Mast cell proliferative disorders: current view on variants recognized by the World Health Organization

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Definition of disease and disease-related criteria

The term mastocytosis denotes a spectrum of disorders characterized by the dysregulated growth and abnormal accumulation of MCs in one or more organ systems [38], [39], [40], [41]. Cutaneous mastocytosis (CM) develops before puberty in most cases [42]. In 15% to 20% of patients with cutaneous infiltrates (mostly adults), a systemic form of mastocytosis is diagnosed. In almost all patients with SM, the diagnosis is established by bone marrow examination [43], [44]. Apart from the bone marrow,

Cutaneous mastocytosis (CM)

CM preferentially develops in childhood [42], [50], [75], [76]. By definition, the disease is confined to the skin. In most cases, a characteristic maculopapular rash is seen [42], [75], [76]. In a smaller group, skin lesions are diffuse or nodular [42], [76]. A positive Darier's sign is a typical finding. The diagnosis of CM is based on the presence of typical skin lesions, demonstration of characteristic focal infiltrates of MCs on histologic examination of lesional skin, and absence of signs

Indolent systemic mastocytosis

Most patients with SM are adults and present with the indolent variant of disease (ie, indolent systemic mastocytosis [ISM]) [38], [39], [40], [41]. ISM is characterized by an indolent clinical course. Significant organopathy (C-Findings) is virtually always absent, and the prognosis is good. In typical cases, UP-like skin lesions are detectable [38], [39], [40], [41], [61]. Mediator-related symptoms are also frequently recorded and may represent a predominant medical problem [72], [73], [74].

Smoldering mastocytosis

Smoldering systemic mastocytosis is another subentity of ISM [51], [52], [53], [54], [55], [61]. In contrast to typical ISM, B-Findings (two or more) are detectable (see Box 2). These B-Findings indicate a high burden of MCs and extension of the clonal disease process to several myeloid lineages. Clinically the smoldering state is reflected by an uncertain prognosis and a variable clinical course [51], [52], [53], [54], [55]. In some cases, the clinical course is long-lasting and silent [51],

Systemic mastocytosis with an associated hematopoietic clonal non–mast cell lineage disorder (SM-AHNMD)

In some patients with SM, an AHNMD is diagnosed during initial evaluation [56], [57], [58], [59], [60], [61]. In these patients, WHO criteria to diagnose an AHNMD and SM criteria should be applied. The nature and biology of a preexisting mastocytosis (SM) may be identical to SM without AHNMD. According to the type of the AHNMD and the type of the SM, the SM-AHNMD group of patients are subdivided further. In fact, myeloid and lymphoid neoplasms can develop [56], [57], [58], [59], [60], [61]. In

Aggressive systemic mastocytosis (ASM)

ASM is characterized by organopathy caused by pathologic infiltration of various organs by neoplastic MCs with consecutive impairment of organ function (with or without organomegaly) [38], [39], [40], [41], [61], [85]. In contrast to mast cell leukemia, the bone marrow smear shows less than 20% MCs [61]. In contrast to ISM and smoldering SM, C-Findings (see Box 2) are present. In particular, patients show one of the following: (1) abnormal myelopoiesis with significant blood count abnormalities

Mast cell leukemia (MCL)

MCL is a rare subentity of SM characterized by circulating MCs and an aggressive clinical course [37], [58], [71]. Patients with MCL typically have progressive organopathy involving the liver, bone marrow, and other organ systems, such as the gastrointestinal tract, skeletal system, and spleen [71]. The bone marrow typically reveals a diffuse and dense infiltration with neoplastic MCs [43], [44], [63], and the bone marrow smear contains 20% or more MCs [37], [61], [71]. These MCs are often

Mast cell sarcoma

MC sarcoma is an extremely rare form of mastocytosis. So far, apparently only three well-documented cases have been reported [87], [88], [89]. The disease is defined by a local destructive sarcoma-like growth of a tumor consisting of highly atypical MCs. The organ sites described include the larynx, ascending colon, and an intracranial site [87], [88], [89]. At initial diagnosis, no systemic involvement was reported. However, secondary generalization with involvement of visceral organs and

Extracutaneous mastocytoma

Extracutaneous mastocytoma is a localized benign tumor consisting of mature tissue MCs. No systemic involvement is found, and SM criteria are not fulfilled. In contrast to mastocytoma of skin, mastocytomas in extracutaneous organs are extremely rare. So far, isolated mastocytomas have been found primarily in the lungs [90], [91]. In contrast to MC sarcoma, the prognosis for patients with mastocytoma seems to be good. Therefore, it is of great importance to differentiate between mastocytoma and

Summary

The term mastocytosis covers a heterogeneous group of disorders characterized by the abnormal growth and accumulation of MCs in one or more organ systems. Clinical symptoms occur from the release of chemical mediators or pathologic infiltration of MCs. CM typically presents as UP and is a benign disease confined to the skin. In many cases, particularly in children, this disease regresses spontaneously. By contrast, SM is a clonal persistent disease of MC-committed or precommitted hematopoietic

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    This article was supported by Fonds zur Förderung der Wissenschaftlichen Forschung in Österreich, FWF, grant # P-12517.

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