Hodgkin's Lymphoma Past Paper PDF

Lymphoma I ILOs At the end of this session, the student will be able to: ▪ Identify specific recurrent cytogenetic abnormalities associated with certain lymphomas. ▪ Explain the diagnostic approach for lymphoma. ▪ List the risk factors for Hodgkin`s lymphoma (HL). ▪ Summ...

Lymphoma I ILOs At the end of this session, the student will be able to: ▪ Identify specific recurrent cytogenetic abnormalities associated with certain lymphomas. ▪ Explain the diagnostic approach for lymphoma. ▪ List the risk factors for Hodgkin`s lymphoma (HL). ▪ Summarize the histopathology and clinical picture of Hodgkin`s lymphoma. ▪ Describe the staging systems of HL. ▪ Recommend the investigations needed to diagnose Hodgkin`s lymphoma. ▪ Outline the treatment strategies for HL. Lymphomas are malignant disorders that derive from lymphoid cells. They may arise from mature T-cells or B-cells. Lymphomas are divided into Hodgkin’s Lymphoma and non- Hodgkin’s Lymphoma. Hodgkin’s Lymphoma is diagnosed histologically by the presence of Reed- Sternberg cells. The overall incidence of Lymphomas is 5-10 cases per/100,000 population each year. There are approximately 2 cases of non-Hodgkin’s Lymphoma for each case of Hodgkin’s. Lymphoma as a class shows a 3:2 predilection for males. Cytogenetics and Molecular Considerations Cytogenetic analysis has identified a number of specific recurring abnormalities that are associated with certain Lymphomas e.g Burkitt’s Lymphoma: In 75% of cases t (8;14) leading to up-regulation and expression of the C-MyC protein→ cell proliferation and a failure of apoptosis. Follicular Lymphoma: t (14;18) → BCL-2 expression leading to failure of apoptosis. Mantle cell Lymphoma: t (11;14)→ BCL-1 (Cyclin D 1) expression→ cellular proliferation. Large cell Lymphoma: characterized by the expression of BCL-6 Diagnosis The diagnosis is based on the histological appearance of an enlarged lymph node or other affected tissues or cytology of blood, BM or cerebrospinal fluid (CSF), but this is usually backed by: Immunophenotyping Cytogenetic Molecular techniques Immunophenotyping The identification of antigenic molecules associated with human white cells, using labeled antibodies may be very helpful for diagnosis. There is now an internationally agreed basis for the nomenclature of Leucocyte molecules, the Cluster of Differentiation = CD Scheme. The CD20 is one such molecule exclusively expressed on B-cells. Besides, CD19, CD22 and CD79 are other examples of B-cell expressed molecules identified by antibody binding, by flowcytometry method. Staging of Lymphomas The “stage” of a disease is a method of determining the extent to which the cancer has grown and spread, and plays a critical role in determining the appropriate course of treatment. Staging Lymphomas are staged by the following investigations Once the diagnosis of lymphoma has been made by biopsy or examination of blood, pleural fluid or perhaps CSF, staging should be undertaken by: 1- CT-scanning; ultrasound; chest X-ray. 2- Bone marrow biopsy is important in non-Hodgkin’s Lymphoma due to the high frequency of bone marrow involvement in this disorder. 3- Serum Lactate dehydrogenase → confers a poor prognosis. 4- Immunoglobulins should be measured and monoclonal proteins. Staging of Lymphomas Ann Arbor staging classification: Stage I: Involvement of a single lymph node group. Stage II: Involvement of two or more lymph node groups on one side of the diaphragm. Stage III: Involvement of lymph node groups on both sides of the diaphragm. Stage IV: Involvement of extralymphatic sites e.g. bone marrow or liver. Patients are said to be: o Stage (A) if they have no systemic symptoms, o Or stage (B) in the presence of any one of ; night sweats, fever or weight loss (10% in past 6 months). International Prognostic Index Worse prognosis is associated with: 1. Extranodal disease: Disease outside Lymphatic sites confers a poor prognosis. 2. Advanced stage disease 3. Elevated LDH 4. Increasing age Hodgkin’s Lymphoma Pathogenesis o First described by Thomas Hodgkin in 1832. o PCR for Immunoglobulin gene amplification demonstrates that the neoplastic cells in Hodgkin’s Lymphoma are clonal B-cells originating in a lymph node germinal center with a crippled immunoglobulin gene caused by mutations that prevent synthesis of full-length immunoglobulin. o Epstein-Barr virus (EBV) genome has been detected in 50% or more of cases of Hodgkin’s Diseases (HD). Incidence o One percent of cancer registration per year. Less common in Japan. o Bimodal age incidence- major peak between 20 and 29 years and minor peak 60 years. o Overall higher incidence in males. o Nodular sclerosing (NS) histology most common subtype in young adults. Risk Factors 1- Association with high socioeconomic status in childhood. 2- Familial aggregations frequently reported genetic or environmental effect. 3- Considerable evidence linking EBV to HD in individuals with past history of infectious mononucleosis. Diagnosis o It is made by histological examination of an excised lymph- node. Reed-Sternberg cells (RS-cell) are central to the diagnosis of the four classic types and RS- cells are also part of the malignant clone. These cells stain with CD30 and CD15 but are usually negative for B-cell antigen expression. Besides, inflammatory cells consist of lymphocytes, neutrophils, eosinophils, plasma cells and variable fibrosis. Histopathologic / Clinical Features of Classic Hodgkin’s Disease Clinical Picture 1- Constitutional Symptoms: Fever in 30% of patients, is continuous or cyclic. Weight loss. Profuse sweating especially at night. Pruritis may be severe, occurs in 25% of cases. Fatigue. Anorexia and cachexia. 2- Nodular enlargement Painless, non-tender, asymmetrical, firm, discrete and rubbery LN that may become matted. Cervical nodes; are involved in 60 – 70 % Axillary nodes; in 10 – 15 % Inguinal nodes; in 6 – 12 % Retroperitoneal nodes; are also often involved but usually diagnosed by CT- scan. Mediastinal L.N. enlargement; in 6-11% of patients. This is a feature of the nodular sclerosing type. There may be associated pleural effusion or superior vena cava obstruction. 3-Organomegaly: Splenomegaly occurs during course of disease in 50% of cases, but seldom massive.  Liver involvement may occur. Other organs e.g. BM, GIT, bone, lung and spinal cord may be involved, but this is unusual. Investigations 1- Confirm diagnosis by biopsy, best histology of lymph node by excision biopsy. 2- Blood picture: normochromic normocytic anaemia, reactive leucocytosis, eosinophilia and / or reactive mild thrombocytosis. 3- ESR/ plasma viscosity: high in active HD and could be good for follow up. 4- LDH: high in advanced disease. 5- Liver functions: may be abnormal in liver involvement in HD. 6- Blood uric acid: high i.e. secondary gout due to lympho-proliferative activity. 7- Abnormal kidney functions: due to involvement by HD or due to secondary gout. 8- Chest X-ray: for LN- enlargement or infections secondary to immune suppression. 9- CT-chest, abdomen and pelvis: to define nodal and extra- nodal involvement. 10- Bone marrow trephine: to exclude marrow involvement. 11- MRI or PET scan: may be necessary in difficult cases. Staging of Hodgkin’s Lymphoma Categories In addition to the stage number, the letters A, B, E or S may be used to further classify the stage of HL. Category A: The patient does not have B symptoms (fever, weight loss or night sweats). Category B: The patient has B symptoms. Category E: The patient has HL cells in organs or tissues outside the lymphatic system. Category S: The patient has HL cells in the spleen. Categories For example, stage IIB would indicate that the patient has Involvement of two lymph node sites near each other (for example, enlarged lymph nodes in the neck and collarbone area or in the neck and the armpit) Fever, excessive sweating and/or weight loss Patients in the B category sometimes require more aggressive treatments. It is important to note that even patients with stage IV (advanced stage) HL are frequently cured with treatment, despite having lymphoma in many areas of the body. Treatment The goal of Hodgkin lymphoma treatment is to cure the disease. More than 80 % of all patients diagnosed with Hodgkin lymphoma can be cured by current treatment approaches. The cure rate is higher, approaching 90 %, in younger patients and those with early- stage favorable disease. Even if disease recurs, many patients can be cured with further treatment. Most patients become long-term survivors of the disease. Treatment goals are to: o Cure at all stages o Minimize both short-term and long-term side effects and complications o Weigh the risks of toxicity against treatment benefits Treatment outlines Chemotherapy Radiotherapy Immunotherapy o Monoclonal antibodies (mAbs) o Check point inhibitors Stem cell transplantation Early disease (Stage IA/IIA ): can be treated with extended field radiotherapy or 3 courses of ABVD+ localized radiotherapy. Advanced disease (Stage IIB-IV) treated with six to eight courses of combination chemotherapy (ABVD) ▪ ABVD = o Adriamycin o Bleomycin o Vinblastine o Decarbazine ▪ HL: Hodgkin Lymphoma; ▪ ABVD: Adriamycin, Bleomycin, Vincristine, Dacarbazine; ▪ eBEACOPP: bleomycin, etoposide, doxorubicin (aka adriamycin), cyclophosphamide, vincristine (aka oncovin), procarbazine, prednisolone; ▪ PET: positron emission tomography; ▪ BV: brentuximab vedotin; ▪ AVD: Adriamycin, Vincristine, Dacarbazine; ▪ GVD: gemcitabine, vinorelbine, liposomal doxorubicin; ▪ CR: complete response; ▪ ICE: ifosfamide, mesna, carboplatin, etoposide; ▪ ASCT: autologous stem cell transplantation; ▪ PD1: programmed cell death 1; ▪ mAbs: monoclonal antibodies; ▪ CPI: checkpoint inhibitors; ▪ Allo-SCT: allogeneic stem cell transplantation; ▪ PT-Cy: post-transplant cyclophosphamide; ▪ GvHD: graft-versus-host disease.