Synchronous bilateral pheochromocytomas and extra-adrenal paragangliomas without specific gene mutations

Abstract

Abstract Introduction/Objective Diagnosis of hereditary paraganglioma-pheochromocytoma syndrome (H-PGL/PCC-S) should be suspected in individuals with pheochromocytoma or paraganglioma, especially those with multifocal lesions, positive family history, or early-onset disease. Recent studies suggest one-third to half of these patients have germline/syndromic associations. We present a challenging case wherein a 44-year-old female with high-risk factors, multiple paragangliomas, and bilateral pheochromocytomas did not have any identifiable syndromic involvement. Methods/Case Report Patient presented seven years ago with epigastric pain, weight loss of 50lbs, and chronic diarrhea. Endoscopic ultrasound revealed 2cm hypoechoic mass behind pancreas, diagnosed as neuroendocrine tumor on fine-needle aspiration. Subsequent SPECT-CT and MRI revealed multiple intra-abdominal lesions, including bilateral adrenal-lesions (right 2cm; left 1.6cm), 2.2cm aortocaval-lesion, and multifocal retroperitoneal lesions, consistent with paragangliomas, gradually increasing in size on follow-up imaging. She also developed intermittent palpitations, flushing, and blood pressure fluctuations. Additionally, multiple thyroid nodules were identified on subsequent ultrasound imaging, suspicious for malignancy on both cytology and Afirma studies. Exploratory laparotomy with left para-adrenal, right infra-renal, and aortocaval nodule-excisions revealed nested tumor cells with abundant granular purple cytoplasm, round central nuclei, prominent nucleoli, diagnosed as moderate to poorly differentiated extra-adrenal paragangliomas with increased metastatic risk based on PASS and GAPP-scoring systems. Additionally, right adrenalectomy revealed pheochromocytoma with 7/20 PASS-score and 4/10 GAPP-score suggesting increased metastatic risk. Results (if a Case Study enter NA) NA Conclusion Young age, strong family-history, multiple high-grade paragangliomas, pheochromocytomas, and suspicious thyroid nodules raise concerns for syndromic association. Multitude of autosomal-dominant syndromes, including paraganglioma-syndromes (PGL1-to PGL5), VHL, MEN2A, MEN2B, and NF1, have been reported. Genes identified in these syndromes include SDHA, SDHB, SDHC, SDHD, SDHAF2, MAX, TMEM127, VHL, NF1, RET, FH, and KIF1B. However, no mutations were identified, thus creating a dilemma in risk-stratification. This leaves out only two considerations: either sporadic PGL/PCC or a yet unidentified genetic-mutation.