SAT-513 - A Rare PDGFRA Mutation in A Patient with Endocrine Tumor Family History

Introduction: Mutations of the platelet derived growth factor alpha (PDGFRA) gene, a tyrosine kinase receptor, have been connected to the development of gastrointestinal stromal tumors (GISTs). Additionally, mutations of this gene have also been found in organs such as the pancreas and gallbladder. Its oncogenic potential has yet to be fully described, though it remains a popular topic of investigation in oncologic research.

Case Report: In this report, we discuss the case of a 54-year-old Caucasian woman with a family history of pancreatic neuroendocrine tumor in her father and a past medical history of pheochromocytoma, cystic pancreatic mass, stage I lobular carcinoma of the left breast, and DCIS of the right breast who was found to have a variant of unknown significance in the PDGFRA gene. The patient initially presented after a left-sided 3.2 cm adrenal mass with central hypoattenuation and peripheral enhancement was incidentally discovered on CT during workup for an ascending colon mass. At that time, she reported having experienced brief episodes of tremors, lightheadedness, and palpitations several times weekly for approximately two decades, though she was never found to be hypertensive. Lab work showed a serum metanephrine level of 338 pg/mL (normal: ≤57 pg/mL) and a serum normetanephrine level of 279 pg/mL (normal: 148 pg/mL). She underwent left adrenalectomy and pathology confirmed suspicion of pheochromocytoma; post-operatively she experienced complete resolution of her symptoms. Her genetic workup was negative for known mutations associated with pheochromocytoma but did identify a variant of uncertain significance missense mutation in codon 8 of the PDGFRA gene resulting in the substitution of lysine for glutamine (c.1189C>A). Interestingly, the patient’s son experienced symptoms similar to those she reported pre-operatively in addition to treatment-resistant hypertension, though he has not yet undergone a formal workup.

Discussion: At the time of writing this report, our patient is the only reported case of this specific mutation of the PDGFRA gene, although over 50 other mutations in codon 8 of this gene have been recorded. The patient's diagnosis and family history of neuroendocrine tumor in her father and high clinical suspicion for pheochromocytoma in her son, prompts consideration regarding the possibility that this mutation—and potentially PDGFRA mutations more broadly—may be associated with a previously unrecognized predisposition to hereditary endocrine tumors. Further investigation is required to determine whether such an association exists.

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