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Notes: Summary The immunopathological features of (1) lymphocytic non-Hodgkin lymphomas (NHL), (2) follicular centre cell tumours and (3) “large-cell” NHL are described with particular emphasis on in situ evaluation of cryostat sections using monoclonal antibodies. The immunological phenotypes of tumour cells and the pattern of “reactive” cellular infiltrates with characteristic differences for the various subtypes are summarized. Immunological membrane features of the following lymphocytic NHL of B lymphocyte origin are discussed in detail: B-CLL (most common phenotype of the lymphoma cells: VIB-C5, To-15, Ia, Leu-1), lymphoplasmocytoid NHL (To-15, Ia), B-prolymphocytic leukaemia (VIB-C5, To15, Ia, Leu (±), FMC-7(±)) and hairy-cell leukaemia (HCL: To-15, Ia, FMC-7). NHL of T-lymphocytes detailed in respect of mycosis fungoides and Sézary syndrome (OKT-3, OKT-4, OKT-11), to subtypes of T-CLL with particular emphasis on the “azurophilic” type, to T-zone NHL, and to adult T-cell leukaemia/lymphoma (OKT-3, OKT-4, OKT-11, anti-tac), all of them with the usual immunological phenotype of T-helper (TH) lymphocytes. NHL with a predominance of T-suppressor (TS) lymphocytes include the immunoblastic lymphadenopathy like T-cell lymphoma (OKT-3, OKT-8, OKT-11) and some lymphoepitheloid (Lennert) lymphomas. Immunological features of follicular centre cell tumours are discussed with emphasis on similarities and differences with the normal germinal centre. Tumour cells usually show the following membrane phenotype: centroblastic/centrocytic (cb/cc: To-15, VIL-A1, Ia; meshwork of non-neoplastic R4/23+, To-5+DRC), centrocytic (VIB-C5, To-15, Leu-1, Ia; R4/23 and To-5 meshwork), centroblastic (cb, To-5, To-15, Ia, VIL-Al±). “Large-cell” NHL include the last entity (cb), immunoblastic (B-ib, T-ib) and lymphoblastic (lb) NHL and are discussed in respect to B-ib (Ia, To-15±, VIL-Al±), T-lb (WT-1, OKT-6±, OKT-11±), pre-B-lb (VIB-C5, Ia, TdT, VIL-Al±) and Burkitt-type NHL (VIB-C5, VIL-A1, Ia, sIg). “Reactive” cellular infiltrates may account for a large fraction of the cellular content of NHL (e.g. the mean TH and TS content amount to about 40% of that seen in normal lymph nodes). In comparison to other NHL B-CLL and cb/cc showed the highest, HCL the lowest number of TH. TS exhibited less typical alterations. With the HNK 1 antibody as marker of putative natural killer (NK cells) high numbers of positive cells were found in cb/cc (and in some CLL and other NHL), sparse infiltrates in lb NHL. The highest number of cells with the phenotype of macrophages were usually found in ib NHL. We conclude that immunological typing of tumour cells as well as of “reactive” cellular infiltrates is of major interest not only in the evaluation of tumour cell characteristics but also with respect to the microenvironment of lymphomas and the host response.

Notes: Summary Cryostat sections of 246 consecutive bone marrow biopsies from 212 patients with lymphoproliferative disease were investigated using a panel of monoclonal antibodies (MOAb's) and an immunoperoxidase technique. Bone marrow involvement was demonstrated by immunohistological examination in 121/160 patients (76%) with non-Hodgkin lymphomas (NHL) and 16/23 patients (70%) with plasma cell malignancies; the definite immunological diagnosis could be performed in 77% and 88%, respectively. Reactivity with the MoAb Ki-67 correlated with clinical parameters: in all cases exhibiting more than 5% positive cells an unfavourable course was seen, independent of the histological subtype. Another MoAb of potential prognostic relevance is KiM4b, which reacts with follicular dendritic cells (FDC). Besides the presence of FDC in germinal center tumors (CB/CC and CC-NHL) we found FDC in a minority of cases with B-CLL (5/44) and IC lymphoma (4/18). In the latter group 3/4 patients showed a favourable clinical course (vs 2/14 without FDC). The MoAb Tü1 could discriminate between the lymphoplasmocytoid (11/12 positive) and the lymphoplasmocytic (0/6 positive) subtype of IC lymphoma and has proven of diagnostic importance. Expression of IL-2 receptors, detected by MoAb anti-Tac (CD25), was demonstrated on leukemic cells from patients with hairy cell leukemia (100%), B-CLL (82%), IC (61%), CC (50%) and CB/CC lymphoma (50%). A considerable number of reactive T-lymphocytes (5%–60% of tissue cells) were identified among the neoplastic B cells with a predominance of CD4+ cells in most cases with NHL, whereas the CD4+/CD8+ ratio was significantly lower in myelomas and non-infiltrated bone marrows. The potential meaning of these findings is discussed. The immunohistological bone marrow analysis represents an important additional method in the diagnostic procedures of lymphoproliferative diseases involving the bone.

Notes: Summary Large granular lymphocytes (LGL) represent a morphologically distinct mononuclear cell type. In healthy individuals an average of 12.5±5.2% of peripheral mononuclear cells exhibit this morphology. Structurally they are characterized by azurophilic granules, light cell density, low surface adherence and expression of Fc-IgG receptors. Functional analyses on LGL suspensions enriched by means of density gradient fractionation and adherence procedures included testing of T-cell and monocyte-specific in vitro reactions as well as evaluation of their natural cytotoxicity (NC). Results indicated a close correlation between the percentages of LGL and the capacity to bind and to lyse NC-susceptible tumor targets. In agreement with others we would thus conclude that LGL embrace the majority of NK-effector cells. The morphological definition of LGL provides an additional tool for the clinical evaluation of this cell mediated immune reactivity.

Notes: Summary This study aimed to investigate high molecular weight surface glycoprotein (S-GP) patterns on various types of human leukocytes. S-GP were externally labelled by the Galactose-oxidase-NaB3H4 technique. Results based on the analysis of 120 samples derived from different types of normal and malignant leukocytes indicate that (i) the relative expression of high molecular weight S-GPs changes during haemopoietic cell differentiation and (ii) to some extent these changes enable the classification of human leukocytes.