Clinical, immunophenotypic, and molecular characteristics of well-differentiated systemic mastocytosis
Clinical, immunophenotypic, and molecular characteristics of well-differentiated systemic mastocytosis
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DOI：
10.1016/j.jaci.2015.05.008
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发表时间：
2016-01-01
影响因子：
14.2
通讯作者：
Escribano, Luis
中科院分区：
文献类型：
--
作者：
Alvarez-Twose, Ivan;Jara-Acevedo, Maria;Escribano, Luis
背景：高分化全身性肥大细胞增多症（WDSM）是一种罕见的全身性肥大细胞增多症（SM），其特征是骨髓（BM）浸润成熟肥大细胞（MCs），通常缺乏17外显子KIT突变。由于其罕见性，WDSM的临床和生物学特征仍然不明确。目的：我们试图确定33例皮肤肥大细胞增多症患者的临床、生物学和分子特征，这些患者与高分化MCs浸润的BM有关，并建立WDSM的潜在诊断标准。方法：对33例皮肤肥大细胞增多症患者进行了研究，并观察了与克隆性MC特征相关的缺乏CD25和CD2强表达的圆形、全颗粒性MC的BM聚集物。结果：我们的患者队列显示女性优势（男女比例为4:1），儿童发病（91%），家族聚集性频繁（39%）。皮肤受累是不均匀的，包括黄斑丘疹（82%）、结节（6%）和弥漫性皮肤肥大细胞增多症（12%）。33例患者中仅有10例（30%）检测到KIT突变，包括KIT D816V （n = 5）、K509I （n = 53）、N819Y （n = 1）和I817V （n = 1）突变。BM MCs表现出独特的免疫表型模式，包括光散射特征增加，细胞质羧基肽酶过表达，CD30异常表达，以及CD25、CD2缺失（79%）或低（21%）阳性，或两者均阳性。尽管33例患者中只有9例（27%）符合世界卫生组织的SM标准，但我们的研究结果使我们能够确定该疾病的全身性，这符合WDSM的定义。结论：WDSM是一种罕见的SM临床和分子异质性变异，需要独特的诊断标准，以避免根据当前世界卫生组织标准误诊皮肤肥大细胞增多症。
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 5 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.