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Contains fulltext : 47723.pdf (Publisher’s version ) (Closed access) Mantle cell lymphoma (MCL) is a distinct lymphoma subtype with a particularly poor clinical outcome. The clinical relevance of the morphological characteristics of these tumours remains uncertain. The European MCL Network reviewed 304 cases of MCL to determine the prognostic significance of histopathological characteristics. Cytomorphological subtypes, growth pattern and markers of proliferation (mitotic and Ki-67 indices) were analysed. In addition to the known cytological subtypes, classical (87.5%), small cell (3.6%), pleomorphic (5.9%) and blastic (2.6%), we identified new pleomorphic subgroups with mixtures of cells (classical + pleomorphic type; 1.6%) or transitions (classical/pleomorphic type; 1.6%), which, however, did not differ significantly in overall survival time. Exactly 80.5% of cases displayed a diffuse growth pattern, whereas 19.5% of cases had a nodular growth pattern, which was associated with a slightly more favourable prognosis. A high proliferation rate (mitotic or Ki-67 indices) was associated with shorter overall survival. Cut-off levels were defined that allowed three subgroups with different proliferation rates to be discriminated, which showed significantly different clinical outcomes (P < 0.0001). Based on this large clinicopathological study of prospective clinical trials, multivariate analysis confirmed the central prognostic role of cell proliferation and its superiority to all other histomorphological and clinical criteria.

Aims: Inguinal lymph nodes are considered to be problematic for the diagnosis of lymphoma due to architectural changes resulting from previous inflammatory processes. The aim was to investigate the morphology and immunophenotype of follicular lymphomas (FL) in order to clarify whether FL presenting in inguinal nodes differs from FL biopsies from other sites. Methods and results: A total of 219 FLs were studied, comprising 78 biopsy specimens of inguinal lymph nodes and 141 from other sites. All samples were assessed for growth pattern, grade, sclerosis and immunophenotype (Bcl-2, CD10, CD23, Mib-1). Cases negative for Bcl-2 were analysed by polymerase chain reaction and fluorescence in situ hybridization. In comparison with the biopsies from other regions, we found a significantly increased number of CD23+ FLs in samples of inguinal lymph nodes (38% versus 21%). Expression of CD23 was more frequently detected in grade 1 FLs than in other grades (grade 1, 37%; grade 2, 18%; grade 3, 23%; transformed, 6%). Other immunohistochemical parameters, however, did not differ between the two groups. Conclusion: There is an unexpectedly high frequency of CD23 expression in FL in general, which is even more pronounced in inguinal nodes.

We report a rare case of primary gastrointestinal lymphoma, stage IE, in a 58-year-old white man who had multiple colonic polyps measuring up to I x 1. 1 cm. The tumor originated in the marginal zone of the follicles infiltrating the interfollicular spaces. Follicular colonization was frequently seen. The mucosa was spared by the infiltrate. Morphologically, the neoplastic cells were monomorph, intermediate-sized blasts. Rare small to intermediate sized cells, some with centrocyte-like morphology, intermingled the blastic infiltrate. The neoplastic cells expressed CD20 and had a monotypic immunoglobulin of cytoplasmic IgM (kappa) on paraffin sections. Tumor cells stained negative for CD45RO, CD5, CD10, IgD, and CD23. Polymerase chain reaction revealed a clonal V-D-J rearrangement. Bcl-1 and bcl-2 rearrangement were not detected. We therefore suggest the diagnosis of primary large cell lymphoma with marginal zone growth pattern mimicking colonic adenomas.

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Transgenic mice overexpressing the interleukin 9 gene were generated to study the biological activity of this cytokine in vivo. Although no major histological or morphological modifications of the lymphoid system were observed in most animals, approximately 7% of transgenic mice developed thymic lymphomas at the age of 3-9 months. The tumor cells, which were clonal, with unique T cell rearrangements, were double positive for the expression of CD4 and CD8. The need for additional transforming events, suggested by the low incidence of spontaneous tumors, was further indicated by the high susceptibility of the transgenic animals to injections of low doses of N-methyl-N-nitrosourea, a chemical carcinogen with a thymic tropism. Expression of interleukin 9 was required for optimal tumor growth in vivo, as one of the tumors studied, which had lost the transgene, was much more efficiently transplanted into transgenic than in normal mice. Moreover, the in vitro proliferative activity of interleukin 9 on cell lines derived from such transgene-negative tumors suggests that an autocrine loop mediates the proliferation of these cells in vivo. Taken together, these results indicate that dysregulated IL-9 expression could be involved in the development of some T cell malignancies.

Nosological classification of sinus histiocytosis with massive lymphadenopathy (SHML; Rosai-Dorfman disease) is difficult, and the normal cellular counterpart of Rosai-Dorfman (RD) cells is uncharacterised. The peculiar S-100+ phenotype of RD cells suggests a relationship with the dendritic cell family. Recent investigations have revealed cathepsin E to be selectively concentrated in antigen-presenting cells, whereas cathepsin D was found to be expressed in cells of macrophage lineage. Cathepsin D and E distribution was investigated by immunohistochemistry in a series of SHML biopsies and in two types of dendritic cell proliferative lesions: dermatopathic lymphadenitis (DL) and Langerhans' cell histiocytosis (LCH). In SHML biopsies, RD cells and monocyte-related elements of the sinuses and pulp coexpressed cathepsin D and E. LCH cells also stained for both these aspartic proteinases. Conversely, in DL cathepsin E and D were localised to separate cells that resembled Langerhans' cells (LC) or macrophages, respectively, in morphology and distribution. Our data outline the peculiar immunophenotype of RD and LCH cells and suggest that caution should be exercised in the identification of their normal cellular counterpart. The common expression of cathepsin D and E and of S-100 protein suggests some phenotypic overlap between SHML and LCH cells, despite their striking morphological divergence.