Clinical, immunophenotypic, and molecular characteristics of well-differentiated systemic mastocytosis

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• 作者：Ivá ; n Á ; lvarez-Twose ; MD^a ; ^b ; ^{ivana@sescam.jccm.es" class="auth_mail" title="E-mail the corresponding author} ; Marí ; a Jara-Acevedo ; MSc^b ; ^c ; José ; Má ; rio Morgado ; MSc^a ; ^b ; André ; s Garcí ; a-Montero ; PhD^b ; ^c ; Laura Sá ; nchez-Muñ ; oz ; MD ; PhD^a ; ^b ; Cristina Teodó ; sio ; PhD^b ; ^c ; Almudena Matito ; MD ; PhD^a ; ^b ; Andrea Mayado ; PhD^b ; ^c ; Carolina Caldas ; MSc^b ; ^c ; Manuela Mollejo ; MD ; PhD^b ; ^d ; Alberto Orfao ; MD ; PhD^b ; ^c ; ^&lowast ; ; Luis Escribano ; MD ; PhD^b ; ^&lowast ;
• 关键词：Mast cell ; mastocytosis ; well differentiated ; KIT ; imatinib
• 刊名：Journal of Allergy and Clinical Immunology
• 出版年：2016
• 出版时间：January 2016
• 年：2016
• 卷：137
• 期：1
• 页码：168-178.e1
• 全文大小：4805 K

文摘

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.