结节性硬化症 (TSC) 是一种罕见的常染色体显性遗传病，由 TSC1 或 TSC2 基因突变引起。这些基因突变可以诱导任何器官系统良性肿瘤的发展，对发病率和死亡率具有重大的临床意义。在极少数情况下，TSC 患者可能患有恶性肿瘤，包括肾细胞癌 (RCC) 和胰腺神经内分泌肿瘤 (PNET)。尽管 TSC 患者肾细胞癌的发生率较低，但它被认为是一种遗传性肾癌综合征。 TSC 通常在产前和儿科患者中被诊断出来，并且经常与神经认知障碍和癫痫发作有关，这些疾病通常在生命早期经历过。然而，TSC 突变的外显率和表达率变化很大。在此，我们提供一份病例报告以及相关文献，以强调存在未确诊的具有较少渗透特征的成年患者，其临床表现可能包含非经典体征和症状，并且具有致病性 TSC 突变。 一名 31 岁女性既往有子宫肌瘤病史，子宫肌瘤切除术后因出血性附件囊肿被送往急诊科。影像学检查偶然发现了可疑肾细胞癌的肾脏肿块。出于对遗传性平滑肌瘤病和肾细胞癌（HLRCC）综合征的担忧，通过手术切除肿块并确认为肾细胞癌。与医学遗传学的讨论确定了肾癌和肾切除手术的家族史以及脚趾上的指甲纤维瘤的患者病史。遗传性肾癌的基因检测发现 TSC1 基因 5'UTR 缺失，从而诊断为 TSC。诊断后，皮肤科发现良性皮肤表现与 TSC 一致。偶然发现RCC后约六个月，胸部CT影像偶然发现胰体/尾部有PNET，将其切除并确定为分化良好的PNET。后来，脑部核磁共振显示有两个小皮质结节，每个额叶各一个，但没有症状；患者的病史和家族史没有癫痫发作或学习迟缓。该患者目前没有表现出复发或转移性疾病的证据，也没有发现其他恶性肿瘤。据我们所知，这是文献中第一篇没有 RCC 和 PNET 神经认知障碍病史的 TSC 患者报告TSC 中罕见发生。该患者有很强的肾病家族史，包括肾细胞癌，并且有其他几种 TSC 的临床表现，包括皮肤和脑部发现。偶然发现肾细胞癌并进行手术切除，促使对 TSC 进行基因评估和诊断，导致该患者的诊断相对较晚。报告 TSC 的广泛疾病，包括更多的恶性表型，例如我们患者中所见的表型，可以帮助医疗保健提供者更好地识别需要基因评估和额外医疗护理的患者。© 2024。作者。

Tuberous sclerosis complex (TSC) is a rare, autosomal dominant genetic disease that arises from TSC1 or TSC2 genetic mutations. These genetic mutations can induce the development of benign tumors in any organ system with significant clinical implications in morbidity and mortality. In rare instances, patients with TSC can have malignant tumors, including renal cell carcinoma (RCC) and pancreatic neuroendocrine tumor (PNET). It is considered a hereditary renal cancer syndrome despite the low incidence of RCC in TSC patients. TSC is typically diagnosed in prenatal and pediatric patients and frequently associated with neurocognitive disorders and seizures, which are often experienced early in life. However, penetrance and expressivity of TSC mutations are highly variable. Herein, we present a case report, with associated literature, to highlight that there exist undiagnosed adult patients with less penetrant features, whose clinical presentation may contain non-classical signs and symptoms, who have pathogenic TSC mutations.A 31-year-old female with past medical history of leiomyomas status post myomectomy presented to the emergency department for a hemorrhagic adnexal cyst. Imaging incidentally identified a renal mass suspicious for RCC. Out of concern for hereditary leiomyomatosis and renal cell carcinoma (HLRCC) syndrome, the mass was surgically removed and confirmed as RCC. Discussion with medical genetics ascertained a family history of kidney cancer and nephrectomy procedures and a patient history of ungual fibromas on the toes. Genetic testing for hereditary kidney cancer revealed a 5'UTR deletion in the TSC1 gene, leading to a diagnosis of TSC. Following the diagnosis, dermatology found benign skin findings consistent with TSC. About six months after the incidental finding of RCC, a PNET in the pancreatic body/tail was incidentally found on chest CT imaging, which was removed and determined to be a well-differentiated PNET. Later, a brain MRI revealed two small cortical tubers, one in each frontal lobe, that were asymptomatic; the patient's history and family history did not contain seizures or learning delays. The patient presently shows no evidence of recurrence or metastatic disease, and no additional malignant tumors have been identified.To our knowledge, this is the first report in the literature of a TSC patient without a history of neurocognitive disorders with RCC and PNET, both independently rare occurrences in TSC. The patient had a strong family history of renal disease, including RCC, and had several other clinical manifestations of TSC, including skin and brain findings. The incidental finding and surgical removal of RCC prompted the genetic evaluation and diagnosis of TSC, leading to a comparably late diagnosis for this patient. Reporting the broad spectrum of disease for TSC, including more malignant phenotypes such as the one seen in our patient, can help healthcare providers better identify patients who need genetic evaluation and additional medical care.© 2024. The Author(s).