title: Thyroid Pathology Findings in Cowden Syndrome: A Clue for the Diagnosis of the PTEN Hamartoma Tumor Syndrome.
abstract: OBJECTIVE
  PTEN hamartoma tumor syndrome (PHTS) is a hereditary disorder caused by germline inactivating mutations of the PTEN gene. PHTS includes Cowden syndrome and Bannayan-Riley-Ruvalcaba syndrome. We describe how the peculiar pathologic and immunohistochemical thyroid features lead pathologists to suggest PHTS.
  
  
  METHODS
  A 28-year-old white Spanish woman had a multinodular goiter. Total thyroidectomy was performed after fine-needle aspiration biopsy. Microscopic, immunohistochemical, and molecular analyses of the thyroid lesions were realized.
  
  
  RESULTS
  The thyroid was multinodular, showing one papillary microcarcinoma, five follicular adenomas, three adenolipomas, 46 tiny adenomatous nodules (microadenomas), scattered foci of adipose tissue, and lymphocytic thyroiditis. Tumors were positive for thyroglobulin, thyroperoxidase, pendrin, cyclin D1, and p27 but negative for calcitonin and PTEN. A germline heterozygous deletion of one adenine at nucleotide 827 in exon 8 of the PTEN gene was confirmed. No BRAF, NRAS, or KRAS somatic mutations were detected in the papillary microcarcinoma, follicular adenoma, adenolipomas, or microadenomas. Negativity for PTEN was also found in the colonic tubulovillous adenoma and the storiform collagenoma.
  
  
  CONCLUSIONS
  Pathologists play a crucial role in recognizing pathologic thyroid findings associated with PHTS for selecting patients for genetic testing.
authors.affiliation: From the Departments of Anatomic Pathology and Department of Anatomic Pathology, Medical Faculty, University of Santiago de Compostela, Santiago de Compostela, Spain; josemanuel.cameselle@usc.es.
authors.forename: José
authors.initials: J
authors.lastname: Cameselle-Teijeiro
authors.affiliation: Departments of Anatomic Pathology and.
authors.forename: Carmen
authors.initials: C
authors.lastname: Fachal
authors.affiliation: Endocrinology, Clinical University Hospital, Health Research Institute of Santiago de Compostela, SERGAS, Santiago de Compostela, Spain;
authors.forename: José M
authors.initials: JM
authors.lastname: Cabezas-Agrícola
authors.affiliation: Departments of Anatomic Pathology and.
authors.forename: Natividad
authors.initials: N
authors.lastname: Alfonsín-Barreiro
authors.affiliation: From the Departments of Anatomic Pathology and.
authors.forename: Ihab
authors.initials: I
authors.lastname: Abdulkader
authors.affiliation: Galician Public Foundation of Genomic Medicine (FPGMX), Clinical University Hospital, Santiago de Compostela, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Vega-Gliemmo
authors.affiliation: Gastroenterology, Hospital do Meixoeiro, SERGAS, Vigo, Spain; and.
authors.forename: José Antonio
authors.initials: JA
authors.lastname: Hermo
mesh_terms: D000328:Adult; D005260:Female; D006044:Goiter, Nodular / Q000235:genetics* / Q000473:pathology* / Q000601:surgery; D006223:Hamartoma Syndrome, Multiple / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D051059:PTEN Phosphohydrolase / Q000235:genetics*; D017384:Sequence Deletion; D013965:Thyroidectomy
chemical_list: D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human
keywords: Adenolipoma; Cowden syndrome; Ganglioneuroma; Gastrointestinal polyps; Hamartoma; PTEN; PTEN-hamartoma tumor syndrome; Papillary carcinoma; Storiform collagenoma; Thyroid