E. Kaiserling

The Histopathology of Malignant Lymphoma

It has been possible to reinterpret non‐Hodgkins lymphomas by applying subtle histological, cytological, and cytochemical techniques and electron microscopy as well as by using modern immunological methods and immune chemical analyses. This has led to the differentiation of four main groups of low‐grade and three main groups of high‐grade malignant lymphomas. Most non‐Hodgkins lymphomas are derived from the B‐lymphocyte system. Only some of the lymphocytic, a small fraction of the lymphoblastic, and very few immunoblastic lymphomas originate from the T‐lymphocyte system. True reticulosarcomas are very rare and will have to be redefined.

Langerhans cells and interdigitating reticulum cells in the thymus-dependent region in human dermatopathic lymphadenitis

Summary14 cases of dermatopathic lymphadenitis were studied by light and electron microscopy. In two instances the ATP-ase reaction was applied to lymphoid tissue. The main morphologic feature of dermatopathic lymphadenitis is an extreme enlargement of the thymus-dependent area which is due to a large number of closely connected, interdigitating reticulum cells (IDC). Enzyme-histochemically IDC are ATPase positive. In all systematically studied cases Langerhans cells are found in the paracortex. They may also be present in the sinuses and the neighbouring lymph node parenchyma. Like IDC, Langerhans cells have an irregularly shaped nucleus, numerous cytoplasmic processes as well as invaginations; in the paracortical area they show intimate connections with each other or with IDC. Frequently they can be differentiated from IDC only by the presence of Langerhans granules. The close topographic apposition to T-lymphocytes typical of IDC is also true of Langerhans cells.The presence of Langerhans cells in the sinuses suggests that these cells are carried to the lymph node parenchyma via afferent lymphatics from the skin. The significance of Langerhans cells in the lymphoid tissue cannot be deduced from the morphologic picture. The cytologic relationship between Langerhans cells and IDC, however, makes it highly probable that both cells have a similar function.The Langerhans cells of the epidermis fix antigen on the cell surface and it has been suggested that they stimulate the proliferation of lymphocytes. The same function has been postulated for IDC, the specific reticulum cells of the thymus-dependent area. Thus, it appears to be possible that IDC and Langerhans cells are involved in cell-mediated immune reactions of the lymphoid tissue.

Evidence for B-cell origin of reticulum cell sarcoma

Sixteen cases of so-called reticulum cell sarcoma (RCS) of the lymph node were systematically studied using histological, cytochemical, electron microscopic, and immunochemical methods. In 8 cases some of the tumor cells showed PAS-positive globular cytoplasmic inclusions. The reactions for non-specific esterase or other marker enzymes were not positive in any case. Electron microscopically the cytoplasm contained many free polyribosomes. There was little ergastoplasm in most cases, but a moderately to strongly increased amount in 3 cases. The tumor tissue homogenate contained significantly increased amounts of IgM in 12 cases and of IgA in one case. Of the 12 IgM-positive RCS 5 showed serum IgM-levels within, 3 below, and only 2 above the normal range. This indicates that most of the RCS produced but did not secrete IgM. 2 cases labeled for surface-IgM revealed a positive reaction on a large number of tumor cells. We conclude that at least most of the RCS in our study were not derived from reticulum cells or histiocytes, but instead from lymphatic cells of the B-cell series. The morphologic similarity of the RCS-cells to “antigen-induced blasts” (called immunoblasts) suggests that RCS are derived from such blasts. This interpretation is especially supported by one case whose cells resembled immunoblasts not only morphologically but also with respect to the site of Ig-production: the perinuclear space. In general we therefore call RCS immunoblastic sarcoma of B-cell type and specify the tumor as plasmoblastic sarcoma if a significant amount of ergastoplasm is electron microscopically detectable.

Mycosis fungoides: model for T‐lymphocyte homing to the skin?

Uptothepresentdaytherehasbeenno satisfactory explanation of why benign or malignant lymphomas can develop in the skin. Recently Goudie, MacFarlane & Lindsay (1974) presented an interesting hypothesis concerning the homing of lymphocytes to non-lymphoid tissues. The authors speculated that the proliferation of extranodal lymphoid tumours might be due to the possibility that neoplastic lymphocytes home on a special tissue by a process called ecotaxis (de Sousa, 1971). Ecotaxis means the accumulation of lymphocytes in territories which display their appropriate microenvironment.

T-cell lymphomas of the stomach: morphological and immunological studies characterizing two cases of T-cell lymphoma

Using cytochemical, electron microscopic and immunohistochemical techniques in 20 primary malignant lymphomas of the stomach, we found 18 B-cell and 2 T-cell lymphomas. Primary T-cell lymphoma in the stomach has not been previously reported. The T cells in both cases were reminiscent of T immunoblasts with prominent nucleoli and a basophilic cytoplasm. Case 1 showed a cytological relationship to pleomorphic T-cell lymphoma, large cell type. Case 2 contained in addition some cells not previously described in T-cell lymphomas, resembling immature plasma cells with abundant rough endoplasmic reticulum. Focal positivity to acid phosphatase and dipeptidylaminopeptidase IV suggests the T-cell nature of both lymphomas. In both cases the tumour cells were OKT 11 and OKT 4 positive, and negative for OKT 8. Thus, both cases represent high-grade malignant T-cell lymphomas which correspond phenotypically to T-helper cell lymphoma. Case 2 revealed a further immunohistochemical peculiarity: atypical immunoblasts reacted positively with Ki-1 antibody. Thus, it is a Ki-1 lymphoma of T-cell type.

Tumour of Wagner-Meissner touch corpuscles. Wagner-Meissner neurilemmoma

Two benign tumours composed mainly or exclusively of Wagner-Meissner corpuscles are described. In the first case the touch corpuscles are composed of closely piled laminar cells and surrounded by argyrophilic fibres. In the second case some Schwann cells are observed in between the tactile corpuscles. The light microscopic, electron-microscopic and immunohistochemical results demonstrate that these corpuscles are comparable with the tactile end organs of the skin. Immunohistochemically, neuron-specific enolase, vimentin and protein S-100 could be demonstrated in the tactile corpuscles. Neural processes present in normal Meissner corpuscles are absent and immunohistochemically no nerve fibres or nerve endings can be demonstrated using antibodies to neurofilaments as they are observed in normal touch corpuscles of the skin. Tumours which consist mainly of multiple touch corpuscles have not been described in the literature. It is suggested to call these tumours Wagner-Meissner neurilemmoma.

IgM-producing malignant lymphomas without macroglobulinemia. Morphological and immunochemical findings

SummaryTwo malignant lymphomas were investigated. They were light microscopically characterized by a large number of PAS-positive cytoplasmic inclusions. Electron microscopically these inclusions were represented by electron-dense condensates lying in distended cisternae of the rough endoplasmatic reticulum. Immunochemical analyses revealed a high increase of IgM in the tumor tissue homogenates, but no macroglobulinemia in the sera. This indicates that the tumor cells produced but could not secrete IgM and that the cytoplasmic inclusions represented accumulated IgM.The first lymphoma showed a wide cytological spectrum from small lymphocytoid cells to cells rich in ergastoplasm. About 8–10% of these tumor cells contained cytoplasmic inclusions. The tumor was therefore cytologically similar to Waldenström’s disease, but distinguished from it by the lack of macroglobulinemia. In the second case the tumor consisted of mostly large cells with large nuclei and a poorly developed endoplasmatic reticulum but numerous polysomes. IgM-condensates were found exclusively in distended cisternae of the perinuclear space. These tumor cells were similar to immunoblasts in both the cytological features and site of Ig-production.In Case 1 there were no morphological clues for the cause of the secretory defect. IgM extracted from the tumor was electrophoretically identified as mainly 8 S IgM-monomer. We therefore assume that the lack of secretion was caused by a defect in the polymerisation mechanism. For Case 2 we conclude that the lack of secretion was based on a disturbance of the IgM-transport from the perinuclear space to the Golgi apparatus due to the nearly complete absence of endoplasmatic reticulum.The two tumors represent a previously not well known group of B-cell lymphomas consisting of secretory cells which accumulate but do not secrete immunoglobulins.

Experimental listeria monocytogenes-lymphadenitis: Pathohistological observations

The auricular lymph nodes of SPF guinea pigs were examined light microscopically at various stages (30 min to 14 days) after subcutaneous injection of Listeria monocytogenes. The bacteria entered the lymph node parenchyma through the marginal sinuses and were phagocytosed by polymorphonuclear leukocytes and monocytes at early stages of the infection (30–60 min). Whereas retothelial cells of the sinuses did not phagocytose bacteria, submarginal reticulum cells showed a high bacterium-phagocytosing activity. Starting at 12 hours after inoculation lymphocyte activation occurred in the interfollicular diffuse lymphatic tissue of the cortex and in the paracortex. The activated lymphocytes were released into the sinuses. There was also paracortical distension, which reached its peak on the 6th day of infection. The submarginal area at the junction of the afferent lymphatic with the cortex and the perivascular regions of the lymph node paracortex were the preferred sites of granuloma formation. On the 8th day with a dose of 106 bacteria the macrophages of the granulomas revealed only unidentifiable debris in the cytoplasm, whereas in the earlier lesions a large number of mononuclear phagocytes, especially in the submarginal granulomas, contained many intracytoplasmic listeria. The granulomas gradually became smaller and smaller. With larger infectual doses the process did not subside within the experimental period; the granulomas developed the appearance of “reticulocytäre abszedierende Lymphadenitis”.

Experimental listeria cystitis

SummaryElectron microscopic studies of cystitis produced by instillation of Listeria monocytogenes into the urinary bladder of guinea pigs were carried out in order to investigate the epithelial phase of the infection.While bacteria lying free in the cytoplasm of epithelial cells showed no sign of damage and were able to multiply there, part of those in phagosomes of epithelial cells were killed. During the course of the infection the number of lysosomes, multivesicular bodies, Golgi complexes, and endoplasmic reticulum were increased in the bacteria-containing cells (epithelial activation).It is suggested that a variable epithelial phase is a characteristic feature of infections caused by intracellular parasitic bacteria when the port of the entry of the bacteria is an epithelial barrier.

Vorkommen intracellulärer Bakterien in Makrophagen beim Typhus abdominalis des Menschen

SummaryLight and electron microscopic studies of lymphadenitis in human typhoid fever are presented. Gram-negative bacteria could be observed in phagosomes within typhus cells as well as in extracellular spaces. Intracellular bacteria were small and coccoid in shape. The extracellular bacteria were larger and strongly stained. Ingested bacteria had formed small groups, suggesting intracellular multiplication similar to intracellular parasitism in cases of animal salmonelloses.Mononuclear cells, which phagocytise bacteria, lymphocytes, and erythrocytes, were evidenced to undergo morphological alterations resembling the transformation of monocytes into macrophages. All transitional forms between blood monocytes and the so called typhus cells could be detected. The findings support the view that typhus cells are of monocytic origin.