Imaging features of myeloproliferative neoplasms.

Transcription

1 Imaging features of myeloproliferative neoplasms. Poster No.: C-0410 Congress: ECR 2016 Type: Educational Exhibit Authors: I. Murphy, E. Mitchell, A. Godfrey, E. M. Godfrey ; Cambridge, Cambridgeshire/UK, Cambridge/UK Keywords: Embolism / Thrombosis, Education, MR, Digital radiography, CT, Vascular, Oncology, Haematologic, Pathology DOI: /ecr2016/C-0410 Any information contained in this pdf file is automatically generated from digital material submitted to EPOS by third parties in the form of scientific presentations. References to any names, marks, products, or services of third parties or hypertext links to thirdparty sites or information are provided solely as a convenience to you and do not in any way constitute or imply ECR's endorsement, sponsorship or recommendation of the third party, information, product or service. ECR is not responsible for the content of these pages and does not make any representations regarding the content or accuracy of material in this file. As per copyright regulations, any unauthorised use of the material or parts thereof as well as commercial reproduction or multiple distribution by any traditional or electronically based reproduction/publication method ist strictly prohibited. You agree to defend, indemnify, and hold ECR harmless from and against any and all claims, damages, costs, and expenses, including attorneys' fees, arising from or related to your use of these pages. Please note: Links to movies, ppt slideshows and any other multimedia files are not available in the pdf version of presentations. Page 1 of 17

2 Learning objectives Myeloproliferative neoplasms (MPN) can have many different imaging manifestations. Unusual thromboses, embolic events, or osseous findings can often be clues to the underlying disease. Our aim is to discuss the different categories of MPN and illustrate the variety of radiological findings associated with these diseases. Knowledge of these conditions may enable the radiologist to suggest an MPN as a possible underlying cause for certain imaging findings, particularly splanchnic venous thrombosis. Page 2 of 17

3 Background Myeloproliferative neoplasms are a diverse group of haematological malignancies including polycythaemia vera (PV), essential thrombocythaemia (ET), primary myelofibrosis (PMF) and chronic myeloid leukaemia (CML). In the last decade identification of specific genetic aberrations, including JAK2 and CALR mutations, has allowed more reliable diagnosis and classification of MPNs (fig 1). Page 3 of 17

4 Images for this section: Fig. 1: Overview of MPN in clinical practice. Page 4 of 17

5 Findings and procedure details Imaging: Thrombosis: ET and PV both predispose to thrombotic events, which can present in an unusual fashion (fig 2). In the brain, arterial thrombi can occur as well as dural sinus thrombosis. The splanchnic circulation can be affected by arterial thrombi as well as portal vein thrombosis or Budd-Chiari syndrome (1). Cavernous transformation of the portal vein is often seen in chronic porto-mesenteric thrombosis (2). Systemic thrombosis can lead to pulmonary emboli; and the risk of cardiovascular thrombotic events is highest in ET (3). Counterintuitively, haemorrhage can also be seen (4), most often in those with very high 3 platelet counts (>1000 x 10 /ml) (5). Osseous findings: Findings are typically as a result of marrow infiltration but cortical bony changes may also be observed (fig 3). In the marrow, we see diffuse infiltration. The normal high T1 signal of bone marrow is typically completely replaced by abnormally low T1 signal. This is more difficult to detect on T2 weighted imaging. On plain radiographs, osteosclerosis is often seen in primary myelofibrosis (6). With diffuse marrow infiltration, bone scintigraphy can result in a "superscan" appearance, with diffusely increased skeletal uptake relative to the kidneys (fig 4). Solid lesions: The most typically encountered solid lesion is extramedullary haematopoeisis. Ineffective red cell production or inadequate bone marrow function can precipitate extra-marrow creation of new blood elements, most commonly in the spleen and liver but occasionally in the paravertebral regions (figs 5, 6 and 7). (7). Transformation of all of the MPNs to acute myeloid leukaemia (AML) may occur, with a poor prognosis (8). This does not usually have imaging features per se, but rarely these patients may develop a focal extramedullary neoplastic mass known as a granulocytic sarcoma, or chloroma (due to their typical green macroscopic colour (fig 8). Other: Page 5 of 17

6 Iron deposition can be a feature of the repeated transfusions required due to marrow failure in PMF. The iron overload is therefore secondary, and is seen in the reticuloendothelial cells of the marrow, spleen and Kupffer cells of the liver (fig 9). On MRI, this manifests itself as low signal intensity on T2, especially T2*, as signal drop-out on inphase imaging, and on CT, as hyperattenuation of the liver on unenhanced imaging (9). Management: The management of MPNs has been revolutionized with the introduction of targeted pharmacologic inhibitors. Those in common clinical use include imatinib to target the BCR-ABL tyrosine kinase, or inhibitors of the JAK/STAT pathway, of which the most widely studied is ruxolitinib in PMF (10, 11). Management of PV and ET remains predominantly centred on prevention of vascular events through the use of antiplatelet agents, addressing cardiovascular risk factors and measures to bring blood counts into an acceptable range (venesection or cytoreductive treatment, most often hydroxycarbamide). Page 6 of 17

7 Images for this section: Fig. 1: Overview of MPN in clinical practice. Page 7 of 17

8 Fig. 2: 1(a). Axial contrast enhanced CT showing shrunken, nodular liver, ascites and absent hepatic veins; the patient had chronic liver disease following Budd-Chiari syndrome in Jak2-positive MPN. 1(b). Axial FLAIR in 50 year old man showing bilateral cerebellar infarcts from vertebrobasilar thrombosis. 1(c). Unenhanced axial CT. Splenic infarct, with rim calcification. Small pleural effusions due to pulmonary infarcts. 1(d). Splenomegaly and cavernous sinus thrombosis with porto-mesenteric thrombosis in ET. Page 8 of 17

9 Fig. 3: 67 year old man with primary myelofibrosis. Diffuse osteosclerosis in the pelvis and lumbar spine. Page 9 of 17

10 Fig. 4: Figure 3. Diffuse osseous lesions. 3(a). Sagittal T1 MRI in a 68 yr old man with CML. Diffuse low signal marrow is noted. 3(b). Bone scintigraphy, showing diffuse sclerosis - the absent of the renal outline is consistent with a "superscan". Page 10 of 17

11 Fig. 5: 52 year old woman, PV transformed to MF, presented with cord compression due to extramedullary haematopoiesis. Sagittal images, showing diffuse low T1 signal throughout the lumbosacral spine Page 11 of 17

12 Fig. 6: Sagittal T2 weighted MRI, showing extramedullary haematopoeisis extending through the left L1-L2 neural exit foramen Page 12 of 17

13 Fig. 7: Axial T2 weighted images showing the cord compression and extramedullary sacral mass Page 13 of 17

14 Fig. 8: Gross examination and histopathology. (A) Gross appearance: Cut surface of the solid, green and well-demarcated tumor. (B) The cells are of small size with scanty cytoplasm, hyperchromatic nuclei and small nucleoli (hematoxylin and eosin stain; magnification, 200). Huang XE, Li YJ, Zhou XD. Oncol Lett. 2015;10(4): Page 14 of 17

15 Fig. 9: 60 year old man with myelofibrosis, requiring repeated blood transfusions. T2 FSE imaging showing marked low signal intensity in the liver, in keeping with iron deposition. Page 15 of 17

16 Conclusion Recognition of the various associated radiological findings, and the possibility of an underlying MPN in the setting of unusual thrombotic events, can lead to timely diagnosis. The use of both established therapies such as aspirin and hydroxycarbamide, and novel therapies such as JAK2 inhibitors can significantly improve prognosis and quality of life. Page 16 of 17

17 References 1. Long-term outcome of liver transplant patients with Budd-Chiari syndrome secondary to myeloproliferative neoplasms. Potthoff A et al. Liver Int. 2015; 35(8): Mesenteric venous thrombosis. Singal A et al, Mayo Clin Proc. 2013;88(3): JAK2 mutations and coronary ischemia. Lata K et al. N Engl J Med 2010 Jul 22;363(4): An unusual cause of cerebellar hemorrhage in a young patient: essential thrombocythemia. Adam R et al, J Stroke Cerebrovasc Dis (5):e Thrombosis and haemorrhage in polycythaemia vera and essential thrombocythaemia. Elliot MA, Tefferi A. Br J Haematol. 2005;128(3): Sclerosing bone dysplasias: review and differentiation from other causes of osteosclerosis. Ihde LL et al. Radiographics 2011;31(7): Extramedullary hemopoiesis. Orphanidou-Vlachou E. Semin Ultrasound CT MR 2014;35(3): Pathogenesis and management of acute myeloid leukemia that has evolved from a myeloproliferative neoplasm. Rampal R, Mascarenhas J. Curr Opin Hematol. 2014;21(2): MR imaging findings of iron overload. Quieroz-Andrade M et al. Radiographics Oct;29(6): Myeloproliferative Neoplasms: A Decade of Discoveries and Treatment Advances. Tefferi A. Am J Haematol 2015 Oct Myeloproliferative Neoplasms: A Contemporary Review. JAMA Oncol Apr;1(1): Page 17 of 17