Lymphomas

"Lymphomas are a heterogeneous group of malignancies that arise from the clonal proliferation of B- cell, T- cell and natural killer (NK) cell subsets of lymphocytes at different stages of maturation." They "are broadly classified into Hodgkin lymphoma (HL), 10% and Non- Hodgkin lymphoma (NHL), 90%," and "For clinical purposes, lymphoma is termed as aggressive (high grade) and indolent (low grade)."

Hodgkin lymphoma has a signature cell. The "Reed-Sternberg (RS) cell is a neoplastic, large multinucleated cell with two mirror-image nuclei (owl eyes) within a reactive cellular background. The RS cell is pathognomonic for classical HL." RS cells "are positive for CD30 and CD15 but typically negative for CD20 and CD45," and they "secrete cytokines to recruit reactive cells" — so most of the node is inflammatory background, not tumor. HL "involves contiguous lymph node chains in a predictable manner with the spread of the disease. Later in the disease course, hematogenous spread occurs with vascular invasion." It "most frequently presents in lymph node groups above the diaphragm and/or in mediastinal lymph nodes."

Non-Hodgkin lymphoma is mostly B-cell and less predictable. "B-cell lymphomas make up about 85% of NHL cases," and "NHL is much less predictable than Hodgkin lymphoma and has a far greater tendency to spread to extranodal sites." The most common type, diffuse large B-cell lymphoma (DLBCL), "makes up 30% of newly diagnosed cases" and "is a clinically aggressive lymphoma." Follicular lymphoma "is an indolent lymphoma," with tumor cells showing "overexpression of the anti-apoptotic protein BCL-2," and low-grade lymphomas "can develop into high-grade through a transformation of disease into DLBCL." Burkitt lymphoma "is a very aggressive B-cell lymphoma" with "a very high proliferation rate (Ki67 of almost 100%)."

The cardinal sign is a painless node. NCI lists "Painless, swollen lymph nodes in the neck, axilla, or inguinal area" for HL; in NHL "More than two-thirds of the patients present with painless peripheral lymphadenopathy." In HL, "Approximately 60 to 70% of patients present with cervical and/or supraclavicular lymphadenopathy," and mediastinal nodes are common. A node deserves biopsy when it shows "significant enlargement, persistence for more than 4 to 6 weeks, and progressive increase in size."

B symptoms carry prognostic weight. "The B designation is given to patients with any of the following symptoms: Unexplained weight loss (more than 10% of body weight in the 6 months before diagnosis). Unexplained fever with temperatures above 38°C. Drenching and recurrent night sweats." "The most significant B symptoms are fevers and weight loss. Night sweats alone do not confer an adverse prognosis." Pruritus is not one of them — NCI lists "Pruritus, especially after bathing or after ingesting alcohol" as a separate feature, and HL has a peculiar clue: "alcohol-induced pain occurring minutes after alcohol intake and localized to regions of lymphadenopathy."

Mass and marrow effects. A large mediastinal mass "can produce chest pain and shortness of breath"; primary mediastinal B-cell lymphoma "may cause respiratory symptoms or superior vena cava syndrome." Marrow infiltration, a big spleen or GI bleeding can produce "anemia, thrombocytopenia, leukopenia, pancytopenia." Rapidly growing tumors — Burkitt above all — can break down and cause tumor lysis syndrome: "resulting in metabolic derangements such as hyperuricemia, hyperkalemia, hyperphosphatemia, hypocalcemia, and subsequent acute renal failure."

Hodgkin lymphoma is highly curable. "Up to 90% of all newly diagnosed patients with HL can be cured with combination chemotherapy and/or radiation therapy." Early favorable disease is treated with ABVD, with or without involved-field radiation. For advanced disease the standard has changed: "For patients with advanced-stage HL, six cycles of N-AVD is now the standard approach" (nivolumab plus doxorubicin, vinblastine and dacarbazine), and "In situations where immunotherapy might be contraindicated (such as active vasculitis or inflammatory colitis), BV-AVD is a good option." For relapse, "High-dose chemotherapy, followed by an autologous stem cell transplant, is the standard of care for the majority of patients who are refractory or relapse."

Aggressive NHL: short-term danger, real cure. "Aggressive NHL has a worse prognosis in the short term, but a significant number of patients can be cured with intensive combination chemotherapy regimens" — "More than 70% of patients with aggressive NHL can be cured." For DLBCL, localized disease is typically treated with R-CHOP; "Among patients with advanced-stage disease, 50% are cured with doxorubicin-based combination chemotherapy and rituximab, typically Pola-R-CHP (polatuzumab, rituximab, cyclophosphamide, doxorubicin, and prednisone) or R-CHOP." For relapsed or refractory DLBCL, StatPearls calls anti-CD19 CAR T-cell therapy "the latest advance." Burkitt lymphoma cannot wait: "BL should be approached as an oncologic emergency," and its "high proliferation rate requires immediate treatment with aggressive chemotherapy regimens."

Indolent NHL: long survival, usually not curable when advanced. "Indolent NHL has a relatively good prognosis, with a median survival as long as 20 years, but it is usually not curable in advanced clinical stages." For follicular lymphoma, "watchful waiting remains a standard of care during the initial encounter and for patients with slow asymptomatic relapsing disease," while "Early-stage (stage I and stage II) indolent NHL can be effectively treated with radiation therapy alone." Gastric MALT lymphoma linked to H. pylori can regress with eradication in 50–80% of selected patients.