Myeloid sarcoma can be observed as a de novo

Myeloid sarcoma can be observed as a de novo malignancy (without leukemic presentation in peripheral blood and bone marrow), during the course of acute myeloid leukemia (AML), affecting 2.5–9% of all AML patients, myelodysplastic syndromes (MDS) or myeloproliferative neoplasms (MPNs, both chronic myeloid leukemia and BCR-ABL1-negative MPNs) or MDS/MPNs such as chronic myelomonocytic leukemia (CMML); it has also been described as a relapse in a previous AML [1,4,5]. Since MS can present at multiple sites that can be often clinically silent, Positron Emission Tomography (FDG-PET) has been demonstrated as a useful tool in detecting extramedullary AML and, as previously revealed, it should be used both in diagnosis and after treatment, in order to evaluate response to therapy [6] Differential diagnosis should be made with other hematological malignancies involving lymph nodes, skin and other extra-hematological sites, such as B-cell lymphomas, cutaneous or peripheral T-cell lymphomas [3]. As far as genetic/molecular lesions are concerned, MS does not differ from AML. In fact, chromosomal aberrations are detected by Fluoresce in Situ Hybridization (FISH) and/or conventional cytogenetics in about half of cases and include: −7, +8, MLL-rearrangement, inv(16), +4, −16/16q-, 5q-, 20q- and +11. About 16% of patients carries nucleophosmin (NPM1) mutations, as shown by aberrant cytoplasmic NPM1 expression [1]. Furthermore, about 20–30% of MS, especially those evolving from AML, harbor mutations of FMS-like tyrosine kinase 3 (FLT3) gene, commonly Internal Tandem Duplications (ITD) [7].
Case report A 53-years-old man was diagnosed with pre-fibrotic PMF in 2000 in another Hospital, because of persistent, severe thrombocytosis. Conventional cytogenetic analysis showed a normal male karyotype. Consequently, he was initially treated with low-dose acetylsalicylic antimalaria medication and hydroxyurea. Ten years later, he was admitted to our Institution and molecular evaluations were done, demonstrating the absence of JAK2V617F and MPL mutations, as well as BCR-ABL1 fusion gene. After one year of follow-up, hematological investigations revealed severe anemia (hemoglobin level of 7.6g/dL). Since the negativity of further diagnostic evaluations, a new bone marrow biopsy was performed, revealing an increase in bone marrow fibrosis (MF-2, according to the EUMNET consensus) [7]. Consequently, the patient stopped assuming hydroxyurea and was started on corticosteroids and transfusional supportive therapy. Further molecular tests showed a type-2 mutation of the CALR gene (ins5-bp). At that point, MySEC score [8] was retrospectively evaluated and it resulted Intermediate − 1. In September 2016 the patient presented with asymptomatic subcutaneous nodules on the chest wall, neck and left arm, with a maximum diameter of 2cm; at ultrasound examination they were hypoechogenic irregular nodules that invaded the surrounding muscle tissue. Furthermore, a FDG-PET detected multiple metabolically active lesions in soft tissues (SUV max 4.5) on right and left shoulder, chest wall, back, epigastric region and legs (Fig. 1). Finally, a biopsy of a sub-cutaneous lesion was performed and the histopathologic examination revealed the presence of a granulocytic sarcoma. Immunohistochemistry showed that the majority of proliferating cells expressed CD34, CD43, CD117(+/-), CD45/LCA(+/-) antigens, but were negative for CD20, CD3, CD30, CD68/kp1, CD68R antigens and for myeloperoxidase. Immunohistochemical positivity of NPM1 with nuclear dislocation was also present, whereas FLT3 mutations were not found (Fig. 2). Subsequently a new bone marrow biopsy showed leukemic transformation of PMF, with a normal male karyotype. The patient underwent “3+7″ induction chemotherapy with daunorubicin and cytarabine, followed by consolidation treatment with three courses of intermediate dose Ara-C, obtaining complete morphologic and immunophenotypic remission with typical features of PMF, clinical disappearance of subcutaneous nodules, but persistence of FDG-PET pathological uptake on both arms. As the pathological uptake on the right arm was in the area of a previous venous access (Fig. 1), we decided to perform radiotherapy (RT) on the contralateral arm.