Germline pathogenic PTEN variant in a patient with a Kaposiform haemangioendothelioma.

BACKGROUND/OBJECTIVES: Kaposiform haemangioendothelioma (KHE) is a rare vascular neoplasm usually presenting in childhood. Its high morbidity and mortality is secondary to compression, invasion, and coagulopathy. The pathogenensis of KHE remains poorly understood although mTOR inhibitors have been used successfully in management. PTENHarmatoma Tumour Syndrome (PHTS) is a well characterised tumour predisposition syndrome with an ∼85% lifetime tumour risk. In addition, over 50% of patients have vascular anomalies. However, malignant vascular tumours are not a recognised association.

CASE: A 28-year-old female with a KHE was enrolled in the IMAGINE study (Integrating Medically Actionable Genomics Into Early Phase Trials). A PTEN heterozygous c.277C>T p.(His93Tyr) pathogenic variant was detected initially in tumour tissue and subsequently saliva confirming a constitutional (germline) variant. Reverse phenotyping revealed the patient had a large head circumference, palmar keratosis and papillomas on the hand, feet, and gums, in keeping with PHTS.

CONCLUSION: As malignant vascular neoplasms have not been well described in PHTS, this case further demonstrates the utility of genomic tumour profiling in early diagnosis of an Inherited Cancer Susceptibility Disorder (ICSD); particularly in young patients or in those where other features may be subtle. A plausible biological mechanism through upregulation of mTOR signalling also suggests malignant vascular tumours may be a rare tumour association with PHTS.