Table 1.

Revised PTEN hamartoma tumor syndrome (PHTS) diagnostic criteria.

Revised PTEN Hamartoma Tumor Syndrome (PHTS) Clinical Diagnostic Criteria [16,17]
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 PHTS 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
Major Criteria
Breast cancer
Endometrial cancer (epithelial)
Thyroid cancer (follicular)
Gastrointestinal hamartomas (including ganglioneuromas, but excluding hyperplastic polyps) (≥3)
Lhermitte–Duclos disease (LDD), adult
Macrocephaly (≥97 percentile)
Macular pigmentation of the glans penis
Multiple mucocutaneous lesions (any of the following):
Multiple trichilemmomas (≥3), at least one biopsy proven
Acral keratoses (≥3 palmoplantar keratotic pits and/or acral hyperkeratotic papules)
Mucocutaneous neuromas (≥3)
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 (i.e., Intelligence Quotient (IQ) ≤ 75)
Renal cell carcinoma
Testicular lipomatosis
Thyroid cancer (papillary or follicular variant of papillary)
Thyroid structural lesions (e.g., adenoma, multinodular goiter)
Vascular anomalies (including multiple intracranial developmental venous anomalies)