What is Non-Hodgkin Lymphoma?

Non-Hodgkin lymphomas represent a heterogeneous group of lymphoproliferative disorders that originate in B-lymphocytes, T-lymphocytes or natural killer (NK) cell. B-cell lymphomas account for 80-90% of all the cases, T-cell lymphomas are responsible for 15-20% of the cases, while NK lymphomas are rarely encountered.

Non-Hodgkin lymphoma has a substantial biologic and clinical heterogeneity, thus a definitive diagnosis can be made only after histopathogical examination. A holistic approach provided by a multi-disciplinary team of specialists and health care professionals is the keystone of ensuring successful treatment outcome.

Pathogenesis of the disease

Similar to other types of malignant diseases, non-Hodgkin lymophomas arise by a multistep accumulation of genetic aberrations that result in a growth advantage of the malignant clone. Recurrent translocations during lymophocite differentiation that lead to deregulated expression of oncogenes often represent an initial step, but secondary genetic alterations are a prerequisite for complete malignant transformation.

The condition has been associated with chronic autoimmune or inflammatory illnesses such as Hashimoto’s thyroiditis, rheumatoid arthritis or Sjögren syndrome. Chronic infection is also linked with its pathogenesis; for example, primary gastric non-Hodgkin lymphoma of mucosa-associated lymphoid tissue (MALT-NHL) has shown strong correlation with Helicobacter pylori infection.

Immune suppression is a known risk factor for non-Hodkin lymphoma. In patients who underwent solid organ transplantation, the risk of the disease has been specifically associated with the duration of immunosuppression and the type of drugs used. Furthermore, this lymphoma is a common complication in patients with human immunodeficiency virus infection that most frequently affects the gastrointestinal tract.

Non-Hodgkin lymphoma epidemiology

The frequency and pattern of non-Hodgkin lymphomas vary in different populations and geographical regions. Taking different subtypes into account, a higher proportion of follicular and diffuse lymphoma can be observed in North America and Europe, whereas in Asia there is a higher proportion of T-cell lymphoma. Not much is known about the etiological role of immunologic characteristics, genetic markers and polymorphisms in the development of the disease.

Non-Hodgkin lymphoma represents the fifth leading type of cancer among both sexes, accounting for 4-5% of new cancer cases and 3% of cancer deaths. The incidence rates in the US doubled between 1970 and 1990, after which they stabilized. Incidence also increased in other high-income countries between 1950 and 1990, with no further increase during the past decade.

Numerous epidemiologic studies that explored nutritional, environmental and occupational exposure to chemicals have not identified any consistent positive associations with either increased risk of the disease or increased mortality. Two possible exceptions are fish intake (associated with a non-significantly decreased risk of lymphoma development in several studies) and read meat intake with a positive association.

Diagnosis and treatment

The most characteristic symptom of non-Hodgkin lymphoma is a painless swelling in a lymph node, usually observed in the neck, armpit or groin. This is characteristic for the patients with indolent lymophomas (such as follicular, marginal zone and lymphoplasmacytic lymophoma). Extranodal involvement and systemic symptoms are less common at presentation, but are often seen as the disease advances or transforms into the aggressive stage.

Histology remains a compulsory step in establishing the diagnosis, which should be made on the basis of excisional lymph node or extranodal tissue biopsy that provide enough material for formalin-fixed samples. Core biopsies are performed only in patients without easily accessible lymph nodes or in patients requiring emergency treatment. Laparoscopy also has a role in establishing a diagnosis in cases of intra-abdominal and retropertioneal masses.

Since the adequate treatment chiefly depends on the stage of the disease, as well as medical status of the patient, a thorough initial work-up is required that can identify all sites of known disease and evaluate baseline organ functions. Based on the Ann Arbor staging system, patients are then categorized into limited (represented by stage I and II) or advanced (stage III and IV) disease.

When a treatment program for an individual with non-Hodgkin's lymphoma is designed, factors such as patient's age and general health, the extent of the lymphoma and the particular histologic subtype must be taken into account. Most patients should receive chemotherapy with or without radiotherapy. Surgery is useful in only a handful of situations – most commonly to establish a correct diagnosis by obtaining a biopsy specimen.

The patient should be involved in the decision process right from the start, and patients should be treated with the least toxic therapy expected to produce a durable complete remission. Furthermore, good supportive care is pivotal in ensuring successful treatment outcome. Recent advances that include the use of monoclonal antibodies and the widespread use of HSCT have increased cure rates for this malignant disease.

Further Reading

Last Updated: Jun 28, 2019

Dr. Tomislav Meštrović

Written by

Dr. Tomislav Meštrović

Dr. Tomislav Meštrović is a medical doctor (MD) with a Ph.D. in biomedical and health sciences, specialist in the field of clinical microbiology, and an Assistant Professor at Croatia's youngest university - University North. In addition to his interest in clinical, research and lecturing activities, his immense passion for medical writing and scientific communication goes back to his student days. He enjoys contributing back to the community. In his spare time, Tomislav is a movie buff and an avid traveler.


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