Autosomal Dominant Inherited Cowden's Disease in a Family
A 52-year-old male patient without any relevant medical history visited the hospital with a symptom of recent lower abdominal pain. The patient had been smoking for 35 years and had a past history of heavy alcohol consumption. He received a lipoma surgery for a palpable mass pressure in the anterior neck portion 3 years ago. For the first time in his life, the patient received colonoscopy, which showed multiple polyps of different size and shape in the terminal ileum, the colon and the rectum (), especially hundreds in the rectum. Several biopsies were taken throughout the entire large bowel including the terminal ileum, and they were histopathologically confirmed as inflammatory and hyperplastic polyps. Physical examination revealed that the head circumference of the patient was 630 mm (for reference, the average and 99 percentile occipitofrontal circumferences of Korean males between 50 and 59 years old are 568 and 601 mm, respectively), suggesting macrocephaly. Also black pigmented cutaneous papules could be seen on the lips and multiple soft humps were found in the posterior neck, arm, and hip. The neck computed tomography (CT) revealed dense fat masses in the posterior neck as well as in both the submandibular and supraclavicular areas (). The upper GI endoscopy revealed multiple mucosal papillomas at the gingiva, oral cavity, soft palate, pharynx, and epiglottic areas (). There were also elevated flat lesions of whitish color in the esophagus, and biopsies showed they were squamous acanthosis. The multiple round gastric and duodenal polyps of various sizes were turned out to be hyperplasia ().\nConsidering all symptoms and the results of the examinations, CD was the most likely clinical diagnosis. Imaging studies of the brain, thyroid, chest, and abdomen as well as PTEN gene mutation test were performed. At thyroid ultrasonography (USG), an oval shaped isoechoic nodule of 1.2 cm in diameter was found in the isthmus. The fine needle aspiration (FNA) was consistent with nodular hyperplasia. The abdominal CT scan presented hemangiomas approximately 2 and 2.7 cm in size in both lobes of the liver, and a gallbladder stone of 7 mm in size. The brain magnetic resonance imaging (MRI) and the chest CT did not show any mass or abnormal finding. The laboratory test results were also within the normal ranges.\nThe examination of the genomic DNA showed a known mutation, c741dupA, in exon 7, which is registered in the Human Gene Mutation Database. It was predicted to lead the frameshift mutation that results in the formation of the premature stop codon (p. Pro248ThrfsX5) for the PTEN protein translocation.\nThe study was extended to the patient's daughters in order to carry out the adequate screening. The eldest daughter, who was 28-year-old at the moment, received a total thyroidectomy with left modified radical neck dissection and high dose 131I therapy (150 mCi) about a year ago. At that time, thyroid USG showed that there were three thyroid nodules and abnormally enlarged multiple lymph nodes in the left upper and mid jugulodigastric chain. FNA revealed papillary carcinoma with lymph node metastases. Biopsy of the surgical specimen showed multifocal intrathyroidal papillary carcinoma and Hashimoto's thyroiditis with the right perithyroidal and the left level IV and V regions lymph nodes metastases (). Breast USG showed multiple cysts of well-defined smooth borders which were less than 1 cm in diameter and a septated cystic mass which was 2.8 cm in diameter. Core needle biopsy of the 2.8 cm sized cystic mass at the outer area of the lower right quadrant revealed intraductal papilloma. She also had the head circumference of 610 mm in diameter, indicating macrocephaly (The average and 99 percentile occipitofrontal circumferences of Korean females aged between 25 and 29 years old are 552 and 583 mm, respectively). The black pigmented lip, the multiple papillomas of the gum and the soft tissue mass in the size of 9×6×5 cm on the right side of the posterior axillary area, were also found, and the excisional biopsy of the soft tissue mass revealed lipoma. GI tract examination, which was the first time in her life, showed multiple acanthosis lesions in the esophagus, numerous polyps in the second and third regions of duodenum, one fundic gland polyp, and the presence of a lot of inflammatory and hyperplastic polyps in the terminal ileum and the rectum.\nIn case of the second daughter who was 25-year-old at the moment, there were no suspicious results on the physical examination, GI tract endoscopy, USG of breast and thyroid, and PTEN mutation test was negative.