Refined diagnostic criteria and classification of mast cell leukemia (MCL) and myelomastocytic leukemia (MML): a consensus proposal

Abstract

Mast cell leukemia (MCL), the leukemic manifestation of systemic mastocytosis (SM), is characterized by leukemic expansion of immature mast cells (MCs) in the bone marrow (BM) and other internal organs; and a poor prognosis. In a subset of patients, circulating MCs are detectable. A major differential diagnosis to MCL is myelomastocytic leukemia (MML). Although criteria for both MCL and MML have been published, several questions remain concerning terminologies and subvariants. To discuss open issues, the EU/US-consensus group and the European Competence Network on Mastocytosis (ECNM) launched a series of meetings and workshops in 2011-2013. Resulting discussions and outcomes are provided in this article. The group recommends that MML be recognized as a distinct condition defined by mastocytic differentiation in advanced myeloid neoplasms without evidence of SM. The group also proposes that MCL be divided into acute MCL and chronic MCL, based on the presence or absence of C-Findings. In addition, a primary (de novo) form of MCL should be separated from secondary MCL that typically develops in the presence of a known antecedent MC neoplasm, usually aggressive SM (ASM) or MC sarcoma. For MCL, an imminent prephase is also proposed. This prephase represents ASM with rapid progression and 5%-19% MCs in BM smears, which is generally accepted to be of prognostic significance. We recommend that this condition be termed ASM in transformation to MCL (ASM-t). The refined classification of MCL fits within and extends the current WHO classification; and should improve prognostication and patient selection in practice as well as in clinical trials.

Chronic mast cell leukemia (MCL) with KIT S476I: a rare entity defined by leukemic expansion of mature mast cells and absence of organ damage

“…In most patients described to date, the survival time was less than one year. However, in exceptional cases, a more chronic form of the disease has been reported [14,15]. We here describe a young female patient in whom chronic MCL was diagnosed.…”

“…We were also unable to detect chymase in neoplastic MCs. Moreover, most of the neoplastic MCs were found to stain negative for Ki-67 (Figure 2) which contrasts the situation in acute MCL [15,31]. Table 2 shows a summary of markers expressed in the cytoplasm of neoplastic MCs in our patient with chronic MCL.…”

“…MCL is a life-threatening condition defined by leukemic expansion of MCs in the BM and other organs, drug resistance and a poor survival [5][6][7][8][9][12][13][14][15]. In most patients described to date, the survival time was less than one year.…”

“…Isolated BM cells were also examined by conventional karyotyping and fluorescence in situ hybridization (FISH). BM studies were performed according to generally accepted standards [15,[18][19][20][21].…”

“…Regardless of the type of MCL, most patients are considered to have a poor prognosis and a short survival-time, lasting for a few months only. More recently, however, a few reports have described patients with MCL who survived more than 12 months or even several years [14,15]. It remains unknown whether these patients are suffering from a less aggressive type of MCL or were diagnosed at an early (premalignant) stage of their disease.…”