Osteolytic bone lesions in patients with primary myelofibrosis: A systematic review

Osteolytic bone lesions in patients with primary myelofibrosis: A systematic review


  • Naim Battukh Hamad Medical Corporation
  • Elrazi Ali Hamad Medical Corporation
  • Mohamed Yassin Medical Oncology, Hematology Section, National Center for Cancer Care and Research, Hamad Medical Corporation, Doha, Qatar


Chronic idiopathic myelofibrosis, myelofibrosis, primary myelofibrosis, osteolytic lesion, lytic bone lesion, MPNs


Philadelphia negative myeloproliferative neoplasms (MPNs) are classically characterized by excess production of terminal myeloid cells in the peripheral blood. They include polycythemia vera, essential thrombocythemia, and primary myelofibrosis. Among this group, primary myelofibrosis is the least common and usually carries the worst prognosis. Bone involvement in primary myelofibrosis has many forms; it affects bone marrow leading to bone marrow fibrosis, it can cause periostitis, in addition to bone and joint pain. A common radiologic finding in primary myelofibrosis is the presence of osteosclerotic lesions. However, the presence of osteolytic lesions in bone imaging was described in few reports. In this review, we searched English literature using the PRISMA guidelines looking for patients with Primary myelofibrosis who had osteolytic bone lesions to assess the impact of such findings on the disease and its effect on prognosis. We found the vast majority of lesions were painful affecting most commonly the vertebral column, pelvis, and ribs, and were detected in patients above 50 years of age with no gender preference, unfortunately they represented advanced disease stages, resulting in inadequate treatment response and poor outcome.


Heuck G. Zwei Fälle von Leukämie mit eigenthümlichem Blut- resp. Knochenmarksbefund. Arch für Pathol Anat und Physiol und für Klin Med [Internet]. 1879;78:475–96. Available from: https://doi.org/10.1007/BF01878089.

Dameshek W. Some speculations on the myeloproliferative syndromes. Blood 1951;6:372-5.

Jackson Jr H, Parker Jr F, Lemon HM. Agnogenic myeloid metaplasia of the spleen: a syndrome simulating other more definite hematologic disorders. N Engl J Med 1940; 222:985-94.

Tefferi A, Thiele J, Vardiman JW. The 2008 World Health Organization classification system for myeloproliferative neoplasms: order out of chaos. Cancer 2009;115:3842-7.

Arber DA, Orazi A, Hasserjian R, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood 2016;127:2391-405.

Tefferi A. Primary myelofibrosis: 2021 update on diagnosis, risk-stratification and management. Am J Hematol 2021;96:145-62.

Barbui T, Thiele J, Gisslinger H, Carobbio A, Vannucchi AM, Tefferi A. Diagnostic impact of the 2016 revised who criteria for polycythemia vera. Am J Hematol 2017;92:417-9.

Mesa RA, Silverstein MN, Jacobsen SJ, Wollan PC, Tefferi A. Population-based incidence and survival figures in essential thrombocythemia and agnogenic myeloid metaplasia: an Olmsted County Study, 1976-1995. Am J Hematol 1999;61:10-5.

Barbui T, Thiele J, Gisslinger H, et al. The 2016 WHO classification and diagnostic criteria for myeloproliferative neoplasms: document summary and in-depth discussion. Blood Cancer J 20188(2):15.

Barosi G, Mesa RA, Thiele J, et al ; International Working Group for Myelofibrosis Research and Treatment (IWG-MRT). Proposed criteria for the diagnosis of post-polycythemia vera and post-essential thrombocythemia myelofibrosis: a consensus statement from the International Working Group for Myelofibrosis Research and Treatment. Leukemia 2008;22:437-8.

Smith RE, Chelmowski MK, Szabo EJ. Myelofibrosis: a review of clinical and pathologic features and treatment. Crit Rev Oncol Hematol 1990;10:305-14.

Tefferi A. Myelofibrosis with myeloid metaplasia. N Engl J Med 2000;342:1255-65.

O'Reilly RA. Splenomegaly in 2,505 patients in a large university medical center from 1913 to 1995. 1913 to 1962: 2,056 patients. West J Med 1998;169:78-87.

Wanless IR, Peterson P, Das A, Boitnott JK, Moore GW, Bernier V. Hepatic vascular disease and portal hypertension in polycythemia vera and agnogenic myeloid metaplasia: a clinicopathological study of 145 patients examined at autopsy. Hepatology 1990;12:1166-74.

Lundh B, Brandt L, Cronqvist S, Eyrich R. Intracranial myeloid metaplasia in myelofibrosis. Scand J Haematol 1982;28:91-4.

Koch BL, Bisset GS 3rd, Bisset RR, Zimmer MB. Intracranial extramedullary hematopoiesis: MR findings with pathologic correlation. AJR Am J Roentgenol 1994;162:1419-20.

Bartlett RP, Greipp PR, Tefferi A, Cupps RE, Mullan BP, Trastek VF. Extramedullary hematopoiesis manifesting as a symptomatic pleural effusion. Mayo Clin Proc 1995;70:1161-4.

Knobel B, Melamud E, Virag I, Meytes D. Ectopic medullary hematopoiesis as a cause of ascites in agnogenic myeloid metaplasia. Case report and review of the literature. Acta Haematol 1993;89:104-7.

Loewy G, Mathew A, Distenfeld A. Skin manifestation of agnogenic myeloid metaplasia. Am J Hematol 1994;45:167-70.

Oon SF, Singh D, Tan TH, et al. Primary myelofibrosis: spectrum of imaging features and disease-related complications. Insights Imaging. 2019;10 :1-4.

Tefferi A, Guglielmelli P, Nicolosi M, et al. GIPSS: genetically inspired prognostic scoring system for primary myelofibrosis. Leukemia 2018;32:1631-42.

Tefferi A, Guglielmelli P, Lasho TL, et al. MIPSS70+ Version 2.0: Mutation and Karyotype-Enhanced International Prognostic Scoring System for Primary Myelofibrosis. J Clin Oncol 2018 ;36:1769-70.

Ballen KK, Shrestha S, Sobocinski KA, et al. Outcome of transplantation for myelofibrosis. Biol Blood Marrow Transplant 2010;16:358-67.

Gangat N, Tefferi A. Myelofibrosis biology and contemporary management. Br J Haematol 2020;191:152-70.

Reeder TL, Bailey RJ, Dewald GW, Tefferi A. Both B and T lymphocytes may be clonally involved in myelofibrosis with myeloid metaplasia. Blood 2003;101:1981-3.

Tefferi A, Vaidya R, Caramazza D, Finke C, Lasho T, Pardanani A. Circulating interleukin (IL)-8, IL-2R, IL-12, and IL-15 levels are independently prognostic in primary myelofibrosis: a comprehensive cytokine profiling study. J Clin Oncol 2011;29:1356-63.

Reilly JT, Snowden JA, Spearing RL, et al. Cytogenetic abnormalities and their prognostic significance in idiopathic myelofibrosis: a study of 106 cases. Br J Haematol 1997;98:96-102.

Tefferi A, Mesa RA, Schroeder G, Hanson CA, Li CY, Dewald GW. Cytogenetic findings and their clinical relevance in myelofibrosis with myeloid metaplasia. Br J Haematol 2001;113:763-71.

Pikman Y, Lee BH, Mercher T, et al . MPLW515L is a novel somatic activating mutation in myelofibrosis with myeloid metaplasia. PLoS Med 2006; 3(7):e270.

Nangalia J, Massie CE, Baxter EJ, et al . Somatic CALR mutations in myeloproliferative neoplasms with nonmutated JAK2. N Engl J Med 2013;369:2391-2405.

Klampfl T, Gisslinger H, Harutyunyan AS, et al. Somatic mutations of calreticulin in myeloproliferative neoplasms. N Engl J Med 2013;369:2379-90.

Pardanani AD, Levine RL, Lasho T, et al. MPL515 mutations in myeloproliferative and other myeloid disorders: a study of 1182 patients. Blood 2006;108:3472-6.

Yamamoto K, Miwa Y, Abe-Suzuki S, et al. Extramedullary hematopoiesis: Elucidating the function of the hematopoietic stem cell niche (Review). Mol Med Rep 2016;13:587-91.

Koch CA, Li CY, Mesa RA, Tefferi A. Nonhepatosplenic extramedullary hematopoiesis: associated diseases, pathology, clinical course, and treatment. Mayo Clin Proc 2003;78:1223-33..

Guermazi A, de Kerviler E, Cazals-Hatem D, Zagdanski AM, Frija J. Imaging findings in patients with myelofibrosis. Eur Radiol 1999;9:1366-75.

Pettigrew JD, Ward HP. Correlation of radiologic, histologic, and clinical findings in agnogenic myeloid metaplasia. Radiology 1969;93:541-8.

Raia TJ Jr, Hentz EC, Theros EG. An exercise in radiologic-pathologic correlation. Radiology 1967;89:941-6.

Kosmidis PA, Palacas CG, Axelrod AR. Diffuse purely osteolytic lesions in myelofibrosis. Cancer 1980;46:2263-5.

Jurisic V, Terzic T, Pavlovic S, Colovic N, Colovic M. Elevated TNF-alpha and LDH without parathormone disturbance is associated with diffuse osteolytic lesions in leukemic transformation of myelofibrosis. Pathol Res Pract 2008;204:129-32.

Varki A, Lottenberg R, Griffith R, Reinhard E. The syndrome of idiopathic myelofibrosis. A clinicopathologic review with emphasis on the prognostic variables predicting survival. Medicine (Baltimore) 1983;62:353-71.

Visani G, Finelli C, Castelli U, et al. Myelofibrosis with myeloid metaplasia: clinical and haematological parameters predicting survival in a series of 133 patients. Br J Haematol 1990;75:4-9.

Maryanovich M, Takeishi S, Frenette PS. Neural Regulation of Bone and Bone Marrow. Cold Spring Harb Perspect Med 2018;8(9):a031344.

Clutterbuck DJ, Morrison AE, Ludlam CA. Osteolytic bone lesions in a patient with idiopathic myelofibrosis and bronchial carcinoma. J Clin Pathol 1995;48:867-8.

Kaufman SD, Putchar WGJ. Case 39-1974. N Engl J Med 2010;291:721–30.

Levy DE, Darnell JE Jr. Stats: transcriptional control and biological impact. Nat Rev Mol Cell Biol 2002;3:651-62.

Thiele J, Kvasnicka HM. The 2008 WHO diagnostic criteria for polycythemia vera, essential thrombocythemia, and primary myelofibrosis. Curr Hematol Malig Rep 2009;4:33-40.

Burnham RR Jr, Johnson B, Lomasney LM, Borys D, Cooper AR. Multi-focal Lytic Lesions in a Patient with Myelofibrosis: A Case Report. Cureus 2020;12(3):e7475.

Adel A, Abushanab D, Hamad A, Abdulla M, Izham M, Yassin M. Assessment of Dasatinib Versus Nilotinib as Upfront Therapy for Chronic Phase of Chronic Myeloid Leukemia in Qatar: A Cost-Effectiveness Analysis. Cancer Control 2021;28:10732748211001796.

Iqbal P, Soliman A, De Sanctis V, Yassin MA. Association of tuberculosis in patients with chronic myeloid leukemia: a treatment proposal based on literature review. Expert Rev Hematol 2021;14:211-7.

Atteya A, Ahmad A, Daghstani D, Mushtaq K, Yassin MA. Evaluation of Hepatitis B Reactivation Among Patients With Chronic Myeloid Leukemia Treated With Tyrosine Kinase Inhibitors. Cancer Control 2020;27(1):1073274820976594.

Yassin MA, Ata F, Mohamed SF, et al . Ophthalmologic manifestations as the initial presentation of chronic myeloid leukemia: A Review. Surv Ophthalmol 2021:S0039-6257(21)00144-2.

Yassin MA, Ghasoub RS, Aldapt MB, et al. Effects of Intermittent Fasting on Response to Tyrosine Kinase Inhibitors (TKIs) in Patients With Chronic Myeloid Leukemia: An Outcome of European LeukemiaNet Project. Cancer Control 2021;28:10732748211009256.

Hamamyh T, Yassin MA. Autoimmune hemolytic anemia in chronic myeloid leukemia. Pharmacology 2020;105:630-8.

Ali E, Soliman A, De Sanctis V, Nussbaumer D, Yassin M. Priapism in Patients with Chronic Myeloid Leukemia (CML): A Systematic Review. Acta Biomed 2021;92(3):e2021193 .

Ali EA, Nashwan AJ, Yassin MA. Essential thrombocythemia with (type2) calreticulin presented as stuttering priapism case report and review of literature. Clinical Case Reports 2021 ;9:399-404.

Yassin MA, Soliman AT, De Sanctis V. Effects of tyrosine kinase inhibitors on spermatogenesis and pituitary gonadal axis in males with chronic myeloid leukemia. J Cancer Res Ther 2014;2:116-21.

Abdulla AJ, Chandra P, El Akiki S, et al. Clinicopathological Variables and Outcome in Chronic Myeloid Leukemia Associated With BCR-ABL1 Transcript Type and Body Weight: An Outcome of European Leukemia Net Project, Cancer Control. Pre-print 2020. 2020080199.

Yassin MA, Kassem N, Ghassoub R. How I treat obesity and obesity related surgery in patients with chronic myeloid leukemia: An outcome of an ELN project. Clin Case Rep 2021; 9:1228-34.







How to Cite

Battukh N, Ali E, Yassin M. Osteolytic bone lesions in patients with primary myelofibrosis: A systematic review. Acta Biomed [Internet]. 2022 Jan. 19 [cited 2024 Jul. 13];92(6):e2021478. Available from: https://mattioli1885journals.com/index.php/actabiomedica/article/view/12350