Presentation is about Hodgkin lymphoma, its incidence and epidemiology, diagnosis, molecular and immunophenotype, work up, staging, treatment and follow up

1. Lymphoma-An Introduction
&
Hodgkin Lymphoma
Dr. Subhash Thakur
Sr.Lecturer, CMC, Bharatpur, Nepal
MD (PGIMER, Chandigarh)
06th May 2021

2. Content
• Introduction to
Lymphoma
• Classification
• Immunophenotyping
evaluation
• Cytogenetic and
molecular evaluation
• Hodgkin Lymphoma
• Incidence/Epidemiology
• Diagnosis
• Staging and risk assessment
• Treatment
A. Classical
• Limited Stage disease
• Intermediate Stage disease
• Relapsed disease
B. NLPHL
• Stage IA without risk factors
• Other Stages
• Relapsed NLPHL
• Response Evaluation
• Prognosis
• Follow up, Long term
implications and
survivorship

3. Lymphoma
• Clonal neoplasm
• Expansion of abnormal
lymphoid cells that may
develop in any organ but
commonly involve lymph
nodes.
Introduction
• Heterogeneous group of
neoplasm with diverse clinical
presentation, prognosis and
response to therapy

4. Classification: WHO
• Official and most correct guideline for diagnosis of lymphoid neoplasm
• Classifies according to type of cell from which they are derived (B Cell, T
Cell or NK Cells)
• Findings determined by morphology, IHC, Clinical, Cytogenetic and/or
molecular features

9. Diagnosis: Biopsy Procedure
• Fresh and unfixed
• Diagnosis is determined not only by cytological features but also on
architectural pattern, So large specimen is preferred (Excisional Biopsy)

10. Immunophenotype Evaluation
• Lineage of Lymphoma Cells can not be determined by morphology alone
• Evaluated by IHC or flow cytometry
B-Cell PAX5, CD19, CD79a, CD20
T-Cell CD-2, CD5, CD7
NK Cell CD3, CD5, CD2, CD7, CD16/56

11. Mature B-cell Lymphoma
• Diffuse large B Cell Lymphoma (DLBCL)
• Follicular Lymphoma
• Small B Cell Lymphoma
• Mantle Cell Lymphoma
• Marginal zone Lymphoma
• Burkitt Lymphoma
• Lymphoplasmacytic Lymphoma

12. Hodgkin Lymphoma
Classical NLPHL
CD 30 + -
CD 15 + -
CD 20 +/- +
CD 45 - 45

13. Cytogenetic and Molecular Evaluation
• When morphologic and Immunophenotype analysis is inconclusive or non-
diagnostic
Molecular Tests:
• Analysis for rearrangements of the variable region of Ig or T-Cell receptor
(TCR) genes
• Mutation of specific genes

14. Hodgkin Lymphoma
• Hodgkin Lymphoma
• Clinical Features
• Incidence/Epidemiology
• Diagnosis
• Staging and risk assessment
• Treatment
A. Classical
• Limited Stage disease
• Intermediate Stage disease
• Relapsed disease
B. NLPHL
• Stage IA without risk factors
• Other Stages
• Relapsed NLPHL
• Response Evaluation
• Prognosis
• Follow up, Long term
implications and
survivorship

15. Clinical Features
• Painless swelling of lymph nodes in
your neck, armpits or groin
• Persistent fatigue
• Severe itching
• Increased sensitivity to the effects
of alcohol or pain in your lymph
nodes after drinking alcohol

16. • B-Symptoms: microscopic spread
of disease around the body
• Fever
• Drenching Night Sweat
• Unexplained weight loss (>10% over
6 months)

17. Incidence and Epidemiology
• Incidence in EU: 2.3
• Mortality: 0.4 cases/100000/year
• Young adult age: 20-40 years most commonly affected
• Slightly Men > Women
• Classical HL: 95%
• NLPHL: 5%

18. Diagnosis
• Excisional Biopsy
• According to WHO classification
• cHL (Classical HL): Reed Sternberg Cell
• NLPHL: detection of Lymphocyte predominant Cells
• IHC
Classical NLPHL
CD 30 + -
CD 15 + -
CD 20 +/- +
CD 45 - 45

19. Hodgkin Lymphoma: classification
• Classical HL
• Nodular Sclerosing
• Lymphocyte Rich
• Lymphocyte Deficient
• Mixed Cellularity
• Nodular Lymphocyte
Predominant Hodgkin
Lymphoma (NLPHL)

20. Nodular Sclerosing
• Common Type, 60 -80 %
• Women>Men, <50 years
• Mediastinum
• Good Prognosis
• Lymph Nodes:
• Classical RS cells
• Lacunar RS Cells

21. Lymphocyte Rich
• 5 % of HL Cases
• Rich in small Lymphocytes
• Small number of classic RS cells

22. Lymphocyte Depletion
• Rarest and aggressive
• Older or HIV patients
• Presents in Stage III/IV
• Poor Prognosis

23. Mixed Cellularity
• 15 -30 % of HL cases
• Usually presents in stage III/IV
• Poor prognosis

24. Work Up (Investigations
• Full Blood Count
• Blood Chemistry analysis: ESR, CRP, ALP, LDH, Liver Enzymes and
Albumin
• Screening for HBV, HCV, HIV

25. Imaging
• Chest X-ray
• CECT-Neck, Chest and Abdomen
• PET-CT, if available
• If PET not available, Bone marrow Biopsy is must

26. Staging
Ann Arbor Staging

27. Risk Stratification

28. Pre-Treatment Examinations
• ECG
• Echocardiography
• Pulmonary Function Tests
• Reproductive counselling for young patients
• Serum Pregnancy test in reproductive age group female

29. Treatment – Classical HL
A. Limited Stage Disease

30. A. Limited Stage Disease
• Combined modality treatment consisting of brief Chemotherapy followed by
Radiotherapy – Superior Tumour control in comparison to RT alone
• 2- 3 Cycles of ABVD followed by conventionally fractionated RT

32. Intermediate Stage Disease

33. Intermediate Stage Disease
• Four Cycles of ABVD followed by conventionally Fractionated RT (30 Gy)
• Elderly patients, age > 60 years, Bleomycin should be discontinued after 2nd
Cycle due to Bleomycin induced lung toxicity

34. Advanced Stage
Disease
• Usually treated with
Chemotherapy alone
• Additional RT is confined to
patients with residual disease
after Chemotherpy

35. Advanced Stage Disease
• Patients < 60 years are usually treated with either ABVD (six Cycles) or
BEACOPPescalated ( 4 – 6 Cycles) optionally followed by localized RT
• Elderly and Patients at increased risk of Lung toxicity: Bleomycin omitted
after 2nd Cycle

36. Relapsed Disease
• High Dose Chemotherapy followed by Autologous Stem Cell Transplant
(ASCT)
• Consolidative Treatment with Brentuximab: improved tumour control in
patients with at least one of the following feature:
• Primary disease progression
• Early disease recurrence <12 months after the end of 1st line treatment and
• Extra nodal disease at the time of relapse

37. Disease Recurrence after HDCT followed by
ASCT and Brentuximab therapy
• Anti PD 1 antibodies: Nivolumab, Pembrolizumab approved by FDA
• In Patients with multiple relapses without further options: Gemcitabine
based palliative ChT

38. Treatment of
B. NLPHL
• Stage IA without Risk Factors:
• Involved Site RT @ 30 Gy alone
•
• Other Stages : R-CHOP
• Rituximab
• Cyclophosphamide
• Adriamycin (Hydroxy-Adriamycin)
• Oncovin (Vincristine)
• Prednisolone

39. Relapsed NLPHL
• Renewed biopsy should be obtained in patients of suspected NLPHL relapse
• Transformation into aggressive NHL must be ruled out
• Localized NLPHL: Anti CD20 antibodies (Rituximab or Ofatumumab) given
as single agent
• Disseminated disease at relapse: aggressive Chemotherapy combined with
Anti CD 20 antibody
• Due to lack of CD30 ab in NLPHL: Brentuximab has no role

40. Response Evaluation
• If PET is not available then CECT-Neck, chest and Abdomen

41. Follow Up
• History, Physical Examination and Lab analysis: every 3 months for first 6
month, every 6 months until 4th year, Once a year thereafter
• TFT once a year if neck had been irradiated
• Young Female: mammogram annual after 8-10 year of RT exposure and
patients who were < 30 years at time of RT exposure, Breast MRI should be
done too.

42. NHL (Non Hodgkin Lymphoma)
• Some other Class
• Few important points
• Chemotherapy and Radiotherapy side effects

43. Thank You !