Soma Lori, Crisan Liliana, Reid Jack, Lee Winston, Song Joo, Afkhami Michelle, Shouse Geoffrey, Fei Fei, Danilova Olga, Pillai Raju, Zain Jasmin, Querfeld Christiane
Department of Pathology, Beckman Research Institute, City of Hope Medical Center, Duarte, CA, US.
Department of Hematology and Hematopoietic Cell Transplant, Division of Lymphoma, Beckman Research Institute, City of Hope Medical Center, Duarte, CA, US.
Am J Clin Pathol. 2025 Feb 12;163(2):298-312. doi: 10.1093/ajcp/aqae124.
Epstein-Barr Virus (EBV) positive primary cutaneous marginal zone lymphoma (PCMZL) is uncommon and subsequent transformation is rare.
We report a patient with EBV positive PCMZL with subsequent transformation to plasmablastic lymphoma and review the literature for transformed PCMZL to assess clinical and pathologic characteristics. In the case we describe, the patient presented with multifocal PCMZL, developed large B cell transformation with plasmacytic differentiation, followed by plasmablastic transformation (PBL), and ultimately died of disease progression despite multiple lines of therapy. Past history was significant for psoriatic arthritis (multiple prior lines of immunomodulatory therapy). The lymphomas and non-involved bone marrow share the same somatic DNMT3A and TET2 mutations, suggesting clonal relatedness and an association with clonal hematopoiesis (CH).
Eighteen cases comprised the cohort (seventeen cases from the literature and the case reported herein). Nearly half of the eighteen cases of PCMZL with transformation died of progressive disease (44%). Transformed cases were more commonly seen in patients with >2 sites at initial diagnosis. EBV was assessed in 5 patients, 3 were positive (all died of disease). Two patients with NGS studies demonstrated TET2 and DNMT3A mutations.
Transformation of EBV positive PCMZL appears to be a poor prognostic indicator, with our reported case being the first well defined case transformed to PBL, suspected to arise from myeloid-CH.
爱泼斯坦-巴尔病毒（EBV）阳性原发性皮肤边缘区淋巴瘤（PCMZL）并不常见，随后发生转化的情况罕见。
我们报告1例EBV阳性PCMZL患者，其随后转化为浆母细胞淋巴瘤，并回顾文献中关于转化型PCMZL的内容，以评估临床和病理特征。在我们描述的病例中，患者最初表现为多灶性PCMZL，随后发展为具有浆细胞分化的大B细胞转化，接着发生浆母细胞转化（PBL），尽管接受了多线治疗，最终仍因疾病进展而死亡。既往史中银屑病关节炎病史显著（曾接受多线免疫调节治疗）。淋巴瘤及未受累骨髓具有相同的体细胞DNMT3A和TET2突变，提示克隆相关性以及与克隆性造血（CH）的关联。
该队列共纳入18例病例（17例来自文献，1例为本报告病例）。18例发生转化的PCMZL病例中近一半死于疾病进展（44%）。转化病例在初诊时累及部位>2处的患者中更为常见。对5例患者进行了EBV评估，3例呈阳性（均死于疾病）。2例接受二代测序研究的患者显示存在TET2和DNMT3A突变。
EBV阳性PCMZL的转化似乎是一个不良预后指标，我们报告的病例是首例明确转化为PBL的病例，怀疑源自髓系CH。
