1. T-cell/histiocyte-rich large B cell lymphoma Monirath Hav, MD, PhD fellow Pathology Department Ghent University Hospital

2. Diffuse large B-cell lymphoma (DLBCL), NOS T-cell/histiocyte rich large B-cell lymphoma Primary DLBCL of the CNS Primary cutaneous DLBCL, leg type EBV + DLBCL of the elderly * WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues 2008 edition

3. Introduction -Characterized by a limited number of scatterd, large, atypical B cells embedded in a background of abundant small T cells and frequently Histiocytes -Age: mainly middle-aged men (12-61 yo, 75% cases are male) -Refractory to present chemotherapy -Postulated normal counterpart: germinal center B cell

4. Morphology Diffuse or less commonly vaguley nodular growth pattern Scattered, single, large B cells (<10%) embedded in the background of small T lymphocytes and variable numbers of histiocytes Tumour cells do not form aggregrates or sheets and mimic popcorn cells in NLPHL but usually show a more pronouced variation in size Cases in which tumour cells form sheets or nests should be classified as a subtype of DLBCL, NOS Eosinophils and plasma cells are not found

5. Immunophenotype The large atypical cells are: –Positive for pan B cell markers, BCL6 & some for BCL2 & EMA –Negative for CD15, CD30, & CD138 The background is composed of CD68+ histiocytes and CD3, CD5 & CD8 + T cells Unlike in NLPHL, rosettes of T-cells around the tumour cells are not found in THRLBCL

6. Differential diagnosis  Main DD: NLPHL  rosettes of T cells around tumour cells, usually no BM involvement, CD57+, small B cells in the background

7. Prognosis Aggressive lymphoma Refractory to presently available therapy IPI score is the only parameter of prognostic significance

8. LHRLBCL Vs NLPHL - similarities Predilection for middle-aged men Both derived from germinal center B cells Diffuse or vague nodularity growth pattern Eosinophils and plasma cells are seldom seen Large atypical tumour cells are (+) for CD20, CD79a, PAX5, CD45, CBL6, & BCL2 in the background of small CD3 + cells Large atypical tumour cells are (–) for CD30 * & CD15 Large atypical tumour cells are usually EBV (–)

9. LHRLBCL Vs NLPHL - differences LHRLBCLNLPHL - CD20 + small reactive B cells are rare or absent in the background - CD8 + cells & histiocytes are common - CD3 + cells do not form rosettes around tumour cells - CD21+ FDC are absent - BM, spleen or liver involvement is frequent - Aggressive lymphoma, refractory to current therapy - CD20 + small reactive B cells are numerous in the background - CD4 and CD57 + cells are common - CD3 & CD57 + cells form rosettes around tumour cells - CD21+ FDC form expanded meshwork - BM, spleen, or liver involvement is rare - Non agressive lymphoma, responsive to therapy (10 y OS >80% for stage I & II)

11. References 1. WHO classification of Tumours of Haematopoietic and Lymphoid Tissues, 2008 edition 2. Frank X. Zhao. Nodular Lymphocyte-Predominant Hodgkin Lymphoma or T cell/Histiocyte Rich Large B-cell Lymphoma: The Problem in “Grey Zone” Lymphomas. Int J Clin Exp Pathol (2008) 1, 300-305 3. Ludmila Boudova et al. Nodular lymphocyte–predominant Hodgkin lymphoma with nodules resembling T-cell/histiocyte-rich B-cell lymphoma: differential diagnosis between nodular lymphocyte–predominant Hodgkin lymphoma and T-cell/histiocyte-rich B-cell lymphoma. Blood. 2003;102:3753-3758. 4. Megan S. Lim et al. T-Cell/Histiocyte-Rich Large B-Cell Lymphoma: A Heterogeneous Entity With Derivation From Germinal Center B Cells. Am J Surg Pathol 26(11): 1458- 1466, 2002. 5. Á. Illés et al. Nodular Lymphocyte Predominant Hodgkin Lymphoma (NLPHL) Clinicopathological Features Based on the Data of Two Hungarian Lymphoma Centres. Pathol. Oncol. Res. (2008) 14:411–421