Molecular characterization of sarcomatous change in a granulosa cell tumor.

Sarcomatous transformation of a granulosa cell tumor (GCT) is a rare event. We describe the development of a rapidly progressive sarcomatous change in a woman who had initially presented with a classical GCT. A first recurrence occurred 23 months after the initial diagnosis when she was treated with external beam radiotherapy to her pelvis. A second recurrence 76 months following her initial surgery was consistent with a GCT. At 92 months, she presented with a further recurrence, outside of the radiotherapy field. This last recurrence had a different histologic appearance with features of sarcomatous change. Molecular analysis, using both reverse transcription-polymerase chain reaction and complementary DNA microarrays, has been used to analyze tissue obtained before and after the observed change in the tumor. The data show that GCT-specific genes, such as inhibin alpha, estrogen receptor, and follicle-stimulating hormone receptor, have been downregulated in the sarcomatous change. Significant upregulation of genes associated with an inflammatory response was also noted in the sarcoma, and this was consistent with the presence of a marked inflammatory infiltrate seen on histopathology. This study represents the novel application of microarray technology and demonstrates the unexpected finding of expression of the fibroblast activation protein gene in normal ovary. Although tumors such as this may be targets for the novel fibroblast activating protein-directed chemotherapeutic monoclonal antibody sibrotuzumab, the finding of expression in the normal ovary suggests the need for caution.

Histologic assessment of equivocal cytologic smears.

OBJECTIVE: To determine if the conversion of equivocal cytologic smears into histologic sections would provide additional diagnostic information in those cases in which it was difficult to obtain additional cytologic samples. STUDY DESIGN: Over a year, eight equivocal cytologic smears were converted to histologic sections by removing the coverslips, rehydrating the smears, scraping off the smears into centrifuge tubes, making cell blocks, and sectioning and staining the blocks. RESULTS: The histologic sections enabled cell patterns to be studied and special staining (including immunoperoxidase studies) to be performed. In the eight cases studied, the additional information provided by histology led to a definitive diagnosis in six (75%). CONCLUSION: When cytologic findings are equivocal and it is difficult to obtain additional cytologic samples, conversion of the smears into histologic sections may provide additional information for diagnosis.

Problems in the histological assessment of hydatidiform moles: a study on consensus diagnosis and ploidy status by fluorescent in situ hybridisation.

Hydropic villi in products of conception continue to pose a diagnostic problem for the anatomical pathologist. It is important to distinguish between complete hydatidiform mole (CM), partial hydatidiform mole (PM) and hydropic degeneration (HD), as hydatidiform moles (especially CM) have a tendency to develop persistent trophoblastic disease. Several studies have demonstrated interobserver variability in the diagnosis of the three conditions, but there have been no studies testing the accuracy of the consensus diagnosis of pathologists experienced in the field. In this study four anatomical pathologists with experience in diagnosing hydatidiform moles selected five cases of HD, seven cases of PM and ten cases of CM on the basis of consensus diagnosis using established criteria. Ploidy studies were done on these 22 cases using fluorescent in situ hybridisation. The 15 cases of HD and CM were diploid, confirming the histological diagnosis. However only five of the seven cases of PM were triploid, the other two being diploid. Review of these two diploid cases showed a mixture of small and large villi with moderate to marked trophoblastic proliferation. On the basis of the significant trophoblastic proliferation and the DNA information, the two cases were reclassified as early complete moles. This study demonstrates that even pathologists experienced in the field have difficulty separating PM from CM. The findings suggest that, in the absence of DNA information, a lesion with hydropic villi showing moderate to marked trophoblastic proliferation should be classified as a complete mole, even if there is a mixture of small and large villi. Ploidy studies are an important adjunct to histological diagnosis, especially when there is an overlap of features.

Aberrant FGF-2, FGF-3, FGF-4 and C-erb-B2 gene copy number in human ovarian, breast and endometrial tumours.

The important role of oncogene amplification and tumour suppressor gene deletion in human tumours is becoming increasingly apparent. However, extensive screening of human tumours is required before the prognostic significance of such genetic abnormalities can be fully appreciated. The present investigation describes a rapid non-radioactive and largely automated procedure for the analysis of aberrant gene copy number in large numbers of tissue samples of different human tumours. This procedure is based on the sequential use of the polymerase chain reaction (PCR) and high performance ion exchange liquid chromatography (HPIEX). Using this rapid PCR/HPIEX technique, we have identified amplification and deletion of the FGF-2 gene and the FGF-3, FGF-4 and c-erb-B2 oncogenes in human tumours of the breast, ovary and endometrium. Comparison of the data with tumour pathology has revealed possible associations between aberrant gene copy number and tumour type, invasiveness and metastases.

Cerebral sparganosis in an East Timorese refugee.

OBJECTIVE: To report the first case of cerebral sparganosis diagnosed in Australia. CLINICAL FEATURES: A 23-year-old East Timorese refugee, whose diet before migration included raw snakes and frogs, presented with a generalised tonic-clonic seizure and a nine-month history of episodic left hemianaesthesia. Computerised axial tomography of the brain showed a right frontal lesion, which was excised, and histological examination demonstrated changes typical of sparganosis. INTERVENTION AND OUTCOME: Excision of the lesion resulted in cure. Postoperative eosinophilia and a subcutaneous nodule presumed to be due to disseminated sparganosis resolved following a course of praziquantel. CONCLUSION: Clinicians should consider the possibility of unusual parasitic infections in refugees who present with intracranial space-occupying lesions, especially those from developing countries. A dietary history may aid the diagnosis.

Concomitant mucinous tumors of appendix and ovary. Result of a neoplastic field change?

BACKGROUND: Mucinous tumors of the appendix and ovary are known to occur together in association with pseudomyxoma peritonei. It has been postulated that this association may be attributable to the development of independent tumors or to metastasis from one site to another. METHODS AND RESULTS: This article reports two patients with concomitant mucinous ovarian and appendiceal tumors in the absence of pseudomyxoma peritonei. CONCLUSIONS: The evidence suggests that these tumors are independent primary neoplasms that develop as a result of neoplastic field change that affects colonic-type epithelium.

The prognostic significance of grading in borderline mucinous tumors of the ovary.

Fifty-three stage I borderline mucinous tumors of the ovary were placed into four histologic grades according to a simple system of grading based on degree of cell layering, nuclear characteristics, and mitotic count. Three patients died of recurrence and spread of their tumors. All three patients had grade 4 tumors, suggesting that there may be some prognostic value in grading borderline mucinous ovarian tumors.

Sarcomatous change in granulosa cell tumor.

Granulosa cell tumors have a tendency for indolent growth and late recurrence. The present case of granulosa cell tumor in a 67-year-old woman is the first, to the authors' knowledge, to be reported as showing sarcomatous transformation with a rapid fatal course. Both the granulosa cell and fibrothecomatous elements appear to have undergone sarcomatous change with some evidence to suggest rhabdomyosarcomatous differentiation. The sarcomatous component was present in metastatic deposits.