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Notes: Histiocyte-rich, T-cell-rich B-cell lymphoma: a distinct diffuse large B-cell lymphoma subtype showing characteristic morphologic and immunophenotypic features Aims: The clinicopathological features of histiocyte-rich, T-cell-rich B-cell lymphoma (HRTR-BCL) were first recognized in 1992. In this study, 60 cases of HRTR-BCL were analysed in order to provide a detailed morphological and immunophenotypical profile of the disorder. Methods and results: HRTR-BCL is easily distinguished from other B-cell lymphomas rich in stromal T-cells by (i) a diffuse or vaguely nodular growth pattern, (ii) the presence of a minority population of CD15−, CD20+ large neoplastic B-cells, (iii) a prominent stromal component composed of both T-cells and non-epithelioid histiocytes, and (iv) the scarcity of small reactive B-cells. These criteria also enable a reliable distinction from lymphocyte-rich classical Hodgkin’s lymphoma (CHL), from lymphocyte-predominant Hodgkin’s lymphoma (LPHL), paragranuloma type and from peripheral T-cell lymphoma. Based on the morphology of the neoplastic cells and on their frequent bcl-6 immunoreactivity, we speculate that HRTR-BCL may be derived from a progenitor cell of germinal centre origin. Conclusions: HRTR-BCL presents characteristic clinical features, affecting predominantly middle-aged men who present with advanced stage disease and are at high risk of treatment failure. Considering these distinctive clinicopathological features, recognizing HRTR-BCL as a lymphoma entity may be justified.

Notes: Tumours of histiocytes and accessory dendritic cells: an immunohistochemical approach to classification from the International Lymphoma Study Group based on 61 cases Neoplasms of histiocytes and dendritic cells are rare, and their phenotypic and biological definition is incomplete. Seeking to identify antigens detectable in paraffin-embedded sections that might allow a more complete, rational immunophenotypic classification of histiocytic/dendritic cell neoplasms, the International Lymphoma Study Group (ILSG) stained 61 tumours of suspected histiocytic/dendritic cell type with a panel of 15 antibodies including those reactive with histiocytes (CD68, lysozyme (LYS)), Langerhans cells (CD1a), follicular dendritic cells (FDC: CD21, CD35) and S100 protein. This analysis revealed that 57 cases (93%) fit into four major immunophenotypic groups (one histiocytic and three dendritic cell types) utilizing six markers: CD68, LYS, CD1a, S100, CD21, and CD35. The four (7%) unclassified cases were further classifiable into the above four groups using additional morphological and ultrastructural features. The four groups then included: (i) histiocytic sarcoma (n=18) with the following phenotype: CD68 (100%), LYS (94%), CD1a (0%), S100 (33%), CD21/35 (0%). The median age was 46 years. Presentation was predominantly extranodal (72%) with high mortality (58% dead of disease (DOD)). Three had systemic involvement consistent with `malignant histiocytosis'; (ii) Langerhans cell tumour (LCT) (n=26) which expressed: CD68 (96%), LYS (42%), CD1a (100%), S100 (100%), CD21/35 (0%). There were two morphological variants: cytologically typical (n=17) designated LCT; and cytologically malignant (n=9) designated Langerhans cell sarcoma (LCS). The LCS were often not easily recognized morphologically as LC-derived, but were diagnosed based on CD1a staining. LCT and LCS differed in median age (33 versus 41 years), male:female ratio (3.7:1 versus 1:2), and death rate (31% versus 50% DOD). Four LCT patients had systemic involvement typical of Letterer–Siwe disease; (iii) follicular dendritic cell tumour/sarcoma (FDCT) (n=13) which expressed: CD68 (54%), LYS (8%), CD1a (0%), S100 (16%), FDC markers CD21/35 (100%), EMA (40%). These patients were adults (median age 65 years) with predominantly localized nodal disease (75%) and low mortality (9% DOD); (iv) interdigitating dendritic cell tumour/sarcoma (IDCT) (n=4) which expressed: CD68 (50%), LYS (25%), CD1a (0%), S100 (100%), CD21/35 (0%). The patients were adults (median 71 years) with localized nodal disease (75%) without mortality (0% DOD). In conclusion, definitive immunophenotypic classification of histiocytic and accessory cell neoplasms into four categories was possible in 93% of the cases using six antigens detected in paraffin-embedded sections. Exceptional cases (7%) were resolvable when added morphological and ultrastructural features were considered. We propose a classification combining immunophenotype and morphology with five categories, including Langerhans cell sarcoma. This simplified scheme is practical for everyday diagnostic use and should provide a framework for additional investigation of these unusual neoplasms.

Notes: Marginal zone cell lymphoma—an update on recent advances The marginal zone represents one of the distinct compartments of the B-cell area in lymphoid tissues. It is especially well developed in the spleen and in Peyer's patches of the gut, but not in lymph nodes, with the exception of the ones in the mesenterium. However, the pronounced proliferation of so-called `monocytoid B-cells' that may be seen in some inflammatory conditions of the lymph node may be regarded as a nodal reactive marginal zone cell expansion. The cellular compositions of the marginal zone and the monocytoid B-cell proliferation are similar and both show a heterogeneous population of B-cells, of which the functions are being slowly unravelled. Neoplasms originating in the marginal zone have been recognized in the past and are listed in the REAL classification as marginal zone B-cell lymphomas including extranodal MALT-type lymphomas, splenic marginal zone lymphomas and nodal (monocytoid) marginal zone lymphomas. Marginal zone cell lymphomas display a broad morphological spectrum, which is reflected by the heterogeneity of the cellular composition and the variation in the growth pattern of the lymphoma, but is independent of the anatomical site. All three marginal zone cell lymphomas share immunophenotypic, genetic and chromosomal similarities which will be discussed. The morphologic features are dealt with only briefly as they have been extensively discussed elsewhere.

Notes: Aims : To evaluate the HER-2/neu status at the mRNA and DNA level of breast carcinomas and to compare it with HER-2/neu receptor overexpression by immunohistochemistry (IHC).Methods and results : In 32 invasive breast carcinomas, frozen tissue was available for real-time detection of HER-2/neu mRNA levels by reverse transcription-polymerase chain reaction (RT-PCR). Corresponding paraffin sections were examined by IHC and fluorescence in-situ hybridization (FISH). Thereby, different IHC and FISH procedures were compared. Using microwave epitope retrieval, all 32 cases scored 3+ on IHC, whereas only 28 out of 32 cases scored IHC 3+ using water bath epitope retrieval. All of these 28 cases showed increased levels of HER-2/neu mRNA. Dual-colour FISH analysis showed corresponding gene amplification in all 28 cases, with two cases showing a peculiar amplification pattern. In the remaining four cases, scoring IHC 2+ using water bath epitope retrieval, mRNA levels were not elevated. Three cases did not have gene amplification and one case showed low-level HER-2/neu gene amplification. All four carcinomas showed chromosome 17 polysomy.Conclusions : Real-time RT-PCR is accurate in selecting breast carcinoma cases scoring 3+ by IHC with high-level gene amplification. Results obtained by dual-colour FISH suggest that mechanisms leading to HER-2/neu receptor overexpression may be different between carcinomas scoring 2+ and 3+ on IHC, with polysomy 17 found in the former and gene amplification in the latter.

Notes: Abstract  In this review, we summarise the patterns of bone marrow involvement by small B-cell lymphomas. Both our own experience and the literature reports on the subject show that each subtype of lymphoma can be recognised from a distinct combination of a suggestive growth pattern and a particular cytological composition. A predominantly paratrabecular infiltrate composed of centrocytes is characteristic of follicle centre cell lymphoma. In mantle cell lymphoma, prominent intertrabecular nodules, each consisting of a monotonous proliferation of small to intermediate-sized lymphoid cells with an irregular nucleus, are the most frequent finding. Marginal zone cell lymphoma displays similar intertrabecular nodules, but the infiltrates are rather loose and polymorphic, whereas the lymphoid cells exhibit monocytoid features. Diffuse infiltrates composed of small lymphocytes with clumped chromatin, of plasma cells with Dutcher bodies and of mast cells are observed in most cases of lymphoplasmacytoid lymphoma/immunocytoma. Although chronic lymphocytic leukaemia / small lymphocytic lymphoma can present with a comparable pattern of bone marrow involvement, an interstitial infiltrate of small lymphoid cells is usually observed. A comparable interstitial pattern also prevails in hairy cell leukaemia. This lymphoma subtype, however, can be readily identified by the abundant clear cytoplasm of the neoplastic cells, erythrocyte extravasation and associated abnormalities in the haematopoietic series.