Recalcitrant Cutaneous Mastocytosis Treated With Genetically Informed Targeted Therapy:A Case Report

作     者：Laura Gleason Volkan Tekmen Alexa Cohen Safiyyah Bhatti Burcu Beksac Jisun Cha Pierluigi Porcu Neda Nikbakht Laura Gleason;Volkan Tekmen;Alexa Cohen;Safiyyah Bhatti;Burcu Beksac;Jisun Cha;Pierluigi Porcu;Neda Nikbakht

作者机构：Department of Dermatology and Cutaneous BiologyThomas Jefferson UniversityPhiladelphiaPA 19107USA Division of Hematologic Malignancies and Hematopoietic Stem Cell TransplantDepartment of Medical OncologySidney Kimmel Cancer CenterThomas Jefferson UniversityPhiladelphiaPA 19107USA Department of DermatopathologySchweiger Dermatology GroupNew YorkNY 10006USA 

出 版 物：《International Journal of Dermatology and Venereology》 (国际皮肤性病学杂志（英文）)

年 卷 期：2023年第6卷第2期

页      面：107-109页

核心收录：

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：supported by a grant from the National Cancer Institute USA(No.R03CA252818 to NN). 

主　　题：mastocytosis c-KIT molecular genetics targeted therapy midostaurin 

摘      要：Introduction:Mastocytosis,a clonal proliferation of mast cells commonly involving the skin and bone marrow,has a varied clinical presentation ranging from cutaneous lesions to systemic disease.Cutaneous mastocytosis is managed symptomatically,but systemic mastocytosis is treated with targeted therapy against the mutated receptor tyrosine kinase c-KIT,the pathogenic driver of mastocytosis.However,there are no guidelines for the treatment of cutaneous mastocytosis refractory to symptomatic management.We herein report a method to select genetically informed therapy for symptomatic and recalcitrant cutaneous mastocytosis.Case presentation:We performed a mutational analysis of dermal mast cells after enrichment by laser capture in a 23-year-old woman with recalcitrant cutaneous mastocytosis.The analysis revealed a aspartic acid to valine substitution at codon 816(D816V)mutation in the protein c-KIT.Based on these results,we initiated treatment with the multi-kinase/KIT inhibitor midostaurin,a treatment effective against the D816V c-KIT mutation.After 3 months of treatment,the patient exhibited a reduction in the number and size of cutaneous lesions and reported resolution of pruritus and decreased severity of other mast cell-related symptoms.Discussion:The treatment of mastocytosis relies heavily on whether the disease is limited to the skin or systemic.However,there are no guidelines for cutaneous mastocytosis that does not respond to symptomatic management.In the present report describing a patient with recalcitrant cutaneous mastocytosis,we describe a strategy in which skin mutational analysis is used to guide the selection of targeted therapy.Conclusion:Performing mast cell mutational analyses in the skin provides a means to select targeted therapy for symptomatic and refractory cutaneous mastocytosis.