HODGKIN LYMPHOMA - DEFINITION, PATHOGENESIS & PATHOLOGY

PATHOLOGY OF HODGKINS LYMPHOMA

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. NODULARLYMPHOCYTE
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),
Extranodal spread is uncommon

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 imagenuclei
Large inclusion-like
owl eyednucleolus,
size of a small
lymphocyte (5-7µm)
Abundant cytoplasm

16. RS CELL VARIANTS
MononuclearHodgkin cell-mixed
cellularity & lymphocyte rich
Mummifiedcell-classical HL
Lacunarcell –Nodular sclerosis
Popcorncell(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. NODULARSCLEROSIS
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. NODULARSCLEROSIS

30. NODULARSCLEROSIS

31. NODULARSCLEROSIS
M=F, Young adults
Involve lower cervical, supraclavicular &
mediastinalnodes
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 -/+
Excellentprognosis

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
Goodprognosis

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