Hodgkin’s Lymphoma

1. 16/8/14 Hodgkin’s Lymphoma Thomas Hodgkin 1798-1866 Dr. Ksheera Pathology

2. Hodgkin’s Lymphoma • Definition • Epidemiology • Pathogenesis • Diagnosis

3. Definition • Heterogeneousgroup of malignant neoplasm, originating primarily in lymph nodes or other lymphoid tissues. • Histologically characterized by presence of Reed-Sternberg cells.

4. Epidemiology • Common in young adult (20-30 years) • Second minor peak after 50 years • Male predominant • 1/3 cases associated with constitutional symptoms (fever, night sweats and weight loss)

5. Hodgkin’s Lymphoma • Lymphocyte predominance • Classical subtypes Nodular sclerosis Mixed cellularity Lymphocyte-rich Lymphocyte depletion

6. Etiopathogenesis • Epstein-Barr virus • Infectious mononucleosis • Secretion of various cytokines • RS cell originate from B lymphocyte originating in germinal center of lymph node • RS cells are neoplastic cells • Granulocytes, Lymphocytes, plasma cells, and fibroblast cells are reactive cells represent the immune reaction against the tumor cells

7. Suppressed TH1 response Monocytes /macrophage Infiltration /activation ↑ Plasma cells ↑ Ig level IL-10 Tissue eosinophilia IL-6 GM-CSF IL-5 C-MET CD-30 CD-30L Eotaxin CD-40 TGF-β bFGF TGF-β HGF CD-40L Dendritic cells Fibrosis Eotaxin Enhanced TH2 response

8. A possible model of pathogenesis loss of apoptosis transforming event(s) EBV? cytokines germinal centre B cell RS cell inflammatory response

9. Reed-Sternberg Cell • The diagnosis rests on identification of RS cells, though uncommonly similar cells can occur in infectious mononucleosis and other forms of lymphomas. • Therefore, additional cellular and architectural features of the biopsy must be given due consideration for making the histologic diagnosis. • There are several morphologic variants • 1. Classic RS cell: is a large cell which has characteristically a bilobed nucleus appearing as mirror image of each other but occasionally the nucleus may be multilobed. • Each lobe of the nucleus contains a prominent, eosinophilic, inclusion like nucleolus with a clear halo around it, giving an owl-eye appearance. The cytoplasm is abundant and amphophilic.

10. 2. Lacunar type RS cell: is smaller and in addition to above features has a pericellular space or lacuna in which it lies, which is due to artefactual shrinkage of the cell cytoplasm. It is characteristically found in nodular sclerosis variety of HD. • 3. Polypoid type (popcorn / lymphocytic-histiocytic L&H) RS cells: are seen in lymphocyte predominance type of HD. This type of RS cell is larger with lobulated nucleus in the shape of popcorn.

11. 4. Pleomorphic RS cells: are a feature of lymphocyte depletion type. These cells have pleomorphic and atypical nuclei. • The nature and origin of RS cells have been a matter of considerable debate. One main reason for this difficulty in their characterisation is that in HD, unlike most other malignancies, the number of neoplastic cells (i.e. RS cells) is very small (less than 5%) which are interspersed with predominant reactive cells. • In general, the number of RS cells is inversely proportional to the number of lymphocytes in a particular histologic subtype of HD.

12. Immunophenotyping of RS cells reveals monoclonal lymphoid cell origin of RS cell from B-cells of the germinal centre in most subtypes of Hodgkin’s disease. • RS cells are invariably accompanied by variable number of atypical Hodgkin cells which are believed to be precursor RS cells but are not considered diagnostic of HD. • Hodgkin cells are large mononuclear cells (rather than with mirror image nuclei) having nuclear and cytoplasmic similarity to that of RS cell.

13. RS cell and variants classic RS cell lacunar cell popcorn cell (lymphocyte predominance) (mixed cellularity) (nodular sclerosis)

14. Diagnosis • Clinical features • Peripheral blood examination • Bone marrow aspiration • Bone marrow biopsy • Fine needle aspiration cytology of lymph node • Histopathology of BONE marrow • Histopathology of lymph node • Immunohistochemistry • Molecular studies

15. Clinicalfeatures • Fever, pyrexia of unknown origin • Night sweats • Weight loss • Regional painless lymphadenopathy • Development of secondary cancer • HL spread is stereotyped: LN  Spleen  Liver  BM / other tissues

16. Gross appearance of lymph nodes involved by Hodgkin’s lymphoma. Note nodularity and sclerosis.

17. Classical Reed-Sternberg cell

18. Classical Reed-Sternberg cell

19. Reed-Sternberg cell Histologic section shows lacunar cells and a Reed-Sternberg cell Papanicolaou stain

20. Reed–Sternberg cell.

21. Lymphocyte predominance

22. Popcorn cell Typical mono nucleated cells, bi nucleated cells and large cells with hyper lobulated Nuclei (popcorn cells) present in background of lymphocytes. The popcorn cells have Pale nuclei and visible nucleoli, they are usually present in the nodular lymphocytePredominant Hodgkin's lymphoma.

23. Nodular sclerosis

24. Various appearances of lacunar cells in nodular sclerosis Hodgkin’s lymphoma.

28. Mixed cellularity

29. Mixed cellularity Hodgkin’s lymphoma. Several diagnostic Reed–Sternberg cells are seen admixed with a polymorphic lymphoid infiltrate rich in eosinophils

30. Lymphocyte-rich

31. Lymphocyte depletion

32. Ann Arbor staging All the stages are further divided on the basis of absence (A) or presence (P) of the constitutional symptoms

34. Hodgkin’s Vs non-Hodgkin’s