A. Julian Garvin

An autopsy study of histologic progression in non‐Hodgkin's lymphomas 192 cases from the national cancer institute

Histologic slides were reviewed from 192 autopsies of patients with non‐Hodgkins lymphomas admitted to the National Cancer Institute (NCI) from 1953 to 1975. Each autopsy was classified according to the systems of Rappaport and Lukes‐Collins. Comparisons with the initial diagnosis were made. The initial histologic diagnoses of the autopsied population were similar in distribution to other published series of non‐Hodgkins lymphomas. Of the 56 cases which initially demonstrated nodular patterns of growth, the following distribution was found at autopsy: 25%, no lymphoma; 6%, nodular lymphoma; 32%, diffuse histiocytic (large cell) lymphoma (DHL); 21%, diffuse undifferentiated (non‐Burkitts) lymphoma (DUL); and 16%, the remaining diffuse morphologies. Of the 136 patients with initial diagnosis of diffuse lymphoma, the following distributions were observed at autopsy: 20%, no lymphoma; 0%, nodular lymphoma; 31%, diffuse histiocytic (large cell) lymphoma; 12%, diffuse undifferentiated (non‐Burkitts) lymphoma; 9%, Burkitts tumor; 14%, diffuse poorly differentiated lymphocytic lymphoma; and 14%, the remaining diffuse morphologic types. One hundred and thirty‐four cases which were initially diagnosed as follicular center cell type within the Lukes‐Collins classification gave the following distribution at autopsy: 21%, no lymphoma; 25%, small noncleaved type; 17%, large non‐cleaved type; 23%, non‐follicular center cell lymphomas (17% immunoblastic B); and the remaining 13% were distributed among the other follicular center cell types. This autopsy review demonstrates the rarity of nodular (follicular) lymphomas at autopsy, and the predominance of the diffuse histiocytic or “transformed” type. This study provides a comparison of the rate of histologic progression of lymphomas in the same patient population at autopsy with a previously published study of progression during life.

Advances in Cytochemical Methods for Detection of Apoptosis

In an earlier article from this laboratory, the current methods developed to detect apoptosis in cells and tissues were highlighted, along with the challenges in their interpretation. Recent discoveries concerning the underlying biochemical mechanisms of apoptotic effector pathways have made possible further assays that allow a more direct measure of the activation of the apoptotic machinery in cells. This article summarizes some of these newer methods and extends the interpretation of the more classical assays of apoptosis in a defined cell system. We present data in KB and PC3 cell model culture systems induced to undergo apoptosis by the plant toxin ricin. Using a modified in situ nick translation assay (ISNT) with either Bodipy or BUdR labeling, we confirm that most cells showing altered nuclear morphology do not show reactivity with this assay until very late in the apoptotic process. We also show that only a minority of cells label with fluorescent annexin V during apoptosis but that apoptotic cells continue to internalize material from the cell surface through endocytosis after becoming reactive with annexin V. In addition, we describe the utility of a prototype of new assays for caspase substrate cleavage products, the detection of cleaved cytokeratin 18. It is these newer cleavage product assays that perhaps hold the greatest promise for specific detection of apoptosis in cells either in cell culture or in intact tissues.

Infantile Fibrosarcoma—a Misnomer?

Two cases of congenital or infantile fibrosarcoma are described that were incompletely excised at the time of primary excision and have not recurred or metastasized after 3 years. The tumors were composed of densely cellular spindle cells with a high mitotic index. Immunohistochemical stains were positive for vimentin but negative for desmin and S-100. The tumor cells were grown in vitro, and a karyotype was obtained. Both tumors had normal diploid modal karyotypes. In addition, fragments of the primary tumor from both cases were injected subcutaneously into nude mice; neither tumor could be heterotransplanted. The clinical course and biologic features of these two tumors suggest that congenital or infantile sarcoma does not have the properties of a malignant neoplasm, and thus the designation of these tumors as a sarcoma may be a misnomer.

Gonadoblastoma: Histologic, ultrastructural, and histochemical observations in five cases

In this series of gonadoblastomas it appeared that the germ cells were the motivating force underlying either tumor proliferation or regression. The ultrastructural morphology confirmed the presence of undifferentiated gonadal cells with active steroid synthesis by the interstitial cells. The Call-Exner-like bodies which showed extensive calcification were composed of basement membrane material containing a sulfated mucosubstance. A histochemical comparison with the noncalcifying Call-Exner bodies of a granulosa-cell tumor differed only in their glycoprotein content. The calcium deposits were identified as oriented hydroxyapatite crystals by electron diffraction, and it is proposed that the basement membrane material serves as a nucleation site for calcification. High serum testosterone levels were correlated with the presence solely of interstitial cells in one case. The finding of a gonadoblastoma without the presence of a Y chromosome contradicts earlier proposals concerning the requirement of a Y chromosome for germ cell proliferation.

Isochromosome 11q in a case of Ewing's sarcoma.

A low passage Ewings sarcoma cell line established from a metastatic lesion was cytogenetically analyzed. The modal karyotype was 44,X, -8,i(11q), -15, +12. Other cells had random chromosome aneuploidy superimposed on this karyotype. No cell had a structural rearrangement involving 11q24 or 22q12 as described in other patients with Ewings sarcoma, but all cells had an isochromosome 11q.

Glycosphingolipids of an alveolar rhabdomyosarcoma and normal human muscle: A case study

The distribution of neutral, or asialosyl-, glycosphingolipids and gangliosides in a rhabdomyosarcoma of alveolar type have been studied. Histologically, this muscle tumor is composed primarily of two cell types: one with oval or round hyperchromatic nuclei and very little cytoplasm, and one a giant cell, with multiple, peripherally placed nuclei and weakly staining eosinophillic cytoplasm. In comparing glycolipids of the rhabdomyosarcoma with normal muscle from the same leg, the striking alteration in the tumor was a virtual disappearance of ganglioside GM2. There was also a slight increase in GM3 and a decrease in GD1a. The asialosyl derivative of GM2 (GalNac-Gal-Glc-Cer) was markedly increased in the tumor. A loss of glucosylceramide was also observed. The results are discussed in terms of glycolipid metabolic changes in muscle oncogenesis and their implications.