Pathophysiology
Summary
Non-hodgkin Lymphoma (NHL) encompasses a spectrum of lymphomas that originate in the lymphoid tissue. While Hodgkin lymphoma is characterized by the presence of Reed-Sternberg cells, NHL notably lacks these cells. The genesis of NHL is mainly attributed to the uncontrolled proliferation of mature B-cells, which are birthed in the bone marrow and go through various maturation phases. Immature B-cells make their way to the spleen, where they acquire the capability to produce both IgD & IgM. As they continue maturing, these cells migrate to secondary lymphoid sites like the spleen, lymph nodes, tonsils, and specific areas in the GI and respiratory tracts. A hallmark of the neoplastic cells in NHL is the expression of B-cell markers, specifically CD19 & CD20. NHL often affects numerous lymph nodes in a non-contiguous manner and might also extend to extra-nodal secondary lymphoid and non-lymphoid tissues, including the CNS.
Several distinct types of NHL exist, each bearing unique characteristics. Burkitt Lymphoma is an aggressive form of B-cell lymphoma that stems from a translocation between chromosomes 8 & 14, termed t(8;14). This results in amplified expression of the c-MYC oncogene, spurring rapid tumor growth. Its typical features are a high Ki-67 fraction, numerous mitotic figures, and a unique ‘starry sky’ histological pattern. There are three primary presentations: the endemic form, usually appearing as jaw tumors in children; the non-endemic form, presenting as a swiftly growing abdominal mass; and the immunodeficiency-related type, which occurs predominantly in older, HIV-infected adults and manifests as lymphadenopathy. Both the endemic and non-endemic Burkitt lymphoma show an association with EBV infection.
Follicular lymphoma arises due to a t(14;18) translocation, leading to the overexpression of the BCL2 oncogene. Clinically, it materializes as nodules mirroring follicles or germinal centers derived from mutated B-cells, and typically presents as intermittent lymphadenopathy. Follicular lymphoma carries the risk transformation into diffuse large B-cell lymphoma.
Diffuse large B-cell lymphoma is predominant in adults and is associated with genetic changes in the BCL-6 gene. Links between this lymphoma and both EBV and HIV are documented, with the co-presence of HIV marking it as an AIDS-defining illness. HHV-8 and HIV co-infections can give rise to a variant known as primary effusion lymphoma.
Mantle cell lymphoma is derived from cells in the mantle zones of lymphoid follicles and is associated with a t(11;14) translocation. This results in enhanced cyclin D1 expression that drives uncontrolled cell division.
General manifestations of NHL include ‘B’ symptoms: fever, weight loss and night sweats.
Lesson Outline
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FAQs
Non-Hodgkin lymphoma (NHL) originates from the lymphoid tissue and is primarily caused by the proliferation of mature B lymphocytes. These mature B-cells migrate to secondary lymphoid organs such as the spleen, lymph nodes, and tonsils. Unlike Hodgkin lymphoma, which is characterized by the presence of Reed-Sternberg cells, NHL lacks these cells. Additionally, NHL affects multiple lymph nodes in a non-contiguous pattern and frequently involves extra-nodal secondary lymphoid tissues including the spleen, tonsils, GI tract, respiratory tract, as well as non-lymphoid tissues like the CNS.
Burkitt lymphoma is an aggressive B-cell non-Hodgkin lymphoma. It is primarily caused by a translocation between chromosomes 8 & 14, leading to the overexpression of the c-MYC oncogene that promotes unregulated cell growth. This rapid growth results in a high Ki-67 fraction and is evident by its ‘starry sky’ appearance on histological examination, characterized by macrophages surrounded by clear spaces amidst sheets of blue tumor cells.
Burkitt lymphoma has both endemic and non-endemic forms. The endemic form typically manifests as a large jaw tumor. In contrast, the non-endemic form often presents as a rapidly growing abdominal mass, affecting areas like the bowel, ovary, or retroperitoneal tissues. Another form, immunodeficiency-related Burkitt lymphoma, commonly seen in HIV-infected patients, usually presents with lymphadenopathy.
Follicular lymphoma is a subtype of NHL caused by a translocation between chromosomes 14 and 18, resulting in the overexpression of the BCL2 oncogene. It is characterized by round hypercellular nodules that resemble the follicles and germinal centers of normal lymph nodes. On the other hand, Diffuse Large B-cell lymphoma, the most prevalent lymphoma in adults, is marked by sheets of large B cells. Some cases also exhibit alterations in the BCL-6 gene. Co-infections with EBV and HIV can lead to this type of lymphoma.
Mantle cell lymphoma is a B-cell non-Hodgkin lymphoma subtype that arises from cells in the mantle zones of lymphoid follicles. It is caused by a translocation between chromosomes 11 and 14, leading to the overexpression of Cyclin D1, which promotes the transition from the G1 to S phase, resulting in uncontrolled cell division. Histologically, it displays a nodular follicular pattern, distinguishing it from other NHL subtypes.
