Acute Promyelocytic Leukemia with FLT3/ITD and RUNX1 Mutation Presenting As Extramedullary Soft Tissue Mass

Background: APL formerly known as AML M3 is a variant of myeloid malignancies characterized by recurrent cytogenetic abnormality of PML/RARA translocation, t(15;17). Myeloid sarcoma, also called granulocytic sarcoma or chloroma, is a very rare presentation of extramedullary APL. In rare cases seen, it presents mainly as CNS disease in relapsed or refractory patients. Extramedullary APL on initial presentation is even rarer. As a result no significant information exists on the prognosis of such patients.

Case report: A 50-year-old Caucasian female with no past medical history, presented with 6-month duration of chest pain, which was treated as costochondritis without any improvement. Three months later, a soft tissue mass was identified on her sternum. Complete blood count revealed pancytopenia with white blood cell 3.24 x 10³/uL, hemoglobin 10.0 g/dL, platelets 58x 10³/uL, absolute neutrophil count 1.13 x10³/uL, and monocytes 0.13 x10³/uL which indicated "low risk disease". A PET/CT scan revealed a 4.6 cm x 4 cm sternal soft tissue mass. The biopsy of the mass confirmed myeloid sarcoma. Bone marrow biopsy showed acute promyelocytic leukemia, approximately 20% blasts in a hypercellular marrow with 70-80% cellularity. Cytogenesis test was negative. FISH analysis subsequently showed a partial RARA transcript inserted at the PML locus suggestive of a cryptic PML/RARA. This was confirmed by PCR for the fusion transcript PML/RARA from the bone marrow. Next generation genome sequencing identified FLT3/ITD and RUNX1 mutation. The patient was treated as a high risk disease due to the presence of chloroma and immediately started on treatment with Daunorubicin, Arsenic Trioxide (ATO), and All-Trans-Retinoic Acid (ATRA).

Conclusion: We present an extremely rare case of APL initially presenting with concomitant extramedullary sternal soft tissue mass with cryptic t(15;17) and somatic mutations in FLT/ITD as well as RUNX1 mutations. To our knowledge this is the first reported case of extramedullary APL with FLT/ITD and RUNX1 mutations. Early recognition of this rare presentation with timely chemotherapy may improve the outcomes of these patients.