We describe a 70-year-old woman with stage IV diffuse large B-cell lymphoma, not otherwise specified (activated B-cell subtype, non-BCL2/MYC double expressor) treated from May to October 2019 on the phase III POLARIX trial (polatuzumab vedotin plus R-CHP versus R-CHOP), who was subsequently in remission.

In December 2020, she developed dyspnea, fever, and cough, eventually testing positive for SARS-CoV-2. Given progressive persistent symptoms, she was hospitalized for seven days in January 2021 and treated with broad spectrum antibiotics and dexamethasone with improvement in her symptoms. Following discharge, the patient endorsed unabating low-grade fevers and fatigue into February 2021. PET/CT imaging revealed new FDG-avid para-aortic, iliac, and inguinal lymphadenopathy concerning for recurrent lymphoma. The largest right external iliac lymph node measured 2.7 × 1.3 cm with an SUVmax of 8.7, and the largest right inguinal lymph node measured 1.9 × 1.1 cm with an SUVmax of 9.5. A bone marrow biopsy was negative for B cell lymphoma and featured mildly increased polytypic plasma cells and a prominent population of large granular lymphocytes (T-LGL), as well as pathogenic genetic variants in DNMT3A, TET2, and STAT3.

An excisional inguinal lymph node biopsy was performed, which showed interfollicular expansion by numerous small lymphocytes, epithelioid histiocytes, and focal sheets of plasmacytoid cells with mostly round nuclei, clumped to moderately condensed chromatin, variably distinct nucleoli, and moderate to abundant amounts of amphophilic cytoplasm. High endothelial venules were prominent. Large lymphoid cells were not seen. Flow cytometric analysis did not show involvement by a B- or T-cell lymphoproliferative disorder, and there was no increase in T-LGLs.

Immunoperoxidase and in situ hybridization studies revealed that the plasmacytoid cells were positive for CD38, MUM1, and CD79a, and were negative for CD138, CD56, cyclin D1, CD117, and Epstein–Barr virus-encoded small RNAs (EBER). The cells showed excess kappa surface light chain expression compared to lambda, and most of them expressed IgG heavy chain, and were negative for IgA, IgD, and IgM. The Ki67 proliferation index was overall 5%. CD3 stain highlighted small T cells in interfollicular areas, and CD20 stain marked subcortical aggregates of small B cells that co-expressed PAX5 and CD79a. A small germinal center containing BCL6 and CD10 positive cells was seen.

Cytogenetic analysis demonstrated a normal karyotype. Molecular analysis did not identify a clonal immunoglobulin heavy chain (IGH) gene rearrangement. Serologic studies were notable for a preserved kappa:lambda ratio, and serum protein electrophoresis showed a biclonal gammopathy with IgG lambda and IgG kappa paraproteins migrating together by immunofixation (Image 1).

During follow-up, PET/CT imaging after 5 months showed resolving lymphadenopathy and no evidence of recurrent malignancy. While the patient's large B-cell lymphoma remains in remission, the population of monotypic plasmacytoid cells in her inguinal lymph node is very unusual. It demonstrates expression of many plasma cell antigens, with the notable exception of CD138. The monotypic kappa light chain expression is particularly concerning for a clonal neoplasm with plasmacytic differentiation; however, an IGH gene rearrangement was not detected. Instead, the morphologic and immunophenotypic findings favor an atypical reactive response, possibly to SARS-CoV-2. Recent literature has documented the presence of plasmacytoid cells in the peripheral blood of COVID-19 patients^{1, 2} and interfollicular expansion of plasmablasts has also been previously identified within COVID-19-infected lymph nodes.³ This case demonstrates that new lymphadenopathy in the setting of COVID-19 infection or recovery may not always represent disease recurrence in patients with a prior malignancy, and a “wait-and-see” approach may be warranted for management. Moreover, pathologists should carefully and thoroughly exclude reactive changes before diagnosing neoplasia in the setting of recent SARS-CoV-2 infection.

我们描述了一名 70 岁的女性，患有 IV 期弥漫性大 B 细胞淋巴瘤，未另行指定（活化 B 细胞亚型，非 BCL2/MYC 双表达），于 2019 年 5 月至 2019 年 10 月在 III 期 POLARIX 试验中接受治疗。 polatuzumab vedotin 加 R-CHP 与 R-CHOP），随后病情缓解。

2020 年 12 月，她出现呼吸困难、发烧和咳嗽，最终 SARS-CoV-2 检测呈阳性。鉴于进行性持续症状，她于 2021 年 1 月住院 7 天，并接受广谱抗生素和地塞米松治疗，症状有所改善。出院后，患者的低烧和疲劳持续到 2021 年 2 月。PET/CT 成像显示与复发性淋巴瘤有关的新的 FDG 强烈的主动脉旁、髂骨和腹股沟淋巴结肿大。最大的右侧髂外淋巴结为 2.7 × 1.3 cm，SUVmax 为 8.7，右侧最大的腹股沟淋巴结为 1.9 × 1.1 cm，SUVmax 为 9.5。骨髓活检 B 细胞淋巴瘤呈阴性，多型浆细胞轻度增加和大量大颗粒淋巴细胞 (T-LGL)，DNMT3A、TET2和STAT3。

进行了切除腹股沟淋巴结活检，结果显示滤泡间扩张，大量小淋巴细胞、上皮样组织细胞和浆细胞样细胞的局灶片，核大多为圆形，染色质聚集成中度浓缩，核仁明显不同，两性细胞质中等至丰富. 高内皮小静脉突出。未见大淋巴细胞。流式细胞术分析未显示 B 或 T 细胞淋巴增殖性疾病的参与，并且 T-LGL 没有增加。

免疫过氧化物酶和原位杂交研究表明，浆细胞样细胞对 CD38、MUM1 和 CD79a 呈阳性，对 CD138、CD56、细胞周期蛋白 D1、CD117 和 Epstein-Barr 病毒编码的小 RNA (EBER) 呈阴性。与 lambda 相比，这些细胞表现出过量的 kappa 表面轻链表达，其中大多数表达 IgG 重链，并且 IgA、IgD 和 IgM 呈阴性。Ki67 增殖指数总体为 5%。CD3 染色突出了滤泡间区域的小 T 细胞，CD20 染色突出了共同表达 PAX5 和 CD79a 的小 B 细胞的皮质下聚集体。可见一个含有 BCL6 和 CD10 阳性细胞的小生发中心。

细胞遗传学分析显示正常核型。分子分析未鉴定出克隆免疫球蛋白重链 ( IGH ) 基因重排。血清学研究值得注意的是，κ:λ 比率保持不变，血清蛋白电泳显示 IgG λ 和 IgG κ 副蛋白通过免疫固定一起迁移的双克隆丙种球蛋白病（图 1）。

在随访期间，5 个月后的 PET/CT 成像显示淋巴结肿大消退，没有复发性恶性肿瘤的证据。虽然患者的大 B 细胞淋巴瘤仍处于缓解期，但其腹股沟淋巴结中的单型浆细胞样细胞群非常少见。它显示了许多浆细胞抗原的表达，CD138 除外。单型κ轻链表达尤其与浆细胞分化的克隆性肿瘤有关；然而，未检测到IGH基因重排。相反，形态学和免疫表型发现有利于非典型反应性反应，可能是针对 SARS-CoV-2。最近的文献记录了 COVID-19 患者外周血中存在浆细胞样细胞^1、2先前在 COVID-19 感染的淋巴结中也发现了浆母细胞的滤泡间扩张和滤泡间扩张。³该病例表明，在 COVID-19 感染或康复的情况下，新的淋巴结病可能并不总是代表先前患有恶性肿瘤的患者的疾病复发，因此可能需要采取“观望”的方法进行管理。此外，在近期感染 SARS-CoV-2 的情况下诊断肿瘤之前，病理学家应仔细彻底地排除反应性变化。