Clinical, immunophenotypic, and molecular characteristics of well-differentiated systemic mastocytosis
Open accessAbstract
Background Well-differentiated systemic mastocytosis (WDSM) is a rare variant of systemic mastocytosis (SM) characterized by bone marrow (BM) infiltration by mature-appearing mast cells (MCs) often lacking exon 17 KIT mutations. Because of its rarity, the clinical and biological features of WDSM remain poorly defined. Objective We sought to determine the clinical, biological, and molecular features of a cohort of 33 patients with mastocytosis in the skin in association with BM infiltration by well-differentiated MCs and to establish potential diagnostic criteria for WDSM. Methods Thirty-three patients with mastocytosis in the skin plus BM aggregates of round, fully granulated MCs lacking strong CD25 and CD2 expression in association with clonal MC features were studied. Results Our cohort of patients showed female predominance (female/male ratio, 4:1) and childhood onset of the disease (91%) with frequent familial aggregation (39%). Skin involvement was heterogeneous, including maculopapular (82%), nodular (6%), and diffuse cutaneous (12%) mastocytosis. KIT mutations were detected in only 10 (30%) of 33 patients, including the KIT D816V (n = 5), K509I (n = 3), N819Y (n = 1), and I817V (n = 1) mutations. BM MCs displayed a unique immunophenotypic pattern consisting of increased light scatter features, overexpression of cytoplasmic carboxypeptidase, and aberrant expression of CD30, together with absent (79%) or low (21%) positivity for CD25, CD2, or both. Despite only 9 (27%) of 33 patients fulfilling the World Health Organization criteria for SM, our findings allowed us to establish the systemic nature of the disease, which fit with the definition of WDSM. Conclusions WDSM represents a rare clinically and molecularly heterogeneous variant of SM that requires unique diagnostic criteria to avoid a misdiagnosis of cutaneous mastocytosis per current World Health Organization criteria.
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Well-differentiated SM (WDSM) is not recognized as an independent subtype according to 2022 ICC and WHO 5th Edition.
“Well-differentiated SM (WDSM) is a variant of systemic mastocytosis not recognized as an independent subtype according to 2022 ICC and WHO 5th Edition.”
From Defining “Normal” basal serum tryptase levels: a context-dependent approach to improve diagnostics in systemic mastocytosis (2025) · cites this paper as [9]
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- Authors
- Álvarez-Twose, I., Jara-Acevedo, M., Morgado, J. M., García-Montero, A., Sánchez-Muñoz, L., Teodósio, C., Matito, A., Mayado, A., Caldas, C., Mollejo, M., Orfao, A., & Escribano, L.
- Affiliations
- Hospital Virgen del Valle (ES)
- Universidad de Salamanca (ES)
- Hospital Virgen de la Salud (ES)
- ORCID
- Venue
- Journal of Allergy and Clinical Immunology
- Publisher
- Elsevier BV
- Published
- 2016-01
- Volume
- 137
- Issue
- 1
- Pages
- 168-178.e1
- ISSN
- 0091-6749 (ISSN-L)
- OpenAlex
- W593231466
- Cited by
- 102
- References
- 4
- Citations by year
- 2026: 4 · 2025: 12 · 2024: 8 · 2023: 17 · 2022: 12 · 2021: 12 · 2020: 10 · 2019: 6 · 2018: 8 · 2017: 6 · 2016: 4 · 2015: 3
- FWCI
- 3.44
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Allergy and Clinical Immunology (publishedVersion)
- PubMed (publishedVersion)
- DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion)
- Funders
- Asociación Española de Mastocitosis (AEDM 2014)
- Instituto de Salud Carlos III
- FEDER
- Ministry of Economy and Competitivity (PI11/02399)
- Fundación Ramón Areces (CIVP16A1806)
- Novartis Farmacéutica
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Mast cells and histamine
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal Tumor Research and Treatment
- Health Sciences › Medicine › Physiology › Histiocytic Disorders and Treatments
- Keywords
- systemic mastocytosis, KIT mutations, KIT D816V, bone marrow mastocytosis, CD30, CD25, CD2, carboxypeptidase, diagnostic criteria, familial aggregation, pediatric onset
- MeSH terms
- Adolescent, Adult, Aged, Child, Child, Preschool, Female, Humans, Male, Mast Cells, Middle Aged, Mutation, Skin, Immunophenotyping, Proto-Oncogene Proteins c-kit, Mastocytosis, Cutaneous, Mastocytosis, Systemic, Young Adult
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