Pathology review identifies frequent misdiagnoses in recurrent classic Hodgkin lymphoma in a nationwide cohort: implications for clinical and epidemiological studies

• Published in: Haematologica (Roma) Vol. 108; no. 5; pp. 1349 - 1358
• Main Authors: Boot, Max V, Schaapveld, Michael, Van den Broek, Esther C, Hijmering, Nathalie J, Group, Palga, Van der Oord, Kimberly, Van Leeuwen, Flora E, Dinmohamed, Avinash G, Koens, Lianne, De Jong, Daphne
• Format: Journal Article
• Language: English
• Published: Italy Fondazione Ferrata Storti 01.05.2023; Ferrata Storti Foundation
• Subjects: Diagnostic Errors; Epstein-Barr Virus Infections - complications; Herpesvirus 4, Human; Hodgkin Disease - drug therapy; Hodgkin Lymphoma; Humans; Lymphoma - complications; Lymphoma, B-Cell - complications; Lymphoma, Non-Hodgkin - complications; Neoplasm Recurrence, Local
• ISSN: 0390-6078; 1592-8721
• DOI: 10.3324/haematol.2022.280840

Patients treated for classic Hodgkin lymphoma (CHL) have a reported 13-fold increased risk of developing subsequent non-Hodgkin lymphoma (NHL). In light of the growing awareness of CHL mimickers, this study re-assesses this risk based on an in-depth pathology review of a nationwide cohort of patients diagnosed with CHL in the Netherlands (2006-2013) and explores the spectrum of CHL mimickers. Among 2,669 patients with biopsy-proven CHL, 54 were registered with secondary NHL. On review, CHL was confirmed in 25/54 patients. In six of these, the subsequent lymphoma was a primary mediastinal B-cell lymphoma/mediastinal gray zone lymphoma, biologically related to CHL and 19/25 were apparently unrelated B-cell NHL. In 29/54 patients, CHL was reclassified as NHL, including T-cell lymphomas with secondary Hodgkin-like B-blasts (n=15), Epstein Barr virus-positive diffuse large B-cell lymphoma (n=8), CD30+ T-cell lymphoma (n=3) and indolent B-cell proliferations (n=3). Higher age, disseminated disease at presentation, extensive B-cell marker expression and association with Epstein-Barr virus were identified as markers to alert for CHL mimickers. Based on these data, the risk of developing NHL after CHL treatment was re-calculated to 3.6-fold (standardized incidence ratio 3.61; confidence interval: 2.29-5.42). In addition, this study highlights the clinicopathological pitfalls leading to misinterpretation of CHL and consequences for the care of individual patients, interpretation of trials and epidemiological assessments.