Adrenal cortical carcinoma is an aggressive and rare malignancy of steroidogenic cells of the adrenal gland. Most adult adrenal cortical carcinomas are sporadic, but a small fraction may be associated with inherited tumor syndromes, such as Li-Fraumeni, multiple endocrine neoplasia 1, Lynch syndrome, and Beckwith-Wiedemann syndrome, as well as isolated case reports of non-syndromic manifestations occurring in the context of other pathogenic germline variants. Birt-Hogg-Dubé (BHD) is a rare autosomal dominant syndrome caused by germline pathogenic variants in the FLCN gene. BHD syndrome causes a constellation of symptoms, including cutaneous manifestations, pulmonary cysts and pneumothorax, and risk of renal tumors. With the exception of a single case of adrenal cortical carcinoma, very few reports on the occurrence of adrenal cortical neoplasia in patients with BHD syndrome have been described. However, information on variant allele fraction in the tumor was not available in the index case, which precludes any mechanism supporting loss of heterozygosity. Here we present a case of an adult-onset adrenal cortical carcinoma in a 50-year-old female, found to harbor a germline likely pathogenic variant in the FLCN gene, denoted as c.694C > T (p.Gln232Ter). Genetic testing on the tumor revealed the same FLCN variant at an allele fraction of 83%, suggesting a contributory role to the pathogenesis of the adrenal cortical carcinoma. This case further supports the expansion of the clinical presentation and tumor spectrum of BHD syndrome and the need to consider germline FLCN testing in the clinical genetic workup of patients with adrenal cortical carcinomas.

肾上腺皮质癌是肾上腺类固醇生成细胞的一种侵袭性和罕见恶性肿瘤。大多数成人肾上腺皮质癌是散发性的，但小部分可能与遗传性肿瘤综合征有关，如 Li-Fraumeni、多发性内分泌瘤 1、Lynch 综合征和 Beckwith-Wiedemann 综合征，以及非综合征性肾上腺皮质癌的孤立病例报告在其他致病性种系变异的情况下发生的表现。Birt-Hogg-Dubé (BHD) 是一种罕见的常染色体显性遗传综合征，由FLCN中的种系致病性变异引起基因。BHD 综合征会引起一系列症状，包括皮肤表现、肺囊肿和气胸，以及患肾肿瘤的风险。除了一例肾上腺皮质癌病例外，很少有关于 BHD 综合征患者发生肾上腺皮质瘤的报道。然而，在指示病例中没有关于肿瘤中变异等位基因分数的信息，这排除了支持杂合性丢失的任何机制。在这里，我们介绍了一名 50 岁女性的成年发病肾上腺皮质癌病例，发现其 FLCN 基因中存在胚系可能致病性变异，表示为 c.694C > T (p.Gln232Ter)。对肿瘤的基因检测揭示了相同的FLCN等位基因分数为 83% 的变异，表明对肾上腺皮质癌的发病机制有促进作用。该病例进一步支持 BHD 综合征临床表现和肿瘤谱的扩展，以及在肾上腺皮质癌患者的临床基因检查中 考虑种系FLCN检测的必要性。