The international consensus classification of eosinophilic disorders and systemic mastocytosis

Abstract

Based on new data and increased understanding of disease molecular genetics, the international consensus classification (ICC) has made several changes in the diagnosis and classification of eosinophilic disorders and systemic mastocytosis. Myeloid/lymphoid neoplasms with eosinophilia (M/LN‐eo) and gene rearrangements have been renamed as M/LN‐eo with tyrosine kinase gene fusions (M/LN‐eo‐TK). The category has been expanded to include ETV6::ABL1 and FLT3 fusions, and to accept PCM1::JAK2 and its genetic variants as formal members. The overlaps and differences between M/LN‐eo‐TK and BCR::ABL1‐like B‐lymphoblastic leukemia (ALL)/de novo T‐ALL sharing the same genetic lesions are addressed. Besides genetics, ICC for the first time has introduced bone marrow morphologic criteria in distinguishing idiopathic hypereosinophilia/hypereosinophilic syndrome from chronic eosinophilic leukemia, not otherwise specified. The major diagnostic criteria for systemic mastocytosis (SM) in the ICC remain largely based on morphology, but several minor modifications/refinements have been made in criteria related to diagnosis, subclassification, and assessment of disease burden (B‐ and C‐findings). This review is to focus on the ICC updates related to these disease entities, illustrated through changes related to morphology, molecular genetics, clinical features, prognosis, and treatment. Two practical algorithms are provided in navigating through the diagnosis and classification systems of hypereosinophilia and SM.

Granularity in disease classification impacts survival prediction in advanced systemic mastocytosis: A single institution study of 329 informative cases

“…At one extreme are ICC‐defined MCL (i.e., WHO‐defined MCL with immature cytomorphology) 5 and mast cell sarcoma, 11,12 with median survival measured in weeks, while a near‐normal life expectancy is possible with ISM 13 . Both the ICC 1,2 and WHO 3 classification systems start with a broad classification scheme that distinguishes SM‐Adv from ISM or SSM, based primarily on long‐term clinical outcome and presence (SM‐Adv) or absence (ISM/SSM) of at least one “C,” as in “cytoreduction‐requiring,” finding; the latter includes (i) cytopenia (hemoglobin <10 g/dL, absolute neutrophil count <1 × 10 9 /L, or platelet count <100 × 10 9 /L) related to BM MC infiltration, (ii) palpable hepatomegaly with liver function test abnormalities or ascites or portal hypertension, (iii) palpable splenomegaly with thrombocytopenia, (iv) malabsorption with weight loss secondary to MC infiltration of the gastrointestinal system, and (v) large osteolytic lesions with or without pathological fractures 1,2 . By contrast, “B,” as in “burden of disease,” findings are used to distinguish ISM from SSM; at least 2 “B” findings are required for classification as SSM and include (i) BM biopsy showing >30% MC infiltration along with serum tryptase level of >200 ng/mL, (ii) cytosis or cytopenia not meeting criteria for “C” finding, and (iii) palpable hepatomegaly without liver function test abnormalities, or palpable splenomegaly without thrombocytopenia, or >1 cm palpable or imaged lymphadenopathy 1,2 ; the WHO classification system, fifth edition, now includes a KIT D816V mutation burden of ≥10% as a “B” finding 3 .…”

“…There are currently two separate classification systems for hematopoietic neoplasms: the International Consensus Classification (ICC) 1,2 and the World Health Organization (WHO), fifth edition 3 ; both systems constitute revisions of the 2016 WHO document (revised fourth edition) 4 . According to both the ICC and WHO fifth edition, systemic mastocytosis (SM) is organized into advanced (SM‐Adv) and non‐advanced variants.…”

Involvement of the JAK‐STAT pathway in the molecular landscape of tyrosine kinase fusion‐negative hypereosinophilic syndromes: A nationwide CEREO study

“…Conversely, mutations with lower VAF were mostly single mutations involving genes reported in age‐related clonal hematopoiesis (e.g., DNMT3A or TET2 ) 17 and were predominantly reported in patients from the control group who responded to corticosteroids. As acknowledged by others, this emphasizes the need for cautious interpretation of molecular alterations implying these genes, which in the setting of unexplained HE, are probably not a surrogate marker of eosinophilic clonal proliferation in all cases 1,18 …”

Case Report: A novel FGFR1 fusion in acute B-lymphoblastic leukemia identified by RNA sequencing

“…In fact, there is some overlap between the BCR-ABL1 like ALL and MLN-TK diagnostic criterion, and some Ph-like ALL cases could also be diagnosed as MLN-TK, for MLN-TK include a broad range of histologic types and have complex clinical manifestations. Although the latest International Consensus Classification (ICC) of myeloid neoplasms and acute leukemias distinguishes BCR-ABL1 like ALL from MLN-TK presenting as B-ALL by identifying involvement of TK gene fusion in the background myeloid cells in addition to o lymphoblasts (7), the 5 th edition of the World Health Organization (WHO) Classification of hematolymphoid tumors does not emphasize the difference between these two groups and holds the opinion that the diagnosis of MLN-TK supersedes other myeloid and lymphoid types from a diagnostic hierarchy standpoint (1). The clinical characteristics (young male, absence of eosinophilia, no MPN history, poor outcome) of our case support a diagnosis of BCR-ABL1 like ALL rather than typical MLN-TK according to ICC.…”