Table 11.

Indications for genetic evaluation for Cowden syndrome (PTEN hamartoma tumor syndrome)^a

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)

^aAdapted 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.

^bIf 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.