela following inguinal lymph node dissection. However, recurrences in the groin are almost always fatal. In the present study, we address the occult lymph node metastases in vulvar squamous cell carcinoma patients by using serial sectioning and immunostaining of lymph nodes in a larger series of vulvar carcinoma patients and relate the findings to clinical follow-up data. METHODS: From 75 vulvar squamous cell carcinoma patients staged surgical FIGO I-III, 421 lymph nodes found negative at the hematoxylin & eosin (H&E) routine investigation were scrutinized. From formalin-fixed and paraffin-embedded tissues, sections were cut with 150 mum interval and stained with H&E and cytokeratin AE1/AE3. Two classes were used to describe the amount of tumor cells: <100 cells and >100 cells. RESULTS: Positive cytokeratin AE1/AE3 staining was found in 25/421 (6%) of the lymph nodes. Occult lymph node metastases were found in 17/75 (23%) of the patients. Correlation was found between lymph node metastasis and site of recurrence (P = 0.01). Twenty-eight percent of the patients had relapse. CONCLUSIONS: The present study underlines the importance of serial sectioning and immunostaining of lymph nodes in the search for micrometastases in vulvar carcinoma patients. However, the results of the present study do not suggest a more thorough examination of non-sentinel lymph nodes in vulvar carcinoma patients where the sentinel lymph nodes are thoroughly examined.     

Effect of human papillomavirus vaccines on vulvar, vaginal, and anal intraepithelial lesions and vulvar cancer

OBJECTIVE: Human papillomavirus (HPV) is a necessary cause for cervical cancer, and it has been associated with vulvar and vaginal cancer and vulvar (VIN) and vaginal (VaIN) and anal (AIN) intraepithelial neoplasia. We assessed the prevalence of HPV (and the types) to estimate the possible effect of a HPV vaccine on lower genital tract disease prevention. METHODS: Two hundred fifty-eight samples of VIN, VaIN, AIN, and vulvar cancer from 241 women were included in the study. The diagnosis of surgical samples was made using published histomorphologic criteria. The DNA was extracted for HPV detection and typed using polymerase chain reaction and sequencing. RESULTS: The analyses were performed on 210 intraepithelial neoplasia samples (VIN2/3, VaIN2/3, AIN2/3) and 48 vulvar carcinoma samples. Human papillomavirus DNA was detected in 92%, 91%, 89%, and 60% of the VIN, VaIN, AIN, and vulvar carcinoma samples, respectively. High-risk HPV types 16 or 18 were detected in 76%, 64%, 81%, and 42% of the VIN2/3, VaIN2/3, AIN, and vulvar carcinoma samples. Women with HPV-positive samples were younger than those with HPV-negative samples (46 years compared with 55 years and 51 years compared with 61 years, for the VIN2/3 and vulvar carcinoma samples, respectively). Human papillomavirus-positive vulvar carcinoma was more frequent in women aged younger than 56 years (77%), than in those aged 56 years or older (41%). CONCLUSION: Based on the data obtained in this study, widely-implemented prophylactic HPV vaccination could make an important contribution to the reduction of the risk for cervical cancer and could also prevent about half the vulvar carcinomas in younger women and about two thirds of the intraepithelial lesions in the lower genital tract. LEVEL OF EVIDENCE: II-3.     

A comparative study of MMP-2 in vulvar neoplasms

OBJECTIVE: To investigate differences in MMP-2 protein expression in VIN, vulvar invasive carcinoma, and lichen sclerosus, we performed an immunohistochemical study in which tissue samples from individuals affected by these conditions were compared with normal vulvar tissue. METHODS: A total of 57 cases were selected, as follows: 14 cases of vulvar invasive carcinoma, 22 of vulvar intraepithelial neoplasia (6 of VIN I, 5 of VIN II, and 11 of VIN III), 9 of vulvar lichen sclerosus, and 12 samples of normal vulvar tissue. Immunohistochemistry was done with primary monoclonal antibodies against MMP-2 and quantification of the immunostaining was done by counting the number of antigen-positive stromal cells per 1000 stromal cells. RESULTS: Normal vulvar tissue had a median score of 37.99 stromal cells positive for MMP-2. The median scores for VIN I/II and lichen sclerosus were 41.98 and 46.51, respectively, with no statistical differences when compared to the normal group. Invasive cancer had a score statistically higher (160.36) than any of the other groups. CONCLUSION: Invasive vulvar carcinoma had a score statistically higher of MMP-2 than normal tissue, VIN, and lichen sclerosus.     

Carcinoma of the vulva. Report of a case originating from Bartholin's gland

A case of vulvar carcinoma arising from Bartholin's gland is described. At admission the patient showed a large suppurated swelling of the left labium maior. The neoformation reached the groin of the same side. Malignant cells were detected in biopsy specimens of both the vulvar swelling and the lymphonodes. The histological test showed a vulvar carcinoma arising from Bartholin's gland. The vulvar swelling and the ulcerated lesion were removed and the patient was treated with radiotherapy, chemotherapy (bleomicina) and immunomodulant therapy (Timostimoline). Pulmonary methastases were detected eighteen months after the operation and the patient died two years later.     

A case of isolated ovarian recurrence from vulvar carcinoma

The hematogenous spread from vulvar cancer is extremely rare. We reported an unusual case of ovarian recurrence from vulvar carcinoma. A 78-year-old woman, with a previous (41 months before) diagnosis of vulvar cancer, was admitted to our Institution. Ultrasound revealed a solid mass of the left ovary. Fluorodeoxyglucose positron emission tomography documented an abnormal uptake in the left pelvis. At definitive pathology, the presence of the same histology in vulvar and ovarian mass and the presence of areas of necrosis and endovascular emboli in the ovarian mass led to the diagnosis of ovarian recurrence from vulvar carcinoma. The patient was triaged to salvage treatment and has currently no evidence of disease. This observation expands the range of unusual clinical presentations of recurrence sites from vulvar carcinoma, and emphasizes the need not to underestimate the role of long complete follow-up program in vulvar cancer patients.     

外阴病变组织中精子相关抗原-9的表达及意义

目的:研究外阴鳞状上皮内瘤变(VIN)和外阴鳞状细胞癌组织中精子相关抗原-9(SPAG9)的表达及其潜在的临床意义。方法:应用免疫组织化学技术检测16例VIN、41例侵袭性外阴鳞状细胞癌和10例正常外阴皮肤组织中SPAG9蛋白的表达。结果:SPAG9蛋白在VIN及侵袭性外阴鳞状细胞癌中的表达率均为100%,在正常外阴皮肤中表达率为0;根据H-score分值比较:SPAG9蛋白在外阴鳞状细胞癌组织中的表达高于VIN组织,G2～G3肿瘤组织中SPAG9蛋白表达高于G1者,有淋巴结转移者肿瘤组织内SPAG9蛋白的表达高于无淋巴结转移者,差异均有统计学意义(P<0.05);外阴鳞状细胞癌Ⅱ～Ⅲ期患者肿瘤组织中SPAG9蛋白的表达高于Ⅰ期,差异无统计学意义(P>0.05)。结论:SPAG9蛋白可能在外阴癌的发生和发展发挥重要作用,有望成为外阴癌早期诊断和预后评估的生物学标记物。     

Analysis of invasive squamous cell carcinoma of the vulva and vulvar intraepithelial neoplasia for the presence of human papillomavirus DNA

We have analyzed a number of invasive squamous cell carcinomas for the presence of human papillomavirus (HPV) DNA using dot blot and Southern blot analysis. Seven of 31 samples (23%) were positive by dot blot and/or Southern blot analysis. In contrast, six of 11 (55%) of vulvar intraepithelial neoplasias contained HPV DNA by dot blot and/or Southern blot hybridization. Less than 50% of the invasive vulvar carcinomas contained detectable HPV DNA. The average age at onset of vulvar carcinoma is higher than that for cervical carcinoma (in which HPV DNA is detected in over 80% of cases). Therefore, the role of HPV in the genesis of vulvar carcinoma may be different from the role of HPV in the genesis of cervical carcinoma.     

A comparative analysis of human papillomavirus types 16 and 18 and expression of p53 gene and Ki-67 in cervical,vaginal, and vulvar carcinomas

This study aimed to investigate the correlation between HPV positivity, p53 overexpression, and cell proliferative activity in cervical, vaginal, and vulvar squamous cell carcinoma. METHODS: Sixteen vaginal and 31 vulvar squamous cell carcinomas were examined retrospectively for overexpression of p53 gene and Ki67 antigen by immunohistochemistry and for the presence of HPV types 16 and 18 DNA using a polymerase chain reaction (PCR) method. The results were compared with those obtained from 40 cervical squamous cell carcinomas. RESULTS: HPV type 16 or 18 DNA was detected in 21 (52.8%) of 40 cases of cervical carcinomas and p53 overexpression in one (2.5%), while HPV DNA sequences were detected in seven (43.7%) of 16 cases of vaginal carcinoma and p53 overexpression in three (18.7%). With regard to vulvar carcinoma, HPV was harbored in four (12.8%) of 31 cases and p53 overexpression in 19 (61.2%). These results indicated statistically significant inverse correlations between HPV positivity and p53 overexpression (R = -0.999, P < 0.0001). Overexpression of Ki-67 was detected in 28 (70.0%) of 40, 12 (75.0%) of 16, and 21 (67.7%) of 31, cervical, vaginal, and vulvar carcinomas, respectively. There was no significant difference among the three groups. CONCLUSIONS: In cervical carcinoma, HPV types 16 and 18 might play a common causal role, and in vulvar carcinoma, p53 gene mutations might be a main causal factor for carcinogenesis. Vaginal carcinoma, on the other hand, is considered to have transitional characteristics between cervical and vulvar carcinoma.     

Clinically inapparent invasive vulvar carcinoma in an area of persistent Paget's disease: a case report

BACKGROUND: Invasive vulvar carcinoma is reported to occur in 5 to 20% of patients with vulvar Paget's disease. We report a case in which a clinically inapparent invasive lesion was discovered on reexcision of microscopically persistent vulvar Paget's disease. CASE: A 58-year-old woman presented with a diagnosis of vulvar Paget's disease. A wide local excision of the lesion was performed and pathologic analysis revealed microscopic Paget's disease at two of the margins. The patient returned for a follow-up 4 months later and a vulvar biopsy revealing persistent Paget's cells was obtained from the area of the prior microscopically positive surgical margin. A reexcision was performed from the normal-appearing vulva and invasive vulvar carcinoma was noted in this specimen. CONCLUSIONS: This case demonstrates several concerning aspects of this disease, most important of which is that the clinically apparent lesion did not contain the clinically significant invasive lesion. Invasive vulvar carcinoma may occur in association with microscopically persistent vulvar Paget's disease, a condition often encountered after primary treatment with wide local excision.     

Transitional cell carcinoma of the bladder mimicking recurrent paget's disease of the vulva: report of two cases, with one occurring in a myocutaneous flap.

BACKGROUND: Transitional cell carcinoma of the bladder may spread superficially along and beyond the urogenital epithelium, mimicking vulvar Paget's disease. CASES: These two cases illustrate unusual aspects of transitional cell carcinoma of the bladder and vulvar Paget's disease. Both patients had a history of breast cancer and previously had multiple operations for recurrent vulvar Paget's disease; one patient had a radical vulvectomy with transverse rectus abdominal muscle flap reconstruction. Both had a history of recurrent transitional cell carcinoma of the bladder. Both presented with recalcitrant transitional cell carcinoma of the bladder and clinically recurrent vulvar Paget's disease. Pathologic evaluation, however, revealed pagetoid spread of carcinoma in situ (CIS) throughout the urothelium, with an invasive component in the cervix and extension of the CIS into the rectum in one patient. CONCLUSION: If the history of the patient includes transitional cell carcinoma of the bladder and vulvar Paget's disease, histologic evaluation is needed for accurate diagnosis and proper treatment.     

Early diagnosis of vulvar neoplasia as a result of vulvar self-examination

Vulvar self-examination was used to facilitate early diagnosis and treatment of vulvar neoplasia in eight patients. Five of them were found to have invasive squamous cell carcinoma of the vulva, two had carcinoma in situ, and one had a vulva melanoma. All eight patients benefited from early diagnosis, which allowed definitive treatment and vulvar conservation.     

Primary lung large cell carcinoma metastatic to the vulva: a case report and review of the literature

BACKGROUND: Metastatic cancer to the vulva is a rare diagnosis and is estimated to account for 5-8% of all vulvar cancers. CASE: A 57-year-old postmenopausal woman was referred for the evaluation of a new vulvar mass. CT scan of the pelvis demonstrated a 4 x 6 cm lobular mass of the left labia. An outpatient excisional biopsy revealed a poorly differentiated large cell carcinoma with prominent necrosis and focal perineural invasion consistent with a bronchogenic carcinoma. A subsequent PET scan of the chest revealed a large primary lung carcinoma confirmed by CT-guided biopsy that was identical to the vulvar tumor. CONCLUSION: This case represents the only literature described primary lung carcinoma presenting as a vulvar metastasis.