A rare case of mesenteric paraganglioma with late-onset metastases possibly accelerated by surgery

Mesenteric paraganglioma is a very rare condition.¹ An incidence rate of 35% to 40% has been reported for metastases in extra-adrenal paragangliomas.² Surgical trauma may accelerate development of residual and micrometastatic disease.³

We present a case of a 63-year-old man with an 11-year history of mesenteric paraganglioma. The lesion had been observed for the first time on abdominal computed tomography (CT) in 2010. However, the patient was lost to follow-up. In 2021, a CT scan performed due to abdominal pain revealed progression of the tumor size (from 7 cm × 5 cm × 3 cm in 2010 to 13 cm × 10 cm × 10 cm in 2021). The patient was referred for laparotomy. Because of a difficult location and a risk of nonradical surgery, a biopsy of the lesion was performed, leading to the diagnosis of paraganglioma based on histopathologic examination.

Hormonal assessment showed elevated urinary levels of fractionated metanephrines (normetanephrine, metanephrine, and 3-metoxythyramine; 76, 20, and 11 times over the upper limits of normal range [ULN], respectively) and chromogranin A (19 × ULN). Genetic testing for SDHB / SDHD, VHL, RET, MEN1, and MAX mutations was negative. The patient did not present any symptoms of sympathetic paraganglioma. Unfortunately, he once again failed to report for a follow-up visit. A control CT scan performed 11 months later revealed left hydronephrosis secondary to ureteral obstruction caused by the tumor mass, and further slow progression of the tumor size (Figure 1A). Additionally, a nonspecific 6-mm osteolytic lesion in the fourth lumbar vertebra (L4) was found. Somatostatin receptor imaging with [⁶⁸Ga]Ga-DOTA-0-Tyr3-Octreotate (DOTATATE) positron emission tomography / CT showed heterogeneously increased tracer uptake in the primary tumor (Figure 1B). There was no explicit evidence of distant metastases or local invasion to adjacent structures, only noncharacteristic increased tracer uptake in L4, consistent with the osteolytic area on CT. The patient was referred for relaparotomy after preparation with an α-receptor blocker. The tumor, which infiltrated the mesocolon region, was successfully excised en bloc with the left colon. Histopathologic examination confirmed mesenteric paraganglioma (Pheochromocytoma of the Adrenal Gland Scaled Score, 10; Ki-67 index, 19%; 12–15 mitotic Figures per 50 high-power fields with capsular, vascular, and fat tissue invasion, pT2 N0 LV1 R0), with negative surgical margins and no evidence of capsular rupture.

Three months after the operation, control abdominal ultrasonography revealed a suspicious para-aortic lymph node. The hormonal assessment showed only a slightly elevated (<⁠2 × ULN) level of urinary fractionated normetanephrine and increased level of chromogranin A (2.8 × ULN). Subsequent abdominal CT, followed by single-photon emission computed tomography / CT somatostatin-receptor scintigraphy and [¹³¹I]I-metaiodobenzylguanidine (MIBG) scintigraphy showed metastases in the liver, retroperitoneal lymph node, L4 vertebra, and metastatic tumor deposit in the rectovesical pouch (Figure 1C–1E). The patient was referred for [¹³¹I]I-MIBG therapy. He already received 3 cycles of treatment (600 mCi in total), resulting in disease stabilization.

The potential protumorigenic effect of surgical trauma is explained by induction of local and systemic inflammatory response, suppression of antitumor immunity, increased shedding of neoplastic cells into the circulation, and facilitation of tumor cell adhesion to target organs. Nevertheless, surgery remains a crucial intervention for patients with neoplasms.^3,4

During the follow-up after paraganglioma removal, even a slight elevation of metanephrine levels requires careful evaluation and additional imaging studies. Chromogranin A, despite being a nonspecific neuroendocrine marker, may have additional value in monitoring the patients with paraganglioma.⁵