Systemic mastocytosis: Determining the subtype of disease
- Cem Akin, MD, PhD
Cem Akin, MD, PhD
- Professor of Medicine
- University of Michigan
- Jason Gotlib, MD, MS
Jason Gotlib, MD, MS
- Professor of Medicine
- Stanford University School of Medicine
- Section Editor
- Sarbjit Saini, MD
Sarbjit Saini, MD
- Section Editor — Urticaria and Angioedema
- Associate Professor of Medicine
- Johns Hopkins University School of Medicine
- Deputy Editors
- Anna M Feldweg, MD
Anna M Feldweg, MD
- Director, Editorial Management — UpToDate
- Deputy Editor — Allergy and Immunology
- Assistant Professor of Medicine, Part-time
- Harvard Medical School
- Alan G Rosmarin, MD
Alan G Rosmarin, MD
- Deputy Editor — Hematology
- Professor of Medicine
- University of Massachusetts Medical School
Mastocytosis describes a group of disorders in which pathologic mast cells accumulate in tissues. In the 2016 revisions of the World Health Organization (WHO) classification of tumors of the hematopoietic and lymphoid tissues, "mastocytosis" was removed as one of the subtypes under the major category of "myeloproliferative neoplasms" and is now classified as its own major category . In systemic mastocytosis (SM), mast cells infiltrate extracutaneous tissues. Once the diagnosis of SM has been reached, the subtype (variant) of disease must be determined, as treatment and prognosis differ for each disorder.
Topics related to other aspects of mastocytosis are found separately:To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
- 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.
- Horny HP, Metcalf DD, Bennett JM, et al. Mastocytosis. In: WHO Classification of Tumors of Hematopoietic and Lymphoid Tissues, Swerdlow SH, Campo E, Harris NL, et al (Eds), Lyon IARC Press, Lyon 2008. p.54.
- Akin C. Molecular diagnosis of mast cell disorders: a paper from the 2005 William Beaumont Hospital Symposium on Molecular Pathology. J Mol Diagn 2006; 8:412.
- Pardanani A, Lasho T, Elala Y, et al. Next-generation sequencing in systemic mastocytosis: Derivation of a mutation-augmented clinical prognostic model for survival. Am J Hematol 2016; 91:888.
- Jawhar M, Schwaab J, Schnittger S, et al. Additional mutations in SRSF2, ASXL1 and/or RUNX1 identify a high-risk group of patients with KIT D816V(+) advanced systemic mastocytosis. Leukemia 2016; 30:136.
- Valent P, Sperr WR, Schwartz LB, Horny HP. Diagnosis and classification of mast cell proliferative disorders: delineation from immunologic diseases and non-mast cell hematopoietic neoplasms. J Allergy Clin Immunol 2004; 114:3.
- Valent P, Horny HP, Escribano L, et al. Diagnostic criteria and classification of mastocytosis: a consensus proposal. Leuk Res 2001; 25:603.
- Lawrence JB, Friedman BS, Travis WD, et al. Hematologic manifestations of systemic mast cell disease: a prospective study of laboratory and morphologic features and their relation to prognosis. Am J Med 1991; 91:612.
- Mican JM, Di Bisceglie AM, Fong TL, et al. Hepatic involvement in mastocytosis: clinicopathologic correlations in 41 cases. Hepatology 1995; 22:1163.
- Valent P. Diagnosis and management of mastocytosis: an emerging challenge in applied hematology. Hematology Am Soc Hematol Educ Program 2015; 2015:98.
- Wimazal F, Geissler P, Shnawa P, et al. Severe life-threatening or disabling anaphylaxis in patients with systemic mastocytosis: a single-center experience. Int Arch Allergy Immunol 2012; 157:399.
- Metcalfe DD. Classification and diagnosis of mastocytosis: current status. J Invest Dermatol 1991; 96:2S.
- Horan RF, Austen KF. Systemic mastocytosis: retrospective review of a decade's clinical experience at the Brigham and Women's Hospital. J Invest Dermatol 1991; 96:5S.
- Escribano L, Akin C, Castells M, et al. Mastocytosis: current concepts in diagnosis and treatment. Ann Hematol 2002; 81:677.
- Lim KH, Tefferi A, Lasho TL, et al. Systemic mastocytosis in 342 consecutive adults: survival studies and prognostic factors. Blood 2009; 113:5727.
- Pardanani A. Systemic mastocytosis in adults: 2015 update on diagnosis, risk stratification, and management. Am J Hematol 2015; 90:250.
- Longley BJ, Metcalfe DD. A proposed classification of mastocytosis incorporating molecular genetics. Hematol Oncol Clin North Am 2000; 14:697.
- Zanotti R, Bonadonna P, Bonifacio M, et al. Isolated bone marrow mastocytosis: an underestimated subvariant of indolent systemic mastocytosis. Haematologica 2011; 96:482.
- Horny HP, Sotlar K, Sperr WR, Valent P. Systemic mastocytosis with associated clonal haematological non-mast cell lineage diseases: a histopathological challenge. J Clin Pathol 2004; 57:604.
- Parker RI. Hematologic aspects of systemic mastocytosis. Hematol Oncol Clin North Am 2000; 14:557.
- Nagata H, Worobec AS, Oh CK, et al. Identification of a point mutation in the catalytic domain of the protooncogene c-kit in peripheral blood mononuclear cells of patients who have mastocytosis with an associated hematologic disorder. Proc Natl Acad Sci U S A 1995; 92:10560.
- Yavuz AS, Lipsky PE, Yavuz S, et al. Evidence for the involvement of a hematopoietic progenitor cell in systemic mastocytosis from single-cell analysis of mutations in the c-kit gene. Blood 2002; 100:661.
- Broesby-Olsen S, Kristensen TK, Møller MB, et al. Adult-onset systemic mastocytosis in monozygotic twins with KIT D816V and JAK2 V617F mutations. J Allergy Clin Immunol 2012; 130:806.
- Castells MC, Friend DS, Bunnell CA, et al. The presence of membrane-bound stem cell factor on highly immature nonmetachromatic mast cells in the peripheral blood of a patient with aggressive systemic mastocytosis. J Allergy Clin Immunol 1996; 98:831.
- Floman Y, Amir G. Systemic mastocytosis presenting with severe spinal osteopenia and multiple compression fractures. J Spinal Disord 1991; 4:369.
- Georgin-Lavialle S, Lhermitte L, Dubreuil P, et al. Mast cell leukemia. Blood 2013; 121:1285.
- Valent P, Sotlar K, Sperr WR, et al. Refined diagnostic criteria and classification of mast cell leukemia (MCL) and myelomastocytic leukemia (MML): a consensus proposal. Ann Oncol 2014; 25:1691.
- Valent P, Sotlar K, Sperr WR, et al. Chronic mast cell leukemia: a novel leukemia-variant with distinct morphological and clinical features. Leuk Res 2015; 39:1.
- Furitsu T, Tsujimura T, Tono T, et al. Identification of mutations in the coding sequence of the proto-oncogene c-kit in a human mast cell leukemia cell line causing ligand-independent activation of c-kit product. J Clin Invest 1993; 92:1736.
- SUBTYPES OF SYSTEMIC MASTOCYTOSIS
- Basic evaluation
- Advanced testing
- Evaluation for organ enlargement or dysfunction
- - B findings
- - C findings
- DETERMINING THE SUBTYPE
- Indolent systemic mastocytosis
- - Isolated bone marrow mastocytosis
- Smoldering systemic mastocytosis
- Systemic mastocytosis with an associated hematologic neoplasm
- Aggressive systemic mastocytosis
- Mast cell leukemia
- SOCIETY GUIDELINE LINKS
- SUMMARY AND RECOMMENDATIONS