Characteristics, merits and some problems of the clinical relevance of the Revised European-American Lymphoma (REAL) classification are described, and the present status of research regarding is discussed. Several retrospective studies including pathologic reviews using the REAL system demonstrated that accurate diagnosis of newly incorporated categories such as mantle cell lymphoma and mucosaassociated lymphoid tissue (MALT)-lymphoma. was clinically significant, and that T-cell phenotype was an unfavorably prognostic factor on multivariate analysis. Although a considerable number of criticisms have been raised against the “REAL classification” such as the paucity of reproducibility studies, too many categories, lack of prognostic groupings, uncertain practicability in the patients whose immunophenotypic or molecular genetic data are not available, and questionable consensus among major hematopathologists, the REAL classification is still an attractive and probably useful classification, because each category is defined according to the presumed cell of origin, and the newly-incorporated categories are well described, using a combination of updated morphologic, immunologic, and genetic information. To evaluate the clinical implications of the REAL classification properly and establish useful clinical groupings, further clinicopathologic studies are needed.

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The splenic sinuses form a specially differentiated unique vascular system. In this study, human spleens were examined electron microscopically and immunohistochemically. The endothelial cells were elongated and lay parallel to the long axis of the sinus. Furthermore, the cells were laterally bound to each other by slender side processes. Interendothelial slits were formed between these processes. Reticular fibers bundled the outside of the sinus similar to hoops embracing staves of a barrel. On immunohistochemistry, sinus endothelial cells were positive for CD4, CD8 and monocyte/macrophage marker in addition to vimentin, factor VIII and UEA-1. Human spleen had a open circulation and blood flowed from the penicillar artery into the splenic cord. The interendothelial slits of the sinus were the major passage way of blood from the splenic cord into the sinus and played an important role in filtering aged or damaged cells from circulation.
Splenic sinuses in idiopathic portal hypertension (IPH) were further studied. In IPH, proliferation of sinus endothelium was activated as compared that in liver cirrhosis. HLA-DR expression was also increased in the sinus endothelium. Scanning electron microscopy disclosed that sinus endothelium were irregular in shape and the interendothelial slits were enlarged.

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Hematopoiesis occurs mainly in the bone marrow tissue in adult mammalian species. In bone marrow, stromal tissue and parenchymal hematopoietic tissue could be discerned. In stromal tissue, three types of fibroblastic cells could be identified, which could be assumed to have a special hematopietic inductive microenvironmental role-1) periarterial adventitial (PAA) cells, 2) intersinusoidal reticular (ISR) cells, 3) sinus adventitial reticular (SAR) cells.
SAR cells covered the adventitial surface of venous sinus wall and formed a bloodmarrow barrier with the collaboration of endothelial cells. ISR cells and SAR cells had well-developed thin cytoplasmic processes and formed a reticular cellular network within the hematopoietic parenchyma, which divided it into many incomplete compartments. Within the adventitia of bone marrow arterioles, PAA cell is characterized by a thin veil-like cytoplasm which concentrically surrounds both nerves and arterioles. Nerve fibers containing unmyelinated axons and nerve terminals are distributed mainly between the layers of PAA cells, but rarely on the sinus walls or within the hematopoietic parenchyma. In this case, efferent (autonomic) nerves and bone marrow stromal cells which are connected by gap junctions (SAR cells, ISR cells, and PAA cells) appear to constitute a potential functional unit for signal conduction. We would like to propose a new term for this anatomical unit in marrow, the “neuro-reticular complex”.
The cellular relationship between the cancellous bone and the hematopoietic bone marrow was also suggested. Gap junctions were observed between osteocytes (within the trabeculae) and osteoblasts (at the trabecular surface) and between osteoblasts and marrow reticular cells. These data emphasise the intimate relationship of the various mesenchymal cells based on processes and intercellular junctions, and point to an anatomical and probably functional integration of trabeculae and marrow.

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In this experiment, we examined the structure and the cellular reaction in lymphatic sinuses and the surrounding regions caused by T-independent (LPS) and T-dependent (SRBC) antigens administration in rats and SMA mice (LPS high responder strain).
Lymphatic sinuses are incompletely lined by smooth lymphatic endothelial cells, and a distinctive basement membrane is lacking. Reticulum cells form a loose meshwork not only the regions around the lymphatic sinuses but also in the lumen of the sinuses. On days 1 and 3 after intraperitoneal injections of either LPS or SRBC, the lymphatic sinuses were dilated, and many macrophages, which bear LPS antigens immunostained by IC6H or EO9, were found in and out of the marginal and trabecular sinuses. After the carbon solution was injected into footpad subcutis, carbon laden-macrophages were also found there in a few minutes. That is to say, antigens reached LN via lymphatics, and spreaded around lymphatic sinuses easily in short time. The structure of lymphatic sinuses allows easy passage of antigens in and out of the sinuses, and the meshwork of reticulum cells causes the stasis of lymphatic flow.
We also found in lymph node (LN) that B-lymphocytes (B-lys), which have the same phenotypes as marginal zone B-lys (MZB), were induced by LPS injection. These B-lys infiltlated around marginal and trabecular lymphatic sinuses on days 1 and 3 after LPS injection. Moreover, plasmacytic B-lys and plasma cells were found in the same regions as the B-lys infiltlated preceding the formation of activated germinal centers (GC) in SMA mice. These findings suggested that the B-lys mature into plasma cells around the lymphatic sinuses independent of B-lys differentiation in GC. Although marginal zone (MZ) do not exist in LN anatomically, it is also suggested that the regions around marginal and trabecular lymphatic sinuses are functionally identical to MZ.

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