Confirmed germline pathogenic / likely-pathogenic variant in the PTEN gene (Cowden syndro...

Deterministic view of the source YAML entity. Clinical authority remains with the cited source IDs and reviewer sign-off state.

ID	`RF-COWDEN-CONFIRMED-CARRIER`
Type	Red flag
Status	reviewed 2026-05-18 \| pending_clinical_signoff
Diseases	`DIS-BREAST` `DIS-CRC` `DIS-ENDOMETRIAL` `DIS-RCC` `DIS-THYROID-PAPILLARY`
Sources	`SRC-NCCN-BCELL-2025` `SRC-NCCN-BREAST-2025` `SRC-NCCN-GENETIC-FAMILIAL-BREAST-OVARIAN-2025`

Red Flag Origin

Definition	Confirmed germline pathogenic / likely-pathogenic variant in the PTEN gene (Cowden syndrome / PTEN hamartoma tumor syndrome, PHTS). Patient has had germline PTEN testing returned positive; the pedigree-suspicion question is settled. No current personal cancer diagnosis in the carrier being assessed. Mandates multi-organ surveillance for the Cowden-spectrum cancers (breast — ~85% lifetime; endometrial — ~28%; thyroid — ~35%; renal — ~34%; colorectal — ~9%; melanoma — ~6%) with protocols starting variously between diagnosis and age 40 depending on organ. Prevention-persona RedFlag (§20, v0.2-B confirmed-carrier surveillance pathway — distinct from RF-COWDEN-FAMILY-HISTORY-SUSPICION which fires before testing).
Clinical direction	investigate
Category	other

Trigger Logic

{
  "any_of": [
    {
      "finding": "germline_pten_pathogenic_variant_confirmed",
      "value": true
    }
  ],
  "type": "lab_value"
}

Notes

v0.2-B confirmed-carrier surveillance pathway — Cowden / PHTS. Fires on documented germline PTEN pathogenic variant positivity in an asymptomatic individual. Engine routes to PreventionPlan recommending: (a) IND-COWDEN-CARRIER-SURVEILLANCE (standard) — annual breast mammography + MRI from age 30 (women); annual thyroid US from diagnosis; endometrial sampling / TVUS q1y from age 35-40 (women); colonoscopy from age 35 then per-finding; annual skin exam; renal US or MRI q1-2y from age 40. (b) IND-COWDEN-CARRIER-INTENSIFIED (aggressive) — standard protocol PLUS risk-reducing mastectomy / hysterectomy discussion post-childbearing. STUB pending two-Clinical-Co-Lead signoff per CHARTER §6.1 dev-mode exemption. Source-set TODO: Tan et al. Lifetime cancer risks in PHTS, Clin Cancer Res 2012 — v0.2-B authoring backlog new SRC entity. Lifetime cancer risk in confirmed PTEN carriers (Tan et al. Clin Cancer Res 2012; NCCN Genetic / Familial High-Risk Breast Ovarian): - Breast (women): ~85% lifetime; often early-onset (40s) and bilateral - Endometrial: ~28% lifetime; often early-onset (under 50) - Thyroid (predominantly follicular, also papillary and Hürthle): ~35% lifetime; multinodular goiter...

Used By

Algorithms

ALGO-COWDEN-CARRIER-SURVEILLANCE - ALGO-COWDEN-CARRIER-SURVEILLANCE

Indications

IND-COWDEN-CARRIER-INTENSIFIED - IND-COWDEN-CARRIER-INTENSIFIED
IND-COWDEN-CARRIER-SURVEILLANCE - IND-COWDEN-CARRIER-SURVEILLANCE

Red flag

RF-COWDEN-FAMILY-HISTORY-SUSPICION - Family pedigree suggestive of Cowden syndrome / PTEN hamartoma tumor syndrome (PHTS): any...