Macroscopic, histologic, histochemical, immunohistochemical, and ultrastructural features of mesothelioma

Mesotheliomas are uncommon neoplasms that arise from the cells forming the serosal membranes of the body cavities. Approximately 90-95% of mesotheliomas arise in the pleural cavity and 5-10% in the peritoneal cavity. Rare mesotheliomas arise in the pericardium and in the tunica vaginalis. Unlike many neoplasms, mesotheliomas grow in a diffuse distribution and tend to encase the organs in the various body cavities. A combination of histochemical, immunohistochemical, and ultrastructural features are often necessary to accurately diagnose mesotheliomas. These techniques are highlighted in this review article on mesothelioma.     

Lymphohistiocytoid Mesothelioma: A Clinical,Immunohistochemical and Ultrastructural Study of Four Cases and Literature Review

Lymphohistiocytoid mesothelioma (LHM) is a term proposed to designate a variant of mesothelioma that assumes a histiocytoid morphology and contains intense lymphocytic infiltrates. Reports on this variant are few, and its clinicopathologic and ultrastructural characteristics are still to be defined. The authors have studied 4 such cases that were identified among 120 mesotheliomas in the electron microscopy (EM) files of a single institution between 1982 and 2002. Histologically, all 4 lesions were composed of diffuse proliferations of cells with a histiocytoid appearance, admixed with an intense lymphocytic infiltrate. All 4 were associated with an unequivocal sarcomatoid component. Immunohistochemical (IHC) studies showed that the majority of histiocytoid cells were positive for CD68 and vimentin in all 4 cases, suggesting fibrohistiocytic differentiation. Immunoreactivity for calretinin and AE1:AE3 was only very focally identified in 3 of 4 cases. All cases were negative for CEA (M), Leu-M1, and B72.3. The lymphocytic component in all 4 cases was almost entirely composed of CD3- and CD8-positive, small, mature T cells, with only a minor component of CD20-positive cells and occasional eosinophils. Although all cases contained numerous CD68 positive atypical cells, co-expression of CD68 and either calretinin or keratin by individual cells was difficult to demonstrate by immunohistochemistry. Ultrastructurally, 3 of the 4 cases demonstrated very focal mesothelial differentiation as evidenced by long and slender surface microvilli, including the case with negative immunoreactivity for calretinin and cytokeratin. Review of the literature yielded 6 additional LHM cases. Analysis of all 10 cases showed a male predominance (8:2) with a mean age of 58 years (31–73 years). All 10 cases involved the pleura. Three of 10 patients had known asbestos exposure. Six of 10 patients died of disease at 2–20 months after the diagnosis (mean, 6.9 months). The findings suggest that LHM is a distinct morphological variant of sarcomatoid mesothelioma for which mesothelial differentiation is difficult to document. Many of the cells composing these tumors exhibit fibrohistiocytic differentiation. The unusual morphological pattern of LHM makes a combined modality approach, including IHC, EM, and a knowledge of the clinical/radiologic findings, essential in achieving a correct diagnosis.     

卵巢粘液性肿瘤组化和免疫组化研究

对50例卵巢粘液性肿瘤进行组化和免疫组化研究。良性、交界性和恶性3组肿瘤酸性粘蛋白的含量和粘蛋白的分布范围形成鲜明对比;在甲苯胺蓝异染性方面有明显差异。这对鉴别卵巢粘液性肿瘤良、恶性有参考价值。3组肿瘤免疫组化阳性反应的程度无明显差异,腺癌分化的程度与CEA细胞阳性率不呈正相关。表明CEA染色不能判断卵巢粘液性肿瘤的恶性程度。正常卵巢组织CEA阴性,如果良性肿瘤内CEA含量较多,从生物化学上已暗示可能己越出良性范畴,但在组织学上尚未表现出来。应注意随访。     

Mucin-Positive Epithelial Mesotheliomas: A Histochemical, Immunohistochemical, and Ultrastructural Comparison with Mucin-Producing Pulmonary Adenocarcinomas

Pathologists routinely use histochemistry, immunohistochemistry, and electron microscopy to differentiate epithelial mesotheliomas from pulmonary adenocarcinomas. Epithelial mesotheliomas are usually mucicarmine-, PAS-diastase, and carcinoembryonic antigen-negative, whereas about 60-75% of pulmonary adenocarcinomas are mucicarmine- and PAS-diastase-positive, and about 90% express polyclonal carcinoembryonic antigen. During a pathologic evaluation of pleural neoplasms between 1975 and 1990, 10 epithelial mesotheliomas were identified that were mucicarmine- and in some instances PAS-diastase-positive (diagnosis of mesothelioma confirmed by ultrastructural examination), with four mesotheliomas focally expressing carcinoembryonic antigen. The mucicarmine, PAS-diastase, and carcinoembryonic antigen staining were usually eradicated or reduced in intensity by pretreatment of the tissue sections with hyaluronidase, suggesting that hyaluronic acid was responsible for the positive mucin reactions. In three cases the epithelial mesotheliomas showed focal regions of mucicarmine, PAS-d-, and Alcian blue-hyaluronidase-resistant staining. In contrast, 10 mucicarmine-, PAS-diastase-, Alcian blue-, and carcinoembryonic antigen-positive pulmonary adenocarcinomas were not affected by hyaluronidase pretreatment of the tissue. Besides the usual ultrastructural features of well- to moderately well-differentiated epithelial mesotheliomas, the mucin-positive epithelial mesotheliomas often showed medium-electron-dense secretory material covering the microvilli, aggregates of medium electron-dense material in association with the microvilli, producing an ultrastructural morphology that has been observed only in epithelial mesotheliomas.     

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.     

原发性骨肉瘤的组织学分型及免疫组化研究

报道65例骨肉瘤组织学分型和免疫组化研究的结果。组织学上区分为以下类型:骨母细胞型(11例,16.92％),软骨母细胞型(8例,12.30％),纤维母细胞型(11例,16.92％),恶纤组型(8例,12.30％),巨细胞型(5例,7.69％),小细胞型(3例,4.62％),上皮样型(2例,3.08％),毛细血管扩张型(2例,3.08％),骨内分化好型(5例,7.69％),透明细胞型(3例,4.62％),骨旁骨肉瘤(4例,6.15％),骨膜骨肉瘤(1例,1.54％),高度恶性表面骨肉瘤(2例,3.98％)。本组对恶纤组型、巨细胞型各1例进行超微结构观察,20例作免疫组化及酶组化染色。较详细地讨论了骨肉瘤的组织学分型。     

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.     

Clinical and Prognostic Features of Erionite-Induced Malignant Mesothelioma

This review analytically examines the published data for erionite-related malignant pleural mesothelioma (E-MPM) and any data to support a genetically predisposed mechanism to erionite fiber carcinogenesis. Adult patients of age ≥18 years with erionite-related pleural diseases and genetically predisposed mechanisms to erionite carcinogenesis were included, while exclusion criteria included asbestos- or tremolite-related pleural diseases. The search was limited to human studies though not limited to a specific timeframe. A total of 33 studies (31042 patients) including 22 retrospective studies, 6 prospective studies, and 5 case reports were reviewed. E-MPM developed in some subjects with high exposures to erionite, though not all. Chest CT was more reliable in detecting various pleural changes in E-MPM than chest X-ray, and pleural effusion was the most common finding in E-MPM cases, by both tests. Bronchoalveolar lavage remains a reliable and relatively less invasive technique. Chemotherapy with cisplatin and mitomycin can be administered either alone or following surgery. Erionite has been the culprit of numerous malignant mesothelioma cases in Europe and even in North America. Erionite has a higher degree of carcinogenicity with possible genetic transmission of erionite susceptibility in an autosomal dominant fashion. Therapeutic management for E-MPM remains very limited, and cure of the disease is extremely rare.     

Lymphohistiocytoid Mesothelioma: A Rare Lymphomatoid Variant of Predominantly Sarcomatoid Mesothelioma

Of 394 “definite” mesotheliomas entered in the Australian Mesothelioma Surveillance Program, three bore a striking resemblance to malignant lymphoma by conventional light microscopy, and each was misinterpreted at some stage as lymphoma. The lymphomalike morphology was a combined result of intense lymphoplasmacytic infiltration and the histiocytoid appearances of the underlying neo-plastic cell population. Immunocytochemical analysis demonstrated cytokeratins coexpressed with vimentin within the tumor cells, whereas immuno-reactivity for leukocyte common antigen was confined to the smaller lymphoid cells. Electron microscopy of two cases revealed a polymorphous population of fibrohistiocytic cells resembling those typical of malignant fibrous histiocytoma, admixed with lymphocytes and plasma cells, but sporadic cells expressed mesothelial properties in the form of sinuous villiform processes, intracytoplasmic neolumina lined by microvilli, and intermediate filaments that were aggregated into tonofilament bundles in some cells. The ultrastructural appearances, the localization of the tumors to the pleura, with effusion, and absence of anterior mediastinal mass lesions facilitated exclusion of lymphocyte-rich thymoma. In addition, a history of prior occupational exposure to asbestos was elicited in each instance. There was no apparent response to radiotherapy or chemotherapy, and the patients died at 4, 5, and 8 months after presentation. Our observations suggest that immunocytochemical or ultrastructural evaluation is mandatory for accurate diagnosis of all pleura-based lymphomatoid lesions with a mixed large and small cell pattern.     

Pulmonary Blastomas of Childhood: Histologic,Immunohistochemical, Ultrastructural Aspects and Therapeutic Considerations

Pulmonary blastomas are rare neoplasms typically occurring in patients of pediatric age, clinically characterized by fever, respiratory distress, and radiologic findings of a pulmonary cystic and/or solid mass with partial or complete obliteration of emithorax. Their behavior is aggressive and outcome is poor due to frequent relapses and metastases. The histological, immunohistochemical, and ultrastructural aspects of a personal series of 6 cases of pulmonary blastoma are described and the differences between childhood and adult types are stressed. Due to the aggressiveness of these rare tumors, therapeutic management is quite difficult. The expression of the transmembrane tyrosin kinase receptor c-kit in all the solid cases of this series leads the authors to hypothize new possible therapeutic implications for these tumors.     

Confronting Cisternae and Ciliated Cells in Malignant Pleural Mesothelioma: An Ultrastructural Study

The incidence of malignant mesothelioma of the pleura has recently increased in Japan, and ultra-structural and immunohistochemical studies can help in the histopathologic diagnosis. Confronting cisternae consist of dense laminae between the cisternae of rough endoplasmic reticula. Cylindric confronting cisternae have recently been found in patients with acquired immunodeficiency syndrome. The pathologic significance of this unusual structure is still obscure, but it has been proposed that trapped ribosomes on the confronting unit membranes of rough endoplasmic reticula produce the dense laminae. In this study, prominent confronting cisternae were found in more than half the tumor cells, and accumulations of an electron-dense fine granular substance surrounded by Golgi vesicles (so-called vesicular rosettes) were noted and found to be continuous with the dense laminae. The nature and origin of the vesicular rosettes are important with regard to the formation and significance of confronting cisternae. Oligocilia have been found in various metaplastic and neoplastic cells and are thought to be nonspecific. There has been only one report of ciliated cells and confronting cisternae in a malignant peritoneal mesothelioma, however, indicating that these unusual cytoplasmic structures might be related to some epithelial-type mesotheliomas.     

Idiopathic Fibrosing Alveolitis: A Review with Emphasis on Ultrastructural and Immunohistochemical Features

Fibrosing alveolitis is a usually chronic pulmonary disease affecting middle-aged men and women and causing progressive dyspnea. This review discusses the nosologic, etiologic, immunopathogenic, histologic, immunohistochemical and ultrastructural features of this condition. A hypothesis is presented suggesting microvascular damage as the primary pathologic change in cases associated with collagen vascular diseases and viral pneumonia.     

Crystals in an Oligodendroglioma: An Optical, Histochemical, and Ultrastructural Study

The report describes an oligodendroglioma that was examined in four biopsies and contained a large number of intracytoplasmic crystals. The crystals appeared in neoplastic cells with eosinophilic cytoplasms and eccentric nuclei. They were positive to periodic acid-Schiff stain and resistant to diastase. A lysosomal genesis of the crystals is proposed on the basis of a transition observed between lysomal bodies with lipid droplets and those with crystalloid electron-dense structures. The morphologic and histochemical features of these crystals are compared to those in other tumors, lesions, and non neoplastic cells.     

Idiopathic Fibrosing Alveolitis: A Review with Emphasis on Ultrastructural and Immunohistochemical Features

Fibrosing alveolitis is a usually chronic pulmonary disease affecting middle-aged men and women and causing progressive dyspnea. This review discusses the nosologic, etiologic, immunopathogenic, histologic, immunohistochemical and ultrastructural features of this condition. A hypothesis is presented suggesting microvascular damage as the primary pathologic change in cases associated with collagen vascular diseases and viral pneumonia.     

Histology,Histochemistry, and Pathology of Mesothelioma

Abstract

Mesotheliomas, rare tumors arising from flat mesothelial cells lining serous cavities, are often difficult to distinguish from carcinomas. The diagnosis is made after examining all the data from clinical findings, radiology, and biopsy. An algorithmic approach to histologic, histochemical, and electron microscopic study of the biopsy is offered. (The J Histotechnol 10:269, 1987)     

Ultrastructural features of diffuse malignant mesotheliomas

The distinction of malignant mesothelioma from tumors metastatic to the serosal membranes can often be made based on the results of histochemical or immunohistochemical studies. However, in some cases, these techniques are inadequate to make a firm diagnosis. In these instances, electron microscopic studies with the observation of a constellation of characteristic ultrastructural findings may permit an unequivocal diagnosis of mesothelioma.     

Asbestos Burden in Cases of Mesothelioma from Individuals from Various Regions of the United States

Mesothelioma is a rare tumor that is considered an asbestos marker disease. It occurs in individuals following a longer latency period from first exposure than other asbestos-related diseases. The tumor also occurs in individuals with a wide range of exposures, including individuals with lower level or secondary exposures. In the present study lung tissue from 54 individuals with a pathological diagnosis of mesothelioma was evaluated for ferruginous body and uncoated asbestos fiber content. The data were compared with an earlier study of mesothelioma cases from the northwestern United States. Tissue was prepared via a digestion procedure, with the collected digestate reviewed by light microscopy for quantification of asbestos bodies and analytical transmission electron microscopy for determination of uncoated fiber burden. Twenty-seven cases in the present study had over 1000 ferruginous bodies per gram of dry tissue. The data suggest that amosite provides a more likely stimulus for ferruginous coating than the other forms of asbestos. All individuals were found to have asbestos fibers in their lung tissue. Amosite was the most commonly found fiber, with anthophyllite being the second most commonly found type of asbestos. The finding of tremolite in the tissue most often was associated with the finding of anthophyllite. A limited number of asbestos fibers of each type would have been seen in the light microscope, with the least detected being chrysotile. The majority of all fiber types were found as short fibers (< 8 μm), although some longer fibers were represented in each type of asbestos. The majority of the individuals were found to have mixed types of asbestos in their lungs.     

Pituitary Adenomas Producing Growth Hormone, Prolactin, and One or More Glycoprotein Hormones: A Histologic, Immunohistochemical, and Ultrastructural Study of Four Surgically Removed Tumors

The morphologic features of four pituitary adenomas, removed from 2 men and 2 women between 31 and 62 years of age, are reported. The tumors contained growth hormone (GH), prolactin (PRL), and one or more glycoprotein hormones-usually thyrotropin (TSH). Three tumors were associated with acromegaly and one with hyperprolactinemia. Hyperthyroidism was not evident in any of the patients. In the tumors of acromegalic subjects, GH-containing cells were the most numerous, whereas PRL cells were dominant in the adenoma accompanied by hyperprolactinemia. Electron microscopy revealed plurimorphous tumors comprised of various proportions of morphologically different cell types: densely granulated GH cells, TSH-like cells, and the less common mammosomatotrophs and PRL cells. It is suggested that pituitary adenomas producing GH, PRL, and glycoprotein hormones derive from the same precursor; their immunocytochemical profile, fine structural appearance, and endocrine function may depend on the degree and direction of the cellular differentiation.     

Pituitary Adenomas Producing Growth Hormone,Prolactin, and One or More Glycoprotein Hormones: A Histologic,Immunohistochemical, and Ultrastructural Study of Four Surgically Removed Tumors

The morphologic features of four pituitary adenomas, removed from 2 men and 2 women between 31 and 62 years of age, are reported. The tumors contained growth hormone (GH), prolactin (PRL), and one or more glycoprotein hormones–usually thyrotropin (TSH). Three tumors were associated with acromegaly and one with hyperprolactinemia. Hyperthyroidism was not evident in any of the patients. In the tumors of acromegalic subjects, GH-containing cells were the most numerous, whereas PRL cells were dominant in the adenoma accompanied by hyperprolactinemia. Electron microscopy revealed plurimorphous tumors comprised of various proportions of morphologically different cell types: densely granulated GH cells, TSH-like cells, and the less common mammosomatotrophs and PRL cells. It is suggested that pituitary adenomas producing GH, PRL, and glycoprotein hormones derive from the same precursor; their immunocytochemical profile, fine structural appearance, and endocrine function may depend on the degree and direction of the cellular differentiation.     

Ovarian Myxoma: Ultrastructural and Immunohistochemical Findings

The ultrastructural and immunohistochemical findings are reported in two ovarian myxomas, one of which was also associated with a sclerosing stromal tumor of the same ovary. Both neoplasms showed a myxoid, moderately cellular proliferation of spindle and stellate cells interspersed with areas of fibrosis and hemorrhage as well as delicate vascular spaces. Ultrastructurally, stellate neoplastic cells with irregular nuclei and occasional nucleoli were embedded in a mucinous and loose collagen matrix. Their cytoplasm showed abundant intracytoplasmic thin filaments that rarely condensed into poorly formed dense bodies. These thin filaments correlated with immunoreactivity for musclespecific actin and vimentin. The neoplastic cells showed no immunoreactivity with antibodies to desmin, S-100 protein, cytokeratin AE1 :AE3, factor Vlll-related protein, or placental alkaline phosphatase. These ultrastructural and immunohistochemical findings are consistent with myofibroblastic differentiation. These ancillary studies exclude important, clinically more aggressive differential considerations such as myxoid rhabdomyosarcoma, myxoid liposarcoma, myxoid neural tumors, mucinous adenocarcinoma showing pseudomyxomatous change, and myxoid-appearing endodermal sinus (yolk sac) tumor.