Table 2.
Revised diagnostic criteria for PTEN hamartoma tumor syndrome/Cowden syndrome [5]
| 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) |
| 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 (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) |
| Three or more major criteria, but one must include macrocephaly, Lhermitte–Duclos disease, or gastrointestinal hamartomas; or |
| 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 |
| Any two major criteria with or without minor criteria; or |
| One major and two minor criteria; or |
| Three minor criteria |
From Pilarski et al. [5]