Magnetic resonance imaging reveals distinct bone marrow patterns in indolent and advanced systemic mastocytosis
- 17 Downloads
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.
KeywordsSystemic mastocytosis Magnetic resonance imaging Bone marrow Osteolytic lesions Osteoporosis
Karl Sotlar and Hans-Peter Horny are acknowledged for histological diagnosis.
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
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 was obtained from all individual participants included in the study.
- 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.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.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.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.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
- 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
- 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
- 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