RESUMO
Adult-onset urticaria pigmentosa/mastocytosis in the skin almost always persists throughout life. The prevalence of systemic mastocytosis in such patients is not precisely known. Bone marrow biopsies from 59 patients with mastocytosis in the skin and all available skin biopsies (n=27) were subjected to a meticulous cytological, histological, immunohistochemical, and molecular analysis for the presence of WHO-defined diagnostic criteria for systemic mastocytosis: compact mast cell infiltrates (major criterion); atypical mast cell morphology, KIT D816V, abnormal expression of CD25 by mast cells, and serum tryptase levels >20 ng/ml (minor criteria). Systemic mastocytosis is diagnosed when the major diagnostic criterion plus one minor criterion or at least three minor criteria are fulfilled. Systemic mastocytosis was confirmed in 57 patients (97%) by the diagnosis of compact mast cell infiltrates plus at least one minor diagnostic criterion (n=42, 71%) or at least three minor diagnostic criteria (n=15, 25%). In two patients, only two minor diagnostic criteria were detectable, insufficient for the diagnosis of systemic mastocytosis. By the use of highly sensitive molecular methods, including the analysis of microdissected mast cells, KIT D816V was found in all 58 bone marrow biopsies investigated for it but only in 74% (20/27) of the skin biopsies. It is important to state that even in cases with insufficient diagnostic criteria for systemic mastocytosis, KIT D816V-positive mast cells were detected in the bone marrow. This study demonstrates, for the first time, that almost all patients with adult-onset mastocytosis in the skin, in fact, have systemic mastocytosis with cutaneous involvement.
Assuntos
Mastócitos , Mastocitoma Cutâneo/diagnóstico , Mastocitose Sistêmica/diagnóstico , Pele , Adolescente , Adulto , Idade de Início , Biomarcadores/análise , Biomarcadores/sangue , Biópsia , Exame de Medula Óssea , Análise Mutacional de DNA , Feminino , Humanos , Imuno-Histoquímica , Subunidade alfa de Receptor de Interleucina-2/análise , Masculino , Mastócitos/química , Mastócitos/patologia , Mastocitoma Cutâneo/sangue , Mastocitoma Cutâneo/química , Mastocitoma Cutâneo/genética , Mastocitoma Cutâneo/patologia , Mastocitose Sistêmica/sangue , Mastocitose Sistêmica/genética , Mastocitose Sistêmica/metabolismo , Mastocitose Sistêmica/patologia , Microdissecção , Pessoa de Meia-Idade , Mutação , Valor Preditivo dos Testes , Proteínas Proto-Oncogênicas c-kit/genética , Pele/química , Pele/patologia , Triptases/sangue , Adulto JovemRESUMO
Canine cutaneous mast cell tumor (MCT) is very common disease in dogs, this is more aggressive than in other species. The biologic behavior of MCT is highly variable and a more accurate prognosis for these tumors needs to performed. The proto-oncogene c-kit is known to play a critical role in development and function of mast cells (MC). The aim of this study was to evaluate the expression of immunohistochemical pattern of c-kit in MCTs and to correlate these results with MC density (MCD) and intratumoral microvessel density (MVD). Our results confirm that a more aggressive biologic behavior of canine MCT is associated with the increased c-kit expression, further suggesting a new role for c-kit, as a useful marker, in diagnostic pathology and in tumor progression.
