Department of Dermatology, Stanford University School of Medicine, Redwood City, California.
JAMA Dermatol. 2014 Aug;150(8):877-9. doi: 10.1001/jamadermatol.2013.8744.
Basal cell carcinomas (BCCs) in patients with Gorlin syndrome have been reported to be extremely sensitive to Smoothened (SMO) inhibitors, a novel targeted therapy against the Hedgehog pathway, because of characteristic mutations in these patients. A few cases of disease refractory to oral therapy with SMO inhibitors have been reported in patients with Gorlin syndrome and nonmetastatic BCCs, but refractory disease in distantly metastatic tumors has not been documented in this high-risk group.
A man with Gorlin syndrome and innumerable cutaneous BCCs presented with biopsy-proven BCC in his lungs. After SMO inhibitor therapy, almost all of his cutaneous tumors shrank, but his lung metastases did not. These lung metastases remained refractory to treatment despite institution of a second SMO inhibitor.
We report a case of Gorlin syndrome in a patient with metastatic BCC refractory to SMO inhibitors. Furthermore, clinical responses in this patient's cutaneous tumors did not parallel the responses in the distant site. However, serial imaging after diagnosis of metastatic disease can be critical to monitor for response to therapy.
由于 Gorlin 综合征患者存在特征性突变，基底细胞癌 (BCC) 对 Hedgehog 通路的新型靶向治疗 Smoothened (SMO) 抑制剂极为敏感。在 Gorlin 综合征和非转移性 BCC 患者中，有少数几例疾病对 SMO 抑制剂的口服治疗具有抗药性，但在该高危人群中，尚未记录到远处转移性肿瘤的难治性疾病。
一名患有 Gorlin 综合征和无数皮肤 BCC 的男性出现了经活检证实的肺部 BCC。在接受 SMO 抑制剂治疗后，他几乎所有的皮肤肿瘤都缩小了，但肺部转移瘤没有。尽管开始使用第二种 SMO 抑制剂，这些肺部转移瘤仍然对治疗有抗药性。
我们报告了一例 Gorlin 综合征伴转移性 BCC 对 SMO 抑制剂耐药的病例。此外，该患者皮肤肿瘤的临床反应与远处部位的反应不一致。然而，转移性疾病诊断后的连续影像学检查对于监测治疗反应至关重要。
