Two cases of concomitant acquired aplastic anemia and systemic mastocytosis

Summary

Reactive bone marrow mast cells reliably lack the morphologic, immunophenotypic, and molecular features of systemic mastocytosis (SM). We report two unusual cases of acquired aplastic anemia (AA) in which multifocal aggregates of bone marrow mast cells fulfilled morphologic and immunophenotypic criteria for SM according to the World Health Organization 2008 classification. In the absence of clinical symptoms attributable to SM, the patients were treated with immunosuppressive therapy directed towards AA. Clinical follow-up and subsequent bone marrow examination revealed no evidence of overt SM in either patient. These cases represent, to our knowledge, the first reported instances in which criteria for SM have been fulfilled in the presence of AA. However, given the clinical courses followed by our patients, the incidental identification of mast cell lesions consistent with indolent SM may be of uncertain significance in the setting of AA.

Introduction

Mastocytosis is a myeloproliferative neoplasm of clonal, bone marrow-derived mast cells with a wide array of clinical and morphologic presentations ranging from cutaneous to systemic, and indolent to aggressive, disease. Among the subtypes of mastocytosis is systemic mastocytosis (SM), defined in the World Health Organization 2008 classification as showing specific combinations of morphologic, immunophenotypic, clinical, and/or molecular findings (Table) [1]. Systemic mastocytosis is diagnosed when the major criterion and one minor criterion, or, alternatively, at least three minor criteria, are present. Adherence to these requirements is recommended to avoid a misdiagnosis of SM in cases of reactive mast cell hyperplasia.

Aplastic anemia (AA) is a bone marrow failure disorder characterized by pancytopenia and marrow hypocellularity in the absence of an abnormal marrow infiltrate or increased reticulin deposition [2]. It is most often acquired, and an autoimmune mechanism is typically implicated [3]. Mast cells are frequently noted in the bone marrow in cases of AA, and in some cases, they are relatively or even absolutely increased in number. These mast cells are benign, reactive in nature, and do not fulfill criteria for a diagnosis of SM. In particular, they are usually scattered in an interstitial distribution and do not form clusters of morphologically atypical cells, they do not show aberrant expression of CD2 or CD25, and no KIT mutation is detectable. In fact, so reliably can these mast cells be differentiated from SM that one authority expressly notes that SM has never been diagnosed in the setting of AA [4]. It is in this light that we report two unusual cases of AA in which the current World Health Organization (WHO) 2008 diagnostic criteria for SM are, in fact, met.