Franque Remington

Tubuloreticular structures and cylindrical confronting cisternae: A review

Tubuloreticular structures (TRS) and cylindrical confronting cisternae (CCC) are unique subcellular structures that arise from the membranes of the rough endoplasmic reticulum of a variety of cell types. In vivo, they occur most frequently in endothelial cells and lymphocytes from patients with autoimmune diseases and viral infections; they are seen in these cells in almost all acquired immunodeficiency syndrome (AIDS) patients. The inducer(s) of TRS and CCC in vivo is (are) not firmly established. However, clinical and experimental studies indicate that the occurrence of these structures in these diseases is directly related to the endogenous elevation of alpha- and beta-interferon but not to gamma-interferon. Although CCC have been seen and reported to occur in human and primate cells since the late 1970s, their presence did not arouse much clinical and scientific interest until 1983 when they were observed in lymph node tissues of AIDS patients. The nature and pathogenesis of TRS and CCC are obscure. Through the years, many hypotheses have been proposed. They range from suggestions of these structures being incomplete viral particles to being nothing more than accumulated proteins; and from reference to these structures as specific markers for diseases to a generalized cell reaction to certain biological stimuli. In vitro investigations with lymphoblastoid cell lines have contributed a great deal in illuminating the potential clinical significance and the in vivo inducer(s) of TRS and CCC. Both the TRS and CCC are now known to be induced in vitro by alpha- and beta-interferon in some lymphoblastoid cell lines. However, only TRS and not CCC are induced in healthy donor lymphocytes and endothelial cells. Isolation of TRS and CCC using the lymphoblastoid cell system will help clarify the nature, the pathogenesis, and the importance of TRS and CCC in human diseases.

The widespread distribution of langerhanscells in pathologic tissues: An ultrastructural and immunohistochemical study

Ultrastructural and/or immunohistochemical analysis of approximately 500 specimens revealed widespread distribution of Langerhans cells in pathologic specimens. More than half of the tissue specimens were from patients with a variety of pulmonary diseases. In all specimens in which Langerhans cells were identified ultrastructurally, they were also identified by an immunoperoxidase technique for the visualization of S-100 protein; the latter technique also revealed the dendritic nature of these cells. Langerhans cells were present in 80 to 93 per cent of 66 pulmonary adenocarcinomas and 17 per cent of squamous cell lung cancers; they were not observed in neuroendocrine lung carcinomas or mesotheliomas. They were also observed in benign inflammatory conditions of the lung of several types and in a variety of other malignant neoplasms and disease processes. The Langerhans cells in these tissues varied from few to many. They were most numerous in bronchioloalveolar cell carcinoma, sometimes appearing almost as frequently as tumor cells, and rare in some benign pulmonary conditions and other tumors. The function of Langerhans cells in these conditions is unknown, but they may have an immunologic function, such as antigen processing and presentation to T lymphocytes.

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.

Ultrastructural and Immunohistochemical Features of Common Lung Tumors: An Overview

Lung cancer is rapidly becoming the most commonly diagnosed malignant neoplasm in the world. Pathologists play a key role in the care of patients with lung cancer by accurately classifying and staging these neoplasms. Immunohistochemistry and electron microscopy have become important tools in the diagnosis of lung tumors, especially those which are histologically undifferentiated. This review discusses the ultrastructural and immunohistochemical features of common lung tumors, with an emphasis on their diagnostic usefulness.

Langerhans Cells and Serum Precipitating Antibodies against Fungal Antigens in Bronchioloalveolar Cell Carcinoma: Possible Association with Pulmonary Eosinophilic Granuloma

In an ultrastructural study of 37 cases of bronchioloalveolar cell carcinoma (BAC), we identified seven cases (19%) in which Langerhans cells (LC) were closely associated with tumor cells. Serum precipitating antibodies against Aspergillus species and/or thermophilic actinomyces were present in five BAC patients whose tumors contained LC and in six patients whose tumors lacked LC. In a simultaneous study we identified marked atypical bronchiolar and alveolar lining cell hypertrophy and hyperplasma in pulmonary eosinophilic granuloma (PEG). Our data plus current information suggesting that PEG is a form of hypersensitivity pneumonitis support our hypothesis that those cases of BAC in which LC are present may rise in localized or diffuse pulmonary scars caused by PEG.

The unusual spectrum of neuroendocrine lung neoplasms.

Neoplasms of the lungs showing neuroendocrine differentiation are classified histologically into the following groups: (1) carcinoid, (2) atypical carcinoid (well-differentiated neuroendocrine carcinoma and malignant carcinoid, (3) small cell neuroendocrine carcinoma (small cell undifferentiated carcinoma and oat cell carcinoma), and (4) large cell neuroendocrine carcinoma (atypical endocrine tumor of the lung and intermediate neuroendocrine carcinoma). Nine examples of neuroendocrine lung carcinomas are discussed that have unusual histologic features that make it difficult to assign them to one of the above groups, have unusual immunohistochemical features, have unusual ultrastructural features, or exhibit a biologic behavior different from what one would have predicted from their morphologic appearance. The findings in these nine cases suggest that the present classification of neuroendocrine lung neoplasms may be too precise and that these neoplasms, like other nonneuroendocrine pulmonary tumors, exhibit a wider morphologic and biologic spectrum than previously appreciated.

Interdigitating Reticulum Cell Sarcoma with Unusual Features

A case of interdigitating reticulum cell sarcoma is reported in a cervical lymph node of a 67-year-old man who had a previously diagnosed nodular lymphocytic lymphoma in the same anatomic location. Ultrastructurally, the neoplastic cells contained cylindrical confronting cisternae, and associated benign lymphocytes had tubuloreticular structures in their cytoplasm. The patient was treated with combination chemotherapy-radiation therapy and is alive and well with no evidence of disease approximately 2 years after completing therapy. The clinical and pathologic features of previously reported cases of interdigitating reticulum cell sarcomas are compared to those of the reported case.

Induction of cylindrical confronting cisternae (AIDS inclusions) in Daudi lymphoblastoid cells by recombinant α-interferon

Cylindrical confronting cisternae (CCC), also known as test-tube and ring-shaped forms, are frequently present in the cytoplasm of lymphocytes and occasionally in other cells from patients with acquired immunodeficiency syndrome (AIDS). Recent data indicate that the presence of these cisternae and tubuloreticular structures (TRS) in lymphocytes from patients at risk for AIDS is predictive of the development of this syndrome. CCC are formed by an alteration of the membranes of the rough endoplasmic reticulum, but the mechanism by which they are formed or demonstration of their induction by specific agents has not been previously reported. We cultured Daudi lymphoblastoid cells in medium containing recombinant alpha-interferon and induced the formation of both TRS and CCC. The number of CCC formed in Daudi cells was directly proportional to the concentration of interferon used and the length of culture. CCC were in direct continuity with TRS, which were induced in cells by interferon at an earlier time. The percentage of cell sections containing TRS stayed the same or decreased somewhat after 72 hours of culture, whereas the number of CCC increased. Our results indicate that CCC could be present in various cells from patients with AIDS and other diseases as a result of elevated interferon levels in these conditions.

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.

Induction of Tubuloreticular Structures in Cultured Human Endothelial Cells by Recombinant Interferon Alfa and Beta

Tubuloreticular structures were induced in human umbilical vein endothelial cells cultured in media containing recombinant interferon alfa and beta but not in media containing recombinant interferon gamma or other agents that induce interferon, such as 5-bromodeoxyuridine or polyinosinicpolycytidylic acid. Recombinant interferon beta induced tubuloreticular structures in endothelial cells at a lower concentration and in a greater percentage of cell sections than recombinant interferon alfa. This report of tubuloreticular structures being induced in vitro in nonlymphoid cells provides evidence that interferon is the substance that causes the formation of tubuloreticular structures in endothelial cells in vivo.