Simultaneous Pheochromocytoma, Paraganglioma, and Papillary Thyroid Carcinoma without Known Mutation

Abstract

Background Pheochromocytoma/paraganglioma is a rare tumor from neuroendocrine cells. 1/3rd of cases have germline mutations. Papillary thyroid carcinoma (PTC) is a common neoplasm from follicular cells of the thyroid. We report a case of pheochromocytoma/paraganglioma and PTC with negative testing for common mutations. Case 32-year-old male with incidental liver mass during laparoscopy for acute appendicitis. His symptoms included abdominal pain and profuse axillary hyperhidrosis. MRI showed an 11x12x14 cm cystic and solid mass in right adrenal gland, and 3.4x2.9x3.8 cm mass in porta hepatis. Urine metanephrines was elevated. After preoperative alpha-blockade, patient underwent total right adrenalectomy. Pathology report confirmed diagnosis of pheochromocytoma. According to the Grading system for Adrenal Pheochromocytoma and Paraganglioma (GAPP), tumor's score was 9, indicating poorly differentiated tumor. Ki67 index 5% and S100 were negative. Postoperatively, plasma free metanephrines normalized but plasma free normetanephrines remained elevated. Based on this biochemical profile, presence of paraganglioma was suspected. CT showed 4.2x3.5 cm round soft tissue mass in porta hepatis which increased in size from previous MRI. Simultaneously, PET scan identified a 1.5 cm thyroid mass. Calcitonin level was normal. Fine-needle aspiration was consistent with PTC. Resection of the mass and total thyroidectomy were performed with confirmation of paraganglioma S100 positive and PTC. Normetanephrines decreased to 283 (<148 pg/mL); free metanephrines remained normal. Gene mutation of EGLN1, FH, KIF1B, MEN1, NF1, RET, SDHAF2, SDHC, SDHD, TMEM127, VHL, and SDHA was negative. Conclusion Whether paraganglioma/pheochromocytoma/PTC combination is coincidental or resulted from an underlying unknown mutation cannot be excluded.

The Value of Histological Algorithms to Predict the Malignancy Potential of Pheochromocytomas and Abdominal Paragangliomas—A Meta-Analysis and Systematic Review of the Literature

“…The survey period for the GAPP studies ranged from 2014 to 2018. Four studies reporting the GAPP scores for PCCs were originally identified [2,24,26,31], but only three met all our inclusion criteria and were included in this meta-analysis [2,24,26]. In total, out of 199 PCCs, GAPP scores were retrievable from 175 PCCs, of which four were malignant (2%) (Table 3A).…”

The Role of TMEM127 in mTOR Pathway and Cancer Suppression

“…Gene mutations such as EGLN1, FH, KIF1B, MEN1, NF1, RET, SDHAF2, SDHC, SDHD, TMEM127, VHL and SDHA were all negative. In the case, it is not clear whether the occurrence of paraganglioma/pheochromocytoma/thyroid papillary carcinoma is accidental or caused by underlying genetic susceptibility [38].…”

Feocromocitoma Pheochromocytoma

“…También hasta un 45% pueden tener alguna mutación de fondo sin historia familiar por ser de penetrancia incompleta. Se han descrito varias mutaciones, siendo las más comunes las de Von Hippel-Lindau, del complejo succinato deshidrogenasa D, B y C, las del protooncogen RET y las de Neurofibromatosis tipo 1 (8)(9)(10)(11) . Un 10% de los pacientes tienen un síndrome hereditario relacionado al tumor, por ejemplo MEN IIA/IIB, Esclerosis Tuberal, Feocromocitoma Familiar, entre otras (6) .…”