Yusuf Kapanci

Expression of a tumor necrosis factor-alpha transgene in murine lung causes lymphocytic and fibrosing alveolitis. A mouse model of progressive pulmonary fibrosis.

The murine TNF-alpha gene was expressed under the control of the human surfactant protein SP-C promoter in transgenic mice. A number of the SP-C TNF-alpha mice died at birth or after a few weeks with very severe lung lesions. Surviving mice transmitted a pulmonary disease to their offspring, the severity and evolution of which was related to the level of TNF-alpha mRNA in the lung; TNF-alpha RNA was detected in alveolar epithelium, presumably in type II epithelial cells. In a longitudinal study of two independent mouse lines, pulmonary pathology, at 1-2 mo of age, consisted of a leukocytic alveolitis with a predominance of T lymphocytes. Leukocyte infiltration was associated with endothelial changes and increased levels of mRNA for the endothelial adhesion molecule VCAM-1. In the following months, alveolar spaces enlarged in association with thickening of the alveolar walls due to an accumulation of desmin-containing fibroblasts, collagen fibers, and lymphocytes. Alveolar surfaces were lined by regenerating type II epithelial cells, and alveolar spaces contained desquamating epithelial cells in places. Platelet trapping in the damaged alveolar capillaries was observed. Pulmonary pathology in the SP-C TNF-alpha mice bears a striking resemblance to human idiopathic pulmonary fibrosis, in which increased expression of TNF-alpha in type II epithelial cells has also been noted. These mice provide a valuable animal model for understanding the pathogenesis of pulmonary fibrosis and exploring possible therapeutic approaches.

Lymphangiomyomatosis: A clinico‐anatomical entity

A 65‐year‐old woman presenting with progressive dyspnea and chylous ascites is reported. Necropsy revealed the presence of masses of spindle cells in and around the walls of lymph vessels, and massively involving the retro‐peritoneal and to a lesser extent the mediastinal lymph nodes. Honeycombing of the lungs was associated with similar spindle‐cell masses arising from pulmonary lymph vessels. These findings are those of a disease known as lymphangiomyomatosis, which has heretofore been characterized by infiltration and obstruction of the thoracic duct, and by chylothorax. In this case, there was no chylothorax but only chylous ascites; furthermore the thoracic duct was patent. These findings argue against the reactive origin of the spindle‐cell proliferation and suggest that these formations are of hamartomatous nature.

Oxygen Pneumonitis in Man

During the last 10 years, because of extensive development of intensive care medicine and the use of artificial atmosphere in space travel, the interest in lung lesions produced by high concentrations of oxygen breathing has been continuously increasing. The early studies of Pratt [1] and later those of Nash et al. [2] demonstrated alveolar damage in patients given high concentrations of oxygen. A detailed description of our findings is given in three recent articles [3, 4, 5].

Histopathologic features of hepatocellular carcinoma in Zaire

The pathology of hepatocellular carcinoma (HCC) was studied based on 223 Zairian HCC cases registered from 1966 to 1985. The observations included the following: (1) hepatitis B surface antigen (HBsAg) status, (2) histologic types, (3) degree of cellular differentiation, and (4) frequency and types of the accompanying cirrhosis. Serum HBsAg was positive in 56.7% of HCC patients and 5.7% of controls (P < 0.001). Immunohistochemical localization of HBsAg was positive in 53.3% in normal hepatocytes and in 10% in neoplastic cells. Morphologically, mixed type HCC (48.4%), trabecular (31.4%), and compact variants (13.5%) were predominant. Clear cell and pseudoglandular variants were rare (< 1%). The majority of tumors (83%) were poorly differentiated HCC (Grades: 2‐3, 3, 3‐4, and 4). Well‐differentiated HCC were extremely rare (0.5%). Fifty percent of HCC arose in a cirrhotic liver, predominantly of the macronodular (67.4%) inactive (55%) type. The micronodular cirrhosis was very uncommon (1.1%). These findings clearly show the excess of poorly differentiated HCC in African patients and suggest a possible link between the morphologic features of HCC in Africa and its extraordinary fast‐running course.

Polymorphic reticulosis (lethal midline granuloma) and lymphomatoid granulomatosis: identical or distinct entities?

Two cases of polymorphic reticulosis were studied. Both cases had a fatal clinical course, that of the second case being rapid and progressive and ending 6 months after the onset of the disease with little demonstrable effect of steroid therapy. Biopsy material was obtained in both patients, and both were submitted to a post-mortem examination. The first case showed typical angiocentric, angiodestructive, polymorphous lymphoreticular infiltrates, involving the pharyngeal region and the tongue. The second case demonstrated these same lesions in the midfacial region, the lungs and the skin. A possible identity between polymorphic reticulosis and lymphomatoid granulomatosis is discussed (because of the coexistance of identical lesions in the midfacial region and in the lung parenchyma in the second case). Wegeners granulomatosis in limited and disseminated forms and malignant lymphoma are considered in the differential diagnosis.

A lymphoproliferative syndrome, “cutaneous dystrophy” and combined immune deficiency with lack of helper T-cell factor

Abstract The case of an 18-month-old boy, born of consanguineous parents, presented at the age of 4 months with fever, widespread lymphadenopathy, hepatosplenomegaly, and thick skin folds with eczematous lesions, is documented. Thymic shadow was not visualized. Extreme T lymphocytosis and eosinophilia were important features. It was possible to demonstrate by immunohistochemistry and ultrastructural studies of the lymph nodes that the hyperplasia was due principally to a benign proliferation of immature cells of T-cell lineage in the paracortical zone. There was a combined immunodeficiency with absence of serum IgG and IgA as well as an abrogated lymphocytic response. The latter was restaured in vitro through interleukin 2 (TCGF). In addition the childs lymphocytes spontaneously suppressed allogeneic cell responses, were deficient for 5-nucleotidase and showed T-cell-subset imbalance. During the 14 months of his illness there was persistent failure to thrive, frequent bouts of fever, and finally diarrhea leading to extreme cachexia and death due to bronchopneumonia.

Measles giant cell pneumonia without rash in a case of lymphocytic lymphosarcoma

A case of measles pneumonia with no rash is reported in an adult woman with lymphocytic lymphosarcoma. It was characterized by the presence of inclusion-bearing giant cells lining the alveoli. Electron microscopic studies of the lung showed that the giant cells were formed by fusion of type II alveolar epithelial cells. Inclusion bodies were filled with tubular and rod-shaped filaments similar to those observed in cell cultures infected with measles virus. The progression of the giant cell pneumonia may have been facilitated by depressed cell-mediated immunity secondary to lymphocytic lymphosarcoma.

Demonstration of the extracellular alveolar lining layer (surfactant) in human lungs

SummaryThe structure of the extracellular alveolar lining layer in 3 human lungs is described. This lining was composed of 2 layers: a) a highly osmiophilic surface layer, b) a base layer.The surface layer consisted of lamellar structures with 40 Å intervals. It was fragile and broken in many areas. The base layer molded the irregularities of the alveolar surface; it frequently appeared in the form of “tubular myelin”. In the latter the intervals between lamellae were about 450 Å.The demonstration of these structures was achieved by routine intratracheal instillation of glutaraldehyde and osmium post-fixation. The lining layer is interpreted as a constituent of pulmonary surfactant.

The Contribution of Electron Microscopy to Normal Morphology and Pathology Research in Switzerland

The aim of this article is to recall some major contributions of Swiss electron microscopy (EM) investigators in the fields of histology and pathology. This review does not claim to cover all investigations done in Switzerland, but to cite a few outstanding ones since the early fifties. We are conscious that possibly some colleagues are forgotten, or citation of some of their important contributions is missing in the following chapter. We hope that they will forgive us.

Immunohistochemical Detection of Prostatic Acid Phosphatase in 110 Cases of Bone Metastases

Despite recent progress in methods of clinical investigation, discovery of the primary site of a metastatic tumor remains a difficult task. Among secondary cancers of undetermined origin, representing 7–15% of nonsquamous carcinomas,1,2 are included a number of cases of bone marrow metastases of prostatic adenocarcinomas. Indeed, elevation of serum acid phosphatase (AP) levels may suggest the prostatic origin of the primary tumor but, since the serum concentration of this enzyme also rises in benign prostatic diseases,4–7 a concomitant unrelated prostatic disorder and metastases from a carcinoma arising elsewhere cannot be ruled out.3,4,7,8