Ji-Youn Sung

Family history is an important risk factor for prostate cancer. Here, we report a whole-exome sequencing (WES)-based study of a Korean family with five prostate cancer cases over three generations, aimed at identifying novel candidate genes for hereditary prostate cancer. Blood samples were collected from nine male family members across the second and third generations, comprising three affected patients (the two remaining deceased cases could not be sampled) and six unaffected relatives. WES was performed on all nine blood samples and on three matched primary tumor tissues from the affected patients. Variants were annotated with ANNOVAR and filtered by calling quality (≥100), population frequency (CCDC170 (c.1146delG, p.E383Sfs*26) was selected as the most promising novel candidate, based on its loss-of-function nature and known association with breast cancer. We propose a frameshift variant in CCDC170 as a novel candidate susceptibility allele for hereditary prostate cancer in this Korean family. Further functional studies are warranted to validate this hypothesis.

Pulmonary manifestations of benign metastasizing leiomyoma (BML) usually include multiple well-defined, round, bilateral nodules. Low-grade endometrial stromal sarcoma (LG-ESS) is a rare uterine tumor. A 70-year-old woman visited the clinic complaining of acute cough and dyspnea in April 2017. Chest computed tomography (CT) revealed pneumothorax and multiple pulmonary nodules. She had a history of hysterectomy for uterine leiomyoma 23 years ago. Biopsy revealed that the pulmonary masses were consistent with BML. However, the patient had two subsequent episodes of acute, recurrent respiratory distress, accompanied by massive pleural effusions and hydropneumothorax over the next two years. A chest CT performed for acute dyspnea revealed large and multiple hydropneumothoraces. The size and distribution of pulmonary masses were aggravated along with cystic changes and bilateral pleural effusions. Given this aggressive feature, additional immunohistochemical findings and gynecologic pathologist review confirmed the correct diagnosis to be LG-ESS. After initiating anti-estrogen therapy, the patient achieved a partial response, without recurrence of symptoms, for 28 months. Metastatic LG-ESS responds well to anti-hormonal therapy. If the clinical pattern of a disease is different than expected, the possibility of a correction in the diagnosis should be considered.