SAT-314 Malignant Pheochromocytoma: A Rare Neoplasm Easily Confounded with Metastasis and Associated with Lynch Syndrome

Abstract

Introduction : Pheochromocytomas are a rare neoplasm of chromaffin cells of the adrenal medulla with an annual incidence in the United States between 500 to 1600 cases, of which about 10% are malignant. Due to this rarity, adrenal masses, especially in the context of other concurrent primary tumors, can be easily confounded with metastasis. Case Report : A 56-year-old male with diabetes mellitus and hypertension presents with left flank pain associated with hematochezia, constipation, and an 8.2kg weight loss over 2.5 months. Physical examination was unremarkable. Abdominal CT scan showed a 4x5cm left adrenal gland mass with infiltration of peri-adrenal tissues and hemorrhage. Dexamethasone suppression test was normal. Plasma metanephrines and aldosterone were not elevated. Repeat CT a month later showed marked increase of the mass to 6.2x5.8cm and an ascending colon mass. Colonoscopy with biopsy revealed a moderately differentiated adenocarcinoma with immunohistochemistry (IHC) staining negative for MSH2 and MSH6 mismatch repair proteins, typical of Lynch syndrome. The patient had a strong family history of malignancy, positive for endometrial cancer (mother) and colon cancer (mother/brothers). A right segmental hemicolectomy and left adrenalectomy-nephrectomy was performed with a presumption that the adrenal mass was a metastatic site. On pathology, the colon specimen confirmed a 5x4x2cm adenocarcinoma. Surprisingly, the adrenal specimen revealed a 7x6x6cm malignant pheochromocytoma with a Pheochromocytoma of the Adrenal Gland Scaled Score (PASS) of 18 with IHC also negative for MSH2 and MSH6. Repeat CT 4 months post-resection showed new lymphadenopathy followed by PET/CT revealing a 2.7x3.4cm FDG avid left para-aortic lymph node consistent with metastasis and a 2.5cm non-FDG avid cystic mass in the pancreatic tail. Discussion : There is a high prevalence of germline mutations associated with pheochromocytomas, commonly including succinate dehydrogenase (SDH) subunit genes, SDHAF2, TMEM127, MAX-gene, and three main associated syndromes including von Hippel Lindau, multiple endocrine neoplasia type 2, and neurofibromatosis type 1. Lynch Syndrome is diagnosed by a mutation in at least one of these mismatch repair genes: MLH1, MSH2, MSH6, and PMS2. It is often associated with extra-colonic cancers including the endometrium, gastric, biliary, urinary tract, pancreas, small intestine, brain, and skin. There is a growing number of cases reporting neuroendocrine tumors in the setting of Lynch Syndrome. To date, there are only two cases reporting an association between pheochromocytoma and Lynch Syndrome, neither of which were described as malignant pheochromocytomas. We present a case of MSH2 and MSH6 mismatch repair protein deficiency in both colon and adrenal masses, suggesting that Lynch Syndrome may be an additional rare risk factor for malignant pheochromocytoma.

Case of Metastatic Pheochromocytoma and Meningiomas in a Patient With Lynch Syndrome

“…There are some case reports of pheochromocytoma in patients with Lynch syndrome but not metastatic cases. [15][16][17][18] In those case reports, the primary pheochromocytoma tissue had loss of MMR genes by IHC. This was not the result in the pheochromocytoma metastasis from our patient.…”