lymphomas 2002 05 slides

8/13/2019 Lymphomas 2002 05 Slides

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History

Thomas Hodgkin 1798-1866 Guys 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)


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History

Thomas Hodgkin 1798-1866 (cont)LAD: cancer, inflammation, TB, syphilis

1832 On Some Morbid Appearances of theAbsorbent Glands and Spleen

Six cases of LAD s pain, heat, or primary tumor

Billrothmalignant lymphomas


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Lymphoproliferative Disorders

Benign reactive lymphoproliferativedisorders

Histiocytosis X (Langerhans-cell) Plasma call neoplasms

Lymphomas

Non-Hodgkins lymphomas Hodgkins Disease


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Immunology Review

Blood WBCs

Lymphocytes

B-cells T-cells

NK-cells

Major histocompatibility complex (MHC)

I: all cellsII: immune cells


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Immunology Review

B-cellsBursa of Fabricius

Secrete immunoglobulin

Ig A, D, E, G, M

T-cellsThymus, thymic education

Tc, Th1, Th2, Ts

NK cellsNon-specific, no memory


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Lymphocyte Differentiation


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B-Cell Development


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Tumorigenesis


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Techniques for Investigation

Cytogenetics

Immunohistochemistry

FISH Flow Cytometry


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Cytogenetics

t(14,18) common (about 30%)Bcl-2

Follicular growth pattern

t(8,14)common in Burkittsc-myc

Multiple anomalies common

Correlation between cytogenetic change andoutcome is variable


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Cytogenetics


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Cytogenetics


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ClassificationHD


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Reed-Sternberg Cell

Described 1898 Sternberg, 1902 Reed

Popcorn cell variant


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Lymphocyte-PredominantMixed Cellularity

Lymphocyte-Depleted Nodular Sclerosis

Lacunar cell


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ClassificationNHLs

Rappaport1956Nodular vs. diffuse

Lymphocytes vs. histiocytes

Kiel, Lukes-Collins, BNLI, Dorfman, WHO

Working Formulation1982

Revised European-American LymphomaClassification (REAL)1994

From International Lymphoma Study Group


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Rappaport


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Kiel


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Kiel


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Working Formulation (1982)

Designed to be a translational schemebetween others, became free-standing

Essentially modified from RappaportHistiocyticLarge cell

Not based on cell of originBased on survival to 1970s chemo

H&E only, no special stains Test/Retest 0.53-0.93

Interobserver concordance 0.21-0.65


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Working Formulation


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Non-Hodgkins Lymphomas


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Small lymphocytic Small cleaved Mixed,

Small cleaved

and large cell


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Large cell,

Cleaved and

Non-cleaved

Mixed,

Non-cleaved

Large cell,

Non-cleaved


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REAL (1994)


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REAL


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Staging


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LN Zones


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Epidemiology


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Epidemiology


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Epidemiology


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Hodgkins Disease

Bimodal peak

Incidence decreasing

Geographic variation


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EpidemiologyHodgkins

Bimodal

Postulated tohave

infectious

association


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EpidemiologyNHLs


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EpidemiologyNHLs


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EpidemiologyNHLs


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Epidemiology


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EpidemiologyHIV

Anti-retroviral tx has decreased incidence


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Workup

H & P

Usually FNAr/o SCCaexcisional bxif 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


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HD vs. NHLClinical Exam


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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


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Gallium Scan


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FDG-PET

PETpositron emission tomography

FDG18-fluoro deoxy-glucose

Taken by actively metabolic cells Good sensitivity/specificity


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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


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Burkitts Lymphoma

AfricanendemicUsually presents in

maxilla or mandible

EBV ++

SporadicSome EBV


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Lethal Midline Granuloma

Polymorphic reticulosis

Lymphomatoid granulomatosis

Idiopathic midline destructive disease Clinically similar to Wegeners

No granulomas or histiocytes

Poor survivial


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Treatment

ChemoHD: MOPP, ABVD

NHLs: CHOP

Radiation

Bone marrow transplant

ImmunotxRituxananti-CD20


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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

BiopsyNon-Hodgkins Lymphoma, low-

grade Bone marrow ++, both sides diaphragm


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Case Report

Rituxan, chemoDisease came back when off

Bone marrow transplant, allogeneic ++ Richters transformation

GVHD

Expired


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12):2-8, 2000.Gaynor ER, Fisher RI. Aggressive non-Hodgkins lymphoma. In Jancock BW, Selby PJ, MacLennan K, ArmitageJO (eds)Malignant Lymphoma.Arnold: London, 2000.Gledovic Z, Radovanovic Z. History of tonsillectomy and appendectomy in Hodgkins disease. Eur J Epidemiol7:612, 1991.Goldberg D, Golz A, Netzer A, et al. Epstein-Barr virus and cancers of the head and neck. Am J Otolaryngol

22(3):197-205, 2001.Green JD, Neel HB, Witzig TE. Lymphoproliferative disorders of the head and neck. Am J Otolaryngol12:26-32,1991.Griesser H, Mak TW. Developmental and functional biology of B and T lymphocytes. In Canellos GP, Lister TA,Sklar JL, (eds) The Lymphomas. Saunders: Philadelphia, 1998.Grillo-Lopez AJ. Rituximab: an insiders historical perspective. Seminars in Oncology27(6) suppl 12 (Dec):9-16,2000.Gupta RK, Gospodarowicz, Lister TA. Clinical evaluation and staging of Hodgkins disease. In Mauch PM,Armitage JO, Diehl V, et al (eds)Hodgkins Disease. Lippincott: Philadelphia, 1999.Hanna E, Wanamaker J, Adelstein D, et al. Extranodal lymphomas of the head and neck: a 20-year experience. ArchOtolaryngol Head Neck Surg 123:1318-23, 1997 Dec.Harris NL, Jaffe ES, Stein H, et al. A revised European-American classification of lymphoid neoplasms: A proposalfrom the International Lymphoma Study Group. Blood84:1361-92, 1994.Hauke RJ, Armitage JO. Treatment of non-Hodgkin lymphoma. Curr Opin Oncol12:412-8, 2000.Healy GB. Malignant tumors of the head and neck in children: diagnosis and treatment. Otolaryngol Clin North Am13(3):483-8, 1980 Aug.Hellmann S. A brief consideration of Thomas Hodgkin and his times. In Mauch PM, Armitage JO, Diehl V, et al

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