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![•classic cytogenetics [~ 90%]:
t(11;14)(q13;q32)
upregulates cyclinD1
expression, dysregulates
cell cycle
immunohistochemically:
intranuclear cyclin D1
Origin: CD5 positive, naïve cells of
the mantle zone
CD19+, CD20+, CD23 -
Mantel cell lymphoma](https://image.slidesharecdn.com/lymphomalecture1-190416123154/85/Lymphoma-lecture-1-57-320.jpg)
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Lymphoma lecture(1)
- 1. 1 Lymphoma by Dr.Hayelom k Finalyear Pathology resident Jimma university medical center hayelomk21@gmail.com
- 2. Lymphocytes in differentphases of maturation ???
- 3. Normal lymph nodearchitecture Cortex Medulla Plasma cells Paracortex T-cells Lymphoid Follicle B-cells Lymphocyte constantly recirculate
- 4. Lymphoid follicle (B-Cellregion) Germinal center Centroblasts, centrocytes Mantle and marginal zones
- 5. Small centrocyte-arrowhead, largecentrocyte-arrow, centroblast - thick arrow Mitosis – curved arrow Germinal center cells
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- 7. Clinical manifestations oflymph node diseases -Enlarged -Tender/non tender -Systemic symptoms
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- 9. reactive changes inthe nodes
- 10. Follicular hyperplasia Rheumatoid arthritis,Toxoplasmosis
- 11. Follicular hyperplasia tingible bodymacrophages Resting lymphocytes in the mantle zone
- 12. Interfollicular/paracortical hyperplasia T-cell response,acute viral infections(mononucleosis)
- 13. Sinus histiocytosis Dilated sinusoids,increased number and size of cells lining the sinusoids
- 14. Toxoplasmosis pink, epitheloidmacrophages, follicular hyperplasia Mixed type lymphadenopathy
- 15. Necrotizing lymphadenitis Microabscesses BartonellaHenselae (silver stain) cats scratch
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- 20. ·Willis (1948) “… nowherein pathology has a chaos of names so clouded clear concepts as in the subject of lymphoid tumors ….” •Hopwood (1957) “… the urge to classify is a fundamental human instinct: like a predisposition to sin, it accompanies us into the world at birth and stays with us to the end …”
- 21. Lymphoma classification Rappaport 1966 Lukes Collins 1974 Workingformula 1982 Kiel 1988 REAL 1994 WHO 2001 2008 Is this the REAL thing…..? WHO ……knows!
- 22. WHO Classification oflymphomas At least 30 types of lymphoma are recognized 3 broad flavors - B-cell lymphomas Precursor (immature), peripheral (“mature”) - T-cell lymphomas - Hodgkin lymphoma ( bona fide lymphoma) ~ 85% in North America and Europe are B-cell · two types account for > 50% of lymphomas - diffuse large B-cell lymphoma (~ 30 - 40%) - follicular lymphomas (~ 25 - 30%) ·
- 23. Etiology of lymphomas Translocationsinvolving the IgH are requent
- 24. Etiology of lymphomas Inheritedgenetic factors-genomic instability: -Down syndrome, NF type I Autoimmune disorders: Sjogren, Hashimoto Viruses: EBV, HTLV1 and herpes virus Environmental agents: -Chronic inflammation, Helicobacter Pylori and MALT lymphoma -Gluten sensitive enteropathy and intestinal lymphoma Iatrogenic: -Radiotherapy -Chemotherapy
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- 26. Diagnosing lymphoid neoplasias HOW? WHY ? Flow cytometry Immunohistochemistry Karyotyping Diagnosis Monitoring Prognosis
- 28. Diagnosing lymphomas CD 20antibody staining B lymphocytes
- 29. Diagnosing lymphoid neoplasias •T-cell markers – CD3 mature T cells – CD4 – helper T cell – CD5 – T cell, small subset of B cells – CD8 – cytotoxic T cell • B cell markers – CD19 - mature B cell – CD20 - mature B cell – CD23 - activated mature B cell – CD10 – Bcl-6
- 30. Lymphoid leukemia versuslymphoma Somewhat arbitrary, distinctions for lymphoid neoplasias Lymphoid leukemia presents with mainly bone marrow and blood involvement Lymphoma presents with nodal or extranodal mass with minimal blood/marrow involvement Many diseases overlap or evolve from one another
- 31. Signs and symptoms Lymphoidleukemias present with signs and symptoms related to bone marrow involvement Anemia, thrombocytopenia, leukopenia Lymphomas present as nontender mass (>2 cm) Extranodal- skin, GI tract, brain, Fever, weight loss, night sweats (B-symptoms) Patients may have any combination of the above
- 32. Origin of B-celllymphomas Marginal zone Mantle zone Germinal center Naive B-cell Mantle cell lymphoma Follicular lymphoma Burkitt lymphoma Large cell lymphoma Memory B-cell CLL/SLL Marginal zone lymphoma Plasma cell Myeloma
- 33. Chronic Lymphocytic Leukemia/Small LymphocyticLymphoma CLINICAL •commonest leukemia •CLL often picked up on routine CBC •typically indolent (but not always!) •rare less than 40 years •complications: • autoimmune (10-15%) (ITP, AIHA) • hypogammaglobulinemia • transformation (DLBCL) PATHOLOGY •diffuse growth pattern Spleen is frequently involved
- 34. proliferation center-mitotically activecells=this is where the tumor cells grow Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
- 35. MORPHOLOGY - small, maturelymphocytes >4000/mm3 - smudge cells characteristic IMMUNOPHENOTYPE CD19, CD20, CD23, CD5 GENETICS 13q deletion (good prognosis) trisomy of 12 11q deletion (bad prognosis) Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
- 36. Chronic Lymphocytic Leukemia/Small LymphocyticLymphoma Nucleated erythrocyte Spherocytes Smudge cells Small lymphocytes
- 37. 3.Chronic Lymphocytic Leukemia/Small LymphocyticLymphoma TRANSFORMATION 1. LARGE CELL LYMPHOMA (Richter) - 10% 2.Prolymphocytic lymphoma -15-30% average survival 1 year
- 38. FOLLICULAR LYMPHOMA 15-20 000/year,less common in Europe, Asia -Middle age patient’s -Most common indolent lymphoma -Peripheral blood 10% -Bone marrow 85% involved -Spleen and liver also commonly involved -Can undergo transformation into large cell lymphoma
- 39. Follicular lymphoma Classic lowpower view - back-to-back follicles - loss of interfollicular zones - extranodal follicles - uniform size of follicles
- 40. Follicular lymphoma Back toback, uniform follicles, attenuated mantle zone, no tingible body macrophages
- 41. Follicular lymphoma diagnostic hallmarkt(14;18) Translocates the bcl-2 gene next to IgH over expression of bcl-2 prevents apoptosis Bcl-2 + Bcl-2 – staining in normal Lymphoid follicle
- 42. APOTOSIS (Hippocratic Greek)APOPTOSIS (modern Greek)
- 43. Follicular lymphoma centrocyte: -cleaved/notched/twisted -raisin -buttock 50% transformsinto large cell lymphoma
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- 45. Splenic involvement infollicular lymphoma
- 46. Origin of B-celllymphomas Marginal zone Mantle zone Germinal center Naive B-cell Mantle cell lymphoma Follicular lymphoma Burkitt lymphoma Large cell lymphoma Memory B-cell CLL/SLL Marginal zone lymphoma Plasma cell Myeloma CB/CC
- 47. Diffuse Large B-cellLymphoma Most common non Hodgkin lymphoma(~40%) - 25, 000 new cases/year - median age 6th decade - all age groups - typically present with a single rapidly enlarging mass - often (~ 40%) extranodal Variable clinical outcome aggressive, has to be treated immediately
- 48. Diffuse Large B-celllymphoma Etiology and clinicopathologic subtypes - de novo -BCL-6 mutation freezes the differentiation of cells in the germinal center + blocks the effect of p53 -can occur anywhere in the body - transformed from either follicular lymphoma (t14;18) or CLL/SLL - immunosuppressed patients - transplant patients, AIDS patients - KSHV, EBV, HHV-8 infection
- 49. Diffuse Large B-cellLymphoma Note the population of large tumor cells, diffuse growth pattern, variation in size and shape of cells, cells with vesicular nucleus and cleaved cells
- 50. Origin of B-celllymphomas Marginal zone Mantle zone Germinal center Naive B-cell Mantle cell lymphoma Follicular lymphoma Burkitt lymphoma Large cell lymphoma Memory B-cell CLL/SLL Marginal zone lymphoma Plasma cell Myeloma CB/CC
- 51. Burkitt’s lymphoma Extremely aggressive,high grade lymphoma T(8;14) activates c-myc oncogene Clinical-genetic classification - endemic - sporadic - immunodeficiency-associated
- 52. Extremely aggressive highgrade lymphoma T(8-14) activates c-myc oncogene Endemic Non-endemic Immunodeficiency children and young adults Site Jaw/Facial Ileocecal area Systemic/non-CNS EBV ~ 100% ~ 15-20% ~ 25% BM not involved can be can be Cure rate high high ? Burkitt lymphoma
- 53. t(8;14) which activatesc-myc oncogene
- 54. Burkitt lymphoma endemicvariant
- 55. Burkitt lymphoma small roundcells in a “starry sky” pattern created by macrophages engulfing cellular debris, mitoses
- 56. Clinically: - typically presentsin elderly males - frequently extranodal: - leukemic phase - GI: lymphomatous polyposis - much more aggressive than other - poor response to conventional chemotherapy - median survival 3 - 4 years Mantle cell lymphoma
- 57. •classic cytogenetics [~90%]: t(11;14)(q13;q32) upregulates cyclinD1 expression, dysregulates cell cycle immunohistochemically: intranuclear cyclin D1 Origin: CD5 positive, naïve cells of the mantle zone CD19+, CD20+, CD23 - Mantel cell lymphoma
- 58. Origin of B-celllymphomas Marginal zone Mantle zone Germinal center Naive B-cell Mantle cell Lymphoma CLL/SLL Follicular lymphoma Burkitt lymphoma Large cell lymphoma Memory B-cell CLL/SLL Marginal zone lymphoma 4.Plasma cell Myeloma CC/CB
- 59. Extra-nodal marginal zonelymphoma, MALToma • Pathogenesis: – Autoimmune disorders: thyroid(Hashimoto), salivary glands (Sjogren) – Chronic infection: stomach, lung, skin, conjunctiva – Begins as a polycloncal reactive process, over time becomes a monoclonal B cell lymphoma – In stomach, highly associated with helicobacter pylori • monocytoid B cells, plasma cells, germinal centers, lymphoepithelial lesions • Survival: indolent in early stages • Cell of origin: marginal zone B cell
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- 61. Origin of B-celllymphomas Marginal zone Mantle zone Germinal center Naive B-cell Mantle cell lymphoma Follicular lymphoma Burkitt lymphoma Large cell lymphoma Memory B-cell CLL/SLL Marginal zone lymphoma 4.Plasma cell Myeloma CC/CB
- 62. typically presents as: -male in 6th decade - splenomegaly - no lymphadenopathy - CBC: - pancytopenia - marked monocytopenia •splenic disease: - red pulp (unique ) Hairy cell leukemia
- 63. Hodgkin lymphoma Incidence - ~1% of all new cancers in USA - ~ 7,500 new cases/year - constant recent increase Age - bimodal age-curve (unique in cancer) - 15 - 35 - > 50 Sex - M:F = ~ 4:3 (except nodular sclerosis)
- 64. Hodgkin Lymphoma • Painlesslymphadenopathy - cervical ~ 70% - axillary ~ 15% - inguinal ~ 10% • Constitutional symptoms - fever - night sweats - weight loss • Infections: fungal, TB
- 65. unique amongst cancers: rarityof the neoplastic cell in involved tissue DIAGNOSTIC REED-STERNBERG CELL or variants Pleomorphic cellular infiltrate: - lymphocytes - macrophages - plasma cells - eosinophils - fibroblasts - neutrophils • predominate • vary according to classification • reactive Hodgkin lymphoma
- 66. LYMPHOCYTE PREDOMINANT nodular sclerosis mixed cellularity lymphocyte depletion lymphocyterich 95% 5% Hodgkin lymphoma
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- 68. Hodgkin lymphoma A B CD A. Classic B. Mononuclear variant C. Lacunar variant D. Lympho-histiocytic variant
- 69. Hodgkin Lymphoma CD15 andCD30 antibodies are used to stain Reed Sternberg cells
- 70. Nodular sclerosing Clinical: -adolescent andyoung adult, -females > males -usually lower cervical, supraclavicular, or mediastinal LN Histology: - occasional R-S cells, Lacunar cells, inflammatory cells, bands of sclerosis Survival: Excellent
- 71. Hodgkin lymphoma, nodularsclerosing
- 72. NS MC LDLR Frequency ~70% ~20% <1% ~5% Usual age 15-30 any/middle >50 any middle Clinically females abdominal advanced early mediastinal splenic marrow stage 5yr survival ~80% ~60% ~30% ~90% Hodgkin lymphoma features
- 73. Staging of HL •I: Single LN region or extra-nodal site • II: 2 or more LN regions on same side of diaphragm • III: LN on both sides of diaphragm, may include spleen • IV: Multiple or disseminated foci • Further divided into absence (A) or presence (B) of fever, night sweats, unexplained weight loss of >10% body weight
- 74. •clinically: - adults - Mycosisfungoides patch, plaque, tumor - Sezary Syndrome - erythroderma - generalized adenopathy - circulating tumor cells - MF: indolent but progressive - SS: unfavorable (10-20%/5 year survival) •pathologically: - classic epidermotropism - papillary dermal fibrosis - cerebriform nuclei •immunophenotype: CD4 T-cell lymphomas
- 75. Mycosis fungoides Plaque phasetumor phase
- 76. Sezary syndrome Generalized exfoliativeerythroderma
- 77. Reference Robbins 10th edition Ackermanhistopathology text book 11th edition Deciy text book of hematology