Effusion cytology of EBV-associated lymphoma: a concise review

Chih-Yi Liu 1 2Yen-Chuan Hsieh 3Sheng-Tsung Chang 4 5Hung-Chang Wu 6Shang-Wen Chen 7Shih-Sung Chuang 8

Affiliations
  1. Department of Pathology, Zhongli District, Ten Chan Hospital, Taoyuan City, Taiwan.
  2. School of Medicine, National Tsing Hua University, Hsinchu City, Taiwan.
  3. Department of Clinical Pathology, Chi Mei Medical Center, Tainan City, Taiwan.
  4. Department of Pathology, Chi Mei Medical Center, Tainan City, Taiwan.
  5. Department of Nursing, National Tainan Institute of Nursing, Tainan City, Taiwan.
  6. Department of Internal Medicine, Chi Mei Medical Center, Tainan City, Taiwan.
  7. Division of Hemato-Oncology, Department of Internal Medicine, Chi Mei Medical Center, Liouying, Tainan, Taiwan.
  8. Department of Pathology, Chi Mei Medical Center, Tainan City, Taiwan. cmh5301@mail.chimei.org.tw.

ABSTRACT

Epstein-Barr virus (EBV)-associated lymphomas can, on rare occasions, involve body cavities, making effusion cytology an important diagnostic tool. This mini-review explores the spectrum of EBV-related lymphomas that may be detected in serous fluids, including EBV-positive nodal T/NK-cell lymphoma (EBV + nT/NKCL), extranodal NK/T-cell lymphoma, primary effusion lymphoma, EBV-positive diffuse large B-cell lymphoma, and classic Hodgkin lymphoma. We present an index case of EBV + nT/NKCL with lymphomatous pleural effusion and discuss the cytologic features, differential diagnoses, and role of ancillary studies such as immunocytochemistry, EBER in situ hybridization, and molecular assays. Accurate diagnosis requires the integration of cytomorphologic, immunophenotypic, and molecular findings with clinical information to establish a definitive diagnosis and distinguish these aggressive lymphomas from reactive and non-hematologic mimics.

Keywords: Azurophilic granules; Cytotoxic phenotype; EBER; EBV; Effusion cytology; Immunophenotyping; T/NK-cell lymphoma.

【Review 】Blood Res. 2025 Jul 2;60(1):37. doi: 10.1007/s44313-025-00088-0.

Primary Effusion Lymphoma: A Timely Review on the Association with HIV, HHV8, and EBV

Chih-Yi Liu 1 2Bo-Jung Chen 3 4Shih-Sung Chuang 5

Affiliations
  1. Division of Pathology, Sijhih Cathay General Hospital, New Taipei City 221, Taiwan.
  2. School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei City 221, Taiwan.
  3. Department of Pathology, Shuang Ho Hospital, Taipei Medical University, New Taipei City 221, Taiwan.
  4. Department of Pathology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan.
  5. Department of Pathology, Chi-Mei Medical Center, Tainan 710, Taiwan.

ABSTRACT

Primary effusion lymphoma (PEL) is defined by the WHO classification as a large B-cell neoplasm without detectable tumor masses. It is universally associated with HHV8, with most cases occurring in the setting of immunodeficiency such as HIV infection, and a poor prognosis. Morphologically, the neoplastic cells range from immunoblastic, plasmablastic, to anaplastic; and phenotypically, most cases express plasma cell but not B-cell markers, i.e., plasmablastic. During the past decade, primary HHV8-negative effusion lymphoma has been reported. Such cases were considered in the WHO classification scheme as effusion-based lymphoma. We performed a systemic review of 167 HHV8-negative effusion lymphomas from the literature and found that only 42% were associated with a fluid overload state, and with low rates of HIV (6%) or EBV (21%) infection. Furthermore, most patients are old (or immunosenescent) with underlying medical conditions/comorbidities, most neoplasms are of B-cell phenotype, and the outcome is more favorable than that of HHV8-positive PEL. These distinctive findings supported our prior proposal of designating these HHV8-negative cases as type II PEL, in contrast to the classic or type I PEL as defined by the WHO. Furthermore, we propose an algorithmic approach for the diagnosis of PEL and its mimickers.

Keywords: EBV; HHV8; HIV; effusion-based lymphoma; primary effusion lymphoma.

< Review >Diagnostics (Basel). 2022 Mar 15;12(3):713. doi: 10.3390/diagnostics12030713.