Benign goiters requiring thyroidectomy as the signal for PTEN hamartoma tumor syndrome diagnosis.

PTEN hamartoma tumor syndrome (PHTS) is a rare genetic cancer and tumor predisposition syndrome. Due to the wide spectrum of clinical manifestations and variable age at onset, the pathways leading to a PHTS diagnosis are difficult and highly variable. Many patients were found to have PHTS after a cancer diagnosis, missing the opportunity of prevention or enhanced cancer screening. This retrospective study evaluated a PHTS cohort followed in a high-risk surveillance clinic in a comprehensive cancer institution. A significant portion of the patients (60.9%, 14/23) had at least one cancer diagnosis (average age 34.6 years at diagnosis). A significant portion (78.3%, 18/23) were affected with clinically significant goiters (age 27.9 years), and many (60.9%, 14/23) had partial or total thyroidectomy (age 27.1 years). The average age at goiter diagnosis or thyroidectomy is younger than a cancer diagnosis. In 12 individuals who were affected with clinically significant goiter and cancer, all cancers were diagnosed after the thyroid disease (6.3 years). As clinically significant thyroid nodules in childhood or early young adulthood are common in PHTS, but uncommon for general population, these early onset thyroid nodules may alert the clinician to initiate PHTS-targeted evaluation and genetic testing.

Cowden syndrome: new clinical features in a large family; joint hyperextensibility, dental abnormalities and gingival enlargement.

A 4-year-old boy presented with his mother to genetics in the 1980s, with a family history (FH) of macrocephaly and intellectual disability (ID). He remained undiagnosed until his mother developed multiple cancers and was diagnosed with Cowden syndrome (CS) in 2017, a rare, multisystem cancer predisposition syndrome. CS was then confirmed in multiple family members. Clinical examination revealed potentially novel features; gingival enlargement, dental abnormalities and joint hyperextensibility. These features could contribute to revised PTEN hamartoma tumour syndrome, National Comprehensive Cancer Network, minor diagnostic criteria. The paediatric CS phenotype is still emerging and features expressed in this family during childhood could potentially aid paediatric diagnosis. This case reminds clinicians to seek genetic input for PTEN testing when macrocephaly is identified alongside, a personal or FH of ID, early-onset tumours (especially breast, bowel or thyroid) or multiple tumours. Thus detailed FH is pivotal to earlier CS diagnosis and improved patient outcomes.

Giant Cerebral Aneurysm in a Patient with Cowden Syndrome Treated with Surgical Clipping.

BACKGROUND: Cowden syndrome is characterized by multiple hamartomas and accompanied by a germline mutation of the phosphatase and tensin homolog gene. Cowden syndrome has been described to be associated with vascular anomalies such as arteriovenous malformation and developmental venous anomalies with high frequency. However, the association of cerebral aneurysms with this syndrome has not been reported yet. CASE DESCRIPTION: A 39-year-old Japanese man presented with a subarachnoid hemorrhage due to a ruptured giant fusiform middle cerebral artery aneurysm. We diagnosed him with Cowden syndrome by clinical presentations as outlined in the National Comprehensive Cancer Network's criteria. As the ruptured fusiform aneurysm involved a middle cerebral artery bifurcation, we prepared for extracranial-intracranial bypass surgery. We successfully performed a surgical clipping using multiple tandem clipping techniques and suction decompression techniques. Bypass surgery was not performed as reconstruction of the M2 trunks was successfully completed. CONCLUSIONS: We present this rare case that potentially indicates an association between cerebral aneurysms and Cowden syndrome. Because vascular anomalies are not included in the diagnostic criteria for Cowden syndrome, intracranial vascular anomalies may be underestimated. We therefore recommended a careful search of vascular diseases, including cerebral aneurysms, in cases of Cowden syndrome.

A case of Cowden's syndrome presenting with gastric carcinomas and gastrointestinal polyposis.

BACKGROUND: A 73-year-old white man was referred to a cancer genetics clinic for evaluation of a approximately 20-year history of mixed upper and lower gastrointestinal polyposis, including hyperplastic, inflammatory and adenomatous polyps, colonic ganglioneuromas, and associated diffuse, esophageal glycogenic acanthosis. Two synchronous gastric carcinomas had been identified before referral and the patient had undergone a total gastrectomy, omentectomy and cholecystectomy. Multiple hyperplastic polyps and small, sessile polyps were also observed in the gastrectomy specimen. INVESTIGATIONS: History and physical examination, upper and lower gastrointestinal endoscopy and biopsy, genetic testing, molecular pathology investigations (immunohistochemistry), thyroid ultrasonography, fine-needle aspiration of a thyroid nodule. DIAGNOSIS: Cowden's syndrome. MANAGEMENT: Genetic counseling, thyroidectomy, vitamin B(12) supplementation, continued endoscopic surveillance and genetic testing of at-risk family members.

Germline mutations in PTEN and SDHC in a woman with epithelial thyroid cancer and carotid paraganglioma.

BACKGROUND: A 43-year-old woman presented to a cancer genetics clinic for a genetic risk assessment because of her personal history of multiple neoplasias. At 37 years of age, she was diagnosed with multifocal papillary thyroid cancer, and within a year was further diagnosed with a paraganglioma of the left common carotid artery. Two years later, she was diagnosed with a paraganglioma of the right carotid body. All three tumors were treated with surgical resection. There was no family history of malignancy. Past medical history includes uterine leiomyoma and fibrocystic breast disease. Physical examination revealed macrocephaly and papillomatous papules. INVESTIGATIONS: CT scan of the neck and thorax, 24-hour urine collection for measurement of metanephrines and catecholamines, MRI of the neck, thorax, and abdomen, metaiodobenzylguanidine scan, germline mutation analysis of PTEN, SDHB, SDHC and SDHD. DIAGNOSIS: Cowden syndrome due to a germline mutation of PTEN, and pheochromocytoma-paraganglioma syndrome due to a germline mutation of SDHC. MANAGEMENT: Clinical surveillance for breast, endometrial, thyroid, and renal cell carcinoma risks associated with Cowden syndrome according to the National Comprehensive Cancer Network guidelines, annual MRI of the neck, thorax, abdomen and pelvis, annual metabolic screening, and where available, annual 18-fluorodopamine PET scanning, predictive genetic testing of both PTEN and SDHC for the patient's daughter and parents.

[Cowden's disease: a new paediatric observation]. / La maladie de Cowden: une nouvelle observation pédiatrique.

We report on a paediatric observation of Cowden's disease in a 6-year-old child. Familial steroid-resistant nephrotic syndrome was associated to papulous and papillomatous lesions of gingiva and oral mucosa, multiple hamartoma of the back and of upper limbs, facial dysmorphism and follicular thyroid cancer. Thyroid cancer evolved favorably after surgical treatment, radioactive iodine and L-thyroxin supplementation. Nephrotic syndrome evolved to chronic renal insufficiency after 11 years. The early diagnosis of Cowden's disease, or multiple hamartoma syndrome, allows a careful monitoring of the patients who are facing the risk of cancer transformation, which is the principal complication of the condition.

Gastrointestinal manifestations of Cowden's disease. Report of four cases.

Four patients with an established diagnosis of Cowden's disease underwent barium meal study, upper gastrointestinal endoscopy, barium enema examination, and colonoscopy. In three, the esophagus was affected by small protrusions, which were diagnosed as glycogenic acanthosis. Numerous hyperplastic polyps were found in the stomach in three patients, and in one an inflammatory fibroid polyp was also detected. Either lymphangiectasia or lymphoid polyps were found in the duodenum in two patients. In all patients, the colon showed polyps that varied in histology and included adenoma, hamartomatous polyp, and ganglioneurofibroma. In addition, jejunal lymphangiomas were found in one of the three patients in whom the small intestine could be precisely evaluated. These findings suggest that the gastrointestinal involvement in Cowden's disease is characterized by various benign lesions, especially esophageal glycogenic acanthosis, numerous gastric hyperplastic polyps, and multiple hamartomatous polyps in the rectosigmoid colon. Detection of these gastrointestinal manifestations may lead to early diagnosis of this potentially malignant disease.