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Malignant lymphomas

Malignant lymphomas. Lymph nodes:. Germinal center (GC) and mantle B-cells. capsule. Paracortical T-cells and high endothelial venules. sinus. mantle. GC. 3-5% of deaths in developed world higher in other areas 3-7 cases per 100,000 in USA males greater than females, white males highest

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Malignant lymphomas

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  1. Malignant lymphomas

  2. Lymph nodes: Germinal center (GC) and mantle B-cells capsule Paracortical T-cells and high endothelial venules sinus mantle GC

  3. 3-5% of deaths in developed world higher in other areas 3-7 cases per 100,000 in USA males greater than females, white males highest increases with age histology varies with age, low grade frequent in adults high grade most frequent in children Lymphoma - incidence and mortality

  4. Hodgkin’s mixed cellularity nodular sclerosis lymphocyte depleted lymphocyte predominant Non-Hodgkin’s lymphoma low grade B-cell small lymphocytic marginal zone mantle cell (B-cell) follicular (B-cell) large B-cell Burkitt’s (B-cell) lymphoblastic (mostly T-cell) T/NK-cell mycosis fungoides (cutaneous T-cell) Classification of lymphoma

  5. ML types in POG 1998-2000 476 NHL 373 HD

  6. Thomas Hodgkin

  7. Hodgkin’s Disease Mixed cellularity Lymphocyte depleted Nodular sclerosis Lymphocyte predominant

  8. Reed Sternberg Cell H&E Wright stain R-S cells: CD30

  9. Incidence of HD • 3-7 per 100,000 • Bimodal • 15-34 & > 55 • NS increasing in young patients • young women • LD decreasing in older patients Medeiros, Cancer 75:357,1995

  10. Hodgkin’s Disease • Reed-Sternberg (RS) cell in immunoproliferative background • RS cells minority • background • lymphocytes, eosinophils, plasma cells, histiocytes • RS cells B-cells (90%) or T-cells (10%) • cervical LN or mediastinum; spread to thoracic para-aortic LN, spleen, liver, abdominal Para-aortic nodes • Association with EBV: 96% MC, 34% NS, 10% LP • radiation for localized disease • chemotherapy or chemo/RT for advanced disease

  11. Mixed cellularity Hodgkin’s Disease • Diffuse infiltrate including relatively frequent RS cells • CD15 and CD30 antigen expression • classical HD

  12. Nodular Sclerosis Hodgkin’s Disease • RS cells and “lacunar” cells in clusters surrounded by collagen fibrosis • CD15 and CD30+ • Often mediastinal mass in young women

  13. Lymphocyte depletion HD • Diffuse infiltrate • numerous RS cells and variants with relatively few lymphocytes • Often older men with advanced disease • Difficult to distinguish from large cell NHL

  14. Lymphocyte predominant HD • Nodular or sometimes diffuse infiltrate containing “L&H” cells (for “lymphocytic and histiocytic LPHD”) • label as polyclonal B-cells • usually localized (often cervical LN) • indolent clinical course

  15. Hodgkin’s disease • Most cases derived from clonal B-cells • Heavy load of somatic mutations • Lack crippling mutations, but do not transcribe IgH due to functional regulatory defects • HD and NHL have derived from same clone Seitz, Blood. 2000 May 15;95(10):3020-4

  16. Non-Hodgkin’s Lymphoma Small lymphocytic Mantle cell Burkitt Lymphoblastic Follicular center cell Large B-cell Peripheral T-cell

  17. Phenotype in diagnosis of NHL CD45Ro (T-cell) ALK-1 CD79a (B-cell) BCL-2

  18. Incidence of NHL in US overall • 7.4-17.1 per 100,000 • Males > females • Racial differences • whites more FL • blacks more PTC Groves, JNCI, 92;1240-51, 2000

  19. NHL in Children • 4.6-9.1 per million • white > black • male > female • 1/3-1/2 SNC, LB, LC • Geographic variation • incidence • histologic type • biology of Burkitt’s POG 1998-2000 Shad, Ped Clin NA 44:863-89, 1997

  20. Human B-cell lymphomas • Sequencing of the variable region genes - somatically mutated in majority of non-Hodgkin’s and Hodgkin’s lymphomas • this indicates germinal or post-germinal center origin • unmutated variable region genes: mantle lymphoma, some CLL’s

  21. Burkitt’s Lymphoma • Medium size cells • nuclei same as histiocyte nuclei • Oval nuclei • 3-5 nucleoli, open chromatin • Basophilic (vacuolated) cytoplasm • High mitotic rate, starry sky • Mature B-cell, surface IG+, analogous to L3 ALL • EBV in endemic areas and immunosuppression

  22. Large B-cell Lymphoma • Average nuclei larger than histiocyte nuclei • Mature B-lineage (CD20+) • Morphologic heterogeneity • Centroblastic • Centroblastic/centrocytic • B-immunoblastic • BCL 6 or BCL2 overexpression in some

  23. Burkitt-Like Lymphoma • Mature B-cell • Average cell medium size (like Burkitt) • More variability than Burkitt • Nuclear size • Nuclear shape • Nucleolar prominence • Sometimes fine fibrosis • Interface between Burkitt & large B-cell lymphoma

  24. Small lymphocytic lymphoma/CLL • slow growing • diffuse infiltrate of small lymphocytes • admixed prolymphocytes; growth centers • often indolent • mature B-cell with CD5 expression

  25. SLL in children • Rare cases described • t(2;14)(p13;q32) in several • Citations: • Fell, et al. Science 232:491-4, 1986 • Yoffe, et al. J Pediatr 116:114-7, 1990 • Ribeiro, et al. Leukemia 6:761-5, 1992

  26. Follicular lymphomas • One of the most common NHL • Mature B-cell • Slow-growing, persistent • t(14;18) with bcl-2 overexpression • graded by cell type

  27. Follicular Lymphoma in children • 1% (17) of 1336 pediatric lymphomas • Ribeiro, et al. Leukemia 6:761-5, 1992 • usually mixed or large cell, • lack bcl-2 or p52 abn; some testicular • generally good outcome • those who fail progressed to DLBCL • Frizzera, Cancer 44:2218, 1979; Winberg, Cancer 48:2223, 1981 • Pinto, Mod Pathol 3:308, 1990; Moertel, Cancer 75:182, 1995 • Atra, Br J Haem 103:220, 1998; Finn, Cancer 85:1626, 1999

  28. Marginal zone lymphoma • mature B-cell • arises from splenic or mucosal (MALT) marginal zone cells • “monocytoid” appearance • Lymphoepithelial lesions in MALT • often indolent • Gastric; H. pylori

  29. Marginal Zone lymphoma in children • Occasional (<1%) • Gastric • associated with H. pylori • may resolve with tx of H. pylori • Many associated with HIV • Salivary gland, lung, GI • Citations: • Teruya-Feldstein, AJSP 19:357, 1995; Blecker, Gastroent.109:973, 1995 • Joshi, AJCP 107:592, 1997; Corr, J Ultrasound Med 16:615, 1997 • Berrebi, J Peds 133:290, 1998; Fukumoto Hihon Rinsho MGK 23:49, 2000

  30. Mantle cell lymphoma Neoplastic mantle zone cells • mature B-cell • arises from follicular mantle • resembles SLL and MZL • t(11;14) with cyclin-D1, CD5, (CD23-) • expresses bcl-2 as do nl mantle cells; long-lived • difficult to eradicate and aggressive Residual germinal center

  31. T-cell lymphomas • Less common that B-cell • Some associations with retroviruses • HTLV-1 • Cytogenetic abnormalities variable • include chr. 14 abnormalities • t(2;5) and variants in ALCL • Generally difficult to eradicate

  32. T-cell development • Maturation/selection in thymus • T-cell receptor gene rearrangement • gamma/delta • alpha/beta • Tdt, CD7, CD5, CD2 • CD1, CD4/CD8, CD3 • Mature cells CD4 or CD8 and CD3

  33. Lymphoblastic Lymphoma • Small cells • nuclei smaller than histiocyte’s • Diffuse chromatin, inconspicuous nucleoli, often nuclear convolutions • High mitotic rate, starry sky • Precursor T-cell • T-zone distribution, infiltrative • Tdt, CD7, CD1, CD4/CD8 • Rare precursor B-lineage

  34. Anaplastic Large Cell Lymphoma • Large cells with abundant cytoplasm • often indented or lobated nuclei • LN sinus, paracortex • CD30 expression • T or null phenotype • t(2;5) • ALK protein expression

  35. ALCL - CD30 and ALK expression CD30 Most cases in children and young adults express ALK due to t(2;5) or variant translocation. ALK1 Most cases over 35 are ALK negative

  36. ALK-1 in recent LCL A majority of T or null LCL in children express CD30 and ALK

  37. Non-anaplastic PTCL • Diverse entities • PTCL, NOS; angiocentric; nasal; T-gamma; panniculitic; ATL; MF • Rare in children • Likely worse than ALCL

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