Health ·

Lymphoma: Cancer of the Immune System

Lymphoma Unmasked: A Scientific and Human Look at the Cancer of the Immune System

 

1. Overview

Lymphoma is a cancer of the lymphatic system, a vital part of the immune network that filters waste, transports lymph, and houses infection-fighting cells. This disease originates when lymphocytes—white blood cells—mutate and proliferate uncontrollably. Unlike other cancers that are typically organ-based, lymphoma is systemic from the start. It’s most commonly categorized into two broad families: Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL), each with unique features, behaviors, and treatment protocols.

2. Types & Classifications

Lymphomas are primarily divided based on their cell origin and molecular markers:

➤ Hodgkin Lymphoma (HL)

Defined by the presence of Reed-Sternberg cells—abnormal, multinucleated B-cells. It represents ~10% of lymphomas.

➤ Non-Hodgkin Lymphoma (NHL)

A heterogeneous group (~90%) that includes multiple B-cell, T-cell, and NK-cell malignancies.

Further classification includes:

  • Cell of origin: B-cell vs. T-cell vs. NK-cell

  • Clinical behavior: Indolent (slow-growing) vs. Aggressive

  • Immunophenotype: Surface marker expression (e.g., CD20, CD3, CD30)

3. Subtypes of Lymphoma

➤ Hodgkin Lymphoma (HL) Subtypes

  • Nodular sclerosis HL (most common in young adults)

  • Mixed cellularity HL

  • Lymphocyte-rich HL

  • Lymphocyte-depleted HL

  • Nodular lymphocyte-predominant HL (lacks Reed-Sternberg cells)

➤ Non-Hodgkin Lymphoma (NHL) Subtypes

B-cell NHLs

  • Diffuse large B-cell lymphoma (DLBCL) — aggressive, most common

  • Follicular lymphoma — indolent

  • Burkitt lymphoma — highly aggressive, often linked to EBV

  • Mantle cell lymphoma

  • Chronic lymphocytic leukemia/Small lymphocytic lymphoma (CLL/SLL)

T-cell & NK-cell NHLs

  • Peripheral T-cell lymphoma

  • Anaplastic large cell lymphoma

  • Cutaneous T-cell lymphoma (e.g., Mycosis fungoides, Sézary syndrome)

  • NK/T-cell lymphoma, nasal type

4. Staging of Lymphoma

Staging follows the Ann Arbor system:

Stage Description
I Single lymph node or localized region
II Two or more lymph nodes on the same side of the diaphragm
III Lymph nodes on both sides of the diaphragm
IV Disseminated involvement of organs beyond lymph nodes

Modifiers:

  • A/B: Absence or presence of systemic symptoms (fever, night sweats, weight loss)

  • E: Extralymphatic involvement

  • S: Spleen involvement

5. Diagnosis & Diagnostic Tools

Clinical Evaluation

  • Enlarged lymph nodes

  • “B symptoms”: unexplained fever, weight loss, drenching night sweats

Diagnostic Tools

  • Biopsy: Excisional preferred for architecture

  • Immunohistochemistry: To identify cell type (e.g., CD20+, CD3+)

  • Flow cytometry

  • Molecular & cytogenetic analysis: e.g., BCL2, MYC, TP53

  • PET/CT scan: For staging and response assessment

  • Bone marrow biopsy

6. Treatment Options

Treatment is based on type, stage, age, and overall health:

Approach Description
Chemotherapy R-CHOP (for DLBCL), ABVD (for HL), Hyper-CVAD (for Burkitt)
Radiation Therapy Often combined with chemo in HL
Immunotherapy Rituximab (anti-CD20), Brentuximab vedotin (anti-CD30)
Targeted Therapy BTK inhibitors (e.g., Ibrutinib), PI3K inhibitors
Stem Cell Transplant For relapsed/refractory cases
CAR T-cell Therapy CD19-targeted cells for aggressive NHL

7. Genetics & Risk Factors

Genetic Mutations

  • DLBCL: BCL2, BCL6, MYC rearrangements

  • Burkitt lymphoma: t(8;14) c-MYC translocation

  • CLL: TP53 mutation, 17p deletion

Risk Factors

  • Immunodeficiency (HIV, post-transplant)

  • Autoimmune disease (e.g., SLE)

  • Epstein-Barr Virus (EBV)

  • Family history

  • Exposure to radiation or certain chemicals (e.g., pesticides)

8. Recent Advances & Future Directions

  • Liquid biopsies: Detect ctDNA for monitoring

  • Bispecific antibodies (e.g., mosunetuzumab): engage T-cells to kill lymphoma cells

  • Checkpoint inhibitors: For Hodgkin lymphoma (e.g., nivolumab, pembrolizumab)

  • CRISPR-Cas9: Editing T-cells for improved CAR T therapy

  • AI-based pathology: Improving diagnosis and subtype prediction

  • Microbiome modulation: Experimental therapy targeting immune interactions

9. Glossary

Term Definition
Lymphocyte A white blood cell central to immune defense
Reed-Sternberg cell Abnormal giant cell found in HL
CD markers Cluster of Differentiation proteins used to classify cells
Indolent Slow-growing or less aggressive
Aggressive Fast-growing and more dangerous
B symptoms Fever, weight loss, and night sweats—often signal advanced disease
R-CHOP Standard chemo for NHL: Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, Prednisone
ABVD Chemo for HL: Adriamycin, Bleomycin, Vinblastine, Dacarbazine
CAR T-cell therapy Patient's T-cells engineered to attack cancer
ctDNA Circulating tumor DNA in blood
Immunophenotype Cell profile based on antigen markers

10. References

  1. Swerdlow, S. H. et al. (2016). WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. IARC Press.

  2. National Cancer Institute. (2024). Lymphoma—Patient Version. https://www.cancer.gov

  3. NCCN Clinical Practice Guidelines in Oncology. Non-Hodgkin’s Lymphomas (2025).

  4. Ansell, S. M. (2022). Hodgkin lymphoma: 2022 update on diagnosis, risk-stratification, and treatment. American Journal of Hematology.

  5. Zelenetz, A. D. et al. (2020). Non-Hodgkin Lymphomas, Version 1.2020. Journal of the National Comprehensive Cancer Network.

  6. Maude, S. L. et al. (2018). Tisagenlecleucel in Children and Young Adults with B-Cell Lymphoblastic Leukemia. NEJM.

  7. Campo, E. et al. (2018). The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood.

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