Leiomyosarcoma of the vulva. A case report.

BACKGROUND: Leiomyosarcoma of the vulva is a rare mesenchymal tumor. Biologic features of a low grade tumor were investigated by an immunohistochemical workup. CASE: A 38-year-old woman presented with a slowly growing vulvar mass. Surgical treatment was performed, and a low grade leiomyosarcoma of the vulva was diagnosed. Immunohistochemical reactions were performed with monoclonal antibodies against desmin, vimentin, smooth muscle actin, cytokeratin, S-100 protein, estrogen, progesterone and androgen receptor, p53 protein, Ki-67 antigen, leukocyte common antigen and polyclonal antibodies to factor VIII-related antigen. Expression of estrogen, progesterone and androgen receptor was present in addition to a moderate number of Ki-67-positive cells and absence of p53 protein overexpression and lymphatic cell infiltration besides adequate microvessel density for smooth muscle tumors. Since the immunohistochemical markers indicated a less aggressive tumor, any further adjuvant therapy was rejected. The patient was without recurrence 24 months later. CONCLUSION: The immunohistologic profile proved the low histologic grade of vulvar leiomyosarcoma. The findings helped to estimate prognosis and plan therapy.

Evaluation of the United States Food and Drug Administration-approved scoring and test system of HER-2 protein expression in breast cancer.

PURPOSE: The purpose of this study was to investigate the prognostic significance of assessment of human epidermal growth factor receptor (HER)-2 oncogene protein overexpression of breast cancer tissue by the United States Food and Drug Administration (FDA)-approved HercepTest and grading system (negative, 0 or 1+; weakly positive, 2+; strongly positive, 3+). Furthermore, results of the HercepTest were correlated with immunohistochemical results obtained using different antibodies and protocols and with HER-2 oncogene gene amplification assessed by fluorescence in situ hybridization (FISH). EXPERIMENTAL DESIGN: HER-2 status in 303 patients with lymph node-positive breast cancer was investigated by using a rabbit polyclonal antibody (DAKO) by conventional immunohistochemistry and by applying the HercepTest. Furthermore, the monoclonal antibody CB-11 was used in conventional immunohistochemistry and with the NexES automatic stainer, which is also under consideration for FDA approval for determination of eligibility for Herceptin therapy. Results were compared with FISH analysis performed in all 2+ and 3+ specimens (103 cases) and 104 HER-2-negative specimens. RESULTS: 3+ positive carcinomas were found in 8.9-15.7% of specimens. FISH revealed that almost exclusively 3+ positive cases were amplified, with the HercepTest and the NexES automatic stainer giving the best results. In univariate analysis, staining with the HercepTest revealed a significantly worse prognosis in 3+ cases. Also, 3+ cases were significantly associated with lower estrogen receptor levels and histological grade III tumors. CONCLUSIONS: This study shows that the results of the FDA-approved HER-2 grading and test system correlated strongly with findings in FISH. Furthermore, HercepTest proved to be of prognostic relevance. Strict adherence to the given protocols is critical.

Cervical cancer screening in Austria.

Austria's target population of women aged 20 years and over consists of 3 million people. There is mainly opportunistic screening, except in one county with a target population of 120000, in which organised screening has been practiced for several years. There are approximately 1.5 million smears annually, exclusively taken by gynaecologists. The recommended screening interval is 1 year. The slides are screened by MTs with a maximum workload of 12000 smears annually in 65 laboratories, mainly headed by pathologists. As shown by Vutuc and colleagues (Wien Klin Wochenschr 1999, 111, 354-359) the opportunistic screening system covers 60% of the Austrian target population leaving an unsatisfactorily high rate of underserved, mainly postmenopausal, women. Nevertheless, the cervical cancer mortality rate could have been decreased to one third during the past 40 years.

Hybrid capture based human papillomavirus typing in cervical screening compared to cytology and histology.

INTRODUCTION: Cervical cancer is frequently associated with infection from various types of human papillomavirus (HPV) with high a oncogenic potential (high-risk types). Commercial systems for HPV typing are available, but the question as to when HPV typing should be performed has not yet been solved. OBJECTIVES: To assess the value of HPV typing in a clinical setting in a population with opportunistic screening. STUDY DESIGN: Cytology, histology and HPV status of 593 patients from a high-risk collective were evaluated retrospectively. For HPV typing, the hybrid capture (HC) system was used. RESULTS: Infection with high-risk types of HPV was associated with more severe cervical lesions. Women with PAP III or PAP IIID who were infected with high-risk HPV were at increased risk for high-grade cervical lesions (CIN III+) (p = 0.006). Conization influenced HPV status: of 63 patients who were HPV high-risk positive before conization, 4 remained positive afterwards. CONCLUSION: HC appears to be a useful system to triage women with PAP III or IIID and to detect patients with residual HPV infection after conization. However, because of high costs and no significant increase in the sensitivity of cytology, the use of HPV typing in routine cervical screening cannot be recommended in countries with opportunistic annual cytological screening.

Comparative evaluation of seven cell collection devices for cervical smears.

OBJECTIVE: To compare the most commonly used cervical sampling devices. STUDY DESIGN: We examined seven cytology sampling devices (Cytobrush, Cervex brush, Szalay spatula, Papex spatula, WrGKK spatula [main social security agency in Vienna], cotton swab and loop). Eight hundred smears were assessed for even distribution of cells, percentage of slide surface covered with cells, and presence and number of endocervical cells. RESULTS: Even distribution of cells was best with the WrGKK spatula. Percentage of slide surface covered with evaluable cells was best with the Cytobrush. Highest ranking for the presence of endocervical cells was found for the Cytobrush. Cotton swabs and loop showed inferior results in all categories. CONCLUSION: The use of cervical cell sampling devices showing the best cytologic results improves the interpretation and validity of cervical smears. Our results suggest that cotton swabs and loops should not be used for cervical cell sampling.

Fluorescence in situ hybridization in cervical smears: detection of numerical aberrations of chromosomes 7, 3, and X and relationship to HPV infection.

BACKGROUND: Human papillomavirus (HPV) is known to play a pivotal role in cervical carcinogenesis. Chromosomal aberrations are known to be related to different biological behaviors of malignant lesions. We analyzed whether numerical chromosomal aberrations, related to more aggressive tumor types, are found not only in high-grade squamous intraepithelial lesions (HSIL) but also in low-grade SIL (LSIL) of the cervix and evaluated their relationship to HPV infection. METHODS: Eighty women (19 to 74 years of age) were included in this study and grouped according to the Bethesda System: within normal limits (WNL), LSIL, and HSIL. By FISH, chromosomes 7 and X, and in part chromosome 3, were analyzed for numerical aberrations. Using the hybrid capture system HPV detection was performed. RESULTS: All 20 patients with cervical smear WNL had regular diploid chromosomal pattern and were negative for HPV. Thirteen of the 29 (41.2%) patients with LSIL showed trisomy 7, in association with trisomy X in 4 cases (12.9%). Single trisomy X was detected in 4 cases (12.9%). In 3 of 15 (20%) cases analyzed for chromosome 3 trisomy was observed. Trisomy 3 was associated with trisomy 7 and X or with trisomy 7 alone. The hybrid capture test was performed in 16 patients of this group. Two patients were positive for HPV probe A, 9 for probe B, and 2 for A and B, and 3 patients were negative. Twenty-three of the 29 patients (79.3%) with HSIL showed trisomy 7. Twelve of the 29 patients (41.3%) had an additional trisomy X. Single trisomy X was seen in only 2 cases (6. 9%). Twenty-two patients with HSIL were tested also for chromosome 3. Nine of the 22 patients (40.9%) showed trisomy 3, associated with trisomy 7 or with trisomy 7 and X. In 25 of the 29 patients HPV detection by the hybrid capture system was performed. HPV probe B was positive in 15 cases (60%). One patient was positive for both probes, A and B. Nine (36%) of the patients with HSIL were negative for both HPV probes. No positivity was observed for HPV probe A alone. CONCLUSION: Our data confirm the pivotal role of HPV in cervical carcinogenesis as it seems to cause changes in the chromosomal pattern of premalignant lesions. Additionally, trisomy 7 may be considered an early event in cervical carcinogenesis, persisting and increasing with progression of the lesion. The roles of trisomy 3 and X need further evaluation.

When applied to facial skin, does estrogen ointment have systemic effects?

We examined cytological vaginal smears of 17 women before and after three months of dermal estrogen (1 g of 0.01% estradiol ointment or 0.3% estriol ointment once daily), applied to the face for dermatological indications. The mean age was 57.1 +/- 7.6 years (range from 46 to 66). Seven women had estrogenic smears (more than 10% superficial cells) before therapy. Nine women were treated with 0.01% estradiol ointment and 8 were treated with 0.3% estriol ointment. Both groups had gynecological examinations including cervical and vaginal smears before and after treatment and also monthly measurements of serum follicle-stimulating hormone, prolactin and estradiol levels. Serum hormone levels and the appearance of vaginal smears showed no significant change during treatment.

Cytologic diagnosis of reactive lymphadenopathy in fine needle aspiration biopsy specimens.

Reactive or benign lymphadenopathies were cytologically diagnosed in the aspirates of 62 (23.5%) of 265 cases with enlarged lymph nodes of the head, neck or inguinal region subjected to fine needle aspiration (FNA) biopsy. The cytomorphologic features characteristic of reactive lymphadenopathy are described in detail; some of the cell patterns were suggestive of a specific disease process. The similarities of cells and cell patterns that may pose differential diagnostic problems with malignant lymphomas are pointed out. This study emphasizes the role of FNA cytology in the diagnosis of some benign conditions.