1. LYMPHOMA
Professor Dr. Rafi Ahmed Ghori
Department of Medicine
LUMHS Jamshoro

2. OVERVIEW
• Concepts, classification, lymphogenesis
• Epidemiology
• Clinical presentation
• Diagnosis
• Staging
• Three important types of lymphoma

3. EPIDEMIOLOGY AND AETIOLOGY OF HODGKIN
LYMPHOMA
Incidence
• Approximately 4 new cases/100 000 population / year
Sex Ratio
• Slight male excess (1.5:1)
Age
•Median age 31 years; first peak at 20-35 years and second at
50-70 years
Aetiology
• Unknown. More common in patients from well-educated
background and small families. Three time more likely with a
past history of infectious mononucleosis but no casual link to
Epstein-Barr virus infection proven

4. EPIDEMIOLOGY OF
LYMPHOMAS
• 5th most frequently diagnosed cancer overall
for both males and females
• Males > females
• Incidence
• NHL increasing over time (Stage III or IV at
Diagnosis)
• Hodgkin lymphoma stable

5. RISK FACTORS FOR NHL
• Immunosuppression or immunodeficiency
• Connective tissue disease
• Family history of lymphoma
• Infectious agents
• Ionizing radiation

6. WHO PATHOLOGICAL CLASSIFICATION AND
INCIDENCE OF HODGKIN LYMPHOMA (HL)
Type Histology Incidence
Nodular Lymphocyte
predominent HL
Classical HL Nodular sclerosing 70%
Mixed Cellularity 20%
Lymphocyte-rich 5%
Lymphocyte-depleted Rare

7. CLINICAL STAGES OF HODGKIN LYMPHOMA
(ANN ARBOR CLASSIFICATION)
Stage Definition
I Involvement of a single lymph node region (I) or extralymphatic site (IA E)
II Involvement of two or more lymph node regions (II) or an extralymphatic
site and lymph node regions or the same side of (above or below) the
diaphragm (IIE)
III Involvement of lymph node regions on both sides of the diaphragm with
(IIIE) or without (III) localised extralymphatic involvement or
involvement of the spleen (IIIS) or both (IIISE)
IV Diffuse involvement of one or more extralymphatic tissues, e.g. liver or
bone marrow
A No systemic symptoms
B Weight loss, drenching sweats
The lymphatic structure are defined as the lymph nodes, spleen,
thymus, Waldeyer’s ring, appendix and Payer’s patches

8. STAGING OF LYMPHOMA
Stage I Stage II Stage III Stage IV
A: absence of B symptoms
B: fever, night sweats, weight loss

9. THE CHALLENGE OF
LYMPHOMA CLASSIFICATION
Biologically rational Clinically useful
classification classification
Diseases that have distinct Diseases that have distinct
• morphology • clinical features
• immunophenotype • natural history
• genetic features • prognosis
• clinical features • treatment

10. LYMPHOMA CLASSIFICATION
(BASED ON 2001 WHO)
• B-cell neoplasms 70%
• Precursor B-cell neoplasms
• Mature B-cell neoplasms
• B-cell proliferations of uncertain malignant
potential
• T-cell & NK-cell neoplasms 30%
• Precursor T-cell neoplasms
• Mature T-cell and NK-cell neoplasms
• T-cell proliferation of uncertain malignant
potential

11. LYMPHOMA CLASSIFICATION
(BASED ON 2001 WHO)
• Hodgkin lymphoma 95%
• Classical Hodgkin lymphomas
• NS 70% (nodular scl.)
• MC 20% (mixed cell.)
• LR 5% (lympho.rich)
• LD RARE (lympho.dep.)
• Nodular lymphocyte predominant Hodgkin
lymphoma 5%

12. A PRACTICAL WAY TO THINK OF
LYMPHOMA
Category Survival of Curability To treat or
untreated not to treat
patients
Non- Indolent Years Generally Generally
Hodgkin not curable defer Rx if
lymphoma asymptomatic
Aggressive Months Curable in Treat
some
Very Weeks Curable in Treat
aggressive some
Hodgkin All types Variable – Curable in Treat
lymphoma months to most
years

13. MECHANISMS OF
LYMPHOMAGENESIS
• Genetic alterations
• Infection
• Antigen stimulation
• Immunosuppression

14. CLINICAL
MANIFESTATIONS
• Variable
• Severity: asymptomatic to extremely ill
• Time course: evolution over weeks, months, or years
• Systemic manifestations
• Fever, night sweats, weight loss, anorexia, pruritis
• Local manifestations
• Lymphadenopathy, splenomegaly most common
• Any tissue potentially can be infiltrated

15. OTHER COMPLICATIONS OF
LYMPHOMA
• Bone marrow failure (infiltration)
• CNS infiltration
• Immune hemolysis or thrombocytopenia
• Compression of structures (eg spinal cord,
ureters) by bulky disease
• Pleural/pericardial effusions, ascites

16. DIAGNOSIS REQUIRES AN
ADEQUATE BIOPSY
• Diagnosis should be biopsy-proven before
treatment is initiated
• Need enough tissue to assess cells and
architecture
• open bx vs core needle bx vs FNA

17. THREE TYPES OF LYMPHOMA
WORTH KNOWING ABOUT
• Follicular lymphoma
• Diffuse large B-cell lymphoma
• Hodgkin lymphoma

18. NON-HODGKIN LYMPHOMA
INCIDENCE
Diffuse
large B-cell Follicular
lymphoma lymphoma
Other NHL

19. FOLLICULAR LYMPHOMA
• Most common type of “indolent” lymphoma
• Usually widespread at presentation
• Often asymptomatic
• Not curable (some exceptions)
• Associated with BCL-2 gene rearrangement
[t(14;18)]
• Cell of origin: germinal center B-cell

20. • Defer treatment if asymptomatic (“watch-
and-wait”)
• Several chemotherapy options if
symptomatic
• Median survival: years
• Although considered “indolent”, morbidity
and mortality can be considerable
• Transformation to aggressive lymphoma
can occur

21. DIFFUSE LARGE B-CELL
LYMPHOMA
• Most common type of “aggressive”
lymphoma
• Usually symptomatic
• Extranodal involvement is common
• Cell of origin: germinal center B-cell
• Treatment should be offered
• Curable in ~ 40%

22. HODGKIN LYMPHOMA
Thomas Hodgkin
(1798-1866)

23. HODGKIN LYMPHOMA
• Cell of origin: germinal centre B-cell
• Reed-Sternberg cells (or RS variants) in the
affected tissues
• Most cells in affected lymph node are
polyclonal reactive lymphoid cells, not
neoplastic cells

24. REED-STERNBERG cell

25. RS CELL AND VARIANTS
classic RS cell lacunar cell popcorn cell
(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)

26. Reed-Sternberg cell The Scream, 1893
Edvard Munch

27. A POSSIBLE MODEL OF
PATHOGENESIS
transforming loss of apoptosis
event(s)
EBV?
cytokines
germinal
centre RS cell
inflammatory
B cell
response

28. HODGKIN LYMPHOMA
HISTOLOGIC SUBTYPES
• Classical Hodgkin lymphoma
• Nodular sclerosis (most common subtype)
• Mixed cellularity
• Lymphocyte-rich
• Lymphocyte depleted

29. EPIDEMIOLOGY
• Less frequent than non-Hodgkin lymphoma
• overall M>F
• Peak incidence in 3rd decade

30. ASSOCIATED (ETIOLOGICAL?)
FACTORS
• EBV infection
• Smaller family size
• Higher socio-economic status
• Caucasian > non-caucasian
• Possible genetic predisposition
• Other: HIV? occupation? herbicides?

31. CLINICAL MANIFESTATIONS:
• Lymphadenopathy
• Contiguous spread
• Extranodal sites relatively uncommon except
in advanced disease
• “B” symptoms

32. TREATMENT AND PROGNOSIS
Stage Treatment Failure-free Overall 5
survival year
survival
I,II ABVD x 4 70-80% 80-90%
& radiation
III,IV ABVD x 6 60-70% 70-80%

33. LONG TERM COMPLICATIONS
OF TREATMENT
• Infertility
• MOPP > ABVD; males > females
• Sperm banking should be discussed
• Premature menopause
• Secondary malignancy
• Skin, AML, lung, MDS, NHL, thyroid, breast...
• Cardiac disease

34. Case
• 25 year old woman
• Persistent dry cough
• Fever, NS, weight loss x 3 months
• Left cervical lymphadenopathy (2 cm)
• Left supraclavicular node (2 cm)
• No splenomegaly

36. W.P. at presentation

37. CASE: DIFFERENTIAL
DIAGNOSIS
• Lymphoma
• Hodgkin
• Non-Hodgkin
Llung cancer
• Other neoplasms: thyroid, germ cell
• Non-neoplastic causes less likely
• Sarcoid, TB, ...

38. WHAT NEXT?
• Needle aspirate of LN: a few necrotic cells
• Needle biopsy of LN: admixture of B- and T-
lymphocytes. A few atypical cells.

39. CASE: LYMPH NODE BIOPSY

40. CASE: LYMPH NODE BIOPSY

41. CASE: LYMPH NODE BIOPSY

42. CASE: STAGING
INVESTIGATIONS
• CT chest/abdo/pelvis
• Bone marrow
• Gallium scan
• Blood work: normal

44. STAGING INVESTIGATIONS
• Bone marrow normal
• CT scan: L supraclavicular adenopathy; large
mediastinal mass; R hilum; no disease below
diaphragm
• Gallium avid

45. What is her diagnosis and stage?
• Nodular sclerosis HD
• Stage IIB
• With bulky mediastinal mass

46. CASE: TREATMENT
• Discussion with patient
• Treatment with ABVD x 6 cycles
• Constitutional symptoms gone after 1st cycle
• Bulky mediastinal mass is a special situation
that merits additional radiation after
chemotherapy

48. CASE: POST-ABVD
• Response to chemo, but residual
mediastinal/hilar mass
• Repeat gallium scan negative, suggesting that
residual mass may just be fibrotic tissue
• Proceed with radiotherapy as originally
planned

49. CASE: POST-RADIOTHERAPY
• Serial CT scans did not show progression
• patient remains in remission

50. Therapeutic guideline for Hodgkin Lymphoma
Indications for radiotherapy
• Stage I disease
• Stage IIA disease with three or fewer areas involved
• After chemotherapy to sites where there was originally bulk
disease
• To lesion causing serious pressure problems
Indication for chemotherapy
• All patients with B symptoms
• Stage II disease with more than three areas involved
• Stage III and IV disease

51. THE ChIVPP REGIMEN FOR
HODGKIN LYMPHOMA
Drug Dose
Chlorambucil 6 mg/m2 (up to 10 mg total) days 1-14 orally
Vinblastine 6 mg/m2 (up to 10mg total) days 1 and 8 i.v.
Procarbazine 100 mg/m2 days 1-14 orally
Prednisolone 40 mg/m2 days 1-14 orally