Table 2.

Clinical criteria for PTEN hamartoma tumor syndrome as suggested by Pilarski et al. [22]

Major criteria
•	Breast cancer
•	Endometrial cancer (epithelial)
•	Thyroid cancer (follicular)
•	Gastrointestinal hamartomas (including ganglioneuromas, but excluding hyperplastic polyps; ≥3)
•	Lhermitte-Duclos disease (adult)
•	Macrocephaly (≥97 percentile: 58 cm for females, 60 cm for males)
•	Macular pigmentation of the glans penis
•	Multiple mucocutaneous lesions (any of the following)
	o Multiple trichilemmomas (≥3, at least one biopsy proven)
	o Acral keratoses (≥3 palmoplantar keratotic pits and/or acral hyperkeratotic papules)
	o Mucocutaneous neuromas (≥3)
	o Oral papillomas (particularly on tongue and gingiva), multiple (≥3) OR biopsy proven OR dermatologist diagnosed
Minor criteria
•	Autism spectrum disorder
•	Colon cancer
•	Esophageal glycogenic acanthosis (≥3)
•	Lipomas (≥3)
•	Mental retardation (ie, IQ ≤ 75)
•	Renal cell carcinoma
•	Testicular lipomatosis
•	Thyroid cancer (papillary or follicular variant of papillary)
•	Thyroid structural lesions (eg, adenoma, multinodular goiter)
•	Vascular anomalies (including multiple intracranial developmental venous anomalies)
Operational diagnosis in an individual (either of the following)
1. Three or more major criteria, but one must include macrocephaly, Lhermitte-Duclos disease, or gastrointestinal hamartomas; or
2. Two major and three minor criteria.
Operational diagnosis in a family where one individual meets revised PTEN hamartoma tumor syndrome clinical diagnostic criteria or has a PTEN mutation:
1. Any two major criteria with or without minor criteria; or
2. One major and two minor criteria; or
3. Three minor criteria.