Paratrabecular myelofibrosis and occult mastocytosis are strong morphological clues to suspect FIP1L1-PDGFRA translocation in hypereosinophilia

Abstract

To study the clinico-haematological and histopathological characteristics of FIP1L1-PDGFRA rearranged hypereosinophilia/hypereosinophilic syndrome (F/P?ve HE/HES), a retrospective analysis of patients with F/P?ve HE diagnosed over a period of 43 months was performed. Peripheral blood smears, bone marrow aspirate (BMA) and biopsies (BMB) were reviewed in each case and; reticulin stain and immunohistochemistry for mast cell tryptase (MCT) and CD117 was performed. F/P?ve HE was diagnosed in a total of ten patients during study period. All patients were males with a median age of 36 years (23-44 years). The median duration of presenting complaints was 7 months (2 months-3 years) which included specific symptoms related to various organs (80% of cases). Anaemia, thrombocytopenia and splenomegaly were seen in 60%, 50% and 90% of the cases respectively.Mastocytosis was not obvious in BMA but identified by MCT on BMB in all cases. Myelofibrosis (grade C 1) was seen in 80% of the cases and includes multifocal paratrabecular fibrosis in 50% of the biopsies. Our study shows that bone marrow mastocytosis and myelofibrosis are very useful morphological indicators to suspect F/P?ve HE and suggests the routine use of reticulin staining and MCT immunohistochemistry in all BMBs performed for the evaluation of HE/HES.

Laboratory Workup of Hypereosinophilia

“…6,31,32 Patients with B lineage ALL also need exclusion of IL3::IGH translocation, where reactive HE occurs as a secondary phenomenon. 33 Other findings which support the diagnosis of neoplastic HE/HES includes spindle shaped mast cell more than 25% (systemic mastocytosis with HE), loose (PDGFRA associated HE) or tight clusters of mast cells (systemic mastocytosis with HE), myelofibrosis and myeloid or megakaryocytic dysplasia 34 (►Fig. 2).…”

“…The presence of mastocytosis favors a diagnosis of MPN, especially FIP1L1::PDGFRA or systemic mastocytosis with HE. It will also help to exclude abnormal lymphoid infiltration 26,34. (f) Flow cytometry and immunophenotyping: Immunophenotyping is a useful investigation to confirm the underlying clonal disorders like acute leukemia (B/T/MPAL), lymphoproliferative disorders and mastocytosis.…”