Adrenocortical Carcinoma in Peutz-Jeghers Syndrome With a Rare STK11 Pathogenic Germline Variant: A Case Report.

backgroundPeutz-Jeghers syndrome (PJS) is an inherited, autosomal-dominant condition, featuring STK11 germline mutations, characterized by hamartomatous gastrointestinal polyps and increased cancer risk. The most commonly associated malignancies are gastrointestinal, pancreatic, and breast cancers. Herein, we report an extremely rare case of PJS with adrenocortical carcinoma (ACC). CASE: A 40-year-old woman was referred to University of Tsukuba Hospital with uncontrolled diabetes mellitus (DM) and hypokalemia in July 2021. Computed tomography (CT) and magnetic resonance imaging (MRI) revealed a 12 cm mass in the right adrenal gland and aortocaval lymph node swelling. Mucocutaneous hyperpigmentation in her lips and fingertips was observed, and multiple stomach and small intestine polyps were visible on CT. We performed open right adrenalectomy with right nephrectomy, partial hepatectomy, and aortocaval lymph node dissection before diagnosing ACC with lymph node metastasis from the pathology. After surgery, multiple lung and liver metastases developed, and combination chemotherapy (etoposide, doxorubicin, and cisplatin, plus mitotane) was started, achieving stable disease for 2 years. We also performed an OncoGuide NCC Oncopanel on the adrenal tumor specimen and blood sample, revealing a rarely reported pathogenic germline variant (c.394T>C, p.C132R) in STK11. This variant was registered as Likely Pathogenic in the NIH Clinvar public database, which led to a PJS diagnosis.

conclusionThis is the second report of ACC associated PJS in a rare germline variant of STK11. Although rare, loss of STK11 function may lead to cancers outside expected sites in PJS cases.