THU614 Neurofibromatosis Type 1 Presenting With Pheochromocytoma And Severe Vascular And Hematological Manifestations Due To A Novel NF1 Mutation
Authors: Alobaid Lulu Abdulaziz , Alsagheir Osamah , Alswailem Meshael , Alghamdi Balgees , Alzahrani Ali Saeed 
Published: October 2023

Disclosure: L.A. Alobaid: None. O. Alsagheir: None. M. Alswailem: None. B. Alghamdi: None. A.S. Alzahrani: None.

Neurofibromatosis (NF) type 1 is an autosomal dominant condition caused by germline mutations in NF1, a tumor suppressor gene encoding neurofibromin. Pheochromocytomas (PCC) and paragangliomas can develop in up to 8% of patients with NF type 1. Vasculopathy leading to vascular narrowing and malformations are also well described manifestations of NF. Finally, a number of hematological manifestations have been described including thrombocytosis, leukocytosis, myelodysplastic syndrome, acute myeloid leukemia, and lymphoma. We present a young woman who has NF type 1 and presented with all of these unusual manifestations including PCC, leukemoid reaction, severe thrombocytosis, vascular malformations and narrowing, extensive skin freckling and café au lait spots. She was found to have a novel truncating NF1 mutation, which explains the severity of her disease. Case description: A 21-year-old lady referred to our hospital with a 4-year history of episodic headaches, blurred vision, on/off palpitations, sweating, and facial redness. She was found to be severely hypertensive at 200-230/95-140 mm Hg. Family history was positive for skin freckling, nodules and café au let spots in her father, two aunts and four siblings. On examination, BP 195/100 mmHg, Pulse 120 bpm. She has widespread skin freckling, and cafe au lait spots of different sizes and shapes. Systemic examination was otherwise normal. Urine metanaphrine was 9.34 umol/day (0-1.49) and normetanephrine 42.16 umol/day (0-3.43). A CT scan of the abdomen showed an 8-cm left adrenal heterogeneously enhancing hypervascular mass and narrowing of the infrarenal abdominal aorta with sever stenosis of celiac artery origin and severe diffuse narrowing of the left external iliac artery. Gallium 68 PET CT scan revealed an uptake at the same mass without other foci of uptake. Laboratory investigations: HbA1c 11.9%, WBC 18-24x109/L, Platelets 850-1,350x109/L. Bone marrow examination was refused by the patient so the exact underlying hematological disorder could not be accurately diagnosed. She was prepared with phenoxybenzamine and labetalol and underwent an open left adrenalectomy. Post operatively, she developed a large right anterior cerebral artery ischemic stroke as a complication of narrow cerebral vessels and the severe thrombocytosis. Histopathological examination confirmed the diagnosis of PCC with Ki67∼20%. Molecular testing revealed a novel truncating NF1 mutation (c.7606C&gt;T, p.Gln2536X). Conclusion: We describe unusually severe haematological and vascular manifestations of NF type 1 in a young girl who presented with a large PCC. These severe manifestations reflect the broad manifestations of NF type 1 due to the important role of neurofibromin in different organs and the significant effects of the underlying NF1 truncating mutation in this patient.

Presentation: Thursday, June 15, 2023