The diagnostic utility of immunohistochemistry and electron microscopy in distinguishing between peritoneal mesotheliomas and serous carcinomas: a comparative study.

The histologic distinction between peritoneal epithelioid mesotheliomas and serous carcinomas diffusely involving the peritoneum may be difficult, but it can be facilitated by the use of immunohistochemistry and electron microscopy. D2-40 and podoplanin are two recently recognized lymphatic endothelial markers that can be expressed in normal mesothelial cells and mesotheliomas. The purpose of this study is to compare the value of these new mesothelial markers with those that are commonly used for discriminating between mesotheliomas and serous carcinomas, and also to determine the current role of electron microscopy in distinguishing between these malignancies. A total of 40 peritoneal epithelioid mesotheliomas and 45 serous carcinomas of the ovary (15 primary, 30 metastatic to the peritoneum) were investigated for the expression of the following markers: D2-40, podoplanin, calretinin, keratin 5/6, thrombomodulin, MOC-31, Ber-EP4, B72.3 (TAG-72), BG-8 (Lewis(Y)), CA19-9, and leu-M1 (CD15). All 40 (100%) of the mesotheliomas reacted for calretinin, 93% for D2-40, 93% for podoplanin, 93% for keratin 5/6, 73% for thrombomodulin, 13% for Ber-EP4, 5% for MOC-31, 3% for BG-8, and none for B72.3, CA19-9, or leu-M1. All 45 (100%) serous carcinomas were positive for Ber-EP4, 98% for MOC-31, 73% for B72.3, 73% for BG-8, 67% for CA19-9, 58% for leu-M1, 31% for keratin 5/6, 31% for calretinin, 13% for D2-40, 13% for podoplanin, and 4% for thrombomodulin. After analyzing the results, it is concluded that Ber-EP4 and MOC-31 are the best negative mesothelioma markers for differentiating between epithelioid mesotheliomas and serous carcinomas. The best discriminators among the positive markers for mesotheliomas are D2-40, podoplanin, and calretinin. From a practical point of view, Ber-EP4 and MOC-31, in combination with calretinin, and/or D2-40 or podoplanin allow the differential diagnosis to be established between mesothelioma and serous carcinoma in nearly all instances. As a clear distinction could be made between these two malignancies in all of the cases in which electron microscopy was performed, this technique can be very useful in establishing the correct diagnosis when the immunohistochemical results are equivocal or further support of a diagnosis of either mesothelioma or serous carcinoma is needed.     

Macrophage colony-stimulating factor mRNA and protein in atherosclerotic lesions of rabbits and humans.

In this study, the authors demonstrate the expression of mRNA and the presence of protein for macrophage colony-stimulating factor (MCSF) in atherosclerotic lesions from humans and rabbits. In situ hybridization of serial sections of human fatty streaks demonstrated expression of MCSF mRNA by cells dispersed throughout the lesions. Immunocytochemical staining with a panel of MCSF-specific antibodies showed extensive cell-associated staining of all of the cell types in the lesions. Immunocytochemical studies of atherosclerotic lesions from Watanabe heritable hyperlipidemic (WHHL) and cholesterol-fed rabbits demonstrated a similar cell-associated pattern of staining. There was no MCSF-specific staining of aortas from normal rabbits or of cultured aortic smooth muscle cells from either humans or rabbits. Macrophage-derived foam cells (MFC) were isolated from the aortas of ballooned, cholesterol-fed rabbits. A Northern blot demonstrated that RNA isolated from the MFC hybridized with a human cDNA probe for MCSF. RNA from alveolar macrophages isolated simultaneously from the same rabbits did not hybridize with the MCSF probe. Conditioned media from an 18- to 24-hour incubation of the MFC contained colony-stimulating activity as demonstrated in a mouse bone marrow culture assay. Most of this colony-stimulating activity was neutralized by preincubating the conditioned media with an MCSF-specific antibody.     

Sarcomatoid carcinoma of the prostate. A clinicopathologic study of 12 patients.

Sarcomatoid carcinoma of the prostate is a rare tumor that can be difficult to distinguish from a true sarcoma. The authors report 12 patients in whom the typical light microscopic appearance of prostatic adenocarcinoma was accompanied by the appearance of spindled or pleomorphic sarcomatoid areas within the same specimen or in subsequent accessions. Immunostaining or electron microscopic study demonstrated epithelial differentiation within the sarcomatoid area(s) in 6 of the 11 patients in whom special studies were performed. All nine patients for whom follow-up data were available died of disease within 3 to 48 months (median time until death, 12.0 months) after the appearance of the sarcomatoid carcinoma, and the clinical course in each instance was characterized by aggressive local recurrence. Our experience confirms that sarcomatoid carcinoma of the prostate is an aggressive variant of prostatic adenocarcinoma.     

Malignant fibrous histiocytoma: an ultrastructural perspective

Malignant fibrous histiocytoma is a frequent diagnosis, but the relationship of the tumors to histologically similar soft tissue neoplasms is controversial. In this study, 157 examples representing the 4 main subtypes were reviewed by light microscopy and each tumor was studied with the electron microscope. Immunohistochemical stains were performed on 77 tumors. Electron micrographs on 100 fibrosarcomas were reviewed for comparison. Malignant fibrous histiocytomas often closely resemble fibrosarcomas at the ultrastructural level and differences between the two are generally of degree only. Evidence for true histiocytic differentiation was not found. The immunohistochemical results did not contradict the authors' impression from electron microscopy that malignant fibrous histiocytoma forms part of the histologic spectrum of tumors of fibroblasts.     

The role of gene rearrangements for antigen receptors in the diagnosis of lymphoma obtained by fine-needle aspiration. A study of 63 cases with concomitant immunophenotyping

To assess the efficacy of performing genotyping in addition to immunophenotyping as an adjunct to cytologic diagnosis, 63 consecutive patients with fine-needle aspirates of lymphoproliferative lesions who had concurrent immunophenotyping and genotyping performed on fine-needle aspirate cell suspensions were studied. Thirty-nine of 63 specimens (62%) that appeared to contain non-Hodgkin's lymphoma and that proved to be of B-cell lineage by genotyping were accurately phenotyped and shown to be monotypic for immunoglobulin light chains by cell suspension immunocytochemistry. Genotyping facilitated lineage assignment and/or confirmed clonality in 17 of 63 specimens (27%) that were difficult to determine based on morphologic data. These include cases of atypical lymphoid proliferations with polyclonal or inconclusive markers (n = 6), peripheral T-cell lymphoma (n = 3), extracutaneous mycosis fungoides (n = 1), lymphoblastic lymphoma (n = 4), null cell lymphoma (n = 1), and specimens with equivocal or technically unsatisfactory markers (n = 2). Based on these results, it is proposed that genotyping for lineage assignment and/or clonality be performed to include cases of atypical lymphoid proliferations, T-cell malignant neoplasms, lymphoid malignant neoplasms with equivocal markers, and differentiation of lymphoid from nonlymphoid neoplasms. Genotyping by antigen-receptor gene rearrangement appears to be redundant in cases with mature B-cell phenotypes that demonstrate monoclonality by immunophenotyping.     

Fine-needle aspiration cytology of metastatic neoplasms in the breast

Twenty cases of metastatic neoplasms in the breast were identified in a series of 1,034 fine-needle aspirations (FNAs) of the breast, of which 389 were malignant. Patients with breast carcinomas in whom metastasis to the contralateral breast developed were excluded from this study. This series consisted of 17 women and 3 men, ranging in age from 28 to 63 years (mean, 49 years). The tumors included oat cell carcinoma (three), melanoma (three), ovarian serous carcinoma (one), bronchogenic adenocarcinoma and squamous carcinoma (four and two, respectively), lymphoma (two), carcinoid (two), transitional cell carcinoma (one), plasma cell myeloma (one), and rhabdomyosarcoma (one). In two patients, the breast mass was the first manifestation of an extramammary cancer (two adenocarcinoma of the lung). Eleven patients died of disseminated cancer shortly after the breast metastasis was diagnosed. In most cases, the aspirates displayed the cytologic features characteristic of the primary tumors, thereby establishing the metastatic nature of the neoplasm. In four cases (two carcinoids, one myeloma, and one rhabdomyosarcoma), the cytologic features were difficult to differentiate from a primary breast carcinoma; however, the final diagnosis was established by electron microscopic examination and immunocytochemical studies on the aspirates. One case (adenocarcinoma of the lung) was misdiagnosed as primary breast carcinoma on both FNA and mastectomy specimen. Because metastatic neoplasms in the breast may mimic primary breast tumors, the authors recommend the following: (1) Evaluation of FNA of breast should be done with complete knowledge of the patient's clinical history. (2) The possibility of metastasis should be suspected in lesions with unusual cytologic patterns. (3) Ancillary studies on FNA can be helpful in interpreting selected cases.     

Determinants of plasma homocyst(e)ine in patients with nephrotic syndrome

Hyperhomocyst(e)inemia is an independent risk factor for atherothrombosis in several clinical settings in which renal function is impaired, but its prevalence in the nephrotic syndrome has not been investigated in detail, even though this syndrome provides an excellent model in which to study a possible link between albuminuria, proteinuria, and hyperhomocyst(e)inemia. We obtained plasma and urine from 27 patients with biopsy-confirmed membranous glomerulonephritis presenting nephrotic syndrome and 27 matched controls and determined the concentrations of homocyst(e)ine and proteins considered putative markers of glomerular and tubular function. Hyperhomocyst(e)inemia, defined as the mean +SD of the plasma homocyst(e)ine concentration of the controls [plasma homocyst(e)ine concentration >10.8 micromol/l] was present in 26% of the patients with nephrotic syndrome but in only 7.4% of the controls. Furthermore, the degree of hyperhomocyst(e)inemia was more severe in the nephrotic patients than in the controls. The existence of renal failure, tubular damage, and, interestingly, relatively well conserved glomerular function barrier were the main predictors of increased levels of plasma homocyst(e)ine. In conclusion, hyperhomocyst(e)inemia is a frequent cardiovascular risk factor present in patients with nephrotic syndrome and renal failure, but it is not directly associated with proteinuria.