HODGKIN AND NON-HODGKIN LYMPHOMA Dr. M. Sofi MD; FRCP (London); FRCPEdin; FRCSEdin

Hodgkin’s Lymphoma Hodgkin's lymphoma (HL) is a potentially curable lymphoma with distinct histology, biologic behavior, and clinical characteristics. The disease is defined in terms of its microscopic appearance (histology) and the expression of cell surface markers (immunophenotype). About half of cases of Hodgkin's lymphoma are due to Epstein–Barr virus (EBV) Most common primary localizations are cervical (60 80%), mediastinal, and inguinal lymph nodes.

Hodgkin’s Lymphoma Epidemiology The incidence rate is at 2-3/100,000 per year. The age peak lies at approx. 32 years. Hodgkin lymphoma is one of the most treatable forms of cancer. About 75 percent of people diagnosed with Hodgkin lymphoma can be cured with treatment. Over 90 percent of people live at least 10 years after treatment.

Classification WHO classification: There are two main types of lymphoma I. Nodular Lymphocyte-predominant Hodgkin’s lymphoma (NLPHL) The NLPHL encompasses almost 5% of all Hodgkin’s lymphomas. As opposed to the classical Hodgkin’s lymphomas the malignant cells are referred to as L&H (lymphocytic and histiocytic) For therapeutic purposes, nodular lymphocyte-predominant HL is managed in the same way as indolent non-Hodgkin lymphoma 

Classification II. Classical Hodgkin’s Lymphoma (cHL) Nodular sclerosing (NSHL) Mixed cellularity (MCHL) Lymphocyte-rich (LRHL) Lymphocyte-depleted (LDHL) Not classified Tumor cells of the classical Hodgkin’s lymphomas are referred to as Hodgkin and Reed-Sternberg cells (H-RS) Stage-adapted therapy allows long term cure in more than 80 percent of all patients. Hodgkin’s lymphoma is one of the oncological diseases with the highest cure rates in adults

Features of Hodgkin lymphoma include: Asymptomatic lymphadenopathy may be present (above the diaphragm in 80% of patients) Constitutional symptoms Unexplained weight loss [>10% of total body weight] Unexplained fever, night sweats are present in 40% of patients; collectively, these are known as "B symptoms" Intermittent fever is observed in about 35% of cases Pel-Ebstein fever is observed (high fever for 1-2 wk, followed by an afebrile period of 1-2 wk)

Features of Hodgkin lymphoma include: Chest pain, cough, SOB, or a combination of those may be present due to a large mediastinal mass or lung involvement; rarely, hemoptysis occurs Pain at sites of nodal disease, precipitated by drinking alcohol, occurs in fewer than 10% of patients but is specific for Hodgkin lymphoma Back or bone pain rarely occur May present with pruritus A family history in NSHL has a strong genetic component and has often previously been diagnosed in the family.

Physical Examination Painless lymphadenopathy can be seen in: the Cervical area (neck) - 60-80% Axilla (armpit) 6-20% Inguinal area (groin) - 6-20% Waldeyer ring (back of the throat, including the tonsils) or occipital (lower rear of the head) or epitrochlear areas is infrequently observed Splenomegaly and/or hepatomegaly may be present Superior vena cava syndrome may develop in patients with mediastinal lymphadenopathy CNS symptoms/signs may be due to Paraneoplastic syndromes: Cerebellar degeneration Neuropathy Guillain-Barre syndrome  Multifocal leukoencephalopathy

Differential Diagnoses Cytomegalovirus Infectious Mononucleosis Non-Hodgkin Lymphoma Systemic Lupus Erythematosus Sarcoidosis Serum Sickness Small Cell Lung Cancer Syphilis Toxoplasmosis Tuberculosis

Investigations Test Comments Laboratory analyses Complete blood cell count, including leukocyte count with differential Erythrocyte sedimentation rate LDH, GOT, GPT, AP, Gamma GT, uric acid, creatinine Imaging Chest X-rays CT scan of the neck (with contrast medium) CT scan of the abdomen (with contrast medium) PET scan: Initial staging of Hodgkin lymphoma Bone-marrow puncture Aspirate (cytology) Biopsy (histology)

Staging according to Ann Arbor Classification Stage I A single lymph node area or single extra-nodal site Stage II 2 or more lymph node areas on the same side of the diaphragm Stage III Lymph node areas on both sides of the diaphragm Stage IV Disseminated or multiple involvement of the extra-nodal organs Addendum A No B symptoms Addendum B Presence of B symptoms

Stage I A single lymph node area or single extra-nodal site Stage II 2 or more lymph node areas on the same side of the diaphragm

Stage III Lymph node areas on both sides of the diaphragm Stage IV Disseminated or multiple involvement of the extra-nodal organs

Reed – Sternberg Cell Lymphocyte Hodgkin's lymphoma, mixed-cellularity type H L: Reed-Sternberg cells, Eosinophils , Plasma cells

Non-Hodgkin lymphomas Non-Hodgkin lymphomas: is a group of blood cancers that includes all types of lymphoma except Hodgkin's lymphomas. Non-Hodgkin lymphomas (NHLs) are tumors originating from lymphoid tissues, mainly of lymph nodes. My result from: Chromosomal translocations Infections Environmental factors Immunodeficiency states Chronic inflammation. Primary extra-nodal involvement and B symptoms: Uncommon presentation with advanced, malignant transformation or end-stage disease. Frequent involve: Bone marrow May be associated with cytopenias(s) Fatigue weakness in advanced-stage disease

Non-Hodgkin lymphomas Signs and symptoms Intermediate- and high-grade lymphomas have a more varied clinical presentation: Extra-nodal involvement: More than one third of patients; most common sites are GI/GU tracts (including Waldeyer ring), skin, bone marrow, sinuses, thyroid, CNS Adenopathy: Most patients will present with lymphadenopathy B symptoms: Temperature >38°C, night sweats, weight loss >10% from baseline within 6 months; in approximately 30-40% of patients

Physical Examination NHL Low-grade lymphomas may demonstrate: Peripheral adenopathy Splenomegaly and Hepatomegaly Intermediate- and high-grade lymphomas may result: Rapidly growing and bulky lymphadenopathy Splenomegaly Large abdominal mass: Usually in Burkitt lymphoma Skin lesions: Associated with cutaneous T-cell lymphoma Mycosis fungoides Anaplastic large-cell lymphoma Angioimmunoblastic lymphoma

Skin lesions: Associated with coetaneous T-cell lymphoma Angioimmunoblastic lymphoma Mycosis fungoides Anaplastic large-cell lymphoma

Complications: Disease-related complications include: Cytopenias (neutropenia, anemia,thrombocytopenia) Bleeding secondary to thrombocytopenia, DIC Infection secondary to neutropenia large pericardial effusion or arrhythmias secondary to cardiac metastases Pleural effusion and/or parenchymal lesions Leukocytosis (lymphocytosis) in leukemic phase of disease Superior vena cava (SVC) syndrome secondary to a large mediastinal tumor Spinal cord compression secondary to vertebral metastases Primary CNS lymphoma GI obstruction, bleeding perforation, in a patient with GI lymphoma Pain secondary to tumor invasion

Testing: Laboratory studies with suspected NHL include: Complete blood cell count studies for anemia, lymphopenia, neutrophilia, or eosinophilia Erythrocyte sedimentation rate Lactate dehydrogenase Serum creatinine Alkaline phosphatase HIV is important because antiviral therapies can improve disease outcomes in HIV-positive patients ; screening for hepatitis B and C should also be considered Serum levels of cytokines (interleukin [IL]-6, IL-10) and soluble CD25 (IL-2 receptor) correlate with tumor burden, systemic symptoms, and prognosis

Imaging studies for NHL include: Plain radiographs: Measurement of mediastinal mass in relationship to thoracic diameter on posteroanterior and lateral chest radiographs remains the gold standard CT- CAP, possible abnormal findings include enlarged lymph nodes, hepatomegaly and/or splenomegaly, lung nodules or infiltrates, and pleural effusions PET Scan: Considered essential to the initial staging of Hodgkin lymphoma An excision lymph node biopsy is always recommended for histological classification. Bone marrow biopsies are indicated in some cases especially in elderly patients and those with advanced-stage disease, systemic symptoms, or a high-risk histology. CNS evaluation by LP and MRI should be performed if symptoms or signs of CNS involvement are present.

Management: General treatment principles include the following Radiation therapy Induction chemotherapy Salvage chemotherapy Hematopoietic stem cell transplantation The induction regimens are given as initial treatment for Hodgkin lymphoma MOPP (mechlorethamine, vincristine, procarbazine, prednisone) ABVD (Adriamycin, bleomycin, vinblastine, dacarbazine) BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone

Management: General treatment principles include the following When induction chemotherapy fails, or patients experience relapse, salvage chemotherapy is given. Commonly used salvage regimens include: ICE (ifosfamide, carboplatin, etoposide) DHAP (cisplatin, cytarabine, prednisone) ESHAP (etoposide, methylprednisolone, cytarabine, cisplatin) High-dose chemotherapy that ablate the bone marrow is feasible with reinfusion of the patient's previously collected hematopoietic stem cells or infusion of stem cells from a donor source. A validated and relatively safe conditioning regimen for autologous transplantation is the BEAM regimen (carmustine [BCNU], etoposide, cytarabine, melphalan)

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