HODGKIN LYMPHOMA (HL)

HL is a lymphoid malignancy of primarily nodal origin with B-cell lineage, accounting for ~40% lymphomas in children, with relatively slower and orderly spread of disease than in NHL.

Epidemiologically, HL is rare below 5 years of age, with a bimodal age distribution in western countries, at 15-35 years and then after 50 years. However, Indian children are frequently affected at younger age without sex difference, except slight male predominance in cases lt;10 years.

Etiology is multifactorial and important risk-factors include—(a) consanguinity or similar disease in family (suggestive of genetic basis), (b) preceding Epstein-Barr virus (EBV) infection, and (c) underlying immuno­deficiency or autoimmune disorders, e.g. JIA or SLE.

Siblings of a case have 7-times higher risk of deve­loping HL, which is 100-times more in monozygotic twins.

EBV infection increases risk of subsequent HL by 4-times and EBV-DNA has been found in hallmark Reid- Sternberg cells.

Pathologically, HL usually arises from cervical (70%) or mediastinal (20%) lymph nodes, though may begin from any other site or extranodal lymphoid tissue. Presence of Reed-Sternberg cell — a giant cell with mirror image nucleus, is hallmark histological feature of HL.

WHO classification of HL includes two major types- nodular lymphocyte predominance (NLPHL) and classic (cHL), with cHL including four subtypes-nodular sclerosing, mixed cellularity, lymphocyte predominance and lymphocyte depletion. Nodular sclerosing HL is the commonest HL globally (50%), followed by mixed cellularity (40%), though the later type is more common in India.

HL spreads via lymphatic channels to adjacent nodes or hematogenously to extra-lymphatic organs, e.g. liver, spleen, bone marrow, lungs and brain.

LN: Lymph node EN: Extranodal

*Or Mediastinal tumor gt; 1#8725;3^rd of transverse intrathoracic diameter

Clinical presentation depends on site of origin, though important features include:

a.

b. Local pressure symptoms, e.g. hoarseness, dyspnea, dysphagia or superior vena caval compression syndrome in mediastinal disease, and

c. Systemic features, e.g. prolonged fever, night sweats, weight loss are prominent in HL, probably due to raised cytokines levels, e.g. interleukins and tumor necrosis factor. Presence of any of these features alters stage of the disease (Table 20.8). Pel-Ebstein fever — a relapsing fever, although pathognomonic is seen in only 10-15% cases.

d. Opportunistic infections, e.g. tuberculosis, herpes zoster and fungal infections are common, due to impaired cell mediated immunity.

Diagnosis depends on excision biopsy of the suspected lymph node, rather than FNAC, to ensure adequate tissue for histology and immunocytochemistry. Once the diagnosis is established, further investigations are necessary to stage the disease (Table 20.8), which include—(i) bone marrow examination, (ii) chest X-ray/ CT for mediastinal or pulmonary disease, (iii) abdominal CT for liver, spleen or node involvement, and (iv) PET scan to stage the disease and assess the response to therapy. ESR, serum LDH and ferritin levels may be monitored serially to assess the effect of treatment.

Treatment depends on the stage of disease and age of patient includes multi-drug chemotherapy with low- dose involved-field radiotherapy (Table 20.9).

Chemotherapy: Most commonly used protocols are preferred ABVD regimen (Adriamycin, Doxorubicin, Bleomycin, Vinblastine, and Dacarbazine) or COPP

LD-RT: Low-dose radiotherapy * or relapse within 12 months regimen (Cyclophosphamide, Oncovin, i.e. vincristine, Procarbazine, and Prednisolone), given for minimum 6 cycles. However, considering toxicities of these regimens, e.g. sterility, cardiopulmonary dysfunction and secondary malignancies, many other regimens have been developed to reduce the doses and duration of therapy.

Trials have shown encouraging results with Rituximab- an anti-CD20 antibody, in relapsed cases. EBV-specific cytotoxic T-lymphocytes have also been developed with promising results.

Radiotherapy is highly effective, but with significant adverse effects, e.g. growth failure, cardiac, pulmonary or thyroid dysfunctions and secondary cancers. Several studies have shown that chemotherapy alone is effective in most cases of HL and only limited-field, low-dose (2000-5000 cGy) radiotherapy is used in bulky disease and poor interim PET response to chemotherapy. Prognosis depends on stage, histological type and systemic features. Important bad prognostic f actors include—(a) sub-category B disease, (b) bulky media­stinal disease, (c) lymphocytic depletion histology, and d) poor response to chemotherapy. Lymphocyte predominance HL has best outcome.

20.3.2