Kosemehmetoglu Kemal, Kaygusuz Gulsah, Fritchie Karen, Aydin Ovgu, Yapicier Ozlem, Coskun Oznur, Karatayli Ersin, Boyacigil Senay, Guler Gulnur, Dervisoglu Sergulen, Kuzu Isinsu
Department of Pathology, Hacettepe University School of Medicine, Ankara, Turkey.
Department of Pathology, Ankara University School of Medicine, Ankara, Turkey.
Virchows Arch. 2017 Jul;471(1):77-90. doi: 10.1007/s00428-017-2138-7. Epub 2017 May 9.
Our aim in this study was to describe the clinical, morphological, and molecular profile of gastrointestinal stromal tumor (GIST) metastatic to bone. We analyzed the morphological, phenotypic, and molecular characteristics of seven cases, and in addition reviewed 17 cases from literature. Sequence analysis of KIT and PDGFRA genes was possible for six cases. For the GIST cases with bone metastasis, the most common primaries were small intestine (29%), stomach (25%), and rectum (21%). Sites of bone metastases were vertebrae (11), pelvis (8), femur (8), ribs (6), humerus (5), skull (3), scapula (1), and mandible (1). The size ranged from 1.5 to 13 cm (median, 3.8 cm). Bone metastases without involvement of any other organ were seen in 17% of the cases and were solitary in 14 (58%). Adjacent soft tissue involvement was present in nearly half of the patients. Bone metastasis was either manifest at the time of diagnosis (28%) or occurred after a mean period of 4.7 years (3 months-20 years). Morphologically, neoplastic cells were spindle in 67%, epithelioid in 13%, and mixed epithelioid and spindle in 20%. CD117, DOG1, and CD34 were positive in 88, 86, and 85% of the cases, respectively. KIT Exon 11 mutations were the most frequent gene alteration (78%), followed by KIT Exon 13 mutations. Of 17 of the cases with available follow-up information, 7 (41%) patients developed bone metastasis under imatinib therapy. Five patients (29%) died of disease within a mean of 17 months. Bone metastases from GIST are usually found in patients with advanced disease and typically present as lytic masses with occasional soft tissue involvement. We could not identify any KIT or PDGFRA alterations predisposing to bone metastasis.
本研究的目的是描述转移至骨的胃肠道间质瘤（GIST）的临床、形态学及分子特征。我们分析了7例病例的形态学、表型及分子特征，并另外回顾了文献中的17例病例。6例病例可行KIT和PDGFRA基因的序列分析。对于发生骨转移的GIST病例，最常见的原发部位是小肠（29%）、胃（25%）和直肠（21%）。骨转移部位包括椎体（11处）、骨盆（8处）、股骨（8处）、肋骨（6处）、肱骨（5处）、颅骨（3处）、肩胛骨（1处）和下颌骨（1处）。大小范围为1.5至13厘米（中位数为3.8厘米）。17%的病例可见骨转移而无任何其他器官受累，其中14例（58%）为孤立性转移。近一半患者存在邻近软组织受累。骨转移在诊断时即出现（28%）或平均在4.7年（3个月至20年）后发生。形态学上，67%的肿瘤细胞呈梭形，13%为上皮样，20%为上皮样和梭形混合。CD117、DOG1和CD34分别在88%、86%和85%的病例中呈阳性。KIT外显子11突变是最常见的基因改变（78%），其次是KIT外显子13突变。在有随访信息的17例病例中，7例（41%）患者在伊马替尼治疗期间发生骨转移。5例患者（29%）在平均17个月内死于疾病。GIST的骨转移通常见于晚期患者，典型表现为溶骨性肿块，偶尔伴有软组织受累。我们未能识别出任何易导致骨转移的KIT或PDGFRA改变。
