Lymphomas for the Otolaryngologist:Lymphomas for the Otolaryngologist Michael E. Decherd, MD Anna M. Pou, MD May 2002


History:History Thomas Hodgkin 1798-1866 Guy’s Hospital, London Accomplishments: Clinicopathologic correlation (pre-microscope) Appendicitis c peritonitis Local spread of cancer to nodes Brought stethoscope to England (Laennac) Histology of RBCs, muscle (Lister) Aortic insufficiency Public health (cholera, lead pipes)


History:History Thomas Hodgkin 1798-1866 (cont) LAD: cancer, inflammation, TB, syphilis 1832 “On Some Morbid Appearances of the Absorbent Glands and Spleen” Six cases of LAD s pain, heat, or primary tumor Billroth—”malignant lymphomas”


Lymphoproliferative Disorders:Lymphoproliferative Disorders Benign reactive lymphoproliferative disorders Histiocytosis X (Langerhans-cell) Plasma call neoplasms Lymphomas Non-Hodgkin’s lymphomas Hodgkin’s Disease


Immunology Review:Immunology Review Blood WBC’s Lymphocytes B-cells T-cells NK-cells Major histocompatibility complex (MHC) I: all cells II: immune cells


Immunology Review:Immunology Review B-cells Bursa of Fabricius Secrete immunoglobulin Ig A, D, E, G, M T-cells Thymus, thymic education Tc, Th1, Th2, Ts NK cells Non-specific, no memory


Lymphocyte Differentiation:Lymphocyte Differentiation


B-Cell Development:B-Cell Development


Tumorigenesis:Tumorigenesis


Tumorigenesis:Tumorigenesis


Techniques for Investigation:Techniques for Investigation Cytogenetics Immunohistochemistry FISH Flow Cytometry


Cytogenetics:Cytogenetics t(14,18) common (about 30%) Bcl-2 Follicular growth pattern t(8,14)  common in Burkitt’s  c-myc Multiple anomalies common Correlation between cytogenetic change and outcome is variable


Cytogenetics:Cytogenetics


Cytogenetics:Cytogenetics


Immunohistochemistry:Immunohistochemistry


Immunohistochemistry:Immunohistochemistry


Immunohistochemistry:Immunohistochemistry


Immunohistochemistry:Immunohistochemistry


Classification—HD:Classification—HD


Reed-Sternberg Cell:Reed-Sternberg Cell Described 1898 Sternberg, 1902 Reed Popcorn cell variant


Slide 21:Lymphocyte-Predominant Mixed Cellularity Lymphocyte-Depleted Nodular Sclerosis Lacunar cell


Classification—NHLs:Classification—NHLs Rappaport – 1956 Nodular vs. diffuse Lymphocytes vs. histiocytes Kiel, Lukes-Collins, BNLI, Dorfman, WHO Working Formulation – 1982 Revised European-American Lymphoma Classification (REAL) – 1994 From International Lymphoma Study Group


Rappaport:Rappaport


Kiel:Kiel


Kiel:Kiel


Working Formulation (1982):Working Formulation (1982) Designed to be a translational scheme between others, became free-standing Essentially modified from Rappaport Histiocytic Large cell Not based on cell of origin Based on survival to 1970s chemo H&E only, no special stains Test/Retest 0.53-0.93 Interobserver concordance 0.21-0.65


Working Formulation:Working Formulation


Non-Hodgkin’s Lymphomas:Non-Hodgkin’s Lymphomas


Slide 29:Small lymphocytic Small cleaved Mixed, Small cleaved and large cell


Slide 30:Large cell, Cleaved and Non-cleaved Mixed, Non-cleaved Large cell, Non-cleaved


REAL (1994):REAL (1994)


REAL:REAL


Staging:Staging


LN Zones:LN Zones


Epidemiology:Epidemiology


Epidemiology:Epidemiology


Epidemiology:Epidemiology


Hodgkin’s Disease:Hodgkin’s Disease Bimodal peak Incidence decreasing Geographic variation


Epidemiology – Hodgkin’s:Epidemiology – Hodgkin’s Bimodal Postulated to have infectious association


Epidemiology – Hodgkin’s:Epidemiology – Hodgkin’s


Epidemiology – Hodgkin’s:Epidemiology – Hodgkin’s


Epidemiology – Hodgkin’s:Epidemiology – Hodgkin’s


Epidemiology – NHLs:Epidemiology – NHLs


Epidemiology – NHLs:Epidemiology – NHLs


Epidemiology – NHLs:Epidemiology – NHLs


Epidemiology:Epidemiology


Epidemiology – HIV :Epidemiology – HIV Anti-retroviral tx has decreased incidence


Workup:Workup H & P Usually FNA  r/o SCCa  excisional bx if lymphoma for architecture, flow cyt. Chemistries, CBC c smear, LFTs c LDH, ESR, beta-2 microglobulin CT chest, abdomen, pelvis Bone marrow (MR directed?) Adjunct: Gallium, FDG-PET


HD vs. NHL – Clinical Exam:HD vs. NHL – Clinical Exam


Gallium Scan:Gallium Scan Gallium-67 isotope Affinity for lymphomas Good sensitivity/specificity If treatment makes Ga scan negative, good chance at lasting remission May find occult disease


Gallium Scan:Gallium Scan


FDG-PET:FDG-PET PET – positron emission tomography FDG – 18-fluoro deoxy-glucose Taken by actively metabolic cells Good sensitivity/specificity


Staging Laparotomy:Staging Laparotomy Looks for infradiaphragmatic disease Important if disease o/w would be Stage I/II supradiaphragmatic May change Tx Largely supplanted by non-invasive techniques Not complication-free Laparoscopy? Controversial


Burkitt’s Lymphoma:Burkitt’s Lymphoma African – endemic Usually presents in maxilla or mandible EBV ++ Sporadic Some EBV


Lethal Midline Granuloma:Lethal Midline Granuloma Polymorphic reticulosis Lymphomatoid granulomatosis Idiopathic midline destructive disease Clinically similar to Wegener’s No granulomas or histiocytes Poor survivial


Treatment:Treatment Chemo HD: MOPP, ABVD NHLs: CHOP Radiation Bone marrow transplant Immunotx Rituxan – anti-CD20


Case Report:Case Report 34 yo WM c/o night sweats Saw ID MD, told he had CMV 2 years later, still night sweats Trouble shaving due to fullness in neck Biopsy—Non-Hodgkin’s Lymphoma, low-grade Bone marrow ++, both sides diaphragm


Case Report:Case Report Rituxan, chemo Disease came back when off Bone marrow transplant, allogeneic ++ Richter’s transformation GVHD Expired


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