A 52-year-old man comes to the office due to a progressively enlarging neck mass, fatigue, and weight loss over the past 2 months. Physical examination shows enlarged, firm, and nontender cervical lymph nodes. The patient also has enlarged tonsils, bilateral axillary lymphadenopathy, and splenomegaly. Excisional lymph node biopsy reveals diffuse sheets of atypical, large B cells that have replaced the normal tissue architecture. In situ hybridization of the tissue specimen is positive for Epstein-Barr virus. Which of the following risk factors is most strongly associated with development of this patient's condition?
This patient likely has non-Hodgkin lymphoma (NHL). Depending on the subtype, NHL may present with a rapidly progressive mass, lymphadenopathy, splenomegaly, and B symptoms (eg, night sweats, weight loss). Diagnosis is typically made with excisional lymph node biopsy, which usually demonstrates a loss of normal tissue architecture with expansion of abnormal lymphocytes (most often B cells, as in this patient with large, atypical B cells).
Lymphoma is frequently associated with Epstein-Barr virus (EBV), a ubiquitous herpesvirus that primarily infects B lymphocytes and causes persistent latent infections. Although viral reactivation is uncommon, the latent EBV genome still transcribes viral gene products that can result in malignant transformation of infected cells. EBV is particularly associated with nasopharyngeal carcinoma, Hodgkin lymphoma, and some forms of NHL (eg, Burkitt lymphoma).
Patients with HIV are at greatest risk for EBV-associated lymphomas (risk is up to 60-fold greater). This is likely due to HIV-related immune dysregulation, which decreases recognition of EBV-infected cells and promotes B-cell proliferation. Some types of NHL (eg, primary central nervous system lymphoma) are considered AIDS-defining conditions and can sometimes be the presenting manifestation of HIV infection.
(Choice B) Aspirin and nonsteroidal anti-inflammatory drugs may decrease the risk of colorectal cancer. Their use is not linked to an increased risk of NHL.
(Choice C) Cigarette smoking is a strong risk factor for the development of many types of cancer (eg, lung, bladder, pancreas) but is not closely linked with the development of NHL.
(Choice D) The link between radiation exposure and the development of NHL is controversial. However, most studies indicate that this is not a strong risk factor.
(Choice E) Although lower socioeconomic status may be associated with worse outcomes in patients with NHL, this marker has not been closely linked with the development of NHL.
Educational objective:
Patients with HIV have much higher rates of lymphoma than the general population. Many cases are due to underlying Epstein-Barr virus infection, which acts synergistically with HIV to promote uncontrolled B lymphocyte proliferation.