{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T05:13:08Z","timestamp":1762060388877,"version":"build-2065373602"},"reference-count":46,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2022,8,7]],"date-time":"2022-08-07T00:00:00Z","timestamp":1659830400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The diagnosis of systemic mastocytosis (SM) is based on various clinical, dermatological, serological, and hematological findings but essentially relies on histological evidence of an abnormal increase in tissue-localized mast cells (MCs). The extra-cutaneous organ most frequently affected is the bone marrow (BM), and therefore, histological examination of trephine biopsy specimens of the iliac crest is mandatory on suspicion of SM. At microscopic examination, neoplastic MCs show aberrant morphology, usually with prominent spindling. Immunohistochemistry is a useful tool in the diagnosis of SM because mast cell (MC) infiltrates may be slight and scarce, in a mixed background of lymphohistiocytic cells, eosinophils, and plasma cells. Moreover, neoplastic MCs exhibit an aberrant phenotype. Recent evidence, largely derived from molecular genetics, has enhanced the diagnostic capability of SM, also providing the basis for adequate prognostic and therapeutic evaluation. The cases herein reported illustrate the variable clinical manifestations and disease course of SM, focusing on diagnostic and therapeutic challenges. In accordance with the World Health Organization (WHO) classification and the International Consensus Classification (ICC) systems, our findings emphasize the importance of an integrated diagnostic approach for SM, with proper application of diverse assessment methodologies in order to improve SM classification and treatment effectiveness.<\/jats:p>","DOI":"10.3390\/ijms23158772","type":"journal-article","created":{"date-parts":[[2022,8,7]],"date-time":"2022-08-07T22:51:46Z","timestamp":1659912706000},"page":"8772","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Histopathology and Molecular Genetics in Systemic Mastocytosis: Implications for Clinical Management"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2689-4482","authenticated-orcid":false,"given":"Francesca","family":"Crupi","sequence":"first","affiliation":[{"name":"Centro Ricerca e Innovazione Malattie Mieloproliferative (CRIMM), AOU Careggi, 50134 Firenze, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3538-429X","authenticated-orcid":false,"given":"Benedetta","family":"Sordi","sequence":"additional","affiliation":[{"name":"Centro Ricerca e Innovazione Malattie Mieloproliferative (CRIMM), AOU Careggi, 50134 Firenze, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fiorenza","family":"Vanderwert","sequence":"additional","affiliation":[{"name":"Centro Ricerca e Innovazione Malattie Mieloproliferative (CRIMM), AOU Careggi, 50134 Firenze, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesca","family":"Gesullo","sequence":"additional","affiliation":[{"name":"Centro Ricerca e Innovazione Malattie Mieloproliferative (CRIMM), AOU Careggi, 50134 Firenze, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Amorosi","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze della Salute, Universit\u00e0 Magna Grecia, 88100 Catanzaro, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4810-6501","authenticated-orcid":false,"given":"Francesco","family":"Mannelli","sequence":"additional","affiliation":[{"name":"Centro Ricerca e Innovazione Malattie Mieloproliferative (CRIMM), AOU Careggi, 50134 Firenze, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raffaella","family":"Santi","sequence":"additional","affiliation":[{"name":"Sezione di Anatomia Patologica, Dipartimento di Scienze della Salute, Universit\u00e0 degli Studi di Firenze, 50121 Firenze, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1703","DOI":"10.1038\/s41375-022-01613-1","article-title":"The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Myeloid and Histiocytic\/Dendritic Neoplasms","volume":"36","author":"Khoury","year":"2022","journal-title":"Leukemia"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Arber, D.A., Orazi, A., Hasserjian, R.P., Borowitz, M.J., Calvo, K.R., Kvasnicka, H.M., Wang, S.A., Bagg, A., Barbui, T., and Branford, S. 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