H. K. Müller-Hermelink

Interdigitating reticulum cells in the human thymus

SummarySeven thymuses from children between 1 and 12 years were examined by electron microscopy. Biopsies had been taken during surgical correction of congenital heart defects.In all cases we found interdigitating reticulum cells (IRC) in the medulla and inner cortex. These cells resembled the IRC which have been described previously in the thymus-dependent regions of the spleen and lymph node. They were characterized by an irregularly shaped nucleus, narrow cisterns of rough endoplasmic reticulum, and widespread interdigitation and invagination of the cell membrane. The surfaces of the IRC were in close contact with those of small lymphocytes, sometimes polysomal lymphatic cells, epithelial cells, and occasionally with those of lymphatic cells containing ergastoplasm.The IRC is apparently a specific cell of thymus-dependent regions. It may be that the IRC in the thymus, lymph node, and spleen contribute to the microenvironment needed for the differentiation of T-cells.

Characterization of the B-cell and T-cell regions of human lymphatic tissue through enzyme histochemical demonstration of ATPase and 5'-nucleotidase activities.

SummaryThe enzyme histochemical demonstration of ATPase and 5′-nucleotidase (5-Nase) activities in cryostat sections of different human lymphatic tissues was compared to the localization of B-cell and T-cell regions, as shown by the binding of EAC (erythrocyteantibody-complement) complexes. EAC-positive areas corresponded to B-cell regions, EAC-negative ones to T-cell regions. Both enzymes, ATPase and 5-Nase, allowed a clear distinction of B-cell and T-cell regions in all peripheral human lymphatic tissues. The different maturation stages of lymphatic B-cells had different enzyme characteristics. T-lymphocytes were always negative. These enzymes also provided an easy means of differentiating the B-cell and T-cell microenvironments: the dendritic reticulum cells of the B-cell regions showed a strong 5-Nase but no ATPase activity, whereas the interdigitating reticulum cells of the T-cell region were strongly ATPasebut not 5-Nase-positive.

Enzyme histochemical observations on the localization and structure of the T cell and B cell regions in the human spleen

SummaryThe capacity of certain B-lymphocytes to bind complement (demonstrated by erythrocyte-antibody-complement complexes, EAC) was used as a marker of the B-lymphocyte regions of the human white splenic pulp. This was carried out on cryostat sections in order to correlate enzyme histochemical findings (5-nucleotidase, ATPase, acid phosphatase, nonspecific esterase, alkaline phosphatase) to immunological functions. EAC were typically found in the follicle centers and marginal zone, whereas periarteriolar lymphocyte sheaths remained negative. The enzyme histochemical patterns of lymphocytes and reticulum cells allowed a clear distinction between areas with and those without EAC-binding. This was shown most clearly when the following enzymes were demonstrated in combination: 5-nucleotidase (5-Nase) + alkaline phosphatase, ATPase + acid phosphatase, and nonspecific esterase + acid phosphatase. 5-Nase correlated best to EAC-positive areas with a positive reaction in follicle wall lymphocytes and dendritic reticulum cells, whereas periarteriolar sheaths contained no 5-Nase-positive structures. Reticulum cells around periarteriolar lymphocyte sheaths at the margin of the red splenic pulp showed a particularly strong alkaline phosphatase reaction. The reticulum cells of the areas containing B-lymphocytes and those of the EAC-negative periarteriolar regions, which probably contain T-lymphocytes, were specifically labeled for different sets of enzymes. These findings suggest that specialized, morphologically different reticulum cells may be the “guide rails” for the different freely circulating lymphocyte populations.

The Cytologic, Histologic, and Functional Bases for a Modern Classification of Lymphomas

Since 1961, when Part A of this Handbook appeared, experimental lymphocyte research and immunology have provided so many revolutionary data that it is necessary to reassess our cytologic and histologic bases of classification. Therefore, some of the most important data will be presented here. This will lead to a substantial widening of our horizons of 1961 and also to certain corrections. These cannot affect the morphology itself, of course, but rather its interpretation, in particular that of the cytogenetic derivation of the cells and their different morphologic appearances. Above all, it has become evident that lymphocytes and plasma cells are not derived from reticulum cells. Instead, stimulation and transformation of small lymphocytes result in the development of large blast cells (immunoblasts, centroblasts), which serve as the precursors of lymphocytes and plasma cells. Some other variants (stimulated lymphocytes, “immature sinus histiocytes”) that have been separated morphologically are probably such transformed or activated lymphocytes. Furthermore, it has been shown that most macrophages and one of their specific functional forms, namely, epithelioid cells, are of monocytic origin.

Interdigitating cells in the white pulp of the human spleen.

SummaryInterdigitating cells are demonstrated as a special type of fixed cell in the periarteriolar lymphocytic sheaths of the human spleen. These cells show typical ultrastructural features as well as a characteristic enzyme histochemical pattern that distinguish them from other reticular cells in the splenic white pulp.

Fibroblastic and dendritic reticulum cells of lymphoid tissue

SummaryFibroblastic reticulum cells of different lymphoid organs were investigated to clarify their relationship to other stationary cells of the lymphoid tissue and to fibroblasts of the connective tissue.Fibroblastic reticulum cells have many ultrastructural characteristics of fibroblasts but differ from them in containing prominent bundles of microfilaments and in reacting strongly with antibodies to smooth muscle type myosin and actin. The fibroblastic reticulum cell may be thus classified as a myofibroblast. Enzyme-histochemical studies showed that fibroblastic reticulum cells contain a definite alkaline phosphatase isoenzyme. During ontogeny fibroblastic and dendritic reticulum cells are derived from the local mesenchyme and may be considered as primary stationary reticulum cells. During the formation of the follicle in the splenic white pulp in young rats fibroblastic and dendritic reticulum cells show a different turnover which speaks in favor of a proliferation of dendritic reticulum cells or their precursors in follicle formation.

Pseudofollikuläre Nester von Plasmazellen (eines besonderen Typs?) in der paracorticalen Pulpa menschlicher Lymphknoten

SummaryA comparative light and electron microscopic study of the so-called Lymphoblastennester (nests of lymphoblasts) (Lennert) in 5 lymph node biopsies was performed. Light microscopically these cells are characterized by a uniform, lightly stained, oval nucleus with a small, but prominent nucleolus. The weakly basophilic cytoplasm is moderately large, well defined and strains grey—blue with Giemsa. These cells are arranged in small or larger groups showing a topographic relation to the postcapillary venules and the intermediary sinuses of the paracortical pulp of the lymph nodes. Electron microscopically the dominating cell type of these “nests” shows a well developed ergastoplasm and a prominent Golgi-apparatus. The ergastoplasm is composed of long, rough-surfaced tubules lying parallel to the nucleus, and of small vesicles. The lightly stained cytoplasm contains only few ribosomes or polysomes. These cells represent a morphologically separate type of plasma cells. Their origin and functional significance, however, remains uncertain.

Human lymphatic microecology - specificity, characterization and ontogeny of different reticulum cells in the B cell and T cell regions.

The well-known phenomenon that the circulating B and T lymphocytes reach the lymphatic tissue by similar routes but dissociate thereafter according to their functional differentiation and localize at different sites, can hardly be understood if lymphocytes alone are considered as responsible. The evidence for specific microenvironments in the lymphatic tissue defining the structural component of a microecological relationship between migrating and resting cells, has been indirect and. up to now, a theoretical chalenge. The term “reticulum cell” is used as a common name for all structural cells in the lymphore-ticular tissue, in spite of the fact that 1) different functional definitions, that have been proposed, may determine different cell types (e.g. fiber formation vs. phagocytosis) and 2) new cell types have been described in the lymphatic tissue of rodents and man, which neither phagocytose nore form fibers. These cells have been called dendritic reticulum cells (DRC)(l) and intergitating reticulum cells (IDC) (2). Our study deals with the morphological demonstration of different structural (“reticulum”) cells in human lymphatic tissue, which as a micro-ecological pattern, may give a formal explanation for the different localization of T and B lymphocytes.

Bacterial lymphadenitis with the picture of a lymphoepithelioid cell lymphoma—Lennert's lymphoma

Three cases with the typical light microscopic picture of lymphoepithelioid cell lymphoma (so‐called Lennerts lymphoma) were investigated by electron microscopy. Surprisingly, Lennerts lymphoma could be excluded in two cases. These two cases exhibited, in addition to pleomorphic lymphocytes and epithelioid cells, macrophages with accumulations of bacteria, indicating that a bacterial infection was the cause of the disease. By comparing the typical case of Lennerts lymphoma with the other cases, we found several criteria for distinguishing between Lennerts lymphoma and bacterial lymphadenitis. In bacterial lymphadenitis: (1) small and medium‐sized lymphocytes exhibited a wide cytological spectrum whereas the lymphocytes in Lennerts lymphoma were relatively uniform; the lymphocytes with prominent lysosome‐like granules found in Lennerts lymphoma were not seen; (2) cytology and distribution of epithelioid cells were similar to those in Lennerts lymphoma; (3) epithelioid venules contained recirculating lymphocytes, which were rarely found in Lennerts lymphoma; (4) numerous interdigitating reticulum cells, fibroblasts and myofibroblasts were seen, but not in Lennerts lymphoma; (5) focal increase in reticulin fibres was the main difference in light microscopy; (6) rod‐shaped bacteria were accumulated in the cytoplasm of a few macrophages. The presence of bacteria could not be demonstrated unequivocally by light microscopy. In both cases the large number of intracytoplasmic bacteria suggests that this unusual and until now unknown lymphadenitis is the result of an infection caused by facultative intracellular parasitic bacteria. The outcome of bacterial lymphadenitis that gives the false impression of Lennerts lymphoma is uncertain. Cure was achieved in one of our cases. The other patient died before therapy was commenced.

Non-Hodgkin-Lymphome

Non-Hodgkin Lymphome (NHL) umfassen eine Gruppe von Erkrankungen, die durch eine monoklonale Proliferation von B- oder T-Lymphozyten (oder ihrer Vorlauferzellen) hervorgerufen sind. Ihr neoplastisches Wachstum erfolgt im lymphatischen System („nodal“) und/oder auserhalb desselben („extranodal“). Die einzelnen Lymphomentitaten konnen als Reifungsstorung („frozen states“) in der Entwicklung normaler B- oder TLymphozyten aufgefast werden. In der vorliegenden Ubersicht beziehen wir uns in erster Linie auf die Kiel-Klassifikation, die neben zytologischen vor allem auch funktionelle Gesichtspunkte berucksichtigt (Ubersicht bei [221, 222, 354]). Daneben wird die Working Formulation (WF) [280] angefuhrt, die sich vor allem nach den von Lukes und Collins erarbeiteten histomorphologischen Kriterien orientiert (z. B. „cleaved cells“ als morphologisches Kriterium vieler Keimzentrumszellen). Sie berucksichtigt auch das Wachstumsverhalten (follikular, diffus). Dies stellt wie zuerst Rappaport und seine Gruppe zeigten [269, 311] ein besonders wichtiges Prognosekriterium dar.