Pathogenesis (disease development)
Non-Hodgkin’s lymphoma (NHL) is a malignant (malignant) disease that originates in the B cells or, less commonly, the T cells of lymphoid tissue.
Mutations can cause activation of oncogenes (cell growth ↑) or loss of tumor suppressor genes (cell growth ↓). Thus, altered cells can grow.
Etiology (causes)
Biographic causes
- Genetic burden from parents, grandparents:
- Translocation of the bcl-2 gene t(14;18)(q32;q21) – follicular lymphoma.
- Translocation of the cyclin d1 gene t(11;14)(q13;q32) – mantle cell lymphoma.
- Translocation of the npm-alk gene t(2;5)(p23;Q35) – anaplastic large cell lymphoma.
- Translocation of the mlt-1 gene t(11;18)(q21;q21) – extranodal marginal zone lymphoma.
- Translocation of the c-myc gene t(8;14)(q24;q32) – Burkitt lymphoma.
- BRCA2 mutation – associated with an increased risk of non-Hodgkin’s lymphoma (Odd Ratio 3.3) in children and adolescents.
- Height – Tall people (above the 95th percentile); increased risk by a quarter; tallest people were three times more likely than short people to develop primary cutaneous lymphoma and 2.2 times more likely to develop DLBCL (diffuse large B-cell lymphoma)
Behavioral causes
- Overweight/obesity: DLBCL (diffuse large B-cell lymphoma) increased by 31%, primary cutaneous lymphoma increased by 44%, marginal cell lymphoma.increased by 70%.
Disease-related causes
Blood, blood-forming organs – immune system (D50-D90).
- Immunodeficiencies such as Wiskott-Aldrich syndrome – X-linked recessive inherited disorder with insufficiency (weakness) of blood clotting and immune system; symptom triad: eczema (skin rash), thrombocytopenia (lack of platelets), and recurrent infections
Infectious and parasitic diseases (A00-B99).
- Viral infections such as.
- HHV8 infection
- HIV infection
- HTVL 1/2 infection
- Epstein-Barr virus infection (can trigger skin lymphomas).
Mouth, esophagus (food pipe), stomach, and intestines (K00-K67; K90-K93).
- Gastritis (inflammation of the gastric mucosa) with Helicobacter pylori.
Musculoskeletal system and connective tissue (M00-M99).
- Autoimmune diseases such as Sjögren’s syndrome (group of sicca syndromes) – autoimmune disease from the group of collagenoses that leads to a chronic inflammatory disease of the exocrine glands, most commonly the salivary and lacrimal glands; typical sequelae or complications of sicca syndrome are:
- Keratoconjunctivitis sicca (dry eye syndrome) due to lack of wetting of the cornea and conjunctiva with tear fluid.
- Increased susceptibility to caries due to xerostomia (dry mouth) due to reduced salivary secretion.
- Rhinitis sicca (dry nasal mucous membranes), hoarseness and chronic cough irritation and impaired sexual function due to disruption of mucous gland production of the respiratory tract and genital organs.
- 5% develop NHL in the long-term course
Injuries, poisonings, and other consequences of external causes (S00-T98).
- Solvents such as benzene, toluene, xylene.
Drugs
- Acquired immunodeficiencies due to immunosuppressants, cytostatic drugs.
X-rays
- Condition after radiatio (radiotherapy).
- Condition after exposure to radioactive substances
Environmental pollution – intoxications (poisoning).
- Demolition of nuclear facilities
- Solvents such as benzene, toluene, xylene.
Other causes
- Breast implants (roughened breast implants) due to breast augmentation or reconstruction (lymphoma cells CD30-positive and negative for anaplastic lymphoma kinase → large cell lymphoma); one disease in 4,000-30,000 implant recipients; diagnosis occurs on average ten years after implantation
