Introduction: PTEN-harmatoma-tumor syndrome is an umbrella term that describes a group of genetic disorders linked to germline mutations of PTEN (Phosphatase and tensin homolog), a tumor suppressor gene that inhibits the PI3/Akt signalling pathway thereby inhibiting proliferation, cell survival and angiogenesis. PTEN-harmatoma-tumor syndrome encompasses Cowdens Syndrome, BannayanRileyRuvalcaba syndrome, and autism spectrum disorder (ASD) associated with macrocephaly. It is associated with increased tumor risk mostly breast, endometrial, thyroid, colon and renal malignancies and with benign growths such as gastrointestinal polyps, brain and skin lesions. It has not been related to osteosarcoma. Here we describe an osteosarcoma in a patient with a familial PTEN mutation.
Clinical case: A 10 year old girl with, ASD, macrocephaly, global developmental delay (GDD), obesity and epilepsy, was found to have inherited a PTEN mutation form her mother, when the mother was diagnosed with Cowden syndrome due to thyroid cancer and mild learning difficulties. The girl was regularly monitored for thyroid malignancy. She presented with a 1 week history of a limp. Imaging revealed periosteal reaction and findings suggestive of osteosarcoma of the distal left femur. Histological analysis of a biopsy confirmed high grade chondroblastic osteosarcoma. Staging was T2,N0,M0,G3, Overall America Joint Committee on Cancer Stage: IIB. She underwent primary surgical resection and insertion of endoprosthesis as behavioural difficulties precluded safe administration of chemotherapy. She developed pulmonary and bone metastases 9 months later, had palliative radiotherapy, but passed away 5 months later. Her younger brother with the same mutation has ASD, GDD, tall stature, obesity and macrocephaly. He developed a thyroid nodule, aged 10. A biopsy was in line with Th2 classification and he is under close surveillance. He had several episodes of leg pain without clear etiology.
Conclusion: This case report suggests the association between PTEN and osteosarcoma confirming two recent case reports. PTEN is expressed in osteoprogenitors and targeted deletion in mice results in increased osteoblast number due to autonomous differentiation from growth plate chondrocytes. Thus, osteosarcoma should be considered in patients with PTEN-harmatoma-tumor syndrome and bone pain. Further research is required to establish incidence and requirement for surveillance.
27 - 29 Nov 2019
British Society for Paediatric Endocrinology and Diabetes