THE LYMPHOMA
Lymphoma : are group of diseases caused by malignant lymphocytes that accumulate in the lymph node and cause the characteristic clinical feature of lymph- adenopathy ,occasionally they may spill over into the blood (leukaemic phase )or infiltrate organs out side the lymphoid tissue. The major subdivision of lymphoma is into Hodgkin s lymphoma and non-Hodgkin s lymphoma and this is based on histological presence of Reed-Sternberg cells (RS)cells in Hodgkin s lymphoma.
• Hodgkin s lymphoma
Pathogenesis:
Hodgkin disease is a lymphoma in which RS cells are found in the disease tissue ,these cells are neoplastic ,its origin from B-lymphoid lineage and often derived from a B-cells with a defective immunoglobulin gene caused by the acquisition of mutation that prevent synthesis of normal immunoglobulin,( morphologically the RS cells are large with enlarged multilobated nucleus with predominant nucleoli and abundant cytoplasm, most RS cells are with two mirror image nuclear lobes ,each containing a large nucleolus surrounding by a clear zone which give an owl-eye appearance ) . The Epstein-Barr virus (EBV) genome is present in the RS cells in about 50% or more of cases ,indicating that EBV playing a causative role in the pathogenesis. The characteristic non-neoplastic ,inflammatory cells infiltrate result from a number of cytokines secreted by RS cells ,such as IL-5 (which attack and activate eosinophils ) and transforming growth factor ? (a fibrogenic factor) ,conversely these reactive inflammatory cells produce factors that can aid in the growth and survival of RS cells ,and contribute further to the tissue reaction.
Histological classification:
Five subtypes of Hodgkin s lymphoma are recognized :
1-Nodular sclerosis: this is the most common form , equally frequent in men and women and has a tendency to involve the lower cervical ,supra clavicular and mediastinal lymph node, most patients are young adults and the prognosis is good.
Morphologically characterized by:
* The presence of collagen bands that divide the lymphoid tissue into circumscribed nodules.
* The presence of particular variant of RS cells ,called lacunar cells .
* The cellular infiltrate may show varying proportions of lymphocytes ,eosinophils ,histiocytes and lacuner cells ,RS cells are infrequent.
2- nodular lymphocytes predominant : most individuals with this type present with isolated cervical or axillary lymphadenopathy and has good prognosis, morphologically characterized by:
* Large number of small lymphocytes mixed with benign histiocytes .
* Large ,poorly-defined nodules .
*The classical RS cells are very scanty with presence of variant of RS cells ,called lymphohistiocytes (L&H) cells .
3-Mixed cellularity :this is the most common form in patients above 50 years old and has male predominance with systemic manifestations, morphologically characterized by :
*Classical RS cells are plentiful within a cellular background including eosinophils, plasma cells and small lymphocytes.
4-Lymphocytes rich: this type is uncommon ,characterized by:
*Scanty RS cells with multiple small lymphocytes and few eosinophils.
5-Lymphocytes depletion: this type also uncommon ,characterized by:
*Frequent RS cells with scanty lymphocytes.
Clinical features:
The disease has a peak incidence in young adult, with male predominance, the following symptoms are common:
1- most patients present with painless, non-tender, firm, asymmetrical and rubbery enlargement of superficial lymph nodes ,cervical nodes are involved in 70% of patients, typically the disease is localized to a single peripheral lymph nodes region and its subsequent progression is by contiguity within the lymphatic system.
2-splenomegaly occurs during the course of disease ,the liver may also be enlarged because of liver involvement .
3-mediastinal involvement in nodular sclerosing type particularly in young women.
4-constitutional symptoms are prominent in patients with wide spread disease, which are :
• fever (continuous or cyclic).
• pruritus.
• weight loss
• night sweating
•weakness
• anorexia and cachexia.
Haematological and biochemical finding:
1-normochromic normocytic anaemia is most common, bone marrow involvement is unusual in early disease but if it occurs bone marrow failure may develop.
2- neutrophelia, eosinophelia is frequent.
3-advanced disease is associated with lymphopenia.
4-plateletes count is normal or increased during early disease and reduced in later stages.
5-the ESR and C-reactive protein are usually raised.
6-serum lactate dehydrogenase (LDH) is raised 40% of cases.
Clinical staging:
The selection of appropriate treatment depends on accurate staging of the extent of disease ,staging is performed by :
1-laboratory tests which are :full blood count, ESR, liver function tests, LDH, C-reactive protein, bone marrow aspirate and biopsy are not routinely done.
2-Radiology by chest radiograph and CT scan of chest, abdomen and pelvis.
3-special tests such as MRI and bone scan.
The staging of Hodgkin s lymphoma:
• Stage I indicates node involvement in one lymph node area.
• Stage II indicates disease involving two or more lymph node areas confined to one side of diaphragm.
• Stage III indicates disease involving lymph node above and below the diaphragm.
• Stage IV indicates involvement outside the lymph node areas and refers to diffuse or disseminated disease in the bone marrow, liver and other extranodal type.
The stage number in all cases is followed by the letter A or B indicating the absence A or presence B of one or more of the following symptoms:
1-unexplained fever .
2-night sweating.
3-loss of more than 10% of body weight within 6 months.
Treatment:
Treatment is with radiotherapy ,chemotherapy or a combination of both .The choice depends primarily on the stage and whether clinically A or B.
1-Radiotherapy :patients with grade I and IIA disease may be cured by radiotherapy alone .Radiotherapy also has a role in the treatment of bulky tumor masses such as mediastinal tumors that remains after chemotherapy .
2- Chemotherapy is used for stage III and IV disease and also in stage I and II patients who have bulky disease ,type B symptoms or have relapse after initial radiotherapy.
Prognosis:
Approximately 5-years survival rates range from 50% to 90% depending on the age ,stage and histology.