Classification of Hodgkin Lymphomas

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1 Lymfómové fórum - Lymphoma forum Radisson Blu Carlton Hotel Bratislava Classification of Hodgkin Lymphomas Lukáš Plank Dept. Pathology and National Consultation Center for Haematopathology Jessenius Faculty of Medicine of Comenius University University Hospital, Martin and Martinské bioptické centrum, s.r.o.

2 Hodgkin Lymphoma (HL) we are living in a (rapidly) changing world (not only) of lymphomas... new lymphoma classifications + changes in terminology, however, the classification of HL remains (relatively) stabile better understanding of the lymphoma biology, better prognosis and effective treatment options.

3 Hodgkin Lymphoma (HL) HL comprises 11% of all lymphomas in the Western world considerable variations (race-, gender-, population-dependent) in developed countries HL: - is relatively rare in children (< 5 years) - is the commonest type of cancer in adolescents, - shows a bimodal age distribution

4 Hodgkin Lymphoma inflammation non-tb inflammation neoplasia uncertain origin of SR cells histiocytes or lymphocytes? (B-) lymphocytes lymphogranuloma Hodgkin s disease Hodgkin Lymphoma Improved survival of patients with HL in British Columbia since the 1960s. Cum indicates cumulative.

5 Thomas Hodgkin and his lymphoma Thomas Hodgkin: medical immortal and uncompromising idealist (by MJ Stone 2005, Baylor University Medical Center) Bedford Square London In France he encountered the newly-invented stethoscope of René Laennec, on which he presented a paper to the Guy's Hospital Physical Society in Hodgkin described the disease that bears his name in 1832, in a paper titled On Some Morbid Appearances of the Absorbent Glands and Spleen. He received 33 years later the eponym through the recognition of British physician Samuel Wilks, who rediscovered the disease.

6 Time line: description and classification Lymphogranuloma Hodgkin s disease Hodgkin Lymphoma

7 Time line: description and classification M. Malpighi publishes the 1st recorded description of Hodgkin Lymphoma in his paper De viscerum structuru exercitatio anatomica

8 Time line: description and classification Thomas Hodgkin publishes his paper on lymphatic disease in Medico-Chirurgical Transactions (the Journal of the Medical and Surgical Society in London). (9 years after he has received MD degree)

9 The 8 Th. Hodgkin s cases Although Hodgkin was aware of light microscopy and had used it, he did not actually examine these cases under the microscope Cases 2, 4 and 6 have fixed tissue archived since 1832 (Guy s Hospital, London) In 1998, Poston proved by histology and IHC that: - cases 2 and 6 represent what we now recognize as HL - case 4 was a case of NHL (possibly a PTCL) - Hodgkin had described both forms of lymphoma in his paper Poston argues that all lymphomas should be called Hodgkin's lymphoma, subdivided into RS and non RS types RN Poston, Cancer Treat Rev 1999, Gordon Museum, King's College London: Ma and Mi appearance of case 2 Case 7 in Hodgkin's report: watercolor drawing by Robert Carswell in

10 Time line: description and classification Dr.. Langhans publishes the first histopathologic features of Hodgkin Lymphoma (German)

11 Time line: description and classification Carl Sternberg: first detailed description of giant cells now called SR cells (Ztschr Heilk /Prague/ 1898;19:21-90) Carl Sternberg (between in Brno) Archives of the Univ. Brno, Czech Rep. (with permission of prof. Hirt) Dorothy Reed independently describes the same cells (Johns Hopkins Hosp Rep 1902;10:133-96) 2011 The microscopic appearance of an involved lymph node (from D. Reed s 1902 paper) Dorothy Mabel Reed Mendenhall

12 Time line: description and classification H Jackson and F Parker: classification of Hodgkin disease: paragranuloma, granuloma, sarcoma (N Eng J Med 231, 1944, 35-44)

13 Time line: description and classification A) The Internat. Workshop on RTX effectiveness, histologic classification, and staging systems (Paris: 4 stages defined) 1666 B) Conference "On Obstacles to the Control of Hodgkin's Disease Rye, NY. The Rye staging system developed based on work done in Paris Lukes & Butler (1966) LaH, nodular Rye Conference (1966) LP, nodular LaH, diffuse NS MC diffuse fibrosis, reticular LP, diffuse 2011 NS MC LD RJ Lukes and JJ Butler: The pathology and nomenclature of Hodgkin s disease (Cancer Res 26, 1966, )

14 Time line: description and classification 1666 Blood 84,1994, REAL Classification: 1st interdisciplinary and intercontinentally integrative lymphoma classification REAL (1994) nodular, LP classical HD, LR (provisional) NS HD MC HD LD HD

15 Time line: description and classification 1666 REAL Classification: Hodgkin s disease contribution of M.-L. Hansmann and others... classical HD HD, LP (paragranuloma)

16 Time line: description and classification WHO 2001 (and 2008) HL Classification: classical HL 1666 Hodgkin s disease Hodgkin Lymphoma NLPHL

17 Classification: historical review Jackson & Parker (1944) Lukes & Butler (1966) Rye Conference (1966) REAL (1994) WHO (2001, 2008) classical HD/HL vs nodular LPHD/HL Paragranuloma HODGKIN S DISEASE (HD) LaH, nodular LP, nodular (most cases) nodular, LP LaH, diffuse LP, diffuse (most) classical HD, LR LP, nodular (some) (provisional) HODGKIN LYMPHOMA (HL) nodular LP HL chl, LR Granuloma NS NS NS HD chl, NS MC MC (most cases) MC HD chl, MC Sarcoma diffuse fibrosis, reticular LD LD HD chl, LD MC (some cases) chl, unclass. grey zone ML L = lymphocyte/lymphocytic, H = histiocyte/histiocytic, LR = lymphocyte rich, LP = lymphocyte predominant, NS = nodular sclerosis, MC = mixed cellularity, LD lymphocyte depletion, chl = classical HL

18 Biopsy Dx of HL The diagnosis of HL is based on the recognition of - SR and/or Hodgkin's cells - in an appropriate cellular background in tissue sections from a lymph node or extra-lymphatic organ, such as the spleen, bone marrow, etc. Fine needle aspiration biopsy is not adequate for the diagnosis. (Open biopsy is required).

19 Case 2 Biopsy Dx of chl chl, MC chl, NS2 CD3- CD15+ CD30+ Bone marrow infiltration MUM1+ LMP EBV+

20 Biopsy Dx of NLPHL CD20 CD45 MUM1-

21 Classification stabile, but a lot of news origin of SR and LP cells in chl and NLPHL the role of EBV gene copy number variation in HRS cells gene expression studies host microenvironment - immune response micrornas SNPs in selected genes in HL mechanisms of chemoresistance etc...

22 Time line: (6th) Lymphoma Forum years 2011

23 Time line: (6th) Lymphoma Forum

24 ... just another SR cell Thank you... CENTRUM EXCELENTNOSTI PRE PERINATOLOGICKÝ VÝSKUM ITMS: DOBUDOVANIE CENTRA EXCELENTNOSTI PRE PERINATOLOGICKÝ VÝSKUM (CEPV II) ITMS: MOLEKULOVÁ DIAGNOSTIKA RAKOVINY KRČKA MATERNICE ITMS: Podporujeme výskumné aktivity na Slovensku Projekt je spolufinancovaný zo zdrojov EÚ