List of main discrepancies between ICC and WHO-HAEM5 classifications with proposed actions needed to resolve outstanding questions

		ICC 2023	WHO-HAEM5	Clinical/Research Implications and Next Steps
Entity	MAIN DISCREPANCIES
Follicular lymphoma (FL)	Grading	Retain morphological grading (with the distinction of 3B FL)	Grading of FL optional in the subtyping of cFL (with the distinction of follicular large B-cell)	1. Assess the utility of morphometry, proliferation index, OMICs data, artificial intelligence or machine learning algorithms in defining robust prognostic subgroups within FL 2. Integrated clinico-molecular studies to investigate outcome of homogenously treated FL based on OMICs features (e.g. mutations, epigenome, transcriptome, single cell analyses) and correlation with histological grading
	Testicular FL	Recognized as distinct subtype of FL in young boys	Not recognized as distinct FL subtype	Determine biologic and clinical features in larger series.
	BCL2r-negative, CD23-positive follicle center lymphoma	Recognized as provisional entity	Partially overlapping with FL with predominantly diffuse growth pattern (dFL)	1. Investigations to determine whether this represents a distinct homogeneous clinicopathology entity within the broader group of BCL2-R-negative FLs 2. Define clinical differences between FL with/without del(1)(p36), STAT6, CREBBP, TNFRSF14 mutation in the context of absence of BCL2r
	FL with unusual cytological features	Not recognized	Recognized	Establish precise diagnostic criteria through integrated clinical, pathological and molecular studies
Diffuse large B-cell lymphoma (DLBCL)	Primary large B-cell lymphoma of immune-privileged sites	No umbrella group included (felt to be premature)	Includes CNS, testis, vitreo-retinal	Comparative genomic studies among different extranodal locations of MCD/C5/MYD88 (°) DLBCL genomic subtypes
	HHV8-negative primary effusion-based lymphoma	EBV-positive cases excluded	EBV-positive cases included	1. Study larger series of cases, with full clinical and pathological annotations, in different countries 2. Asses diagnostic criteria and clinical relevance for EBV positivity 3. Establish precise diagnostic criteria and consensus nomenclature
DLBCL/High grade B-cell lymphoma (HGBL)	HGBL DH BCL6/MYC	Provisional entitiy	No a specific entity; encompassed within DLBCL, NOS or HGBL, NOS	1. Assess the clinical behavior and outcome of BCL6r and MYCr HGBL and underlying biology. 2. Specific research to address the cases with MYC::BCL6 mutual translocation (MYCr with BCL6 locus as partner)
	DHL terminology	High-grade (irrespective of morphology)	High grade or Large cell (based on morphology)	1. Establish more precise diagnostic criteria. Clinico-pathological studies to determine whether cytological subtype influences diagnosis or therapy. 2. Clinical studies/trials to determine the clinical relevance, underlying biology and diagnostic criteria of HGBL, NOS 3. Consensus conference to determine the appropriate terminology for cases with concomitant rearrangements of MYC and BCL2 as well as MYC and BCL6
Immunodeficiency LPDs	Immunodeficiency LPDs	ICC emphasizes the clinical context for diagnosis and treatment	WHO-HAEM5 systematically applies histopathological, viral and immunodeficiency characteristics seen across different clinical settings	1. Consensus conference to determine the appropriate terminology and the impact of the underlying immune scenario in influencing therapy. 2. Determine the prognostic significance of cases EBV+ vs. EBV- 3. Studies to improve diagnostic criteria for polymorphic vs. monomorphic (lymphoma) categories
	Epstein-Barr virus-positive mucocutaneous ulcer
	EBV positive polymorphic B cell LPD, NOS
	Inborn error of immunity-associated lymphoid proliferations and lymphomas
Plasma cell myeloma/Multiple Myeloma	Molecular subclassification	YES Subclassification based on genetic features.	No genetic subclassification	Comprehensive clinical studies or trials with genetic annotations to determine the clinical relevance of genetic classification in patients receiving novel therapies.
B-PLL and HCLv vs. SBLPN		No changes. B-PLL and HCLv remain as distinct entities	SBLPN entity created to encompass B-PLL and HCLv and some other rare splenic B-cell lymphoma cases	1. Study of large cohorts to define clinical, immunophenotypic and genomic features of the different entities 2. Development of blood-based genomic biomarkers to subclassify splenic B cell lymphoid neoplasms

Abbreviations: ICC, International Consensus Classification; WHO-HAEM5, 5th edition of the WHO Classification of Hematolymphoid Tumours; CNS, central nervous system; NSCHL, nodular sclerosis classic Hodgkin lymphoma; LPD, lymphoproliferative disorder; MGZL, mediastinal grey zone lymphoma; PMBL, primary mediastinal B-cell lymphoma; PLL, prolymphocytic leukemia; HCLv, Hairy cell leukemia, variant; SBLPN, splenic B-cell lymphoma/leukemia with prominent nucleoli; NOS, not otherwise specified; LBCL, large B-cell lymphoma. (°) refers to genetic subgroups of DLBCL as summarized in ¹¹