MR Imaging in non-hepatosplenic extramedullary hematopoiesis in primary myelofibrosis.

Abstract

A 49-year-old man, diagnosed 2 years earlier with primary myelofibrosis (PMF), presented with a complaint of progressive dysesthesias involving the left leg and foot. When PMF was diagnosed, grade 3 fibrosis at bone marrow examination, an atypical CALR mutation, wild type JAK2 and MPL genes, male karyotype with translocation t(8;12), and 1% blasts in peripheral blood were present; additional findings included splenomegaly of 17 cm at longitudinal diameter and night sweats, consistent with intermediate-2 IPSS score 1, low molecular risk for absence of mutations in ASXL1, EZH2, IDH1/2, and SRSF2 genes 2. Immediately after the diagnosis, he was enrolled in a phase I/II trial of association ruxolitinib-sonidegib. During treatment, dysesthesias worsened. Electromyography showed peripheral symmetric sensory and motor neuropathy. Spin cerebellar ataxia, autoimmune disorders, and atypical infections were excluded. Magnetic resonance imaging (MRI) of brain was negative, but spine MRI showed a bulky mass surrounding vertebral bodies from D4 to S4; this tissue was thicker in the middle dorsal segment, with early neural foramen involvement (L4-L5; L5-S1), without bone erosion. The lesion was smooth, well defined and it displayed cleavage planes with the great vessels (Image A–E arrows). A CT-guided biopsy of the paravertebral mass was performed and extramedullary hematopoiesis (EMH) was diagnosed. The correlation between molecular and calreticulin immune-histochemical assays was confirmed (Image F–H) 3. No changes was detected at bone marrow re-examination and the class of risk was DIPSS intermediate-1 for peripheral blasts >1% 4 and DIPSS plus intermediate-2 for platelet count <100 × 109/L, respectively. The t(8;12) was still present but not included in unfavorable karyotypes 5. The patient was treated with radiotherapy (30 Gray) on the lumbar localization. No improvement was reported; later, bone marrow transplantation procedure was performed, but patient died due to acute graft versus host disease. EMH, generally found in liver, spleen and lymph nodes 6, occurs as a compensatory response by hyperplastic hematopoietic tissue in chronic hemolytic conditions or bone marrow infiltration by neoplastic/fibrotic tissue. Intrathoracic EMH is frequently seen in thalassemia, while it is less common in PMF 6, 7. Only a few cases of non-hepatosplenic EMH have been described in PMF, and none of those with a complete imaging report 8, 9. Paraspinal masses are usually detectable but not easily characterized by imaging. Our report emphasizes the importance of EMH in the differential diagnosis of paraspinal masses—comprising abscesses, hematomas, lymphomas, metastases, neurogenic tumors—despite the rarity of the condition and nonspecific radiological features. (A) Spine MRI on sagittal fat-sat T2-weighted scan shows a paraspinal soft tissue swelling (white arrows), strongly hyperintense to muscle and bone marrow. (B, C) Axial MRI scans confirm the paravertebral lesion (white arrows) isointense to muscle and slightly hyperintense to bone marrow on T1-weighted images (B), slightly hyperintense to muscle and bone marrow on T2-weighted images (C). (D) After Gadolinium chelate contrast agent administration, a uniform and clear enhancement was detectable (white arrows). (E) Heavily diffusion-weighted axial scan show mild signal intensity (white arrows). (F–H) Histological examination of the paravertebral mass shows EMH with scattered multinucleated cells and atypical megakaryocytes, gathered in clusters, admixed with adypocytes in the context of a fibrous stroma (F, H&E, original magnification ×40). Immunoreactivity for factor VIII antigen identifies large elements as megakaryocytes with atypical morphology (G, original magnification ×40). Calreticulin antibody stains atypical megakaryocytes (H). (I–L) Outline of paraspinal EMH (black thick arrows) derived from our case (I) and typical localization derived from Orphanidou-Vlachou et al. 9 (L).