WHO 2022 & ICC-B cell

Overview of Lymphoma & Related Disorders

Authors: Pichayut Nithagon, M.D., Patricia Tsang, M.D., M.B.A.Editorial Board: Julie Feldstein, M.D.Last updates on the document:

  • Author update: 21 March 2023

  • Staff update: 30 April 2023Copyright: 2022-2024 by PathologyOutlines.com, Inc.

Digital Resources

New educational videos are available from the CAP 2024 meeting in Las Vegas, enhancing the learning experience for professionals in the field.

Content Includes:

  • Definition / General: Initial understanding of lymphoma as a malignancy originating from lymphocytes, an essential component of the immune system.

  • Major Updates: Notable shifts in classification and understanding, integrating updates from WHO (2016), WHO (2022), and ICC (2022).

  • Microscopic (histologic) images: Visual aids to illustrate the histological features observed in various lymphoma subtypes.

  • Additional References: A comprehensive list of literature for further reading and exploration.

  • Board Review Style Questions and Answers: Helps healthcare professionals prepare for board examinations with relevant case studies and questions.

Classification Systems

Two new classifications for B cell lymphoid neoplasms were introduced in 2022:

  1. WHO 5th Edition (WHO HAEM5): Focusing on modern diagnostic criteria and therapeutic implications, reflecting global consensus in the field.

  2. International Consensus Classification (ICC): Emphasizing collaborative classification that incorporates diverse research findings and expert opinions.

The evolution from the 2016 WHO 4th Edition reflects significant advances in:

  • Genomic Profiling: Leveraging genetic insights to inform diagnosis, prognosis, and treatment.

  • Evidence-based Clinical Data: Utilizing data derived from recent clinical trials to inform diagnostic criteria.

Major Updates Include:

  • New Subtypes and Umbrella Terms: Introduction of broader categories for better understanding of related lymphomas.

  • Deletion of Older Entities: Streamlining classifications by removing outdated terminologies that no longer reflect current understanding.

  • Modified Nomenclature: Ensuring clarity in classification naming conventions, thus enhancing communication among healthcare providers.

  • Provisional Designations in WHO HAEM4 and ICC: Existing provisional terms were discarded in WHO HAEM5 to foster more rigorous classifications.

Major Updates in B Cell Classification

New categories specific to only one classification:

  • WHO HAEM5: Introduces nonneoplastic tumor-like lesions such as IgG4-related disease, unicentric, and idiopathic multicentric Castleman disease, broadening the scope of diagnosis.

New Entities Under ICC

  • EBV+ Polymorphic B Cell Lymphoproliferative Disorder, NOS: A newly recognized entity involving EBV+ lesions that do not meet the criteria for lymphoma diagnosis, emphasizing the necessity for nuanced diagnostic approaches.

  • Multiple Myeloma (MM): Now classified based on recurrent genetic abnormalities, with specific subtypes recognized under NOS classifications.

  • B Prolymphocytic Leukemia (B PLL): No longer an independent entity under WHO HAEM5; now categorized based on notable transformations from various small B cell lymphoma entities.

Specific Lymphoma Classifications

  • Splenic B Cell Lymphoma / Leukemia with Prominent Nucleoli: Synonymous with hairy cell leukemia variant.

  • Marginal Zone Lymphomas: Pediatric and primary cutaneous marginal zone lymphoma acknowledged under both classifications, enhancing pediatric recognition.

  • Follicular Lymphoma: New subtypes categorized based on BCL2 gene rearrangement, further dissecting this prevalent form of lymphoma:

    • Classic follicular lymphoma (cFL)

    • Follicular large B cell lymphoma (FLBL)

    • Follicular lymphoma with uncommon features (uFL)

  • High-Grade B Cell Lymphomas (HGBCL): Now differentiated into two distinct entities based on MYC and other genetic rearrangements, aiding in tailored treatment approaches.

  • Burkitt Lymphoma: Strikingly categorized based on EBV status fundamentally altering its epidemiological associations.

Notable New Terminology

  • Lymphoplasmacytic Lymphoma (LPL): Includes refined subsets based on specific genetic mutations (e.g., MYD88, CXCR4) that guide therapeutic decisions and monitoring.

  • Monoclonal Gammopathy of Renal Significance (MGRS): Marked as a distinct entity with clinical implications differing from the previously recognized Monoclonal Gammopathy of Undetermined Significance (MGUS).

Conclusion

The continual recognition of new entities, evolving classification systems, and updated nomenclature is a testament to the progress being made in the understanding of B cell neoplasms in hematopathology. This document serves as an invaluable resource for pathologists and laboratory personnel, equipping them with the latest insights into the changing landscape of lymphoma classifications as established in WHO HAEM5 and ICC. It underscores the critical nature of precise classification in guiding effective patient management and therapeutic strategies.