An Unusual Case of Classic Hodgkin Lymphoma With Strong Expression of B‐Cell Markers

A 69-year-old male presented with fever, anemia (hemoglobin: 83 g/L), and thrombocytopenia (platelets: 104 × 109/L) in April 2023. A CT scan showed splenomegaly (17 cm) and a 2-cm right neck lymph node. Biopsy of the node was non-diagnostic due to sampling error, showing dermal fibrosis with no lymph node tissue. By August 2023, the cytopenias improved (hemoglobin: 113 g/L; platelets: 246 × 109/L), and the spleen size had reduced slightly (15 cm). An infectious/inflammatory disorder was suspected clinically, and no further action was pursued at that time. The patient was admitted in January 2024 with unintentional 30-lb weight loss and features concerning for hemophagocytic lymphohistiocytosis, including fever and elevated ferritin (23 913 μg/L), IL-2Rα (2 115 pg/mL), and CRP (136 mg/L). PET/CT showed hepatosplenomegaly, right-sided cervical lymphadenopathy, and intraosseous FDG uptake in the cervical, thoracic, and lumbar spine and left first rib. Bone marrow aspirate/biopsy and liver biopsy were performed. The bone marrow biopsy showed a hypercellular marrow infiltrated with Hodgkin/Reed-Sternberg (HRS) cells in a background of histiocytes, lymphocytes, plasma cells, and eosinophils (Figure 1A). Immunohistochemical studies demonstrated positivity for CD30 (strong) and PAX5 (weak to moderate) in the HRS cells, and negativity for CD45 (Figure 1B–D). The HRS cells showed strong, diffuse positivity for CD20 and OCT2, diffuse positivity for CD79a (varying intensity), and were negative for BOB1 (Figure 2A–D). The HRS cells were positive for CD15, MUM1, and EBER (rare), and negative for CD19, CD3, CD5, CD43, CD68, and ALK (not shown). The same morphology and immunophenotype were demonstrated on the liver biopsy (not shown). The patient was diagnosed with Classic Hodgkin Lymphoma (CHL) and treated with six cycles of adriamycin, vinblastine, and dacarbazine, after which they achieved complete remission. This case of CHL is unique in the number and staining pattern of B-cell markers in the neoplastic cells. CHLs are known to express variable levels of B-cell markers, including CD20, CD19, CD79a, OCT2, and BOB1. However, these markers are typically weakly expressed in only a minority of cells 1, 2. It is estimated that fewer than 5% of CHL cases exhibit strong or uniform CD20 1 expression, and expression of multiple B-cell markers is relatively rare 1, 2. In contrast, this case shows a diffuse pattern for three B-cell markers, with particularly strong CD20 and OCT2 expression. These findings can make it challenging to distinguish CHL from other entities typically in the differential diagnosis, including primary mediastinal large B-cell lymphoma (PMBL), mediastinal grey zone lymphoma (MGZL), EBV-positive diffuse large B-cell lymphoma (EBV+ DLBCL), nodular lymphocyte predominant Hodgkin lymphoma (NLPHL), T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL), anaplastic large cell lymphoma (ALCL), and others 1, 2. In this case, the cytomorphology of the neoplastic cells (large, occasionally multinucleated with prominent eosinophilic nucleoli) combined with a staining pattern showing strong, uniform expression of CD30 and CD15, absence of CD45, and weak to moderate PAX5 support the diagnosis of CHL. The lack of mediastinal involvement would also make diagnoses of PMBL and MGZL unlikely. The prognostic impact of this unusual B-cell marker expression pattern in CHL is unclear. Several studies have suggested that CD20 expression has no significant prognostic impact, and chemotherapy with or without radiotherapy remains the standard first-line treatment 3. Overall, this case adds to the limited literature of CHL positive for multiple B-cell markers, which can be challenging to diagnose. Careful attention to the CD30/CD15/CD45/PAX5 staining pattern, morphology, and clinical findings is important to distinguish such cases of CHL with strong expression of several B-cell markers from various non-Hodgkin large B-cell lymphomas. All authors contributed to the paper's conception and design. Christopher Liwski and David Conrad collected clinical and histological data and drafted the manuscript. All authors read and approved the final manuscript. All authors would like to acknowledge the work of the laboratory technologists who were involved in preparing the histology slides that were used in this case. The authors have nothing to report. This article does not contain any studies with human participants or animals performed by any of the authors. Informed consent has been obtained from the patient. The data that support the findings of this study are available from the corresponding author upon reasonable request.