Juliana Schwaab1, Nicole Cabral do O Hartmann2, Nicole Naumann1, Mohamad Jawhar1, Christel Weiß3, Georgia Metzgeroth1, Alicia Schmid1, Johannes Lübke1, Lukas Reiter1, Alice Fabarius1, Nicholas C P Cross4, Karl Sotlar5, Peter Valent6, Hanneke C Kluin-Nelemans7, Wolf-Karsten Hofmann1, Hans-Peter Horny8, Jens Panse2, Andreas Reiter9. 1. Department of Hematology and Oncology, University Hospital Mannheim, Heidelberg University, Mannheim, Germany. 2. Department of Hematology, Oncology, Hemostaseology and Stem Cell Transplantation, University Hospital RWTH Aachen, Aachen, Germany. 3. Department of Medical Statistics and Biomathematics, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany. 4. Wessex Regional Genetics Laboratory, Salisbury, and Faculty of Medicine, University of Southampton, Southampton, United Kingdom. 5. University Hospital Salzburg, Paracelsus Medical University, Salzburg, Austria. 6. Department of Internal Medicine I, Division of Hematology and Ludwig Boltzmann Institute for Hematology and Oncology, Medical University of Vienna, Vienna, Austria. 7. Department of Hematology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. 8. Department of Pathology, Ludwig-Maximilians-University, Munich, Germany. 9. Department of Hematology and Oncology, University Hospital Mannheim, Heidelberg University, Mannheim, Germany. Electronic address: andreas.reiter@medma.uni-heidelberg.de.
Abstract
BACKGROUND: Little is known about the epidemiology of advanced systemic mastocytosis (advSM). OBJECTIVES: To investigate epidemiologic features and diagnostic pitfalls of advSM in Germany. METHODS: Therefore, 140 patients from a single German reference center of the European Competence Network on Mastocytosis between 2003 and 2018 were analyzed. RESULTS: The patients' median age was 68 years (range, 26-86 years), and male versus female ratio was 2:1. An elevated serum tryptase, a KIT D816 mutation, and additional somatic mutations, for example, in SRSF2, ASXL1, or RUNX1, were identified in 95%, 91%, and 74% of patients, respectively. Median overall survival was 3.5 years (range, 0.03-14.3 years; male vs female 2.6 vs 4.2 years; P = .02). Two categories of misdiagnoses were identified in 51 of 140 (36%) patients: First, systemic mastocytosis (SM) was overlooked in 28 of 140 (20%) patients primarily diagnosed with various subtypes of myeloid neoplasms. Second, 23 of 140 (16%) patients were diagnosed with supposed progression from indolent SM to advSM; however, combination of an elevated KIT D816V variant allele frequency in peripheral blood (n = 22), monocytosis (n = 9), eosinophilia (n = 6), and/or mutations in SRSF2, ASXL1, or RUNX1 (n = 10) suggest that distinct signs of potential advSM were overlooked in virtually all patients. Based on locally diagnosed patients in an area of 2.5 million inhabitants, but obviously without considering more, yet unrecognized cases, the incidence and prevalence of advSM is at least 0.8 and 5.2, respectively, per 1 million inhabitants. CONCLUSIONS: Adequate analyses of tryptase levels, bone marrow morphology, and genetics in patients with myeloid neoplasms or SM would help to prevent the significant underdiagnosis of advSM.
BACKGROUND: Little is known about the epidemiology of advanced systemic mastocytosis (advSM). OBJECTIVES: To investigate epidemiologic features and diagnostic pitfalls of advSM in Germany. METHODS: Therefore, 140 patients from a single German reference center of the European Competence Network on Mastocytosis between 2003 and 2018 were analyzed. RESULTS: The patients' median age was 68 years (range, 26-86 years), and male versus female ratio was 2:1. An elevated serum tryptase, a KIT D816 mutation, and additional somatic mutations, for example, in SRSF2, ASXL1, or RUNX1, were identified in 95%, 91%, and 74% of patients, respectively. Median overall survival was 3.5 years (range, 0.03-14.3 years; male vs female 2.6 vs 4.2 years; P = .02). Two categories of misdiagnoses were identified in 51 of 140 (36%) patients: First, systemic mastocytosis (SM) was overlooked in 28 of 140 (20%) patients primarily diagnosed with various subtypes of myeloid neoplasms. Second, 23 of 140 (16%) patients were diagnosed with supposed progression from indolent SM to advSM; however, combination of an elevated KITD816V variant allele frequency in peripheral blood (n = 22), monocytosis (n = 9), eosinophilia (n = 6), and/or mutations in SRSF2, ASXL1, or RUNX1 (n = 10) suggest that distinct signs of potential advSM were overlooked in virtually all patients. Based on locally diagnosed patients in an area of 2.5 million inhabitants, but obviously without considering more, yet unrecognized cases, the incidence and prevalence of advSM is at least 0.8 and 5.2, respectively, per 1 million inhabitants. CONCLUSIONS: Adequate analyses of tryptase levels, bone marrow morphology, and genetics in patients with myeloid neoplasms or SM would help to prevent the significant underdiagnosis of advSM.
Authors: Oscar González-López; Javier I Muñoz-González; Alberto Orfao; Iván Álvarez-Twose; Andrés C García-Montero Journal: Cancers (Basel) Date: 2022-05-18 Impact factor: 6.575
Authors: Julia Riffel; Johannes Lübke; Andreas Reiter; Philipp Riffel; Nicole Naumann; Sebastian Kreil; Georgia Metzgeroth; Alice Fabarius; Karl Sotlar; Hans-Peter Horny; Mohamad Jawhar; Daniel Overhoff; Stefan Schoenberg; Wolf-Karsten Hofmann; Thomas Henzler; Juliana Schwaab Journal: Sci Rep Date: 2022-08-20 Impact factor: 4.996