Cancer - Hodgkin's Lymphoma Pathophysiology

Lymphocyte is a type of white blood cell that is a key component of the body's defense against diseases and infections, but then there can still be a disease that has to do with Lymphocytes itself. In this post, I will be looking at Hodgkin's Lymphoma, which is a cancer that has to do with dysfunction or an alteration in the lymphocyte pathway. Quickly, you should have heard of the T-lymphocyte, B-lymphocyte, and the Natural Killer cells, they are the main types of lymphocytes, but to understand Hodgkin's lymphoma, I will quickly take you through the lymphocyte pathway.

This pathway starts in the hematopoietic bone marrow where red blood cells are produced. In the red bone marrow, the hemocytoblast grows to become the myeloid and lymphoid stem cell which is important in the production of lymphocytes. The lymphoid Stem cells then produce the precursor B cells and the Precursor T cells. The Precursor T and B cells are pushed into the bloodstream, then the precursor T cell goes to the Thymus while the precursor B cell goes to the lymph nodes. In the thymus, the precursor T cell becomes the CD4+ cells (T-helper cell), and the CD8+ cell (Cytotoxic T cell). In the Lymph nodes, the precursor B-cell goes to the Mantle Zone where it is exposed to antigens. The precursor B-cell that isn't exposed to antigens remains in the mantle zone, while the ones that are exposed go to the germinal center. When the precursor B-cell is exposed to antigens, it becomes a centroblast thereby having affinity to antigens similar to the antigen it is bound to. If the affinity of the B-cell receptor to the antigen is weak, then the cells should die (apoptosis), but if there is a strong affinity, then it goes to become the centrocyte. The centrocyte can interact with the T-cell and Dendritic cell. The dendritic cell possesses antigens, and the T-cell possesses mhc class2 molecules which can expose antigens. When it interacts with antigens, it can become a memory B-cell, and when it interacts with plasma cells, it will become a plasma blast, after which it moves to the marginal zone. Hodgkin's lymphoma occurs when centroblasts which are supposed to die or undergo apoptosis do not die. This causes the continuous replication of the cell without differentiating fully. The centroblast has large nuclei known as Reed-Sternberg Cell as a result of not undergoing apoptosis. ^,

This inability of the cell to die can be caused if there are antiapoptosis genes in the cell but they both continue to survive. Nuclear factor kappa beta in its high amount is responsible for preventing apoptosis of the Reed-Sternberg cells leading to the increase of the cell in the lymph nodes This will lead to lymphadenopathy where there is a large lymph node in the cervical region, supraclavicular region, axillary, and in the medial sternal lymph nodes. Lymphadenopathy is usually painless, and continuous, and the compression of this on other structures nearby such as the heart, the lungs, and the superior vena cava can cause cough, chest pain, and shortness of breath. Reed-Sternberg cells secrete different cytokines such as Interleukin-1, Interleukin-6, and tumor necrotic factor alpha which then stimulates different tissues such as the hypothalamus which in turn increases the body temperature causing fever, and weight loss, and it is continuous which can lead to Pel-Ebstein fever and it is specific for Hodgkin's lymphoma.^,

The cytokine produced can cause the liver to increase its production in erythrocyte sedimentation rate, and CRP. It would also cause the bone marrow to reduce the number of red blood cells, and increase the number of eosinophils leading to eosinophilia. This can also cause the basophils to increase histamine release leading to pruritus. With Hodgkin's lymphoma, the spleen can also be involved where the Reed-Sternberg cells populate within the spleen leading to an enlargement of the spleen (Splenomegaly) which would lead to nausea, vomiting, easy being full, as a result of it being close to the stomach. There can be external involvement such as the gastrointestinal tract (causing bowel obstruction, and bowel pain), the central nervous system (causing seizures, and tumors), the liver (causing hepatomegaly), the lacrimal gland (dry eye, and mouth), the bone marrow (low production of cells), the pleura, and the skin (causing skin lesion) but it isn't common with Hodgkin's lymphoma.^.

When diagnosing hodgkin's lymphoma, it is very important to know that patients will have lymphadenopathy, since it is the primary symptom. The patients come in with either cervical lymphadenopathy, axillary lymphadenopathy, or supracavicular lymphadenopathy or any other lymphadenopathy which can lead to compression of other structures causing cough, shortness of breath, chest pain, and so on. To identify this, a lymph node biopsy should be done, to identify Reed-Sternberg cells or a pop corn variant cells, if the cells are found, then the next step is to identify if it is Reed-Sternberg cells or a pop corn variant cells and this will be done using Flow Cytometry. This will be used to differentiate them via the protein used to express them. In the Reed-Sternberg cells CD15 and CD30 are being targetted while for the pop corn variant cells the protein CD20 and CD45 are targetted. With the presence of the CD15 and 30, then it is regarded as a classical hodgkin's lymphoma, and it possess 4 subtype. If after the flow cytometry, the CD20 and CD45 are present, then it is referred to as a non-classical hodgkin's lymphoma which has one subtype. To identify the subtypes, a histopathology of the hudgkin's lymphoma is used. For classical hodkin's lymphoma, there are Nodular Sclerosis which is the most common type of hodgkin's lymphoma. The next is the mixed cellularity which is the second most common type of hodgkin's lymphoma. Another subtype is the lymphocyte rich, and the lyphocyte depleted (this one is the least common and has a poor prognosis). The non-classic hudgkin's lymphoma subtype is the nodular lymphocyte predominant. It is important to check if the lymph nodes spread to other parts and to identify that, the staging of the hodgkin's lymphoma is checked. This can be identified using a Pet-CT scan, and Florodioxy glucose which is a Radioactive isotope, and MRI can be done to check if the central nervous system is affected. To treat classical hodgkin's lymphoma, then using Doxorubicin (Adriamycin), bleomycin, Vincrestin (oncovin), and Dacarbazine. If the lymph adenopathy is in the stage 3 and 4, affecting other organs then using Bleomycin, Etoposide, Adriamycin, Cyclophosphamide, Vincrestin, procarbazine, and steroids (prednisone). In non-classical Hodgkin's lymphoma treatment with Rituximab is neccessary. To treat the Reed-Sternberg cells with CD15 and CD30, Brentuximab Vedotin is used.^{, , , , , ,}

• Image 1 || Wikimedia Commons || Hodgkin Disease, Axillary Nodes

• Image 2 || Wikimedia Commons || Hodgkin disease, nodular sclerosis type Case 236