Hodgkin’s Disease (HD)

1. Hodgkin’s Disease (HD) A disease of lymph nodes with a predictable pattern of spread

2. Epidemiology • Age: bimodal peak age • Third decade • After 50 • Gender: male to female = 1.3 to 1.0

3. Etiology and Risk Factors • Unknown • Possible etiologic factor • 1) Familial factor • 2) Viruses - EBV

4. Signs and Symptoms • HD is a lymph node-based malignancy • Common = asymptomatic lymphadenopathy • Systemic symptoms • Extranodal involvement

5. Location of Lymphadenopathy • 80% LN above the diaphragm • Anterior mediastinum • Cervical, supraclavicular, axillary

6. Systemic Symptoms • 40% of patients -> systemic symptoms • B-symptom => Fever, Night sweat, Weight loss • Chronic pruritus

7. Extranodal Involvement • “E” lesion by direct invasion • Hematogenous metastasis (Stage IV): spleen, lungs, liver, bone marrow

8. Diagnosis • Biopsy • Pathology : “Reed - Sternberg Cell” • Diagnostic tumor cell • Must be identified • Large size, binucleated, large eosinophilic nucleoli

9. Histology • 1. Lymphocyte predominant (LP) = few RS cells, good prognosis • 2. Nodular sclerosis (NS) = the most common, young adult, female • 3. Mixed cellularity (MC) = generalized lymphadenopathy • 4. Lymphocyte depletion (LD) = numerous RS cells, poor prognosis

10. Staging : The Coltswolds Classification for HD • I: A single LN region or a lymphoid structure (eg., spleen, thymus, Waldeyer’s ring) • II: Two or more LN regions on the same side of the diaphragm • III: LN regions or structures on both sides of the diaphragm • 1: with/without involement of splenic, hilar, celiac, or portal nodes • 2: with involvement of paraaortic, iliac, or mesenteric nodes • IV: Extranodal site(s) beyond that designated E ( a single extranodal site, contiguous or proximal to a known nodal site)

11. Designations applicable to any disease stage • A: No symptoms • B: Fever, drenching sweats, weight loss • X: Bulky disease • > 1/3 the width of the mediastinum • > 10 cm maximal dimension of nodal mass • E: Involvement of a single extranodal site, contiguous or proximal to a know nodal site

12. Prognostic Factors • Stage of disease: the most important prognostic factor • Number of sites of involvement • Bulky disease ( particularly in the mediastinum) • B symptoms • Age

13. Investigations • 1. Imaging : CT scan of the chest/ abdomen • 2. Lab tests: CBC, ESR, LDH • 3. Bone marrow biopsy: B-symptoms • 4. Staging laparotomy : consist of • Splenectomy • LN sampling: celiac/splenic/hilar/paraaortic/paracaval/iliac nodes • Wedge/needle biopsy of the liver • open iliac crest Bone Marrow Biopsy • Oophoropexy

14. Treatment • Stage I-II = Radiotherapy • Stage III-IV = Chemotherapy

15. Radiotherapy • Subtotal lymphoid irradiation = Mantle + Paraaortic field • Mantle field = base of mandible to diaphragm • Cover LN above diaphragm -> submandibular, cervical, supraclavicular, infraclavicular, axillary, mediastinum, hilar • Dose = 3,600 cGy

16. Side Effects of Radiotherapy • Acute • N/V, Dermatitis, Fatigue • Delay • Pneumonitis • Herpes zoster infection • Subclinical hypothyroidism • Infertility • Secondary malignancies • secondary solid tumors ( lung, breast) • chemotherapy -> most common = leukemia

17. Non-Hodgkin’s Lymphoma Heterogeneous group of lymphoproliferative malignancies

18. Epidemiology • The incidence has been increasing worldwide. • This increase is more marked for older persons.

19. Etiology and Causative Factors • The origin is UNCERTAIN. • Causative factors with a predisposition • Immunosuppression • Infectious agents (EBV, HTLV-1, Herpes type 8, H.pylori)

20. NHL • Usually originates in lymphoid tissues • Can spread to other organs • Prognosis depends on the histologic type, stage and extent of disease, age, and treatment

21. Clinical Manifestations • Asymptomatic LN enlargement (most common presentation) • 1) Location of lymphadenopathy • most common = neck, inguinal, and abdominal LNs • 2) Systemic symptoms • fever, weight loss, night sweats ( usually heralding more advanced disease) • 3) Primary extranodal lymphoma • depend on the site of origin

22. Staging Evaluation • Pathologic diagnosed by an experienced hematopathologist. • Staging Evaluation includes: • History + Physical Exam • Lab : CBC, LDH • Bone marrow biopsy • Chest X-Ray • CT abdomen and pelvis/chest • Gallium scan

23. Histology: 2 prognostic groups • Indolent lymphoma • Aggressive lymphoma

24. Staging: Ann Arbor System (commonly used) • I: A single nodal region (I) or single extralymphatic site (IE) • II: 2 or more nodal regions on the same side of diaphragm(II) or a single localized extralymphatic site and its regional nodes on the same side of diaphragm (IIE) • III: Nodal regions on both sides of the diaphragm • IV: Diffuse or disseminated involvement of 1 or more extralymphatic organs with/without associated nodal involvement

25. Designations applicable to any stage • A: No symptoms • B: Weight loss, unexplained fever, night sweats • E: Localized involvement of extralymphatic tissue • S: Spleen involvement

26. Treatment • Indolent Lymphoma • Stage I + II = RT • Stage III + IV = Chemotherapy + RT • Aggressive Lymphoma • Stage I + II = combined modality ( Chemotherapy + RT) • Stage III + IV = Chemotherapy ( Doxorubicin based)

27. Radiotherapy • Involve-field RT: • Involved region + first-echelon adjacent LN region • Extended field RT: • involve field + second-echelon adjacent LN region

28. Example

29. Radiation Dose: • Indolent: 2,500 - 3,500 cGy • Aggressive: 3,500 - 4,500 cGy

30. Late effects of treatment • Normal tissue toxicity • Secondary cancers