Diagnostic value of microvillus-matrix associations in tumors.

Until now microvillus-matrix associations have been reported to occur only in mesotheliomas and hence this phenomenon is thought to be of value in distinguishing mesothelioma from pulmonary adenocarcinoma. We report here the occurrence of microvillus-matrix associations in two pulmonary adenocarcinomas which reduces the value of this phenomenon in the differential diagnosis of these tumors.

Pathology of the peritoneum: a review of selected topics.

Mesothelial lesions of the peritoneum may pose significant diagnostic problems. Accurate identification of these lesions is important because of their distinctive behavior and treatment requirements. This review discusses the clinical, pathological, and differential diagnosis of a variety of mesothelial lesions of the peritoneum, which includes mesothelial hyperplasia, multilocular peritoneal inclusion cysts (benign cystic mesothelioma), well-differentiated papillary mesotheliomas, and diffuse malignant mesothelioma, and the role of immunohistochemistry in the distinction from the more common primary peritoneal serous carcinomas. In addition, borderline serous tumors, psammocarcinomas, and solitary fibrous tumors of the peritoneum are briefly mentioned.

Diagnosis of diffuse malignant mesothelioma: experience of a US/Canadian Mesothelioma Panel.

The experience of the US/Canadian Mesothelioma Panel with its first 200 cases is reviewed. The light microscopic diagnosis, histochemical findings, immunohistochemical findings, and electron microscopic features of malignant mesotheliomas are reviewed in the context of differential diagnosis. Reasons for referral of case material to the panel and lessons from follow-up of difficult and controversial cases are reported. Recommendations to general pathologists are made regarding evaluation and review of possible mesotheliomas.

Solitary fibrous tumors ('fibrous mesotheliomas') of the peritoneum. A report of three cases and a review of the literature.

The clinical and pathologic features of three new and seven previously described solitary fibrous tumors of the peritoneum are reviewed. The male-female ratio has been 7:3, and the patients have ranged from 27 to 64 (average, 54) years of age. Most of the tumors have been large (over 9 cm) and have been responsible for significant symptomatology. Microscopic examination has typically shown mildly to moderately cellular fibrous tumors with prominent hyalinization, although occasional tumors have exhibited focal marked cellularity. Cytologic atypicality and mitotic figures have been rare or absent. Immunohistochemical stains have shown positivity only for vimentin. There has been no evidence of recurrence in any of the cases. The clinical, gross, histologic, and immunohistochemical features of these tumors are identical to those of fibrous tumors of the pleura, and a similar origin from submesothelial mesenchyme is likely.

Well-differentiated papillary mesothelioma of the peritoneum. A clinicopathologic study of 22 cases.

Twenty-two cases of well-differentiated papillary mesothelioma of the peritoneum (WDPMP) are described. Eighteen of the 22 patients were women. The peritoneal tumor was usually multifocal. Many of the tumors appear to be indolent or inactive and for practical purposes are benign. However, a few patients receiving adjuvant therapy have died under circumstances that make it difficult to determine whether the tumor was responsible for the death. It is suggested that adjuvant therapy be withheld from patients with WDPMP, unless there is clear evidence of progression. The cause of these rare tumors is not apparent, although three patients had had possible exposure to asbestos and two were sisters.

Mesothelioma and asbestos fiber type. Evidence from lung tissue analyses.

Lung tissue samples from 78 cases from autopsy of mesothelioma in Canada, 1980 through 1984, and from matched referents were examined by optical and analytical transmission electron microscopic study. Concentrations of amosite, crocidolite, and tremolite fibers, and of typical asbestos bodies discriminated sharply between cases and referents. The distributions of chrysotile and anthophyllite/talc fibers and of all other natural and man-made inorganic fibers (greater than or equal to 8 microns) in the two series were quite similar. Relative risk was related to the concentration of long (greater than or equal to 8 microns) amphibole fibers with no additional information provided by shorter fibers. The proportion of long fibers was much higher for amphiboles than chrysotile and, except for chrysotile, systematically higher in cases than referents. Amphibole asbestos fibers could explain most mesothelioma cases in Canada and other inorganic fibers, including chrysotile, very few. Fibrous tremolite, contaminant of many industrial minerals including chrysotile, probably explained most cases in the Quebec mining region and perhaps 20% elsewhere.

Frequency of alpha-fetoprotein production by Sertoli-Leydig cell tumors of the ovary: an immunohistochemical study of eight cases.

Eight Sertoli-Leydig cell tumors (SLCT) of the ovary were studied by immunostaining for alpha-fetoprotein (AFP). Immunostaining was positive only in cells resembling Leydig cells in three cases and in both Sertoli and Leydig cells in one instance. In one SLCT with positive immunostaining, serum AFP was available and was elevated. Serum level was not measured in the seven other cases. Despite the small number of cases, this study suggests that AFP expression in ovarian SLCT is not unusual. The serum AFP level may, however, depend on the size of the tumor, the proportion of Leydig cells present, and their ability to produce and to release AFP into the bloodstream.

Observer variation in the pathologic diagnosis of malignant lymphoma in Canada.

Biopsies from "poor prognosis" non-Hodgkin's lymphomas were studied to assess diagnostic variations among pathologists. The original diagnosis and the diagnoses of a nationwide panel of local reference pathologists (LRPs) from 104 cases were reviewed and the technical quality of each biopsy evaluated. Using a modified Rappaport classification, there was agreement in 57% of cases among the panel. This increased to 84% when diagnoses were grouped according to Working Formulation grades. Of the 90 cases in which a comparison of the contributing pathologist's diagnosis and the most common panel diagnosis was possible, there was exact agreement in 51% (kappa = 0.311) of cases and agreement regarding WF grade in 68% (kappa = 0.318). Major panel disagreements occurred in 26 (25%) cases, involving the distinction of metastatic anaplastic carcinoma or Hodgkin's disease from non-Hodgkin's lymphoma in 17 cases and follicular versus diffuse architecture in 16 (overlap present). The contributing pathologist had a major disagreement with the panel in 18 cases (20%), of type and frequency similar to those within the panel itself. Poor fixation (complete or partial) was present in 49 cases (47%); this resulted in significantly fewer majority agreements than in the well-fixed group (25% versus 60%, P = 0.020) and also increased rates of disagreement in the diagnosis of lymphoma versus anaplastic carcinoma. Thus improvements in the technical quality of biopsy material could further improve the diagnostic accuracy of lymphoma diagnosis.

Clear-cell epithelial neoplasms of the large intestine.

We report four cases of primary clear-cell adenoma and adenocarcinoma of the large intestine. The neoplasms grossly resembled ordinary colonic adenomas and adenocarcinomas but microscopically were composed of uniform cells with optically clear cytoplasm. Mucin stains were negative, and the clear nature of the cytoplasm was due to glycogen accumulation. Areas of transition between normal colonic epithelial constituents and the clear-cell lesion were observed. Three of the four cases stained strongly positively for carcinoembryonic antigen. These lesions are apt to give rise to considerable diagnostic confusion and, in particular, resemble metastatic renal cell carcinoma. The usual strong positive carcinoembryonic antigen reaction is helpful in establishing this diagnosis.

Diffuse epithelial mesothelioma: a review of the ultrastructural spectrum.

Traditionally, diffuse epithelial mesotheliomas are mainly identified at the ultrastructural level by the numerous, long, wavy-appearing surface microvilli. By electron microscopy of a series of diffuse mesotheliomas of varying subtype (epithelial, biphasic, sarcomatous, and poorly differentiated), it can be demonstrated that the differentiation of this specialized surface organelle is quite variable even in well-differentiated lesions. The presence of only a few, scattered, short microvilli does not exclude a diagnosis of epithelial mesothelioma, particularly if historical, surgical, and radiologic findings support this diagnostic conclusion. Indeed, even the complete absence of surface microvilli is compatible with a diagnosis of diffuse epithelial mesothelioma. It is important to become aware of the spectrum of tumor cell differentiation in serosal tumors, as all of the fine structural diagnostic criteria in mesotheliomas are expressed to varying degrees in individual cases.

Unusual thymic seminomas.

Although most thymic seminomas have a histologic appearance similar to those arising in the testis, some seminomas undergo pronounced secondary changes that may obscure the diagnosis. We found three cases that showed a combination of reactive follicular hyperplasia (three cases), large cysts (three cases), epithelioid granulomas (two cases), and fibrosis (two cases), to such a degree that the seminoma component was indistinct. Immunoperoxidase staining for keratin in one case highlighted the intimate association of the positively staining thymic epithelial cells with the nonstaining seminoma cells. The seminoma cells in this case were reactive with placental alkaline phosphatase. No other group of thymic or mediastinal tumors, including those of Hodgkin's disease, exhibited this combination of secondary reactive changes to a similar degree. Because of the favorable prognosis of thymic seminomas, these variants should not be confused with other mediastinal tumors.

Extraovarian pelvic serous tumor with marked calcification.

We report two cases of low-grade extraovarian pelvic serous tumor. Each contained large numbers of psammoma bodies. The tumors belong to the small group of serous carcinomas that arise from the peritoneum. In both cases the tumor permeated the myometrial lymphatic vessels extensively. One patient is well eight years after surgery.

Aggressive angiomyxoma of pelvic soft parts: a clinicopathologic study of nine cases.

Nine cases of aggressive angiomyxoma (AAM) of the pelvic soft parts were studied by light and electron microscopy and immunohistochemistry. The tumors were confined to the vulva, vagina, pelvic floor, and perineum in the seven women. The perineum and the para-anal region were involved in the two men. The patients ranged in age from 18 to 63 years. Aggressive angiomyxoma presented as a slowly growing, polypoid or cyst-like tumor. Six of the nine cases were followed up; all of the tumors recurred within nine to 84 months, and one recurred for the second time at 144 months. Recurrences were attributed to incomplete tumor excision. None of the six patients died or had metastases. The aggressive angiomyxomas had infiltrative borders and rubbery, white or soft, gelatinous cut surfaces. Histologically, the lesions were composed of stellate and spindle-shaped neoplastic cells embedded in a collagenous and hyaluronic acid-containing stroma. Nuclear atypia and mitoses were absent. Typically, the lesions had an important vascular component, often displaying medial hypertrophy and vascular grouping. Ultrastructurally, the neoplastic cells resembled fibroblasts rather than myofibroblasts. They showed strong immunoreactivity for actin but were negative for S-100 protein, Factor VIII, carcinoembryonic antigen, and keratin. The morphoimmunocytochemical characteristics of AAM cells favor a fibroblastic origin and differentiation. Aggressive angiomyxoma should be distinguished from the more common benign and malignant myxoid neoplasms or tumor-like conditions of the pelvic soft parts. Recurrence of AAM may be avoided by wide, local excision.

Analysis of hyaluronic acid in the diagnosis of malignant mesothelioma.

Using a modified papain digestion cetylpyridinium salt precipitation method, glycosaminoglycans were isolated from 21 mesotheliomas, 34 primary lung carcinomas, 12 carcinomas of other sites, and 7 soft tissue sarcomas. Qualitatively, hyaluronic acid (HA) was present in 20 of 21 mesotheliomas, about half of the primary lung adenocarcinomas, and all of the soft tissue sarcomas. On the average, HA constituted 45% of the total glycosaminoglycans in the mesotheliomas and 28% of the total in the lung cancers. Quantitatively, mesotheliomas contained statistically greater amounts (mean value, 0.74 mg/g) of HA than primary lung adenocarcinomas (mean value, 0.08 mg/g), but were not statistically different from soft tissue sarcomas (mean value, 2.01 mg/g) or primary ovarian serous neoplasms (mean value, 0.92 mg/g). The study concludes that, contrary to previous reports, HA is neither the sole nor the predominant glycosaminoglycan in most mesotheliomas, but, given the proper clinical and histologic setting, the finding of sufficiently high levels (greater than 0.4 mg/g dry tissue extract) supports the diagnosis of mesothelioma when the alternative diagnosis is primary adenocarcinoma of lung.