Dr. Hasan Fahmawi, MRCP(UK), FRCP(Edin) HODGKIN LYMPHOMA Dr. Hasan Fahmawi, MRCP(UK), FRCP(Edin)

The whole mark of Hodgkin lymphoma (HL) is the presence of Reed Stemberg cells which are large , malignant lymphoid cells of B-Cell origin. They are present only in small numbers, but are surrounded by large numbers of reactive non malignant cells T-cells, plasma cells and eosinophils. 1-Nodular lymphocyte predominant HL is slow growing, localised and rarely fatal. 5% of cases 2-Classical HL.

Clinical features: painless, rubbery lymph adenopathy usually in the neck or supraclavicular fossae; the lymph nodes may fluctuate in size. Young patients with nodular sclerosing type may have large mediastinal masses that are surprisingly asymptomatic, but may cause dry cough and some breathlessness. Hepatosplenomegaly may be present, but doesn’t always indicate disease in those organs. Spread is contiguous from one node to the next, and extranodal disease, such as bone, brain or skin involvement ,is rare.

Investigations Done for diagnosis and to determine the extent of the disease. FBC may be normal. If normochromic normocytic anaemia, or lymphopenia is present, this is a poor prognostic factor. An eosinophilia or neutrophilia may be present. ESR may be raised. RFT should be normal before treatment. LFT may be abnormal in the absence of disease, or may reflect hepatic infiltration. An obstruction pattern may be caused by nodes at the porta hepatis. LDH when high is an adverse prognostic factor. Chest X-ray may show a mediastinal masses. CT scan of chest abdomen and pelvis help staging bulky disease (over 10 cm. in a single node mass), which is an adverse prognostic sign. PET identifies nodes involved with HL which are fluorodeoxyglucose-avid for more accurate staging and monitoring response. Lymph node biopsy may be undertaken surgically or percutaneous needle biopsy under radiological guidance. Extra lymphatic involvement - bone marrow ,bone, lung and liver. Any other site involved search for HIV or should promt questioning the diagnosis

Management Stages 1A, 11A, chemotherapy and radiotherapy. ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine), women receiving radiotherapy are at higher risk of breast cancer, and should participate in screening program. Male smokers are at particular risk of lung cancer. Doxorubicin is cardiotoxic and bleomycin is pulmonary toxic. Resistant disease may benefit from an allogenic stem cell transplant. Prognosis: over 90% of patients with early stage HL achieve complete remission when treated with chemotherapy followed by involved field radiotherapy, and the great majority are cured. The major challenge is how to reduce treatment intensity, and hence long term toxicity, without reducing the excellent cure rate in this group. Omitting radiotherapy in the majority of PET negative patients is one major step towards this regard.

NON-HODGKIN LYMPHOMA NHL

Presents a monoclonal proliferation of lymphoid cells of B-cells(90%) or T-cells (10%) origin. Incidence increase with age. Classification: clinically the most important is grade, which is a reflection of the proliferation rate. High grade NHL has a high proliferation rate, rapidly produces symptoms, is fatal if untreated, but is potentially curable. Low grade NHL has low proliferation rate, may be asymptomatic for many months or even years before presentation, runs an indolent course, but is not curable by conventional therapy. Less common NHL are, Burkitt lymphoma, mantle cell lymphoma, mucosa associated lymphoid tissue (MALT) lymphoma, and T cell lymphoma.

Clinical features: NHL is widely disseminated at presentation, including extranodal sites, which may be associated with systemic upset, fever, sweats, loss of weight, and itching. Hepatosplemegaly may be present. Sites of extranodal involvement include the bone marrow, gut , thyroid, lung, skin, testis brain and more rarely the bone. Compression syndromes may occur, including gut obstruction, ascites, superior vena cava obstruction and spinal cord compression. Staging for HL and NHL are the same, but NHL is more likely to be stage 111 or 1V a presentation.

Investigations: Bone marrow aspiration or trephine. Immunophenotyping of surface antigen to distinguish B-cell from T-cell. Cytogenetic analysis to detect chromosomal translocation and molecular testing for T-cell receptor or immunological gene re-arrangement. Immunoglobulin determination. Some lymphomas are associated with IgG or IgM paraprotein, which serves as a marker for treatment response. Uric acid level as it precipitate renal failure in high levels. HIV testing. Hepatitis B and C testing. This should be done prior to Rituximab.

Management: Low grade NHL, the majority (80%) present with advanced stage disease and will run a relapsing and remitting course over several years. Asymptomatic patients are managed by watching and waiting. Indication for treatment are marked systemic symptoms, lymphadenopathy causing discomfort or disfigurement, bone marrow failure or compression syndrome. In follicular lymphoma the options are: Radiotherapy for type 1. Chemotherapy, chlorambucil give better life quality but no improved survival. Monoclonal antibody treatment. Humanised monoclonal antibodies (biological therapy) can be used to target surface antigen on tumour cells and to induce tumour apoptosis directly. The anti- CD20 Rituximab has been shown to induce clinical responses in up to 60% of patients when given alone, and (R) in combination with cyclophosphamide, doxorubicin, vincristine, and prednisolone(R-CHOP). Kinase inhibitors. Idelalisib for relapsing follicular, ibrutinib is approved for mantle cell lymphoma, a poor prognostic lymphoma with low- grade histology. The targeted therapies are likely to become more widely used in low-grade lymphoma in the near future. HSCT. High dose chemotherapy and HSCT can produce long remissions in patients with relapsed disease, used in young patients.

High grade NHL. Patients with diffuse B-cell NHL need treatment at initial presentation. Chemotherapy. The majority over 90% are treated with intravenous combination chemotherapy, typically with the CHOP regimen. Monoclonal antibody therapy, R-CHOP. Radiotherapy. 1-Stage 1, no bulky disease after cycles of R-CHOP. 1-Residual bulky disease after chemotherapy. 1-Spinal cord and other compression syndromes. HSCT. Autologous HSCT benefit patients with relapsed disease that is sensitive for salvage immunochemotherapy, as with HL, achieving PET negative prior to autologous transplantation is desirable. Prognosis. Low-grade NHL with overall median survival of 12 yrs. In diffuse B-cell NHL treater with R-CHOP, some 75% of patients overall respond initially to therapy, and 50% will have disease free-survival at 5 years. Relapse is associated with a poor response to further chemotherapy (less than 10% 5-years survival), but in patients under 65 years HSCT improve survival.