Extracavitary Primary Effusion Lymphoma: Diagnostic Challenges and Differential Diagnosis in a Resource-Constrained South African Setting

Aims Primary effusion lymphoma (PEL) is an aggressive, human herpesvirus 8 (HHV8)-associated large B-cell lymphoma characterised by malignant effusions in serous cavities (classic PEL). However, a subset of tumours may present exclusively as solid masses, referred to as extracavitary primary effusion lymphoma (EC-PEL). Despite the high regional prevalence of human immunodeficiency virus (HIV) and Kaposi sarcoma-associated virus /HHV8, PEL is likely under-reported in Sub-Saharan Africa. This study reports on the clinicopathologic features and differential diagnoses of EC-PEL. Methods A retrospective review of biopsies with a diagnosis of PEL from 2010 to 2019 was performed. Seven patients met the 2024 WHO criteria for PEL. Clinical information was collected and histopathological and immunohistochemical features were reviewed independently. Results Seven patients with a median age of 38 years (range, 25-51 years) were identified. Most patients were men (86%), and all were Black African. Five patients (71%) were living with HIV, with CD4 + counts ranging from 137 to 348 cells/µL. Tumour sites were lymph nodes, stomach, maxillary sinus, and soft tissue. All tumours showed diffuse sheets of plasmablastic or immunoblastic cells. Immunohistochemistry showed expression of plasma-cell markers (VS38C, CD138), lacked pan B-cell markers (CD20 and PAX5), and had high proliferative indices (Ki-67: 90-95%). All tumours were positive for HHV8 (LANA-1) and EBER in situ hybridisation was positive in 86%. Conclusion Extracavitary PEL in Sub-Saharan Africa exhibits the characteristic clinicopathologic profile described globally and remains strongly associated with HIV-related immunosuppression. Improved recognition of this rare but aggressive lymphoma can be achieved with increased awareness of the diagnosis and improved access to HHV8 immunohistochemistry.