Vimentin has been regarded as the intermediate filament characteristic of normal and neoplastic mesenchymal cells and keratins as typical of epithelial cells and the neoplasms derived from them. However, many epithelial cells in tissue culture or in effusion, as well as cells in some solid epithelial neoplasms such as renal, endometrial, ovarian, pulmonary, and thyroid adenocarcinomas, have been shown to coexpress vimentin and keratin. The recent availability of monoclonal antibodies that work reasonably well in paraffin-embedded tissue led us to carry out a comprehensive immunohistochemical study on formalin- and alcohol-fixed specimens of neoplasms in which we used monoclonal antibodies against vimentin. These results were compared with our previous study in which the same tumor tissues were investigated using antibodies against keratin. The antigenicity of vimentin was found to be preserved in all alcohol-fixed specimens and in 63% of formalin-fixed tissues. Vimentin was the sole intermediate filament present in virtually all sarcomas, meningiomas, schwannomas, and melanomas. In addition, variable percentages (10-57%) of carcinomas, neuroendocrine carcinomas, neuroblastomas, thymomas, and mesotheliomas were positive for vimentin, which, except in the neuroblastomas, was coexpressed with keratins. Among the adenocarcinomas, more than 50% of papillary carcinomas of the thyroid, as well as renal, endometrial, ovarian, and lung carcinomas, coexpressed keratins and vimentin. A distinctive paranuclear and basal localization of vimentin was observed in the cells of many of these tumors, in contrast to the predominantly apical distribution of the keratins. The authors conclude that coexpression of vimentin and keratin is more widespread than previously reported and that antibodies to vimentin, by themselves, are of limited value for the differentiation of epithelial from mesenchymal neoplasms.

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To investigate the cellular differentiation of adenoid cystic carcinomas (ACC), a comparative immuno-histochemical study of 12 normal salivary glands and eight specimens of ACC was performed. Antibod-ies were used against S l O O protein (S), keratins (K) of various molecular weights, vimentin (V), muscle-specific actin (A,), epithelial-membrane antigen, human milk fat globules, and collagen type IV. A panel of four of these antibodies (SKVA) was identified as the most helpful in characterizing cells in normal salivary glands and ACC. The immunophenotypes depended on the histologic patterns of ACC. Cells in morphologically recognizable duct structures in the cribriform and trabecular areas expressed a phenotype similar to that of the intercalated duct. Cell layers around pseudocysts and occasional cellular islands had an immunophenotype suggesting myoepithelial-cell differentiation. The most clear cut epithelial/myoepithelia.l bilaminar differentiation was present in areas with a trabecular pattern, in which the layers facing the stroma and the central ductal elements had SKVA phenotypes of myoepithe-lial and ductal differentiation, respectively. In areas with a reticular pattern, most of the cells showed ductal differentiation. Many of the cells in the cribriform and basaloid regions were immunophenotypi-cally undifferentiated. These results indicate that ACC consists of undifferentiated cells and of cells that are differentiating toward ducts, predominantly intercalated ducts, and toward myoepithelium. These findings support previous observations by electron microscope. Cancer 60:1589-1598, 1987. DENOID CYSTIC CARCINOMA (ACC) is a distinct A type of relatively low-grade adenocarcinoma most commonly involving minor salivary glands and, less frequently, other sites such as the parotid glands, breasts, skin, uterine cervix, esophagus, lungs, and prostate.' U1-trastructural studies of ACC of the salivary gland'-4 and have indicated that ACC is composed of undif-ferentiated cells and of cells with myoepithelial and ductal differentiation. Immunohistochemical investigations of ACC have been rather limited, and only SlOO protein was employed as a marker for myoepithelial-cell differentiation in most previous The results of these studies are somewhat contradictory, since some investigators reported no, or virtually no, myoepithelial I whereas otheirs'0.'2 demonstrated that From the Sylvia

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Histiocytosis X (HX) is characterized morphologically by a proliferation of Langerhans' cells (LC), and most often has an indolent, chronic course. To determine whether a distinct clinicopathologic entity of malignant histiocytosis X exists, the authors examined tissues from 31 patients with HX and divided them into four categories. Group A (19 patients) was characterized morphologically by benign‐appearing LC and had an indolent course. The male:female (M:F) ratio was 10:9, and the mean age was 21 years (range, 2 months to 60 years). The immunophenotype of this group was S‐100+, vimentin+, LN‐2+, LN‐3+, lysozyme−, LCA−, Leu‐M1−. Group B (three patients) had benign‐appearing LC, yet had an aggressive clinical course. All patients were male, with a mean age of 47 years (range, 3 years to 72 years). Organs involved included the liver, spleen, heart, thymus, lung, kidney, and pancreas. The immunophenotype was the same as for Group A. Group C (two patients) had atypical and malignant appearing LC, yet a relatively benign clinical course. The ages were four and 65 years, with one female and one male patient. In both patients, the cells were S‐100+, vimentin+, LN‐2+, LN‐3+, and LCA−. Group D (seven patients) was characterized by atypical and malignant‐appearing LC and an aggressive clinical course. The mean age was 25 years (range, congenital to 54 years) with one female and six male patients. Organs involved were the thymus, lungs, spleen, liver, kidney, brain, heart, pancreas, stomach, and muscle. Birbeck granules were found in two patients, and the one patient on which fresh tissue was available was CD1+. The typical immunophenotype was S‐100+, vimentin+, LN‐2+, LN‐3+, Leu‐M1−, lysozyme—. The results of our study indicate that (1) a distinct clinical entity of malignant HX, characterized morphologically by malignant‐appearing LC and clinically by male predominance, atypical organ involvement, and an aggressive clinical course, does exist; and (2) the morphologic appearance of the LC is an imperfect predictor of the clinical severity of HX.

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This prospective study was designed to investigate whether patients with short activated partial thromboplastin times (aPTTs) have increased thrombin generation and are at increased risk for thromboembolism. During a 4-month period, routine coagulation specimens were screened for the presence of a short or normal aPTT, and, accordingly, 250 specimens were collected. Prothrombin fragment F1 + 2 (F1 + 2) was measured to evaluate thrombin activation, and a second aPTT was performed with a different reagent. Diagnoses were obtained from medical records after conclusion of sample collection. Five to 9 months later, patients were questioned on thromboembolic events during the previous 18 months by questionnaire and telephone interview. F1 + 2 and the incidence of venous thromboses were elevated significantly in the short aPTT group. Unexpectedly, patients with acute bleeding had short aPTTs, but 36% of these also had thromboembolic events during the 18 months proximal to blood collection. These findings were confirmed with the second aPTT reagent. Patients with short aPTTs have increased thrombin generation and are at increased risk for thromboembolism, mainly venous thromboses, despite the fact that a short aPTT can occur in the acute setting of bleeding.

Precursor B-lymphoblastic lymphoma (B-LBL) may present as a solitary bone tumor. Fewer than 10 cases with a proven precursor B-cell phenotype have been reported in the English literature. In this report, we describe four cases of B-lymphoblastic lymphoma presenting as a localized intraosseous mass, which clinically and histologically mimicked Ewing's sarcoma. Three tumors occurred in the tibia and one in the humerus. In all four cases, the initial diagnosis was either "Ewing's sarcoma" or "consistent with Ewing's sarcoma." All four patients were female. Three were children and one was an adult; mean age was 12.5 years (range, 4 to 31 years). All had extremity pain without significant constitutional symptoms. In three cases, the tumors were osteolytic on radiographic evaluation, and in one case, osteosclerotic. Immunohistochemical stains on paraffin-embedded tissue showed that the neoplastic cells expressed terminal deoxynucleotidyl transferase, CD43, vimentin, and CD99 (MIC2 gene product) in all cases. Three cases were negative for CD45. CD79a was positive in all four cases studied; however, CD20 (L26) was positive in only two of four cases. CD3 was negative in all cases. Two cases showed focal granular cytoplasmic staining for keratin. Two cases analyzed by polymerase chain reaction (PCR) revealed clonal rearrangement of the immunoglobulin heavy chain (IgH) gene. Follow-up revealed that the three pediatric patients, who received a high-dose multiagent chemotherapy regime for LBL, are disease free at follow-up intervals of more than 1, 11, and 12 years, respectively. The adult patient died two years after diagnosis with disseminated disease. Although rare, B-lymphoblastic lymphoma should be considered in the differential diagnosis of small round cell tumors of bone. A diagnosis of Ewing's sarcoma should be made only after complete immunophenotyping and, if necessary, molecular diagnostic tests to exclude lymphoblastic lymphoma. A limited panel of antibodies can lead to an erroneous diagnosis; B-lymphoblastic lymphoma may be negative for CD45 and CD20 but positive for CD99 and even for keratin, mimicking Ewing's sarcoma. Correct diagnosis is extremely important because LBL usually is curable in the pediatric age group with appropriate therapy.