Background Infection with human immunodeficiency virus (HIV) increases risk for developing cancer.1 However, clinical presentations of malignancies may be subtle. Clinical suspicion for cancer in patients living with HIV (PLWH) should remain high.

Case Presentation A 50-year-old male with history of HIV with undetectable viral load on ART and unilateral orchiectomy for testicular cancer presented to the emergency department for evaluation of left eye blurriness, ptosis, and ophthalmoplegia. History was notable for emergency department and outpatient ophthalmology visits one month prior resulting in a diagnosis of cranial nerve six palsy. Magnetic resonance angiography (MRA) did not reveal any acute findings. He developed difficulty opening his left eye and reported having weight loss over the past month.

On exam, vital signs were within normal limits. Labs notable for uric acid 8.0 mg/dL and WBC 9.34 K/uL. Repeat orbital imaging showed infiltrative soft tissue throughout the cavernous sinuses. Magnetic resonance imaging of the brain and positron emission tomography revealed widely distributed lesions and lymphadenopathy throughout the brain, chest, abdomen, pelvis, and skeleton suspicious for malignancy. Bone marrow and lymph node biopsy revealed B cell lymphoma, CD10+/CD5- lambda monotypic. Cytogenetic analysis revealed IGH::MYC rearrangement. Pathology confirmed diagnosis of Epstein-Barr virus (EBV) negative Burkitt lymphoma (BL). Patient began chemotherapy, EPOCH-R, and follow up 6 months later shows continued response to therapies.

Discussion HIV is a known carcinogen for eleven different types of cancer, including so-called “AIDS-defining cancers” (ADC), and non-AIDS defining cancers (NADC).1 A 2017 study including 448,258 HIV-infected individuals showed PLWH have a standardized incidence ratio of 1.69 for cancer compared to the general population (ADC 14.0, NADC 1.21).2 Introduction of ART has decreased the burden caused by ADC, but has increased the burden caused by NADC.3,4 Specifically, Burkitt lymphoma and Hodgkin lymphoma have been noted in the literature to occur paradoxically in patients with higher CD4 counts (e.g. >250 cell/mcL).3,5 Our patient presented with an undetectable viral load, CD4 count of 776 four days prior, and an incomplete earlier infectious workup. His ultimate diagnosis of EBV-negative BL highlights the importance of investigating cancer etiologies in the absence of positive serology. Patients with HIV are at increased risk of malignancy due to alterations in their immune system. Evaluation of atypical illness should include early imaging and biopsy. Preventive actions include thorough routine history and physical (including skin and mucosal exams), optimization of HIV treatment, and comprehensive vaccination (HBV, HPV, VZV). References

1. Engels EA, Shiels MS, Barnabas RV, et al. State of the science and future directions for research on HIV and cancer: Summary of a joint workshop sponsored by IARC and NCI. Int J Cancer. 2024;154(4):596-606. doi:10.1002/ijc.34727
2. Hernández-Ramírez RU, Shiels MS, Dubrow R, Engels EA. Cancer risk in HIV-infected people in the USA from 1996 to 2012: a population-based, registry-linkage study. Lancet HIV. 2017;4(11):e495-e504. doi:10.1016/S2352-3018(17)30125-X
3. Rubinstein PG, Aboulafia DM, Zloza A. Malignancies in HIV/AIDS: from epidemiology to therapeutic challenges. AIDS. 2014;28(4):453-465. doi:10.1097/QAD.0000000000000071
4. Ceccarelli M, Venanzi Rullo E, Marino MA, et al. Non-AIDS defining cancers: a comprehensive update on diagnosis and management. Eur Rev Med Pharmacol Sci. 2020;24(7):3849-3875. doi:10.26355/eurrev_202004_20852
5. Guech-Ongey M, Simard EP, Anderson WF, et al. AIDS-related Burkitt lymphoma in the United States: what do age and CD4 lymphocyte patterns tell us about etiology and/or biology?. Blood. 2010;116(25):5600-5604. doi:10.1182/blood-2010-03-275917