Hodgkin's lymphoma accounts for about 30% of malignant lymphomas. It originates in the lymphatic system and was first described by Thomas Hodgkin in 1832. There are four main subtypes: nodular lymphocyte predominant, nodular sclerosing, mixed cellularity, and lymphocyte depleted. It typically presents as painless, enlarged lymph nodes and has a bimodal age distribution, most commonly affecting those aged 25-30 and over 55. Staging involves imaging such as CT and PET scans to determine the extent of disease. Treatment depends on the stage but commonly involves chemotherapy, radiation, or a combination. Prognosis is generally good even for advanced stages.

1. Hodgkin’s Lymphoma
By-Dr Satyajeet Rath
Moderator-Prof Kamal Sahni

2. INTRODUCTION
• Accounts for ~ 30% of all malignant lymphomas
• Are group of cancers which originates from Reticuloendothelial systems
• It was named after Thomas Hodgkin who first described it in 1832.
• Dorothy Reed and Carl Stenberg first described the malignant cells of
Hodgkin’s lymphoma called Reed Stenberg cells.
• Hodgkins lymphoma was the first cancer which could be successfully
treated by radiation therapy and also by combination chemotherapy.

3. Epidemiology
• Accounts for 0.58% of all cancers diagnosed and 0.23% of all cancer
deaths in U.S each year.
• Incidence is less than 3 per 100,000
• It has a slightly male predominance (1.1:1)
• It is rare in children younger than 10 years
• Median age of patients at the time of diagnosis is 26 years
• It has Bimodal peak of distribution (25-30 yrs and >55 yrs)

4. Risk Factors
• First degree relatives have five fold increase in risk for Hodgkins
Disease.
• Associated with EBV infection mainly with mixed cellularity type.
• Associated with Infectious Mononucleosis. Incidence is about 2.55 times
higher
• High socio economic status.
• Prolonged uses of human growth hormone

5. Natural History
• Hodgkins lymphoma arises in a single node or a chain of nodes and spreads first
to anatomically contiguous lymphoid tissue.
• If contiguity is assumed among the supraclavicular lymph nodes and upper para-
aortic nodes/celiac axis/spleen, 90% of patients present with contiguous sites of
involvement.9,10
• In addition, disease spread after treatment with limited irradiation also occurs in a
contiguous fashion in most instances.9
• Visceral involvement by Hodgkins lymphoma may be secondary to extension from
adjacent lymph nodes.
• Haematogenous spread occurs to liver or multiple bony sites
• It rarely involves the gut associated lymphoid tissue such as Waldeyer ring and
Peyers patches.
• Mechanism of spleen involvement is unclear but almost all pts with hepatic and
bone involvement are associated with splenic involvement.

6. Spread
• May have direct extension into perinodal tissue.
• 85% of Stage I/II disease are above diaphragm.
• Spleen: if >400g, almost always positive.
• Liver: if positive, spleen and retroperitoneal LN’s are also positive.
6

7. Clinical features
• Most common presentation is asymptomatic lymphnode enlargement
typically in the neck i.e, painless,non-tender,rubbery lmphadenopathy
• Cervical lympnodes are involved in 80% cases .
• Mediastinal involvement is seen in about 50% cases .they produce
symptoms like
• Chest pain
• Cough
• Dyspnoea
• Infradiaphragmatic involvement is seen in 5% cases and usually seen with
older patients.

8. Clinical features cont…
• B symptoms
 About 33% presents with B symptoms overall.
 Only 15-20% of stage I-II have B symptoms like
o Fever(>38oC)
 May first present as fever of unknown origin
 Fever persists for days to weeks followed by afebrile intervals and then recurrence
 Such type of pattern is called Pel Ebstein Fever
o Drenching night sweats
o Weight loss(> 10% in 6 mths)

9. Clinical features cont…
• Other less frequently symptoms are
 Pruritus
 Alcohol induced pain over involved lymph nodes
 Nephrotic syndrome
 Erythema nodosum
 Cerebellar degeneration
 Immune hemolytic anaemia, Thrombocytopenia
 Hypercalcaemia

10. Clinical Features
• Involvement of the spleen is dependent on histologic subtype.
• It is involved in 60 percent of mixed cellularity and lymphocyte-depleted
cases compared with 34 percent of nodular lymphocyte-predominant and
nodular sclerosis cases.
• Hepatic and marrow disease are invariably associated with splenic
involvement
Symptom Percentage
involved
Lymphadenopathy 90
Cervical Lmphadenopathy 70
Mediastinal mass 60
B symptoms 30
Axillary nodes 12
Inguinal nodes 9
Bone marrow involvement 5
Hepatosplenomegaly 25

11. Paediatric Hodgkin’s Lmphoma
• Historically, children have had a particularly good prognosis
compared with adults
• The nodular lymphocytepredominant subtype of the disease is
more frequent.
• Overall, the incidence is highest in developed countries (North
America and Europe) and very rare in Asian populations
• Histologic subtypes also vary by age at presentation.
• Pathologic features of Hodgkin’s lymphoma are similar in adults
and children

12. • The childhood form, which
presents in patients younger
than 15 years of age, is
associated with a marked
male predominance,
increasing family size, and
decreasing socioeconomic
status.
• The young adult form, which
presents in patients ages 15 to
34 years, is associated with a
higher socioeconomic

13. • Mediastinal lymphadenopathy occurs in up to 66%
• Axillary or inguinal lymphadenopathy is less frequently seen
as the first presenting sign
• Splenic involvement occurs in 30% to 40% of pediatric
patients with Hodgkin’s lymphoma, whereas hepatic
involvement is exceedingly rare
• pulmonary parenchyma, chest wall, pleura, and pericardium
are the most commonly involved extranodal sites of disease
• Approximately 65% of children have stage I and II disease
and 35% have stage III and IV disease

14. Lymphnodes group

16. >10 cm
Bulky disease

19. Patient Evaluation and Staging
• A separate diagnostic CT
scan is not necessary if it was
done as part of an integrated
PET/CT scan.
• The performance of bone
marrow biopsy should be
limited to patients with
advanced-stage disease or
those with constitutional
symptoms given the low
yield in patients with early-
stage, favorable-prognosis
disease of less than 1%.

20. Prognostic Factors
Prognostic factor for Early stage Hodgkins disease

21. Prognostic factors cont…
Advanced stage hodgkins lymphoma International prognostic score
• Hasenclever - data
from over 5000
patients with
advanced-stage
Hodgkin’s lymphoma,
mostly treated with
doxorubicin-based
combination
chemotherapy
• Seven factors were
found to have similar
independent prognostic
values in predicting
freedom from
progression (FFP) and
overall survival (OS).
*Each of the following factors carries a score of 1: hypoalbuminemia, anemia,
male sex, age ≥45 years, stage IV disease, leukocytosis, and lymphocytopenia.

22. PET SCAN
• PET Scan has become an integral
component of initial staging.
• Information provided by PET has
been recently incorporated in the
lymphoma guidelines for response
evaluation after completion of
treatment.
• Useful for follow up study to
evaluate residual masses , dx of
early recurrence and predicting
outcome.
• It has a specificity of 90-95%

23. Revised International Workshop Criteria With PET Scan

24. Bone Marrow Biopsy
• Less commonly put into practice
• Overall involvement of bone marrow in Hodgkins
lymphoma is 5%.
• Indicated in pts with
B symptoms
Clinical evidence of sub diaphragmatic disease
Stage iii-iv
Recurrent disease

25. JACKSON AND
PARKER
(1947)
SMETANAAND
COHEN’S ADDITION
(1956)
LUKES
(1963)
PARAGRANULOMA PARAGRANULOMA LYMPHOCYTIC AND
HISTIOCYTIC,
NODULAR
LYMPHOCYTIC AND
HISTIOCYTIC,
DIFFUSE
GRANULOMA GRANULOMA
NODULAR
SCLEROSIS
MIXED
CELLULARITY
NODULAR
SCLEROSIS
SARCOMA SARCOMA DIFFUSE FIBROSIS
RETICULAR
Early Classifications
25

26. Later Classifications
• The Lukes-Butler classification of HL, modified at the Rye Conference
in 1966, described the criteria for the four familiar subtypes of HL:
lymphocyte-predominant, nodular sclerosing, mixed cellularity, and
lymphocyte-depleted.
• The REAL classification separated the nodular lymphocyte-predominant
(NLP) subtype from so-called classic HL based on the
immunophenotypic and genotypic differences
• The REAL classification of HL was carried forward to the 2001 WHO
classification of HL and the 2008 WHO classification.
26

27. Pathologic Classification

28. Reed Sternberg cell
Common feature of ALL Hodgkin Lymphomas.
• Large cells ( >45um in diameter) with classically binucleate or bilobed
central nucleus each with a large acidophilic central nucleoli surrounded
by a clear halo. “owl’s eye appearance”
• Variants: mononuclear (Hodgkin’s cell), mummified cell, lacunar cell,
L/H cell.
• Requirement of Reed-Sternberg cell for initial diagnosis is
“absolute”(less strict for LPHL or recurrent disease)
• Classic Reed-Sternberg cell:
+ CD15, CD30, CD25
– CD45, pan-B, S-100, keratin, EMA
• Most current studies indicate the RS cells of HL are lymphocytic in
nature and, in the great majority of cases, are of B-cell origin.

29. Reed-Sternberg cell

30. lacunar cell
(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)
RS Cell variants

31. Ann Arbor Staging Classification-1971
• four-stage system formulated
to provide prognostic
information and to guide
therapeutic decisions
• The clinical stage (CS)
denotes the stage as
determined by all diagnostic
examinations and a single
biopsy only. If a second
biopsy of any kind has been
obtained,whether negative or
positive, the term pathologic
stage (PS) is used
• It does not reflect other
important prognostic factors
such as bulky disease or
multiple sites of involvement,
however

33. Cotswold’s Staging Classification for Hodgkin’s Lymphoma
• The availability of improved imaging techniques has also changed its
applicability.
• In 1988, a meeting was held in the Cotswolds, England, where revisions to
the Ann Arbor staging system were made
• The following main changes were made:
• (1) The use of computed tomography (CT) scanning is allowed to assess
disease involvement below the diaphragm.
• (2) For stage II disease, the number of anatomic nodal sites is indicated by
a subscript (e.g., stage II3)
• (3) For stage III disease, upper and lower abdominal involvement was
subdivided as III1 and III2, respectively
• (4) Bulky disease is denoted by X, defined as more than one-third
widening of the mediastinum at the T5 to T6 level or more than 10 cm
maximum dimension of the nodal mass
• (5) Unconfirmed/uncertain complete remission (CRu) was introduced to
denote the presence of a residual imaging abnormality but the absence of
pathologically confirmed residual disease.

34. Cotswolds Staging Classification for Hodgkin’s Lymphoma

35. Pathological Classification
Histologic Subtypes
Nodular lymphocyte predominant Hodgkins lymphoma
(NLPHL)
Classical Hodgkins lymphoma(CHL)
1 Nodular sclerosis Hodgkins lymphoma
2 Lymphocyte rich classical Hodgkins lymphoma
3 Mixed cellularity Hodgkins lymphoma
4 Lymphocyte depletion Hodgkin lymphoma

36. Lymphocyte predominant Hodgkin lymphoma
• <5% of Hodgkin lymphoma
• Mainly involves cervical, axillary or mediastinal
• L&H cells or Popcorn cells are seen
• Positive for CD20, 45, CD79a, Bcl-6, J-chain, and PAX-5. EMA
positive in 50% cases.
• Negative for CD15, 30.
• Differential Diagnosis: Well differentiated lymphocytic lymphoma,
mononucleosis, malignant melanoma,, progressive transformation of
germinal centers

37. • Hodgkin lymphoma, lymphocyte predominance type. Numerous mature-
looking lymphocytes surround scattered, large, pale-staining
lymphohistiocytic variants (“popcorn” cells).

38. Nodular Sclerosis
• Most common type diagnosed.
About 70%
• Lacunar ceells are seen
• CD 15 and 30 positive
• EBV negative
• Only subtype without a male
predominance
• Seen in younger pts with stage I –II
disease

39. LACUNAR VARIANT RS CELL : These variants possess large,
multilobated, or irregular nuclei with finely dispersed chromatin; nucleoli
are usually small. The cytoplasm of lacunar cells retracts when fixed in
formalin, so the nuclei gives the appearance of cells that lie with empty
spaces between them. (lacunae)
This retraction in absent in tissues fixed in Zenker and B5.

40. Mixed Cellularity
• Constitutes about 20%
• More common in young children
• CD 15,30 EBV positive
• Presents in advanced stages
• Tendency to involve spleen,bone
marrow

41. Lymph node, mixed-cellularity Hodgkin lymphoma disease. Diagnostic Reed-
Sternberg cells are usually found without difficulty in mixed-cellularity
Hodgkin lymphoma. The reactive component consists of small, round
lymphocytes, histiocytes, plasma cells, and eosinophils,

42. Lymphocyte Depleted
• Constitutes <5%
• Worst prognosis of all subtypes
• Older males, rare in children
• Present as febrile illness with
pancytopenia, hepatomegaly, and no
peripheral lymphadenopathy
• Advanced stage, Stage IV
• The biologic hallmark of LDHL is a
collapse of cell-mediated immunity,
HIV infection
• RS cells CD15+, CD30+; most EBV+
• Differential Diagnosis: Large cell Non-
Hodgkin’s lymphoma. Nodular sclerosis
HL

43. Lymphocyte-Rich
• RS cells CD15+, CD30+; 40% EBV+
• Uncommon
• M > F
• Tends to be seen in older adults
• This is an uncommon form of classical HL
• Reactive lymphocytes make up the vast majority of the cellular infiltrate. In
most cases, involved lymph nodes are diffusely effaced, but vague
nodularity due to the presence of residual B-cell follicles is sometimes seen.
• Differential Diagnosis: This entity is distinguished from the lymphocyte
predominance type by the presence of frequent mononuclear variants and
diagnostic Reed-Sternberg cells with a “classical” immunophenotypic
profile.
• Very good to excellent prognosis.

44. Thank You