Granular cell tumors: a new clinically important histologic finding.

OBJECTIVE: The objective of this study was to review clinical characteristics, histological findings, and surgical treatment of patients with granular cell tumors of the vulva at Hartford Hospital and examine histologic characteristics associated with those cases that recurred. MATERIALS AND METHODS: A retrospective case review of 13 patients diagnosed with granular cell tumors of the vulva at Hartford Hospital from April 1982 through May 1998 was undertaken to compare age, size and location of the lesion, histopathologic features, presenting symptoms, progression of disease, and treatment. RESULTS: Tumor growth patterns were divided into those with confluent expansile growth (nodular) and those that infiltrated the dermis and soft tissue in a haphazard fashion interdigitating with native connective tissue and skin appendages (infiltrative). The advancing edge of the tumors was assessed as having either a "pushing" or an infiltrative border. The advancing edge of the tumor was noted to be irregular and infiltrative in 8 of the 13 cases. The tumor edge in the remaining 5 was pushing and well demarcated. Five of the eight tumors with an infiltrative edge recurred despite the fact that 3 of the 5 cases had negative surgical margins at resection. None of the 5 cases with "pushing" borders developed recurrence. CONCLUSIONS: Although rare, vulvar tumors are the most common variety of granular cell tumors encountered in the female genital tract. Histologic evaluation seems to indicate that patients are more likely to have a recurrence if an infiltrative growth pattern is present at the advancing edge of the granular cell tumor even with negative margins at resection. An appropriate management strategy may be to recommend reexcision of "infiltrative border" lesions rather than clinical observation alone.

Cytology of thymomas: emphasis on morphology and correlation with histologic subtypes.

BACKGROUND: Aspirates of thymomas are distinguishable from other lesions and fine-needle aspiration (FNA) is a proven method for investigating mediastinal masses. METHODS: Thirty-four cytology specimens of thymomas from 31 patients were examined. Corresponding surgical materials were available in 32 cases. Ten cases were benign and 22 were malignant. Cytologic features of these thymomas were correlated with various histologic classification systems and with biologic behavior. Dual epithelial and lymphoid populations and irregular cohesive tissue fragments of varying proportions of lymphoid and epithelial cells were characteristic of all aspirates. RESULTS: Using the Lattes-Bernatz classification, 10 cases predominately were lymphocytic, 3 cases predominately were epithelial, 3 cases predominately were spindle, 15 cases predominately were mixed, and 1 case was a thymic carcinoma. In the Muller-Hermelink classification, 3 cases were medullary, 12 were mixed, 8 predominately were cortical, 2 were cortical, 6 were well differentiated thymic carcinoma, and 1 was a poorly differentiated thymic carcinoma. In the majority of the cases the epithelial cells were round to oval. Spindle cells and a mixture of round to oval and spindle cells also were observed. No cytologic feature was found to correlate significantly with any classification scheme. Necrosis was present in 5 of the 32 aspirates, most frequently in malignant tumors. Thymomas showing predominately spindle cells frequently were encapsulated. Tumors with predominantly round to oval cells or a mixed population behaved more aggressively than those with spindle cells. Tumors that were well encapsulated and benign clinically tended to possess benign-appearing nuclei. Among the 22 invasive or malignant lesions, 8 exhibited moderate to marked cytologic atypia and 14 showed little or no atypia. No atypia was observed in benign tumors. CONCLUSIONS: The presence of cytologic atypia of epithelial cells may be helpful in predicting aggressiveness. However, the absence of atypia and necrosis may not imply a benign course. Correlation with clinical and radiographic findings should be sought.

Rapid detection of HSV from cytologic specimens collected into ThinPrep fixative.

OBJECTIVE: Herpes simplex virus (HSV) infection is associated with substantial morbidity and mortality in neonates. A diagnosis of HSV on cervical cytologic studies could lead to a cesarean section, with an increase in the risk of maternal morbidity. The identification of viral lesions in sexually active women has medical and social implications. There have been reports of false positive diagnoses of HSV in patients with altered endocervical cells and with cervical intraepithelial neoplasia 3. We evaluated a polymerase chain reaction (PCR)-based assay to detect HSV-1 and HSV-2 in routinely collected cervical cytology specimens in ThinPrep fixative (Cytyc Corp., Marlborough, Massachussets, U.S.A.). STUDY DESIGN: DNA was extracted from five cases that demonstrated cytologic changes suggestive of an HSV infection. PCR amplification with subsequent gel electrophoresis was performed to detect the presence of HSV. RESULTS: HSV DNA was detected in three of five cases that were cytologically diagnosed as suspicious or strongly suspicious for HSV infection. CONCLUSION: The combination of the ThinPrep liquid-based method for cervical cytology with PCR allows prompt confirmation of the diagnosis of HSV without sacrificing the diagnostic morphology on the slide.

Malignant mixed mesodermal tumors of the ovary.

OBJECTIVE: To review the experience at Women & Infants Hospital and Hartford Hospital of patients with malignant mixed mesodermal tumors of the ovary, and to review the pertinent literature. METHODS: Fourteen cases of malignant mixed mesodermal tumors of the ovary at the two hospitals over a 5-year period were identified through their tumor registries. Demographic data, pathology, treatment, and survival rates were reviewed. RESULTS: The median survival of the patients in our series was 7 months, with 64% dead of disease in 1 year. A review of the pertinent literature indicated median survivals of 6-12 months, with more than 70% of the patients dead of disease at 1 year, despite treatment. CONCLUSION: Further investigation is needed to determine the proper management for malignant mixed mesodermal tumors of the ovary. Meanwhile, current treatment strategies should recognize the present therapeutic limitations, so as not to diminish any further the quality of life for women with this malignancy.

Accumulation of 2,3,7,8-tetrachlorodibenzo-p-dioxin equivalents by double-crested cormorant (Phalacrocorax auritus, Pelicaniformes) chicks in the North American Great Lakes.

Concentrations of polychlorinated biphenyls (PCBs), and 2,3,7,8-tetrachlordibenzo-p-dioxin equivalents (TCDD-EQ) were determined in eggs and chicks of double-crested cormorants (DCC) which were collected in 1989 from eight locations in the Laurentian Great Lakes. The mean biomagnification factor (BMF) from forage fish to eggs was found to be 31.3. Absolute and relative concentrations as well as rates of accumulation of total concentrations of PCBs and TCDD-EQ were measurable in all of the samples. The concentrations of both PCBs and TCDD-EQs decreased immediately upon hatching of chicks, due to growth dilution. Initial decreases in absolute masses of TCDD-EQ in chicks were also observed, which indicates that there can be significant elimination of these compounds during early development. The initial rates of accumulation by chicks were dependent only on the mass of fish consumed. After the chicks began thermoregulating, the rates of accumulation, expressed as a concentration, normalized to body weight, became greater. Rates of accumulation of both PCBs and TCDD-EQ were correlated with their respective concentrations in forage fish consumed by the chicks. The relative potency, expressed as the ratio of the concentration of TCDD-EQ to that of total PCBs was calculated to determine if there was significant trophic-level enrichment of the TCDD-EQs, relative to total concentrations of PCBs. A significant enrichment was observed at the more and less contaminated locations, but the degree of enrichment was greater at the less contaminated locations (26 vs 72 micrograms/g).

Utility of gastric brushing in the diagnosis of malignant lymphoma.

The gastric brushings (GBRs) and endoscopic biopsies obtained concurrently from 27 patients in whom malignant lymphoma was diagnosed or suggested by either modality were assessed to evaluate the utility of cytologic examination in the diagnosis of gastric lymphoma. GBRs provided a definitive diagnosis of lymphoma in 2 (28%) of 7 patients with a prior history of lymphoma and 10 (56%) of 18 patients with primary gastric lymphoma, yielding an overall sensitivity of 48%. All the lymphomas diagnosed cytologically were large cell type. GBRs were suspicious for a malignant neoplasm in four lymphoma patients whose concurrent biopsies were negative. GBRs obtained from two patients who had gastritis were reported as suspicious for lymphoma. There were no false-positive diagnoses.

Embryonic abnormalities and organochlorine contamination in double-crested cormorants (Phalacrocorax auritus) and Caspian terns (Hydroprogne caspia) from the upper Great Lakes in 1988.

Persistent organochlorine contaminants including polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs) and polychlorinated biphenyls (PCBs) were determined in eggs with normal and deformed embryos collected in 1988 from different colonies during an epizootiological survey of double-crested cormorants (Phalacrocorax auritus) and Caspian terns (Hydroprogne caspia) from the upper Great Lakes. PCBs and p,p'-DDE were found in the highest concentrations in eggs of both species. The residue pattern of PCB isomers and chlordane compounds suggested that double-crested cormorants have greater metabolic capacity to degrade contaminants than Caspian terns. According to the toxicity evaluation using the 2,3,7,8-TCDD equivalents (TEQs) approach, non-ortho coplanar PCBs contributed much more toxicity than PCDDs and PCDFs. Total TEQ of dioxin-like compounds was likely associated with occurrence of live-deformed embryos in double-crested cormorants eggs. The toxic effects of these contaminants were also estimated in Caspian tern eggs, where elevated levels of coplanar PCBs, PCDDs and PCDFs were observed in concordance with increased rate of anomalies in eggs during a breeding season in the Great Lakes.

Lymphangioma of the kidney: a pathologic entity distinct from solitary multilocular cyst.

A case of primary renal lymphangioma is reported. This represents the first documented example of such a lesion confirmed by immunocytochemical and ultrastructural studies. Whereas previously regarded as synonymous terms, the recognition of lymphangioma as a pathologic entity distinct from solitary multilocular cyst of the kidney appears warranted. Although rare, lymphangioma should be considered in the differential diagnosis of multicystic lesions of the kidney.

Fine needle aspiration cytology of pulmonary carcinoid tumors.

Twenty-four cases coded as pulmonary carcinoid tumors initially sampled by fine needle aspiration (FNA) biopsy were reviewed in order to determine the cytologic features most useful in making the FNA diagnosis. The diagnosis of carcinoid tumor had been confirmed in 23 cases; the remaining case, though closely resembling a carcinoid tumor on the FNA specimen, proved to be a sclerosing hemangioma of the lung. Comparison of the original and review interpretations of the FNA specimens revealed that all typical spindle cell carcinoids and all atypical carcinoids were correctly diagnosed and classified. Of the 15 typical round cell carcinoids, the original cytologic diagnosis was lymphoma in 2 cases and benign bronchial lining cells in 2 cases. Thus, it appears that diagnostic errors are most likely in "typical" carcinoids. Review of the FNA findings suggests that the frequently stripped cytoplasm (with resulting non-cohesive bare nuclei), coupled with the almost universal plexiform vascularity (seen in 21 of 23 cases), should allow an accurate cytologic diagnosis in virtually all cases.

Small cell neuroendocrine carcinoma of the urinary bladder: report of three cases with ultrastructural analysis.

Three cases of small cell neuroendocrine carcinoma of the urinary bladder were studied by light and electron microscopic techniques. Dense-core, membrane-bound granules were identified in the cytoplasm of all 3 cases, substantiating the light microscopic impression of a morphologic similarity to other neuroendocrine carcinomas, such as small cell (oat cell) carcinoma of the lung. Two of the three cases showed clinical evidence of distant metastases, suggesting an aggressive biologic potential of this tumor similar to oat cell carcinoma of the lung. A partial remission was induced in these 2 cases using chemotherapy protocols similar to the drug regimens for small cell (oat cell) carcinomas of the lung. Recognition of this distinct entity has important clinical implications regarding therapeutic approach.

Genital condyloma virus infection following pelvic radiation therapy: report of seven cases.

Six women who underwent radiation therapy for gynecologic malignancies demonstrated cytologic evidence of condyloma virus infection 2 or more years following radiation. Histologic confirmation was obtained in two of the cases. A seventh patient developed in situ and invasive squamous cell carcinoma in a vulvar condyloma acuminatum following radiation therapy for Hodgkin's disease. This venereal infection is found most frequently in sexually active younger women (average age, 27 years). It is felt that depressed cell-mediated immunity consequent to the radiation therapy allowed the development of this infection in the older patients described in this report. The evolution of invasive squamous cell carcinoma in the condyloma acuminatum may indicate a possible oncogenic or cocarcinogenic effect of the virus. The immunologic responses to infection caused by the human papillomavirus group are discussed, as well as its potential for malignant transformation.

Primary malignant melanoma of the esophagus.

Three cases of primary malignant melanoma of the esophagus are presented with emphasis on the gross and histopathologic features. Grossly, the tumors tended to be polypoid with a smooth predominantly intact overlying mucosa. Microscopically a junctional lentiginous growth pattern was characteristic as well as a tendency to expand and fill the submucosa without invading the muscularis. A given tumor invariably was more extensive than grossly suspected and the lateral junctional spread was striking in two of the cases. Primary malignant melanoma should be included in the preoperative differential diagnosis of radiographically unusual esophageal tumors, particularly if the lesion is polypoid. Because of the potentially widespread intramucosal component, surgical treatment of esophageal melanoma required a radical procedure with a far greater margin than for the usual squamous cell carcinoma. Intracavitary radiotherapy may be a useful form of adjuvant therapy in selected patients.

Cervical condylomatous atypia and its relationship to cervical neoplasia.

Seven hundred fifty-six consecutive cervical biopsy specimens were obtained for abnormal Pap smear results or abnormality on physical examination to determine the incidence of condylomatous atypia (CLA) and its association with true dysplasia (cervical intraepithelial neoplasia; CIN). Histopathologic criteria for the diagnosis of CLA and its distinction from CIN were developed and are defined and illustrated. Clinicopathologic evaluation disclosed (1) CLA is often overdiagnosed as dysplasia; (2) cervical CLA is often associated with CLN in the same patient and may represent a potential precursor lesion; (3) CLA occurs more frequently than CIN in younger patients; and (4) the mean age of patients with pure CLA is younger than combined CLA-CIN, which is in turn younger than individuals with pure CIN. The results of this study are evaluated in light of induced squamous carcinoma and in view of the known associated of condylomata and cancer of the external genitalia in humans. The results strongly indicate a need to examine the cervical CLA-CIN association with careful epidemiopathologic studies.

Malignant mixed tumor of the lacrimal gland.

This paper reports a case of carcinoma arising in a benign mixed tumor of lacrimal gland following multiple recurrences. The patient had eight recurrences of the benign lesion and after 32 years developed an adenocarcinoma associated with recurrent nodules of still recognizable benign mixed tumor. The literature on malignant mixed tumors of the lacrimal gland is reviewed noting the confusion in diagnostic terminology in early reports. Our patient illustrates the resemblance between malignant mixed tumor (carcinoma arising in pleomorphic adenoma) of lacrimal and salivary gland both clinically and pathologically.