Hodgkin Lymphoma

 

 Hodgkin Lymphoma

P.K.Ghatak, MD

Thomas Hodgkin, a British physician and pathologist, published a paper in 1832 describing the autopsy findings of 7 patients with painless enlarged lymph nodes associated with an enlarged spleen. In subsequent studies more such cases were described by others and in 1912 the disease was named as Hodgkin Lymphoma. Dorothy Reed Mendenhall of the U.K. and Carl Sternberg of Germany published in 1902 their histological studies of Hodgkin's lymphoma. They detected large cells with binucleated nuclei due to the non-separation of cytoplasm after cell division. Sternberg mistook the cause of this illness as tuberculosis, but Dorothy Reed showed these cells had no relation with Mycobacterium tuberculosis. Now, these multinucleated cells are called Reed-Sternberg cells. These cells are formed in the germ center of B- type progenitor lymphocytes due to the mutation of genes, perhaps due to prior infection of Epstein Barr virus. Numerous leukocytes and immune cells gather around the Reed-Sternberg cells, producing engagement of the lymph nodes and spleen. The Reed-Sternberg cells are malignant. The cells express C 15 and CD30. Lacunar type of Reed-Sternberg cells are mono or binucleated cells with a small nucleolus and has a large pale cytoplasm, the Classic type of Reed-Sternberg cells are large, have binucleated nuclei with multiple eosinophilic nucleoli and clear cytoplasm.

Hodgkin lymphoma and lymphocytic leukemia both are malignant transformations of lymphocytes. But they are different diseases. Malignancy of B-type of lymphocytes produces Hodgkin lymphoma. The malignant cells adhere together and remain within the lymph nodes, and no malignant cells appear in the peripheral blood. In lymphatic leukemia, both B-lymphocytes and T-lymphocytes of the bone marrow turn malignant and cancer cells are present in the peripheral blood and dominate among the other blood cells. Mutations of DNA are responsible for both cases but the exact cause is unknown why in one instant it becomes a lymphoma in another leukemia. The chronic form of lymphocytic leukemia is an indolent disease and requires no treatment unless patients develop anemia or the immature lymphocytes called Lymphoblasts are seen in numbers more than 20 % of the lymphocytes (acute lymphoblastic leukemia).

Hodgkin lymphoma is closely related to another malignancy of lymph nodes called Non-Hodgkin lymphoma. The main points of difference between them are summarized in this table.

Points of difference

	Hodgkin lymphoma	Non-Hodgkin Lymphoma
Lymphocyte type	B-cell	T- cells and B-cells
Reed-Sternberg cell	Present	Absent
Location of Glands	Neck and above the diaphragm in chest	Any lymph nodes, both above and below the diaphragm
Age of patients	Young	Generally 65 yrs and over
Sex of patients	Generally male	Both sexes
Race	White	Asian and African
Response to treatment	Good	Poor
Prognosis	Good	Not good

Symptoms of Hodgkin lymphoma.

General Symptoms: Like all malignancies, unintended weight loss, poor appetite, nausea, and weakness also develop in Hodgkin lymphoma.

Specific symptoms: Though no one symptom can identify Hodgkin lymphoma, but these symptoms are suggestive of this disease. Painless cervical lymph node enlargement which persists. Profuse night sweats. Breathing difficulty due to pressure on airways in the lungs. Itching which intensifies after bathing or drinking alcohol. Fever of unknown origin, skin rashes and neuropathy.

Investigation.

Diagnosis of Hodgkin lymphoma depends on finding Reed-Sternberg Cells in the biopsy of a lymph node or bone marrow. Other tests are performed to find the disease stage and other organ involvement.

Cellular types and classification of Hodgkin lymphoma (HL).

The WHO classify Hodgkin lymphoma, based on histological and clinical features into 5 types of Hodgkin lymphoma.

1. Nodular Sclerosis. This type HL is most common. The bands of fibrous tissue divide the mass into several nodular areas. R-S cells are Lacunar type. The nodes are detected in the mediastinum and supra diaphragmatic locations. Patients are generally teens and young adults

2. Mixed cellular. This type is the next common HL. The R-S cells are classical R-S cells. Patients are generally HIV positive, the disease stage is advanced and enlarged nodes are found in the abdomen in addition to usual places. Patients are generally older around 65 years.

3. Lymphocyte depleted. This is a rare type of HL. R-S cells are abundant, these cells express Epstein virus antigens. Leukocytes and immunocytes are few.

4. Lymphocyte rich. This type is also rare. R-S cells are lacunar and classical types. Profuse Infiltration by other cells, among them lymphocytes predominate.

5. Nodular lymphocyte dominant. R-S cells are infrequently present, dominant cells are normal lymphocytes and histiocytes. The lymphocyte expressing CD 20 but not CD15 or CD39.

Staging: Like any other cancer, HL are classified accordingly using well established criteria into 4 classes and treatment is prescribed accordingly.

Several modalities of treatment are available, as follows.

1. Combination chemotherapy

2. Radiation therapy

3. Immunotherapy including Check point inhibitors, CART therapy. Monoclonal antibodies and Small molecules.

4. Bone marrow and Stem cell transplantation.

Stage I and II.

Combination of chemotherapy agents are given is 2 cycles, each one of 4 weeks duration. This is followed by radiation therapy. The prognosis is very favorable. Those who have additional risk factors like immunosuppression are given 4 cycles of chemotherapy and in increased dosages.

Stage III and IV.

Combination chemotherapy with additional agents are given in 6 cycles, followed by radiation and Immunotherapy. The prognosis is poor to unfavorable.

Separate protocols are available for recurrence of the disease and poor initial response to the therapy.

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