Hodgkin lymphoma is a type of lymphoid neoplasm distinguished by the presence of Reed-Sternberg cells, typically presenting in young adults with symptoms such as painless swelling of lymph nodes, weight loss, high fevers, and night sweats. It is classified into various subtypes, including classical Hodgkin lymphoma and lymphocyte-predominant Hodgkin lymphoma, with different prognoses and cellular characteristics. The disease is usually localized but can spread to contiguous lymph nodes and has a bimodal incidence peak in young adults and older populations.

1. Case Scenario
 Young adult
 painless swelling in armpit , neck
 unexplained profound weight loss, high
fevers, and drenching night sweats.

2. HODGKIN LYMPHOMA
PA19.4

3. Specific Learning Objectives
 Define Hodgkins Lymphoma
 Pathogenesis of Hodgkins Lymphoma
 Pathology: Gross
: Microscopy
 Clinical Features
 Difference between Hodgkins & Non
Hodgkins Lymphoma

6. Characteristics of HL
 Usually arise in LNs, cervical
 Manifest clinically in young adults
 Scattered large mononucleated &
multinucleated tumor cells called
Hodgkin & Reed-Sternberg cells in an
abundant heterogenous admixture of
non neoplastic infl cells (L,P,E,H)

7. WHO Classification
1. CLASSICAL HODGKIN LYMPHOMA
 NODULAR SCLEROSIS
 MIXED CELLULARITY
 LYMPHOCYTE – RICH
 LYMPHOCYTE – DEPLETION
2. NODULAR LYMPHOCYTE
PREDOMINANT (NLPHL)

8. HODGKIN LYMPHOMA - Definition
Hodgkin’s Disease encompasses a group of
lymphoid neoplasms that differ from NHL
by :
 Presentation similar to infection
 No leukemic state
 Arise in a single node / chain of nodes &
spreads characteristically to contiguous
lymph nodes
 Reid - Sternberg cells
(distinctive neoplastic giant cell derived
from germinal center B - cells),

9. HD - Epidemiology
 0.7% of all new cancers (USA),
 50 % of Malignant Lymphomas
 Incidence is bimodal – young adults (32
yrs)
 Now it is curable;

10. ETIOPATHOGENESIS: HL
 CONTROVERSIAL!!!
 Cell of origin:
 ? Germinal centre/post GC B cell.
 (rare) transformed T cells.
 Role of EBV ??
 LMP-1 of virus—transcription factor
activation—avoid apoptosis.
 ? Inappropriate activation of NF-κB
 RS cells are aneuploid, diverse clonal
aberrations+

12. HD - Macroscopy
 Enlargement of cervical nodes most
frequent
 Individual nodes discrete
 C/S greyish tan or pale tan

13. RS CELL

15. CLASSICAL
REED-STERNBERG CELL
 15 - 45µm in
diameter
 Binucleate / bilobed
mirror image nuclei
 Large inclusion-like
owl eyed nucleolus,
size of a small
lymphocyte (5-7µm)
 Abundant cytoplasm

16. RS CELL VARIANTS
 Mononuclear Hodgkin cell-mixed
cellularity & lymphocyte rich
 Mummified cell- classical HL
 Lacunar cell – Nodular sclerosis
 Popcorn cell(L&H) – lymphocyte
predominant HL

17. LACUNAR CELL
 Delicate folded or
multilobate nuclei
 Abundant pale cytoplasm
that is disrupted during
cutting - lacunae
 Seen in
Nodular Sclerosis HL

18. MUMMIFIED CELL
 Cell shrinks &
becomes pyknotic
 Form of cell death
 Seen in:
Classical forms
of HL

19. MONONUCLEAR VARIANT
 Single round oblong
nucleus
 Large inclusion like
nucleolus
 Seen in :
Mixed cellularity &
Lymphocyte-rich

20. IMMUNOPHENOTYPE OF
RS CELL in Classical HL
 CD 15 +
 CD 30 +
 CD 20 -
 CD 45 -

22. L & H VARIANT
 L & H cells
 Polypoid nuclei
 Resemble popcorn
kernels (popcorn cells)
 Inconspicuous nucleoli
 Moderate amount of
cytoplasm
 Specific to
Lymphocyte
predominant HL
 CD 15, CD 30 :
negative

23.  RS like cells also seen in
 Infectious mononucleosus
 Solid tissue cancers
 NHL

25. CLASSICAL HODGKIN LYMPHOMA
 NODULAR SCLEROSIS
 MIXED CELLULARITY
 LYMPHOCYTE – RICH
 LYMPHOCYTE – DEPLETION
 LYMPHOCYTE PREDOMINANCE

26. CLASSICAL HODGKIN LYMPHOMA
 Cervical LNs – 75%, mediastinal,
axillary & para aortic LNs
 55% of patients have localised
disease
 Associated with EBV infection
 RS cells are CD 15 & CD 30 positive

27. LYMPH NODE GROSS
 Homogenous white
cut surface
 Fish flesh
appearance

28. NODULAR SCLEROSIS
 Most common form, 65-75% of HL
 Stage 1 or 2 disease common
 MICROSCOPY:
1. Presence of a variant of RS cell – LACUNAR
CELL. Classical RS cell : Less frequent.
2. Collagenous bands dividing the lymphoid
tissue into circumscribed nodules
3. Polymorphous background of small T
lymphocytes, eosinophils, plasma cells &
macrophages

29. NODULAR SCLEROSIS

30. NODULAR SCLEROSIS

31. NODULAR SCLEROSIS
 M=F, Young adults
 Involve lower cervical, supraclavicular &
mediastinal nodes
 Involvement of spleen, liver, bone
marrow in due course of disease
 RS cells less frequent
 Tumor cells are
CD 15 and CD 30 +ve
(CD 45, CD 20 –ve)
 EBV -/+
 Excellent prognosis

32. MIXED CELLULARITY
 Accounts for 20-25% of HL
MICROSCOPY
 Diffuse effacement of nodal architecture
 Heterogenous cellular infiltrate composed of small
lymphocytes, eosinophils, plasma cells &
macrophages
 Admixed with plentiful neoplastic cells – Classical
Reed-Sternberg cells & Mononuclear variants
 RS cells are CD 15 & CD 30 positive
 70% EBV positive

33. MIXED CELLULARITY

34. MIXED CELLULARITY
 More common in males
 Biphasic incidence – young adults &
>55yr
 Systemic symptoms – Night sweats &
weight loss
 Advanced tumor stage - 50% Stage 3
or 4
 Good prognosis

36. Mixed cellularity, CD15+ RS cells

37. LYMPHOCYTE DEPLETION
 Least common :< 5%
 Microscopy :
Paucity of lymphocytes
Abundant RS cells and pleomorphic cells.
 Older patients, HIV + patients
 Often EBV asssociated
 Advanced stage and systemic symptoms
common.
 Overall outcome : less favourable

38. Lymphocyte depleted
 Has few lymphocytes
 Plenty of classic RS cells
 Poor prognosis

39.  RS cells are CD15+’CD30+,MostEBV+

40. LYMPHOCYTE DEPLETED

41. LYMPHOCYTE-RICH
 Uncommon form of HL
 M>F, Older age
 Vast majority of cellular infiltrate
is composed of reactive lymphocytes
 Frequent Mononuclear & RS cells
 CD15+ve; CD30+ve (CD20 & 45 –ve)
 40% EBV +ve
 Good to Excellent prognosis

42. LYMPHOCYTE-RICH

43. LYMPHOCYTE PREDOMINANCE
HL
Uncommon variant; 5% of HL
MICROSCOPY
 Nodular pattern
 Popcorn cells (L&H cells)
 Nodular infiltrate of small lymphocytes
admixed with variable benign histiocytes
 Typical RS cells difficult to find
 Lymphohistiocytic variant(popcorn cell) ++
 Scant neutrophils, eosinophils & plasma cells
 No necrosis or fibrosis

44. LYMPHOCYTE PREDOMINANCE
 Common in males < 35 years
 Cervical or axillary lymphadenopathy
 Mediastinal & bone marrow involvement is
rare
 CD 15 -, CD 30 -,
 CD 20+, Bcl 6 +ve
 EBV -ve
 May recur
 Excellent prognosis

45. LYMPHOCYTE PREDOMINANCE

46. Lymphocyte predominance – paucity of RS cells

47. SPREAD
 Node  Spleen Liver Bone Marrow
 Extranodal

48. ANN ARBOR
CLASSIFCATION

50. HD - Clinical features
 Younger patients - more favorable
histologic types , clinical stage I OR II ,
no systemic symptoms
 Disseminated disease - stage III or IV ,
MC or LD , systemic symptoms
 Prognosis:: LP > NS > MC > LD

51. Differences
HODGKIN’S LYMPHOMA NHL
single axial group multiple peripheral nodes
spread by contiguity non-contiguos spread
mesenteric & Waldeyers not
involved
mesenteric &Waldeyers
involved
extranodal uncommon extranodal common

52. Question & Answer
 Define Hodgkin's Lymphoma
 RS cell
 Variants of RS Cell
 Difference between Hodgkins & Non
Hodgkins Lymphoma