Table 11.
Individual from a family with a known PTEN mutation |
Individual meeting clinical diagnostic criteria for Cowden syndrome (CS) as outlined below |
Individual with a personal history of any of the following: |
Bannayan–Riley–Ruvalcaba syndrome (BRRS) |
Adult Lhermitte–Duclos disease |
Autism spectrum disorder and macrocephaly |
Two or more biopsy-proven trichilemmomas |
Two or more major criteria (one must be macrocephaly) |
Three major criteria, without macrocephaly |
One major and ≥three minor criteriab |
≥Four minor criteria |
At-risk individual with one major or two minor criteria and a relative with a clinical diagnosis of CS or BRRS for whom testing has not been performed |
Major criteria |
Breast cancer |
Endometrial cancer |
Follicular thyroid cancer |
Multiple gastrointestinal hamartomas or ganglioneuromas |
Macrocephaly (megalocephaly, ≥97th percentile) |
Macular pigmentation of glans penis |
Mucocutaneous lesions alone if: |
One biopsy proven trichilemmoma, or |
Multiple palmoplantar keratoses, or |
Multifocal or extensive oral mucosal papillomatosis, or |
Multiple cutaneous facial papules (often verrucous) |
Minor criteria |
Autism spectrum disorder |
Colon cancer |
Esophageal glycogenic acanthosis (≥3) |
Lipomas |
Mental retardation (i.e., IQ ≤75) |
Papillary or follicular variant of papillary thyroid cancer |
Thyroid structural lesions (e.g., adenoma, nodule(s), goiter) |
Renal cell carcinoma |
Single gastrointestinal hamartoma or ganglioneuroma |
Testicular lipomatosis |
Vascular anomalies (including multiple intracranial developmental venous anomalies) |
Adapted with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Genetic/Familial High-Risk Assessment: Breast and Ovarian V.4.2013.(3) 2014 National Comprehensive Cancer Network. All rights reserved. The NCCN Guidelines and illustrations herein may not be reproduced in any form for any purpose without the express written permission of the NCCN. To view the most recent and complete version of the NCCN Guidelines, go online to NCCN.org. NATIONAL COMPREHENSIVE CANCER NETWORK, NCCN, NCCN GUIDELINES, and all other NCCN content are trademarks owned by the National Comprehensive Cancer Network.
If an individual has two or more major criteria, such as breast cancer and nonmedullary thyroid cancer, but does not have macrocephaly, one of the major criteria may be included as one of the three minor criteria to meet testing criteria.