The clinical and phenotypic spectrum of PTEN hamartoma tumor syndrome: a retrospective cohort study.

PTEN

Germline pathogenic PTEN variants, including one case of constitutional mosaicism identified by tumour sequencing after negative blood testing

This retrospective cohort gathered 62 adults followed in specialised high-risk clinics who met the diagnostic criteria for PTEN hamartoma tumour syndrome, either through identification of a germline pathogenic or likely pathogenic variant or through NCCN clinical criteria. Median age at inclusion was 39.5 years (IQR 28-52) and a pathogenic or likely pathogenic PTEN variant was identified in 50 patients (80.6%). Colonic polyps were present in 40 patients and malignancies were reported in 61% (n = 38), most frequently breast (n = 13) and thyroid cancer (n = 7). Three patients (4.8%) had rare soft tissue tumours: a desmoid tumour at age 18, concurrent axillary osteosarcoma and bilateral chest liposarcoma, and a skull-base sarcoma. Macrocephaly was observed in 33.8% of patients (n = 21) and developmental delay, including autism spectrum disorder, in 8 patients (12.9%); one case of PTEN mosaicism was identified through tumour sequencing after negative germline blood testing.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

The most operational message is not the tumour spectrum, which is already known, but the mosaicism case found by tumour sequencing after a negative blood test: faced with a suggestive clinical picture and normal germline testing, analysing lesional tissue must stay on the table. The rare soft tissue tumours in 3 of 62 patients widen a spectrum that surveillance protocols do not cover, although such small numbers do not support any change in management. Macrocephaly in only 33.8%, well below the proportions usually reported in this syndrome, signals recruitment skewed toward the gastrointestinal presentation and warns against reading the 61% cancer rate as a penetrance figure.

Analysis by Dr Thibaut Benquey