Uterine tumor resembling ovarian sex-cord tumor--a case report and review of the literature.

A uterine tumor resembling an ovarian sex-cord tumor (UTROSCT) is a very rare lesion with only 38 cases reported in the literature so far. Here, we show an additional case of a pure UTROSCT with a DNA stemline at 1c in a 49-year-old woman presenting with abnormal vaginal bleeding. Problems in differential diagnosis arise mainly due to the variable histological picture of UTROSCT. Immunohistochemically, these tumors express cytokeratin, epithelial membrane antigen, vimentin, and smooth muscle actin. Moreover, in some cases, CD99 and alpha-inhibin are detectable. Although 36% of UTROSCT have infiltrative margins, almost all of them behave benignly. It is thus questionable whether the same prognostic criteria apply for these tumors as for endometrial stromal sarcomas. However, in the so-called mixed UTROSCT, the endometrial stromal sarcoma component determines the outcome.

[Treatment of 9 squamous epithelial carcinoma in situ lesions of the conjunctiva (CIN) with mitomycin C eyedrops in cytological and DNA image cytometric control]. / Behandlung von 9 plattenepithelialen Carcinomata in situ der Bindehaut (CIN) mit Mitomycin-C-Augentropfen unter zytologischer und DNA-bildzytometrischer Kontrolle.

BACKGROUND: Conjunctival intraepithelial neoplasia (CIN) is a frequent conjunctival tumor. Following excision alone recurrences are frequent. An effective postsurgical recurrence prevention is therefore highly desirable. In this study we aimed to evaluate the effectivity of postsurgical chemotherapy of conjunctival squamous cell carcinoma in situ (CIN) with mitomycin C eyedrops. We introduced the otherwise established diagnostic tools of cytology and DNA-image-cytometry to the diagnosis and therapy-monitoring of CIN. PATIENTS AND METHODS: We treated 9 patients with CIN. For diagnosis the results of cytology and cytometry of presurgically obtained brush smears were compared with the histologic evaluation of the excised tissue. After surgery, we administered topical chemotherapy with mitomycin C eye drops 0.02% (MMC). Conjunctival brush smears were again evaluated by cytology and DNA-image-cytometry for postsurgical therapy monitoring. RESULTS: The clinical diagnosis of CIN was fully confirmed by cytology, DNA-image-cytometry and histology respectively in 7 patients. In one patient, the results of the applied diagnostic methods differed in results: Histologic evaluation indicated a moderate dysplasia but DNA-image-cytometry showed significant DNA-aneuploidy unequivocally indicating neoplasia like squamous cell carcinoma. In another patient the preoperatively obtained conjunctival brush smears could not properly analyzed by cytometry but clinical diagnosis was confirmed by histology. MMC-therapy was well tolerated except for a self-limited conjunctivitis. A complete remission of CIN was obtained in 8 of 9 patients (89%) who were free of CIN recurrences during a follow-up period of 27.2 months (11-48). Only one patient suffered from a recurrence 14 months after surgery and after 2 MMC-cycles. CONCLUSION: Adjuvant topical mitomycin C appears to be effective in the prevention of recurrences of conjunctival CIN after surgical removal. Our results indicate that at least 4 cycles of topical MMC are required to prevent local recurrences in the long term. Cytology and DNA-image cytometry are highly sensitive and specific methods for diagnosis and therapy monitoring of conjunctival squamous cell carcinoma in situ (CIN).

Telomerase activity in cervical smears.

It is well known that almost all carcinoma cells including those of the uterine cervix have re-established their telomerase activity. However, until now there is no conclusive picture on the telomerase activity in cervical dysplasias and about their relationship to HPV infection. To investigate this question, material from 34 patients (15 with normal epithelium, 11 with LGSIL, 8 with HGSIL) obtained by conventional cervical brushing was used and subjected to non-radioactive TRAP-ELISA (Boehringer Mannheim). The HPV analysis was performed by PCR on formalin-fixed, paraffin-embedded biopsy material obtained after cytological investigation. We could show that telomerase activity is detectable in normal cervical epithelium, and that an gradual increase exists for both telomerase activity and HPV positivity from normal epithelium to HGSIL. However, HPV infection and telomerase activity appear to be independent of each other. The high frequency of telomerase positivity in patients with normal cervical epithelium indicates that telomerase activity is not a useful differential diagnostic aid. Whether patients with telomerase-positive dysplasias have a higher probability to progress into an invasive carcinoma remains to be clarified by follow-up studies.

[Clinical behavior of serous and mucinous borderline tumors of the ovary with diploid DNA stem line. Follow-up studies after organ preserving and non-organ preserving therapy]. / Zum klinischen Verhalten von serösen und muzinösen Borderline-Tumoren des Ovars mit diploider DNA-Stammlinie. Verlaufsbeobachtungen nach organerhaltender und nicht-organerhaltender Therapie.

Even today, the situation is still unclear with regard to the radicality of the operation and any adjuvant therapy required in treatment of borderline tumors of the ovary. In the last two decades, treatment of these tumors in the Department of Gynecology and Obstetrics at our hospital has depended on the stage of the disease and the age of the patient. It ranged from laparoscopic cyst extirpation to hysterectomy with bilateral adnectomy and omental resection and regional lymphnodectomy. From the end of 1985 to the end of 1992, 35 patients with borderline tumors of the ovaries were operated on. Histologically, 14 borderline tumors were mucinous, 21 were serous. A follow-up investigation was carried out five to 11 years after primary operation. In this period, no patient died of borderline tumor. Twenty-eight patients who were followed up were clinically free of recurrence, five patients are alive, but could not be followed up. Two patients have died of other diseases after five years. Only one patient received adjuvant chemotherapy. She could not be followed up. In the meantime, peritoneal implants were demonstrated at second-look laparoscopies in four out of 18 patients. Later, these could no longer be demonstrated (one patient) or did not affect the survival time (three patients) and thus ultimately was not pathologically relevant. Primarily, two of these four patient had stage Ia-Ic. The paraffin blocks of the preparations are still available from 26 patients, and additional investigations could be carried out. Nineteen percent of the borderline tumors showed micropapillary structures of an MPCS (= micropapillary serous carcinoma), which evidently did not have a negative effect on the prognosis. All borderline tumors showed diploid distributions in DNA cytometry. It is not possible to make a definitive treatment recommendation on the basis of this investigation because the number of patients followed up was too small.

Cytologic and DNA cytometric diagnosis and therapy monitoring of squamous cell carcinoma in situ and malignant melanoma of the cornea and conjunctiva.

OBJECTIVE: To investigate the diagnostic accuracy of exfoliative cytology of the cornea and conjunctiva and DNA image cytometry for quality control and monitoring of therapy for malignant neoplasms. STUDY DESIGN: Conjunctival or corneal smears from six cases clinically suspicious for malignant melanomas and eight suspicious for carcinomas in situ were investigated. Smears from 18 cases clinically nonsuspicious for neoplastic diseases served as negative controls. Repeated smears were obtained during and after local mitomycin C (MMC) therapy. RESULTS: In none of 18 nonsuspicious cases, cytology revealed abnormal cells. DNA cytometry showed nonaneuploidy in all of these. All smears from patients with histologically proven malignant melanomas (MM) and squamous cell carcinomas in situ revealed abnormal cells. Image cytometry demonstrated DNA aneuploidy in 66.6% of patients with MM and 80% with carcinoma. Sensitivity of cytology thus was 100% for both MM and carcinoma; specificity also was 100%. DNA measurements after MMC therapy revealed euploid polyploidization of nonneoplastic squamous cells. DNA cytometry provided an objective identification of tumor cell regression. CONCLUSION: Cytologic examination of corneal and conjunctival smears is a noninvasive tool with high diagnostic accuracy for detection of epithelial neoplasms. DNA image cytometry can serve for quality control and for objective monitoring of the effect of local chemotherapy.

Diagnostic accuracy of effusion cytology.

The aim of this investigation was to report on the diagnostic accuracy of conventional effusion cytology. Cytological diagnoses of 300 pleural effusions and 300 ascites were compared with clinical and/or histological follow-ups of the respective patients. Sensitivity of our cytological diagnoses on pleural effusions was 50.0%, specificity 97.0%, positive predictive value 95.7%, and negative predictive value 86.4%. Sensitivity in ascitic effusions was 62.4%, specificity 98.0%, positive predictive value 100.0%, and negative predictive value 88.3%; 5.8% of diagnoses for pleural and 4.4% for peritoneal effusions were suspicious or doubtful. The overall false-positive rate was 0.5%, while the false-negative rate was 31.5%. False-negative results were due to sampling errors in 71% of pleural and 73% of peritoneal effusions and to screening errors in 29% and 27%, respectively. Our data and those from the literature show that diagnostic accuracy of effusion cytology is still unsatisfactory and should be improved. Therefore, the use of different adjuvant methods is recommended.

DNA aneuploidy as a specific marker of neoplastic cells in FNAB of the thyroid.

OBJECTIVE: To investigate whether DNA image cytometry (ICM) could be of value in the specific identification of neoplastic cells in cytologic specimens of the thyroid. STUDY DESIGN: FNABs of thyroid from 162 patients with different benign and neoplastic diseases were investigated. Nuclear DNA content in thyroid cells was measured after Feulgen staining using a TV image analysis system. Data were correlated with clinical and histologic patient follow-up. The occurrence of abnormal DNA stemlines was used as a marker for aneuploidy and thus for neoplasia. RESULTS: None of the 89 cases without tumor cells revealed DNA aneuploidy. An abnormal DNA stemline was found in 55% of histologically proven benign thyroid tumors (follicular or oncocytic adenomas) and in 59.5% of malignant tumors. The positive predictive value of DNA aneuploidy in FNABs of the thyroid for neoplasms was 100%. The negative predictive value of DNA nonaneuploidy for the prediction of tumor-free histologic or clinical follow-up was 79.4%. CONCLUSION: DNA image cytometry may be helpful in the specific identification of neoplastic follicular cells. DNA ICM on FNABs of the thyroid is an additional tool to achieve early identification of patients with nodular lesions of the thyroid that have to be operated on. DNA euploidy excludes the presence of neither malignancy nor neoplasia.

Immunocytochemistry and DNA-image cytometry in diagnostic effusion cytology I. Prevalence of markers in tumour cell positive and negative smears.

To determine the prevalence of immunocytochemical positivities for a panel of antibodies in benign and malignant cells in effusions with known follow-up in order to use these as diagnostic markers. Besides their ability to identify malignant epithelial cells their contribution to the differential diagnosis between carcinomatoses and mesotheliomas was investigated. 101 tumour cell positive and 53 negative effusions were stained with 12 different antibodies. Results were scored semiquantitatively per cell type. Furthermore, DNA-image cytometry was performed. While prevalence of Ber-EP4 positivity was 95.4% in metastatic carcinoma cells, it was 0% in those from mesotheliomas. No cell type reacted with this marker in benign effusions (0%). Ber-EP4 correctly differentiated between metastatic carcinoma and mesothelioma in 98.0%. Prevalence of DNA-aneuploidy was 95.4% in metastatic carcinomas, 57.1% in mesotheliomas and 0% in reactive effusions. Combining immunocytochemistry (Ber-EP4 positivity) and DNA-image cytometry (aneuploidy) results in a 100% detection of metastatic carcinomatoses and 57.1% of mesotheliomas. Both markers furthermore allowed a correct differentiation of these entities in 98%.

Immunocytochemistry and DNA-image cytometry in diagnostic effusion cytology. II. Diagnostic accuracy in equivocal smears.

To determine sensitivity and specificity of different antibodies for the immunocytochemical detection of malignant cells in diagnostically equivocal effusions in comparison with those achieved by DNA-image cytometry. 65 cytologically doubtful effusions of the serous cavities were stained with twelve antibodies. Furthermore, DNA-image cytometry was performed. Data were correlated with patient follow-up. Sensitivity of cellular staining of Ber-EP4 for the identification of malignant cells was 77.8%, specificity of absent staining for benign cells was 100%. Positive predictive value for the identification of malignant cells was 100%, negative value 65.5%. Sensitivity of DNA-aneuploidy for the identification of malignancy was 82.9%, specificity of DNA-non-aneuploidy for benignity 94.7%. The positive predictive value of DNA-aneuploidy for the occurrence of malignant cells was 96.7%. Negative predictive value of DNA-non-aneuploidy was 72.0%. Combining immunocytochemistry applying Ber-EP4 only and DNA-cytometry in equivocal effusions resulted in a sensitivity of 88.9% for the identification of malignant cells associated with a 95.0% specificity. Positive predictive value was 97.7%, the negative one 79.2%.

Static DNA cytometry as a diagnostic aid in effusion cytology: I. DNA aneuploidy for identification and differentiation of primary and secondary tumors of the serous membranes.

OBJECTIVE: To determine whether DNA aneuploidy is a sensitive and specific marker for the identification of tumor cells in effusions and whether the pattern of DNA aneuploidy can provide important information for the differential diagnosis of primary and secondary tumors of the serous membranes. STUDY DESIGN: One hundred eight malignant mesotheliomas as well as 102 metastatic carcinomas of the serous membranes were obtained from routine cytologic and histologic material. One hundred reactive effusions were investigated as controls. Nuclear DNA contents were measured after Feulgen staining using a TV image analysis system. RESULTS: DNA aneuploidy was assumed if abnormal DNA stemlines, a coefficient of variation of the first DNA stemline > or = 10%, or cells > 9c were observed. On this basis the prevalence of DNA aneuploidy in mesotheliomas was 83% for cytologic and 84% for histologic material. In effusions of metastatic carcinomas it was 100%. None of the 100 reactive effusions revealed DNA aneuploidy (prevalence, 0%). Positive predictive value for mesotheliomas was 100%; negative predictive value was 88% for cytologic and 82% for histologic material. Positive predictive value for metastatic carcinomas was 100%; negative predictive value was 100%. Seventy-two percent of the mesotheliomas revealed their greatest stemline within the range 1.80c-2.20c, whereas none of the metastatic carcinomas showed this stemline position. CONCLUSION: DNA image cytometry might be a very sensitive and highly specific, additional tool for identification of neoplastic cells in effusions as well as for the differential diagnosis of mesothelioma vs. metastatic carcinoma of the serous membranes.

Static DNA cytometry as a diagnostic aid in effusion cytology: II. DNA aneuploidy for identification of neoplastic cells in equivocal effusions.

OBJECTIVE: The sensitivity of conventional cytology for identification of neoplastic cells in effusions is unsatisfactory, about 58%. The rate of diagnostically equivocal effusions in routine cytology is about 6%. DNA aneuploidy has previously been proven to be a sensitive and specific marker for the identification of tumor cells in effusions. In the present study we determined if malignancy can be identified in cytologically equivocal cells in effusions using DNA aneuploidy as a marker, thus decreasing the rate of cytologically equivocal diagnoses in effusions. STUDY DESIGN: One hundred cytologically equivocal effusions of the serous cavities were obtained from routine diagnostic material. Nuclear DNA content was measured after Feulgen staining using a TV image analysis system. Data were correlated with patient follow-up. RESULTS: DNA aneuploidy was assumed if abnormal DNA stemlines, a coefficient of variation of the first DNA stemline > or = 10% or cells > 9c were observed. The sensitivity of DNA aneuploidy for the identification of malignancy was 55.9%. Specificity of DNA nonaneuploidy for benignity was 94.1%. The positive predictive value of the marker DNA aneuploidy for the occurrence of malignant cells was 97.9% since all but one DNA aneuploid case showed malignancy in follow-up. CONCLUSION: Image cytometry applying DNA aneuploidy as a parameter is able to detect the occurrence of malignant cells in cytologically equivocal effusions in about every second case. Thus, this method is able to increase diagnostic accuracy of conventional effusion cytology by decreasing the rate of diagnostically equivocal effusions.