An unusual type of myeloid sarcoma localization following myelofibrosis

Myeloid sarcoma (MS) is defined as “a tumor mass consisting of myeloid blasts with or without maturation occurring at an anatomic site other than the bone marrow”. It can present as a de novo malignancy (without leukemic presentation) during the course of AML, MDS or MPN, but also as a relapse of a previous AML. MS most commonly involve the lymph nodes, skin, soft tissues and testis, with a multifocal presentation in less than 10% of cases. Here we report an unusual case of MS presenting with multiple skin, subcutaneous and muscular lesions in a patient affected by myelofibrosis (MF) which was diagnosed about 16 years before. A 53-years-old man was diagnosed with pre-fibrotic MF in 2000. Subsequent molecular evaluations demonstrated the absence of JAK2V617F mutation. Eleven years later, because of appearance of severe anemia a bone marrow biopsy was performed and showed an increase in bone marrow fibrosis (MF-2). Further molecular tests showed mutation of CALR gene (ins5-bp). In September 2016 the patient presented with asymptomatic subcutaneous nodules on the chest wall, neck and left arm (2cm). A FDG-PET detected multiple metabolically active lesions on soft tissues (SUVmax 4.5) on right and left shoulder, chest wall, back, epigastric region, and legs. A subcutaneous excisional biopsy revealed the presence of a granulocytic sarcoma (the majority of proliferating cells expressed CD34, CD43, CD117(+/), CD45/LCA(+/-) antigens, while were negative for CD20, CD3, CD30, CD68/kp1, CD68R antigens and for MPO). Immunohistochemical positivity of NPM1 with nuclear dislocation was also present, whereas FLT-3 mutations were not found. Subsequent bone marrow biopsy showed leukemic transformation of MF, with a normal male karyotype. The patient underwent “3+7” induction chemotherapy, followed by consolidation with 3 courses of intermediate dose Ara-C, obtaining complete bone marrow remission, clinical disappearance of subcutaneous nodules, but persistence of FDG-PET pathological uptake on both arms. In conclusion MS and in particular MS following MF is a rare entity. Indeed, in the two largest patients series reported so far, only few patients had a diagnosis of MS concurrent or after MF. Furthermore, muscles involvement is reported as anecdotal. Since its pathogenesis and genomic landscape are not well established, the prognosis remain dismal, even in the novel agent era. Therefore, each case description is fundamental to enhance our knowledge about this disease.