O-02 RADIOTHERAPY-INDUCED MALIGN PERIPHERAL NERVE SHEATH TUMOR IN A PATIENT WITH ACROMEGALY AND AIP-RELATED FIPA

Abstract Introduction We report a patient with an AIP gene mutation who developed a malignant peripheral nerve sheath tumor (MPNST) within the sellar region following surgery and fractionated radiotherapy for a growth hormone secreting pituitary adenoma. AIP mutations are associated with familial isolated pituitary adenoma (FIPA) and typically present with aggressive tumors at a young age. While radiotherapy remains an important treatment modality for residual or recurrent pituitary adenomas, it may also increase the risk of secondary malignancies. The coexistence of a predisposing germline mutation and prior cranial irradiation raises concern for a potential synergistic effect on tumorigenesis. Clinical Case A 64-year-old male with a history of pituitary macroadenoma underwent transsphenoidal surgery in 1995 in the USA due to diplopia, with pathology revealing a plurihormonal pituitary adenoma. He was followed by a second surgery in 2002 in Turkey for tumor recurrence, after which fractionated radiotherapy (54 Gy in 30 fractions) was administered for residual disease. In 2024, he presented with new-onset left eye exotropia and ptosis. Cranial MRI revealed a sellar mass, and transsphenoidal resection was performed. Histopathology confirmed a radiotherapy-induced malignant peripheral nerve sheath tumor. Family history revealed a son with acromegaly carrying the same AIP mutation (c.646-1G>C) identified in the index patient, and a daughter with a pituitary adenoma. The patient’s sister also carried the AIP mutation. These findings were FIPA, and also the patient’s mother and sister had a history of breast cancer. He had panhypopituitarism after surgery and was started on levothyroxine and glucocorticoid replacement. Postoperative FDG-PET/CT showed no additional hypermetabolic lesions suggestive of metastasis or other malignancies. Temozolomide therapy was initiated by the oncology team as adjuvant treatment, and the patient was scheduled for close clinical and radiological follow-up. Conclusion Patients with AIP-related pituitary adenomas who have undergone cranial radiotherapy may have an increased risk of developing secondary malignancies. The potential interplay between genetic predisposition and radiation exposure should be considered, but confirmation of this association requires larger cohorts and further studies. Long-term follow-up is advisable in such cases.Figure 1Index case's family history