Magnetic resonance imaging reveals distinct bone marrow patterns in indolent and advanced systemic mastocytosis

  • Philipp Riffel
  • Mohamad JawharEmail author
  • Kristina Gawlik
  • Juliana Schwaab
  • Henrik J. Michaely
  • Georgia Metzgeroth
  • Wolf-Karsten Hofmann
  • Stefan O. Schoenberg
  • Andreas Reiter
Original Article


Systemic mastocytosis (SM) is broadly subcategorized according to mast cell (MC) burden and organ involvement into indolent (ISM), smoldering (SSM), and advanced SM (AdvSM). However, the pattern and extent of bone involvement remains controversial. In this institutional review board (IRB)-approved study, 115 patients with different forms of SM (ISM (n = 37, 32%), SSM (n = 9, 8%), and AdvSM (n = 69, 60%)) underwent a whole-body magnetic resonance imaging including sagittal and coronal T1 and turbo inversion recovery magnitude (TIRM) sequences of the spine. The evaluation included the pattern and extent of pathologic bone marrow (BM) signals in the spine and extremities, osteolytic lesions, and vertebral fractures. A pathologic BM pattern was observed in 4/37 (11%), 8/9 (89%), and 66/69 (96%); affection of the appendicular skeleton in 3/37 (8%), 8/9 (89%), and 67/69 (97%); and vertebral fractures in 7/37 (19%), 0/9, and 13/69 (19%) patients with ISM, SSM, and AdvSM, respectively. In AdvSM, pathologic BM pattern included activated (62%), diffuse sclerotic (25%), and small-spotted BM (9%), respectively. Only activated/sclerotic BM was associated with significantly higher MC burden, organ damage, and inferior median survival (2.9 years, p = 0.04). Vertebral fractures resembled classical multi-segmental osteoporotic fractures in ISM but not in AdvSM in which they were only found in activated/sclerotic BM. Only one patient with AdvSM had a focal osteolytic lesion in the femur. Activated/sclerotic BM changes of the spine and affection of the appendicular skeleton are indicative for SSM or AdvSM. Osteolytic lesions, which are very rare, and osteoporotic fractures are ineligible for the diagnosis of AdvSM.


Systemic mastocytosis Magnetic resonance imaging Bone marrow Osteolytic lesions Osteoporosis 



Karl Sotlar and Hans-Peter Horny are acknowledged for histological diagnosis.

Funding information

This study was funded by the “Deutsche José Carreras Leukämie-Stiftung” (DJCLS 01 R/2018) and the SEED program of the Mannheim Medical Faculty, Heidelberg University, Heidelberg, Germany.

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Supplementary material

277_2019_3826_MOESM1_ESM.docx (114 kb)
ESM 1 (DOCX 114 kb)


  1. 1.
    Metcalfe DD (2008) Mast cells and mastocytosis. Blood 112:946–956CrossRefGoogle Scholar
  2. 2.
    Valent P, Akin C, Sperr WR, Horny HP, Arock M, Lechner K, Bennett JM, Metcalfe DD (2003) Diagnosis and treatment of systemic mastocytosis: state of the art. Br J Haematol 122:695–717CrossRefGoogle Scholar
  3. 3.
    Horny HP, Parwaresch MR, Lennert K (1985) Bone marrow findings in systemic mastocytosis. Hum Pathol 16:808–814CrossRefGoogle Scholar
  4. 4.
    Arber DA, Orazi A, Hasserjian R et al (2016) The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood 127:2391–2405CrossRefGoogle Scholar
  5. 5.
    Valent P, Akin C, Metcalfe DD (2017) Mastocytosis: 2016 updated WHO classification and novel emerging treatment concepts. Blood 129:1420–1427CrossRefGoogle Scholar
  6. 6.
    Tefferi A, Shah S, Reichard KK, Hanson CA, Pardanani A (2018) Smouldering mastocytosis: survival comparisons with indolent and aggressive mastocytosis. Am J Hematol. CrossRefGoogle Scholar
  7. 7.
    Pardanani A (2016) Systemic mastocytosis in adults: 2017 update on diagnosis, risk stratification and management. Am J Hematol 91:1146–1159CrossRefGoogle Scholar
  8. 8.
    Jawhar M, Schwaab J, Meggendorfer M, Naumann N, Horny HP, Sotlar K, Haferlach T, Schmitt K, Fabarius A, Valent P, Hofmann WK, Cross NCP, Metzgeroth G, Reiter A (2017) The clinical and molecular diversity of mast cell leukemia with or without associated hematologic neoplasm. Haematologica 102:1035–1043CrossRefGoogle Scholar
  9. 9.
    Jawhar M, Schwaab J, Naumann N, Horny HP, Sotlar K, Haferlach T, Metzgeroth G, Fabarius A, Valent P, Hofmann WK, Cross NCP, Meggendorfer M, Reiter A (2017) Response and progression on midostaurin in advanced systemic mastocytosis: KIT D816V and other molecular markers. Blood 130:137–145CrossRefGoogle Scholar
  10. 10.
    Jawhar M, Schwaab J, Schnittger S, Meggendorfer M, Pfirrmann M, Sotlar K, Horny HP, Metzgeroth G, Kluger S, Naumann N, Haferlach C, Haferlach T, Valent P, Hofmann WK, Fabarius A, Cross NC, Reiter A (2016) Additional mutations in SRSF2, ASXL1 and/or RUNX1 identify a high-risk group of patients with KIT D816V(+) advanced systemic mastocytosis. Leukemia 30:136–143CrossRefGoogle Scholar
  11. 11.
    Jawhar M, Schwaab J, Hausmann D, Clemens J, Naumann N, Henzler T, Horny HP, Sotlar K, Schoenberg SO, Cross NC, Fabarius A, Hofmann WK, Valent P, Metzgeroth G, Reiter A (2016) Splenomegaly, elevated alkaline phosphatase and mutations in the SRSF2/ASXL1/RUNX1 gene panel are strong adverse prognostic markers in patients with systemic mastocytosis. Leukemia 30:2342–2350CrossRefGoogle Scholar
  12. 12.
    Schwaab J, Schnittger S, Sotlar K, Walz C, Fabarius A, Pfirrmann M, Kohlmann A, Grossmann V, Meggendorfer M, Horny HP, Valent P, Jawhar M, Teichmann M, Metzgeroth G, Erben P, Ernst T, Hochhaus A, Haferlach T, Hofmann WK, Cross NC, Reiter A (2013) Comprehensive mutational profiling in advanced systemic mastocytosis. Blood 122:2460–2466CrossRefGoogle Scholar
  13. 13.
    Metzgeroth G, Dinter D, Erben P, La Rosee P, Hehlmann R, Hastka J (2007) Systemic mastocytosis simulating osseous metastatic disease. Br J Haematol 136:1CrossRefGoogle Scholar
  14. 14.
    Deb A, Tefferi A (2003) Images in clinical medicine. Systemic mastocytosis N Engl J Med 349:e7CrossRefGoogle Scholar
  15. 15.
    Myers B, Grimley C, Jones SG, Clark D, Kerslake R (2003) Skin, bone marrow and magnetic resonance imaging appearances in systemic mastocytosis. Br J Haematol 122:876CrossRefGoogle Scholar
  16. 16.
    Epelboym Y, Keraliya AR, Tirumani SH, Hornick JL, Ramaiya NH, Shinagare AB (2017) Differences in the imaging features and distribution of non-indolent and indolent mastocytosis: a single institution experience of 29 patients. Clin Imaging 44:111–116CrossRefGoogle Scholar
  17. 17.
    Huang TY, Yam LT, Li CY (1987) Radiological features of systemic mast-cell disease. Br J Radiol 60:765–770CrossRefGoogle Scholar
  18. 18.
    Avila NA, Ling A, Metcalfe DD, Worobec AS (1998) Mastocytosis: magnetic resonance imaging patterns of marrow disease. Skelet Radiol 27:119–126CrossRefGoogle Scholar
  19. 19.
    Roca M, Mota J, Giraldo P, Garcia Erce JA (1999) Systemic mastocytosis: MRI of bone marrow involvement. Eur Radiol 9:1094–1097CrossRefGoogle Scholar
  20. 20.
    Siegel S, Sadler MA, Yook C, Chang V, Miller J (1999) Systemic mastocytosis with involvement of the pelvis: a radiographic and clinicopathologic study--a case report. Clin Imaging 23:245–248CrossRefGoogle Scholar
  21. 21.
    Di Leo C, Lodi A, Pozzato C et al (2003) Systemic mastocytosis: bone marrow involvement assessed by Tc-99m MDP scintigraphy and magnetic resonance imaging. Haematologica 88:Ecr26Google Scholar
  22. 22.
    Sperr WR, Valent P (2012) Diagnosis, progression patterns and prognostication in mastocytosis. Expert Rev Hematol 5:261–274CrossRefGoogle Scholar
  23. 23.
    Travis WD, Li CY, Bergstralh EJ, Yam LT, Swee RG (1988) Systemic mast cell disease. Analysis of 58 cases and literature review. Medicine (Baltimore) 67:345–368CrossRefGoogle Scholar
  24. 24.
    Armingaud P, Zerkak D, Lespessailles E et al (2002) Bone evaluation in ten adults with cutaneous mastocytosis. Ann Dermatol Venereol 129:170–172PubMedGoogle Scholar
  25. 25.
    Grieser T, Minne HW (1997) Systemic mastocytosis and skeletal lesions. Lancet 350:1103–1104CrossRefGoogle Scholar
  26. 26.
    Brumsen C, Hamdy NA, Papapoulos SE (2002) Osteoporosis and bone marrow mastocytosis: dissociation of skeletal responses and mast cell activity during long-term bisphosphonate therapy. J Bone Miner Res 17:567–569CrossRefGoogle Scholar
  27. 27.
    Lim AY, Ostor AJ, Love S, Crisp AJ (2005) Systemic mastocytosis: a rare cause of osteoporosis and its response to bisphosphonate treatment. Ann Rheum Dis 64:965–966CrossRefGoogle Scholar
  28. 28.
    Jawhar M, Schwaab J, Horny HP, Sotlar K, Naumann N, Fabarius A, Valent P, Cross NC, Hofmann WK, Metzgeroth G, Reiter A (2016) Impact of centralized evaluation of bone marrow histology in systemic mastocytosis. Eur J Clin Investig 46:392–397CrossRefGoogle Scholar
  29. 29.
    Barete S, Assous N, de Gennes C, Grandpeix C, Feger F, Palmerini F, Dubreuil P, Arock M, Roux C, Launay JM, Fraitag S, Canioni D, Billemont B, Suarez F, Lanternier F, Lortholary O, Hermine O, Francès C (2010) Systemic mastocytosis and bone involvement in a cohort of 75 patients. Ann Rheum Dis 69:1838–1841CrossRefGoogle Scholar
  30. 30.
    Kluin-Nelemans HC, Jansen JH, Breukelman H et al (1992) Response to interferon alfa-2b in a patient with systemic mastocytosis. N Engl J Med 326:619–623CrossRefGoogle Scholar
  31. 31.
    Rossini M, Zanotti R, Bonadonna P, Artuso A, Caruso B, Schena D, Vecchiato D, Bonifacio M, Viapiana O, Gatti D, Senna G, Riccio A, Passalacqua G, Pizzolo G, Adami S (2011) Bone mineral density, bone turnover markers and fractures in patients with indolent systemic mastocytosis. Bone 49:880–885CrossRefGoogle Scholar
  32. 32.
    Manara M, Varenna M, Cantoni S, Parafioriti A, Gallazzi MB, Sinigaglia L (2010) Osteoporosis with vertebral fractures in young males, due to bone marrow mastocytosis: a report of two cases. Clin Exp Rheumatol 28:97–100PubMedGoogle Scholar
  33. 33.
    Theoharides TC, Boucher W, Spear K (2002) Serum interleukin-6 reflects disease severity and osteoporosis in mastocytosis patients. Int Arch Allergy Immunol 128:344–350CrossRefGoogle Scholar
  34. 34.
    Brockow K, Akin C, Huber M, Metcalfe DD (2005) IL-6 levels predict disease variant and extent of organ involvement in patients with mastocytosis. Clin Immunol 115:216–223CrossRefGoogle Scholar
  35. 35.
    Kanzaki S, Takahashi T, Kanno T, Ariyoshi W, Shinmyouzu K, Tujisawa T, Nishihara T (2008) Heparin inhibits BMP-2 osteogenic bioactivity by binding to both BMP-2 and BMP receptor. J Cell Physiol 216:844–850CrossRefGoogle Scholar
  36. 36.
    Johansson C, Roupe G, Lindstedt G, Mellstrom D (1996) Bone density, bone markers and bone radiological features in mastocytosis. Age Ageing 25:1–7CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Philipp Riffel
    • 1
  • Mohamad Jawhar
    • 2
    Email author
  • Kristina Gawlik
    • 2
  • Juliana Schwaab
    • 2
  • Henrik J. Michaely
    • 3
  • Georgia Metzgeroth
    • 2
  • Wolf-Karsten Hofmann
    • 2
  • Stefan O. Schoenberg
    • 1
  • Andreas Reiter
    • 2
  1. 1.Institute of Clinical Radiology and Nuclear MedicineUniversity Hospital Mannheim, Heidelberg UniversityMannheimGermany
  2. 2.Department of Hematology and OncologyUniversity Hospital Mannheim, Heidelberg UniversityMannheimGermany
  3. 3.MVZ Radiologie KarlsruheKarlsruheGermany

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