Fibrosarcoma of ovary. A new component in the nevoid basal-cell carcinoma syndrome.

An 8-year-old child with nevoid basal-cell carcinoma syndrome who developed abdominal pain underwent exploratory laparotomy. Both ovaries were enlarged and replaced by fibroblastic proliferations having cellular foci with high mitotic indices (greater than 4 mitoses/10 high-power fields) diagnostic of fibrosarcoma. Two years following salpingo-oophorectomy, a metastasis was excised from one adnexa. Further recurrence or distant metastasis was not evident after 6 more years of follow-up. The association of fibrosarcoma of the ovary in a patient with nevoid basal-cell carcinoma further expands the multifarious nature of this syndrome.

DNA ploidy by image cytometry and karyotype in spontaneous abortion.

We compared the DNA content (DI) by cell image analysis with the karyotype and morphological phenotype of paraffin-embedded tissues from 51 spontaneous abortions. The study included 21 cases with triploid, 19 cases with diploid, and 11 cases with aneuploid (monosomic, trisomic, or mosaic) karyotype. Measurements were performed by image analysis on the trophoblastic and stromal cells of chorionic villi using 5-microm-thick, Feulgen-stained sections. At least 200 cells were analyzed. Results were interpreted using DI ranges of 1.3 to 1.7 for triploid and 0.9 to 1.1 for a diploid profile. All 21 cases with a cytogenetically confirmed triploid karyotype had DI values within the triploid range, and all 19 cases with a diploid karyotype had DI values within the diploid range. All of the trisomies and monosomies also had a DNA mass within the diploid range. However, eight cases with a triploid karyotype also had a peak in the diploid range: one case with a diploid karyotype and one case with a trisomic karyotype each had an additional peak in the triploid range. We did not find a morphological correlation either with image analysis or with karyotype. We conclude that cell image analysis is a reliable method for detection of triploidy in spontaneous abortions. This relatively rapid method allows visual discrimination of the areas to be analyzed, avoids the problem of maternal cell contamination, and may unmask mosaic karyotypes that would go unrecognized by cytogenetic studies alone.

Binary nature and radiographic identifiability of craniosynostosis.

RATIONALE AND OBJECTIVES: Two independent gold standards and diagnoses from three-dimensional computed tomography (CT) images were used to examine the possibility that craniosynostosis is a binary abnormality that potentially may be diagnosed without error. METHODS: Surgical reports, histology of excised sutures, and three-dimensional CT images were compared for 25 children undergoing surgical management of craniosynostosis. Surgical reports identified sutures as normal or abnormal. Histology reported suture closure on a 5-point scale. Four radiologists used three-dimensional CT images to diagnose sutures on a 6-point rated response scale. RESULTS: Sutures with histology 0, 1, or 2 were normal on surgical reports, and those with histology 3 or 4 were abnormal. Most readers achieved nearly perfect sensitivity and specificity. Reader confidence was unrelated to degree of pathology. CONCLUSION: Craniosynostosis appears to be binary in our sample. Surgical reports, pathology results, and three-dimensional CT images read by experienced viewers achieved nearly perfect agreement.

Bacterial infection stimulating granulocytic sarcoma of the small bowel.

A 57-year-old white man who had abdominal pain and distension, died after a short hospitalization for increasing ascites, anorexia, and deteriorating mental status. At autopsy, the principal gross finding was a dilated, hyperemic, thickened proximal jejunum that by light microscopy consisted of a transmural infiltrate of large mononuclear cells. Intense naphthol AS-D chloroacetate esterase (NASD) positivity was observed within most of the cells, suggesting granulocytic sarcoma. However, bacterial strains and electron-microscopic examination revealed that the massive jejunal infiltrate was composed of macrophages containing numerous phagocytosed bacteria. Although occasional cells had primary and secondary granules characteristic of myeloid precursors present within their cytoplasm, most cells lacked specific granules. Attempts to reproduce this markedly enhanced NASD result experimentally in peritoneal macrophages of mice were unsuccessful. This case shows that intense NASD cytoplasmic staining may occasionally occur macrophages that have phagocytosed large numbers of bacteria.

Verruciform xanthoma of the penis.

We describe herein a patient with a verruciform xanthoma of the penis. This histologically distinctive lesion is usually confined to the oral mucosa, although two cases occurring on the vulva have recently been reported. To our knowledge, this lesion has not been previously described in other sites. Biopsy for histopathologic examination is required to aid in the identification of this unusual entity. Verruciform xanthomas have been benign, although a squamous cell carcinoma subsequently developed in one patient whose oral lesions were associated with leukoplakia.

Craniosynostosis: diagnostic imaging with three-dimensional CT presentation.

PURPOSE: To measure diagnostic performance and preference of two three-dimensional CT reconstruction modalities (voxel-gradient and surface-projection) displayed two ways (conventional and unwrapped) in craniosynostosis confirmed by surgical inspection and histologic analysis of resected sutures. METHODS: High-resolution 2-mm contiguous CT sections were obtained and three-dimensional reconstruction images generated for 25 infants and children with skull deformities before surgical treatment of craniosynostosis. Two pediatric radiologists and two neuroradiologists first ranked images by their own preferences for diagnostic use. Then they diagnosed craniosynostosis from images presented in random order and blinded. The standard of reference was inspection during surgery and histologic evaluation of excised sutures. Finally, reviewers repeated their subjective preference tests. RESULTS: The least experienced radiologist had 100% sensitivity for all imaging modalities and specificities ranging from 43% to 83%. The two most experienced radiologists performed nearly identically, with sensitivities of 96% and specificities of 100%. After performing diagnostic tasks using all image types, all radiologists preferred conventional surface projections. CONCLUSION: Experienced readers can achieve nearly perfect diagnostic performance using the latest three-dimensional CT reconstruction images, making it a contribution to the diagnostic process. Although performance is nearly identical for all modalities, readers strongly prefer conventionally presented surface-projection images.

Improving accuracy in gynecologic cytology. Results of the College of American Pathologists Interlaboratory Comparison Program in Cervicovaginal Cytology.

The College of American Pathologists Interlaboratory Comparison Program in Cervicovaginal Cytology (PAP) is a quarterly mailed glass-slide quality improvement program. This growing program started as a pilot in 1989 with 207 laboratories. In 1991, 605 laboratories participated. The diagnostic menu is modified from the Bethesda System and divides referenced slides into a negative series (normal, infectious, and reactive) and a positive series of epithelial lesions. A facsimile option facilitates immediate educational feedback. The 1989 through 1991 major discrepancy rate averaged 5%. The consensus laboratory response had higher concordance than either pathologist or cytotechnologist responses. Low-grade squamous intraepithelial lesion was the leading cause of false-negative participant response, while reactive/reparative change was the leading cause of false-positive response. Pathologist false-negative and false-positive responses from group or large case-volume practices were significantly lower than those from solo or small case-volume practices. Cytotechnologists in multiple-technologist or large-volume laboratories had significantly lower false-negative responses than solo technologists or those in low case-volume laboratories, but false-positive rates did not differ. Experienced participants had fewer major discrepancies. The Interlaboratory Comparison Program in Cervicovaginal Cytology illustrates the feasibility of a large, mailed glass-slide program, and offers laboratories a continuous method for monitoring and improving performance in gynecologic cytology.

Frozen section diagnosis and the thyroid.

The diagnostic problems arising from frozen section evaluation of thyroid lesions are complex and beclouded in controversy. Prime examples include follicular and Hurthle cell neoplasms, both of which lack standardization in classification and management. The seemingly straightforward identification of papillary carcinoma is often complicated by the frequent absence of its distinguishing features, some of which are reportedly restricted to formalin-fixed paraffin embedded material. Thyroiditides and thyroidal ectopias present unique and separate differential diagnostic considerations that at the time of frozen section may pose problems for surgeon and pathologist alike. These issues and their controversial aspects are addressed, and potential diagnostic pitfalls related to frozen section diagnosis of thyroid lesions in general are outlined. An analysis of 300 thyroid frozen sections over a 5-year period and the histologic frozen section features of 40 papillary thyroid carcinomas are also presented. The presence of optically clear nuclei was identified in frozen sections from 15 cases, and was extensive in one. Thirty-eight of 40 cases displayed optically clear nuclei within permanent sections. It is suggested that this cytologic feature is not the exclusive domain of permanent section, and when present in the frozen section may be helpful in identifying papillary carcinoma, especially when an obvious papillary component is lacking.

Quality assurance activities of the College of American Pathologists.

Since its inception, the College of American Pathologists (CAP) has played a fundamental and pivotal role in the development and execution of quality assurance programs for laboratories. Within the realm of anatomic pathology, operational programs include those in surgical pathology, immunohistochemistry and cytopathology. The emphasis of prior cytopathology programs on cervical cytology has now been expanded to include body fluids and fine needle aspiration material. CAP's role in the expansion of quality assurance programs in cytology may be enhanced in the future by intersociety cooperation with established cytology organizations and will also be influenced by and closely linked to the expansion of its quality assurance programs in surgical pathology. As for the Papanicolaou smear, it can no longer be regarded as the "Cinderella of cytology"; it is in fact the present-day cynosure in the laboratory. In recognition of this, CAP has undertaken efforts to help heighten public awareness about the value of Papanicolaou smear testing and is encouraging women to become more informed about the process involved in the examination of their smears.

DNA image analysis study of lesions of the gallbladder and biliary system.

DNA ploidy analysis of 22 lesions arising from the intrahepatic and extrahepatic biliary systems and gallbladder was performed on Feulgen-stained 5-microns sections from archival paraffin-embedded tissue on an image analyzer (CAS-200). The cases included intrahepatic cholangiocarcinoma (n = 6), extrahepatic bile duct carcinoma (n = 5), carcinoma of the gallbladder (n = 11), and appropriate controls. All malignancies were stage III and IV adenocarcinomas with the exception of 1 stage II moderately differentiated gallbladder adenocarcinoma. No correlation with ploidy and stage could be made, most likely because of the advanced stage of the tumors at the time of presentation. When DNA ploidy was compared with the grade of tumor, the 3 well-differentiated adenocarcinomas (2 cholangiocarcinomas, 1 bile duct carcinoma) were predominantly diploid; however, diploid peaks were also found in moderately differentiated adenocarcinomas of all 3 sites and in a poorly differentiated adenocarcinoma of the extrahepatic bile ducts. Finally, 15 of 22 (68%) of cases showed only aneuploid populations. Multiple populations were observed in 19 of the 22 cases; this finding may reflect intratumoral heterogeneity and correlate with the advanced stage and aggressive nature of malignancies of the gallbladder and biliary system.

Small cell carcinomas of the parotid gland. A clinicopathologic study of three cases.

Clinical, histological and ultrastructural features of three small cell carcinomas arising in the parotid gland are presented. The light microscopic appearance of two of the neoplasms suggested neuroendocrine cell derivation, confirmed by electron microscopy in both instances. The fine structure of the third neoplasm suggested intercalated duct cell differentiation. The possibility that both types of neoplasm may arise from the same primitive precursor cell is considered. The findings from this study confirm the occurrence of two different types of small cell carcinoma of salivary gland origin. A distinction between duct cell and neuroendocrine subtypes may be impossible by conventional light microscopic evaluation.

Primary splenic presentation of malignant lymphoma and related disorders. A study of 49 cases.

The diagnosis of malignant lymphoma presenting as an initial splenic manifestation may go unrecognized as such when peripheral lymph nodes are not enlarged and when results of bone marrow biopsies are negative. Tissues from 49 patients, ranging in age from 15 to 78 years, in whom the original diagnosis of malignant lymphoma and related conditions was made at splenectomy, were classified as: diffuse small lymphocytic (20), diffuse large cell (11), diffuse small cleaved (5), diffuse large cell, immunoblastic (5), follicular small cleaved cell (3), and follicular mixed small cell and large cell (2). Two additional spleens, diagnosed as acute blastic leukemia, were initially confused with malignant non-Hodgkin's lymphoma by light microscopy. One patient presented with Hodgkin's disease confined to the spleen. For the non-Hodgkin's lymphoma group, parameters of age, sex, splenic weight (range, 226-4000 g), lymph node, bone marrow, or liver involvement did not adversely influence prognosis. Abdominal lymph nodes were positive in 31 of 37 patients having splenic hilar and/or abdominal lymph nodes available for review. Of 29 patients with adequate follow-up, 7 died of disease, 5 were free of disease at 3 years, 2 were free of disease at 5 years, 2 were alive with disease at 3 years, 4 were alive with disease at 5 years, and 9 died from second malignancies, unknown, or unrelated causes. Six of the 7 patients who died of lymphoma were classified as large cell (four diffuse large cell and two diffuse large cell, immunoblastic), with a mean 2-year survival. One patient died of leukemia. Those lymphomas classified as low grade behaved in an indolent fashion. The morphologic diversity of these cases emphasizes the need for the initial recognition and correct classification of lymphomas which present in the spleen, since survival is best determined according to histologic type.

Malignant melanoma of soft parts: an ultrastructural study of four cases.

Malignant melanomas of soft parts from 4 patients were studied by light microscopy, immunocytochemistry for S-100 protein, and electron microscopy. Each patient presented with a deep soft tissue mass in an extremity. Histologically, the tumors were composed of epithelioid and spindle cells, and in one, neoplastic giant cells were present. The tumors did not stain for melanin but were all positive for S-100 protein. Ultrastructurally, premelanosomes were identified in every tumor and in a cell line established from one tumor. Schwann cell features were present in one of the tumors. Although the clinical presentation of malignant melanoma of soft parts is similar to that of epithelioid sarcoma and synovial sarcoma, the combined light microscopic, immunocytochemical, and ultrastructural features should serve to distinguish it from other soft tissue sarcomas.

DNA flow cytometry of thyroid neoplasms.

Mechanically dispersed cell suspensions from 23 thyroid lesions were studied by acridine orange flow cytometry. Eight of 14 carcinomas (three papillary, two medullary, two Hürthle cell, and one follicular) manifested abnormal DNA indices ranging from 0.6 to 2.0. Six carcinomas (four papillary and two medullary) were diploid. Four patients having papillary carcinomas with diploid DNA content were young women whose clinical course of disease was indolent. Three papillary carcinomas with abnormal DNA content were found in older men with clinically aggressive disease. One benign adenomatoid nodule displayed a small population with a low-degree hyperdiploid stemline (DNA index = 1.1) with low proliferative activity. Differentiation between clinically indolent and aggressive carcinomas may be possible by nuclear DNA determination, but further work is needed to determine the importance of proliferative activity in thyroid carcinoma.

Topical 16,16-dimethyl-prostaglandin E2. Effects on gastric morphology, hydrogen ion loss, and bicarbonate secretion.

Using a canine chambered stomach preparation, the effects of topical 16,16-dimethylprostaglandin E2 (dmPGE2) on gastric mucosal morphology, H+ loss and HCO3-secretion were assessed. Compared to control studies in which acid alone (100 mM HCl) bathed the epithelium, dmPGE2 (1 or 4 micrograms/ml), when applied to gastric mucosa in acid medium, significantly (P less than 0.01) enhanced H+ loss from the bathing solution in a dose-related fashion. These effects, however, were independent of any injury to the epithelium as confirmed by both light and electron microscopy. In other studies in which dmPGE2 was applied to gastric mucosa in neutral solution (150 mM NaCl, pH 7.0) using identical doses, a dose-related increase (P less than 0.01) in HCO3-secretion was observed. When the net HCO3-output (microEq/15 min) for each dose of dmPGE2 employed was compared with the net H+ loss (microEq/15 min) for each dose of PG used, no differences were noted. The correlation between H+ loss and HCO3-secretion was highly significant (r = 0.87; P less than 0.01). We conclude that with the doses studied, dmPGE2 is not damaging to gastric mucosa and that the apparent increase in H+ loss elicited by dmPGE2 in acid medium is due to acid neutralization secondary to HCO3-secretion.