AUTHORS
Oscar Felipe Borja Montes, MD, Stephanie Rosenberg, DO2, Mikaela Kosich3, Vernon Shane Pankratz, PhD4, Jacqueline C. Barrientos, MD, MS5, Alina S. Gerrie, MD, FRCPC, MPH6, Philip Thompson, MB, BS7, Sameer A. Parikh, MBBS8, Justin Taylor, MD9, Versha Banerji, MD10, Clive S. Zent, MD11, Gerard Lozanski, MD12, Christopher C Oakes, PhD13, James Stewart Blachly, MD14, Seema Ali Bhat, MD15, Kerry A. Rogers, MD16, Mirela Anghelina, MD, MPH17, Michael Grever, MD18, Narendranath Epperla, MD, MS, FACP19, Leslie Andritsos, MD20
AFFILIATIONS
1 University of Florida, Gainesville, Florida, United States
2 University of New Mexico, Albuquerque, New Mexico, United States
3 University of New Mexico, Albuquerque, New Mexico, United States
4 University of New Mexico, Albuquerque, New Mexico, United States
5 Mount Sinai Medical Center, Miami, Florida, United States
6 BC Cancer Research Centre, Vancouver, British Columbia, Canada
7 Peter MacCallum Cancer Centre Royal Melbourne Hospital, Melbourne, Victoria, Australia
8 Mayo Clinic, Rochester, Minnesota, United States
9 Sylvester Comprehensive Cancer Center, Miami, Florida, United States
10 University of Manitoba, Winnipeg, Manitoba, Canada
11 UR Medicine Wilmot Cancer Institute - Greece, Rochester, New York, United States
12 The Ohio State University, Columbus, Ohio, United States
13 The Ohio State University, Columbus, Ohio, United States
14 The Ohio State University, Columbus, Ohio, United States
15 The Ohio State University, Columbus, Ohio, United States
16 The Ohio State University, Columbus, Ohio, United States
17 The Ohio State University, Columbus, Ohio, United States
18 The Ohio State University, Columbus, Ohio, United States
19 Huntsman Cancer Institute - Cancer Hospital South, Salt Lake City, Utah, United States
20 University of New Mexico, Albuquerque, New Mexico, United States
ABSTRACT
Introduction: Splenic B-cell lymphoma with prominent nucleoli (SBLPN) is a newly recognized entity in the 5th edition of the World Health Organization (WHO-HAEM5) Classification of Haematolymphoid Tumors. Historically, many patients with SBLPN were diagnosed with hairy cell leukemia variant (HCL-v), while others were classified using terminology such as atypical hairy cell leukemia. The Hairy Cell Leukemia Foundation (HCLF) Registry is the largest international collaborative registry for patients with hairy cell leukemia and related disorders. Using the registry data, we reassessed patients with historical diagnoses of HCL-v, atypical HCL, and related entities according to WHO-HAEM5 criteria to identify patients meeting contemporary diagnostic criteria for SBLPN.
Methods: We conducted a retrospective review of the Hairy Cell Leukemia Patient Data Registry, a multicenter collaborative registry of approximately 800 patients with hairy cell leukemia and related disorders, funded by the Hairy Cell Leukemia Foundation. Patients with historical diagnoses of HCL-v, atypical HCL, or other related B-cell lymphoproliferative disorders were identified for retrospective review. Classic HCL patients were not reviewed in this preliminary study. Cases were first evaluated by BRAFV600E or MAP2K1 mutation status, then by flow cytometry or immunohistochemistry (IHC), including CD25, CD103, CD123. A final WHO-HAEMS5 diagnosis was assigned based on a summary of the mutational, flow cytometry and IHC status. Of note, not all records possessed data for each variable. For example, 28 of the 67 patients reviewed did not have recorded data for BRAFV600E mutation status.
Results: Of 872 patients in the HCLF Registry, 805 (92.3%) had a historical diagnosis of classic HCL, 52 (6.0%) HCL-v, 10 (1.1%) atypical HCL, and 5 (0.6%) another related B-cell lymphoproliferative disorder. A total of 67 patients (7.7%) met criteria for retrospective review under the WHO-HAEM5 classification framework. Following independent review by three investigators (OB-M, SR, LA), 6 (9%) patients met criteria for SBLPN, 37 (55.2%) probable SBLPN, 6 (9%) were reclassified as classic HCL, and 18 (26.9%) were unclassifiable due to mixed or unavailable data. Among the patients with a historical diagnosis of HCL-variant and atypical HCL, 35 of 52 (67.3%) and 6 of 10 (60.0%), respectively, were reclassified as SBLPN or probable SBLPN.
Conclusion: Systematic application of the WHO-HAEM5 framework successfully identified patients meeting diagnostic criteria for SBLPN within the HCLF Registry. More than half of patients historically labeled as atypical HCL or HLC-variant were reclassified in this review, highlighting the degree of diagnostic overlap between these entities under prior classification schemes. Importantly, approximately a quarter of reviewed cases remained unclassifiable, reflecting either unavailable molecular testing or inconsistent immunophenotypic and molecular findings. These data emphasize the importance of comprehensive diagnostic evaluation, including molecular testing of patients suspected to have SBLPN. Establishing this cohort provides a foundation for future studies characterizing the clinical features and outcomes of SBLPN in comparison to classic-HCL.
DISCLOSURES
Oscar Felipe Borja Montes, MD: No relevant conflicts of interest to declare.