A 26-Year-Old Female with Systemic Mastocytosis with Associated Myeloid Neoplasm with Eosinophilia and Abnormalities ofPDGFRB, t(4;5)(q21;q33)

Abstract

Various translocations involving the PDGFRB gene are identified in myeloid neoplasms. However, the PRKG2/PDGFRB fusion gene associated with t(4;5)(q21;q33) has previously been reported in only 3 patients. We present the case of a 26-year-old woman with microcytic anemia, basophilia, thrombocytosis, and massive splenomegaly, who was found to have systemic mastocytosis and associated clonal hematological non-mast cell lineage disease (SM-AHNMD), with myeloid neoplasm with PRKG2/PDGFRB rearrangement. Initial findings included basophilia (37%, 4.1 k/μL), hypercellular marrow with eosinophilia, and increased and atypical megakaryocytes, suggestive of myeloproliferative neoplasm. Additional studies revealed large clusters of CD25 positive mast cells, fulfilling the criteria for the diagnosis of systemic mastocytosis. Consistent with prior reports of this translocation, our patient has responded well to imatinib. This case, in conjunction with others in the literature, suggests a possible connection between t(4;5)(q21;q33) PRKG2/PDGFRB and systemic mastocytosis and highlights their favorable response to imatinib.

Systematic use of fluorescence in‐situ hybridisation and clinicopathological features in the screening of PDGFRB rearrangements of patients with myeloid/lymphoid neoplasms

“…We found that the BM specimens from these patients were abnormal, with frequent hypercellularity (90% cases), abnormal megakaryocytes with either MDS, MPN or mixed MDS/MPN features, significant fibrosis, and, less frequently, dysgranulopoiesis, dyserythropoiesis, and abnormal eosinophils. Similarly to what is seen in PDGFRA ‐rearranged neoplasms, proliferation of mast cells with aberrant CD25 expression 33,34 was frequent, being detected in three of five cases with mast cell work‐up performed, with one case fulfilling the diagnostic criteria for systemic mastocytosis. Interestingly, none of the three B‐ALL cases with PDGFRB rearrangement had eosinophilia, monocytosis, or morphological or immunophenotypic features that could distinguish them from other B‐ALL cases.…”

Case Report: Evolution of KIT D816V-Positive Systemic Mastocytosis to Myeloid Neoplasm With PDGFRA Rearrangement Responsive to Imatinib

“…Up to 40% of all SM cases are associated with another hematological disease, which rarely can be a myeloid/lymphoid neoplasm with eosinophilia ( 2 , 4 ).…”

“…Eosinophilia (≥1.5x10 9 /L) is one of the most common features of these neoplasms. In the subgroup associated with PDGFRA rearrangement, the most common genetic abnormality is the FIP1L1-PDGFRA gene fusion, caused by 4q12 deletion (Figure 1) (1,(4)(5)(6). Patients frequently complain of fatigue, pruritus, and symptoms related to eosinophilic infiltrates in different organs; splenomegaly and hepatomegaly are common findings (4)(5)(6).…”

The international consensus classification of eosinophilic disorders and systemic mastocytosis

“…In some cases, the MC proliferation may form dense clusters, showing histopathological features reminiscent of SM. 16,[18][19][20][21] Such cases often have accompanying eosinophilia and are often diagnosed as SM-AMN before the detection of the TK fusion. Some characteristic histopathological features have been observed in association with certain specific fusion genes.…”

“…Atypical MCs either spindle or round, with aberrant CD25 expression, scattered and in loose aggregates, were initially described as a feature characteristic of PDGFRA rearranged cases, but have subsequently been reported in cases with other TK gene rearrangements. In some cases, the MC proliferation may form dense clusters, showing histopathological features reminiscent of SM 16,18–21 . Such cases often have accompanying eosinophilia and are often diagnosed as SM‐AMN before the detection of the TK fusion.…”