Pathophysiology
Summary
Hodgkin lymphoma (HL) is a malignancy of the lymphoid tissue that differentiates it from non-Hodgkin lymphomas. It originates from a mutated B lymphocyte in the germinal center, vital for B-cell somatic hypermutation and antibody class-switching. Resulting mutations prompt clonal B-cell proliferation mainly within the germinal centers of lymph nodes, especially in regions like the cervical, supraclavicular, or mediastinal. However, it can also appear in the liver and spleen.
Central to HL's cellular identity is the presence of Reed-Sternberg cell with its distinctive bifurcated nucleus and an acidophilic nucleolus encircled by a clear zone. Although sparse, these cells consistently appear amidst an array of inflammatory cells and express markers CD15 & CD30.
A significant link exists between HL and Epstein-Barr virus (EBV) infection, which can activate NF-kappaB, enabling the mutant B-cells to evade apoptosis. A history of autoimmune disorders also increases the risk of developing HL. Hodgkin lymphoma exhibits a bimodal age distribution, primarily peaking around ages 20 and 65. Patients typically present with ‘B’ symptoms, namely fever, night sweats, and unintentional weight loss, attributed to cytokine release.
Distinct subtypes of HL include nodular sclerosis, mixed cellularity, and lymphocyte predominant. Nodular sclerosis HL is most common in developed countries and features nodules of inflammatory cells partitioned by fibrous collagen. Unique lacunar Reed-Sternberg cells arise due to cytoplasmic retraction during slide creation. Mixed cellularity HL is more prevalent in developing countries and has a strong correlation with EBV, especially with concurrent HIV infection. Typically stemming from abdominal lymph nodes or the spleen, it displays nodules without fibrous septae. Lymphocyte predominant (‘non-classic’) HL diverges from standard HL as it doesn't display Reed-Sternberg cells and hence doesn't express CD15 & CD30. Instead, it features lymphohistiocytic cells with a multilobed nucleus, positive for CD19 & CD20.
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FAQs
Hodgkin lymphoma originates from a mutated B lymphocyte in the germinal center that leads to proliferation of clonal B cells and the development of lymphomas. While these can arise in various germinal centers, including those in the liver and spleen, they most frequently develop within the lymph nodes, especially the cervical, supraclavicular, or mediastinal lymph nodes. A defining characteristic of Hodgkin lymphoma is the presence of Reed-Sternberg cells in histological examinations.
Hodgkin lymphoma often presents with a set of symptoms known as 'B' symptoms, which include fever, night sweats, and unintentional weight loss. These symptoms are a result of cytokine production by the tumor cells. The disease primarily originates in the germinal centers of lymph nodes, but it can also involve the liver, spleen, and specific lymph nodes such as the cervical or supraclavicular nodes. A distinctive feature of Hodgkin lymphoma is its tendency to spread contiguously, moving from one lymph node to its adjacent nodes, rather than jumping to distant sites.
Reed-Sternberg cells, which are characteristic of Hodgkin lymphoma, predominantly express the markers CD15 and CD30. However, not all subtypes of Hodgkin lymphoma contain these cells. For example, lymphocyte predominant Hodgkin lymphoma is devoid of Reed-Sternberg cells, instead featuring lymphohistiocytic cells that predominantly express CD19 and CD20 markers.
The Epstein-Barr virus (EBV) is closely associated with Hodgkin Lymphoma. EBV infection can activate the NF-kappaB pathway, aiding mutant B-cells in evading apoptosis. The mixed cellularity Hodgkin lymphoma subtype, prevalent in developing countries and often found in abdominal lymph nodes or the spleen, has a strong correlation with EBV infection. Additionally, HIV infection, especially when co-infected with EBV, increases the risk for this subtype.
Hodgkin Lymphoma has several subtypes, each with distinct features. Nodular sclerosis, the most prevalent subtype in developed countries, is characterized by nodules of inflammatory cells separated by fibrous collagen and the presence of lacunar Reed-Sternberg cells. Another subtype, mixed cellularity Hodgkin lymphoma, is more common in developing countries and has a strong association with EBV infection. Notably, the lymphocyte predominant Hodgkin lymphoma subtype doesn't display Reed-Sternberg cells but instead features Lymphohistiocytic cells.
