Hu Boyu, Patel Jay L, Tao Randa, Cannon Richard B, Monroe Marcus, Goyal Gaurav
1Division of Hematology/Hematologic Malignancies, Department of Internal Medicine, Huntsman Cancer Institute/University of Utah, Salt Lake City, Utah.
2Division of Clinical Pathology, Department of Pathology, ARUP Laboratories and University of Utah, Salt Lake City, Utah.
J Natl Compr Canc Netw. 2022 Mar 24;20(6):618-621. doi: 10.6004/jnccn.2022.7001.
Survival outcomes of patients with histiocytic neoplasms are poor, with no standard-of-care treatments available for these malignancies. Recent characterization of the genomic landscape of various histiocytic neoplasms have shown a predominance of activating driver mutations within the MAPK/ERK pathway (ie, BRAF, MEK, KRAS, MAPK, and NRAS). Subsequently, successful treatment of these malignancies with BRAF and MEK inhibitors has been reported. This report presents the first patient with histiocytic sarcoma harboring a somatic KRAS Q61H mutation who was subsequently treated to a near complete response with the MEK inhibitor trametinib. Due to patient preference, lack of standard of care treatments, and associated morbidity from head and neck dissection, initial disease reduction provided by trametinib therapy allowed for a less morbid resection. This case report highlights the utility of up-front next-generation sequencing and the efficacy of MEK inhibition in patients with histiocytic sarcoma harboring activating KRAS mutations.
组织细胞肿瘤患者的生存预后较差，目前尚无针对这些恶性肿瘤的标准治疗方案。最近对各种组织细胞肿瘤基因组图谱的特征分析显示，丝裂原活化蛋白激酶/细胞外信号调节激酶（MAPK/ERK）通路（即BRAF、MEK、KRAS、MAPK和NRAS）中存在大量激活驱动突变。随后，有报道称使用BRAF和MEK抑制剂成功治疗了这些恶性肿瘤。本报告介绍了首例患有体细胞KRAS Q61H突变的组织细胞肉瘤患者，该患者随后接受MEK抑制剂曲美替尼治疗，达到了接近完全缓解的效果。由于患者的偏好、缺乏标准治疗方案以及头颈清扫术相关的发病率，曲美替尼治疗最初带来的疾病缓解使得手术的创伤性降低。本病例报告强调了 upfront 二代测序的实用性以及MEK抑制对携带激活型KRAS突变的组织细胞肉瘤患者的疗效。
