
==== Front
Urol Case Rep
Urol Case Rep
Urology Case Reports
2214-4420
Elsevier

S2214-4420(24)00196-7
10.1016/j.eucr.2024.102842
102842
Oncology
Malignant pheochromocytoma invading the ureteral wall muscle layer: A case report
Li Guang-Jie liguangjie6911@163.com

Zhang Chao-Hong
Jiang Li-Xing
Fan Hai-Qing
Fang Hui-Long
Wu Yu-Ye wuyuye2023@gmail.com
⁎
Department of Urology, The Second People's Hospital Affiliated to Fujian University of Traditional Chinese Medicine, Fuzhou, 353003, China
⁎ Corresponding author. wuyuye2023@gmail.com
03 9 2024
11 2024
03 9 2024
57 10284226 6 2024
18 8 2024
27 8 2024
© 2024 The Authors
2024
https://creativecommons.org/licenses/by-nc/4.0/ This is an open access article under the CC BY-NC license (http://creativecommons.org/licenses/by-nc/4.0/).
Pheochromocytoma is a neuroendocrine tumor for which surgical resection is the main treatment.Malignant pheochromocytoma is very rare. Here,we present a case of adrenal pheochromocytoma invading the ureteral wall muscle layer, which resulted in left adrenal and left nephrectomy.

Keywords

Malignant pheochromocytoma ureter
==== Body
pmc1 Introduction

Pheochromocytoma is a type of neuroendocrine tumor with genetic correlation. There is no significant difference in incidence between men and women. Headache, palpitation and hyperhidrosis are typical clinical manifestations. The diagnostic criterion for malignant pheochromocytoma is the presence of tumor metastasis in non-pheochromocytoma tissue areas (common sites are bone, lung, liver, lymph nodes, etc.), and the incidence rate accounts for about 10 % of all pheochromocytomas. Recently, many studies have pointed out that the metastasis potential of pheochromocytoma is also related to some gene mutations. Gene detection is becoming an important means of tumor diagnosis and prognosis prediction, which may provide new ideas for the clinical diagnosis and treatment of pheochromocytoma.

2 Case presentation

A 54-year-old male was found to have an unknown nature of a left retroperitoneal mass during treatment at an external hospital before being transferred to our institution, with blood pressure as high as 170/110 mmHg. He occasionally experiences symptoms such as excessive sweating at night, rapid heartbeat, and lumbar soreness. He sought medical treatment in our hospital, and MRI (Magnetic Resonance Imaging) examination of both kidneys showed:a left renal portal mass with cystic degeneration and bleeding, which was considered to be a high possibility of paraganglioma (Fig. 1). Renal CTA (Computed Tomography Angiography)showed a rich blood supply in the left renal hilum area (Fig. 2). Laboratory tests showed 3 blood catecholamines (lying position): dopamine (DA) 61.30pg/ml↑, norepinephrine (NE) 4338.10pg/ml↑, epinephrine (E) 7.10pg/ml.Blood catecholamines 3 (orthostatic): dopamine (DA) 78pg/ml↑, norepinephrine (NE) 4735pg/ml↑, epinephrine (E) 6.70pg/ml.After 2 weeks of preoperative preparation with phenoxybenzamine, during the operation, it was found that the renal portal vessels had dense adhesion with the tumor under laparoscopy, and malignant tumors could not be ruled out in combination with preoperative imaging, and the left retroperitoneal tumor was completely removed (Fig. 3).Fig. 1 The MRI image of the patient. (A and B): Sagittal image of the tumor and its relation to the left-sided kidney; (C and D):Axial view demonstrating the close relationship of the tumor to the left kidney.

Fig. 1

Fig. 2 The CTA image of the patient. (A and B): Sagittal image of the tumor and its relation to the left-sided kidney; (C and D):Axial view demonstrating the close relationship of the tumor to the left kidney.

Fig. 2

Fig. 3 A:Left retroperitoneal mass (The tumor size is 13 ∗ 11.4 ∗ 5.6cm, of which the adrenal gland size is 2.5 ∗ 1.5 ∗ 0.7cm.); B:The tumor was densely adhered to the renal hilus blood vessels; C:The tumor cell atypia was obvious; D:The left adrenal gland is connected to the tumor.

Fig. 3

Pathological examination showed: (left retroperitoneal mass) invasive pheochromocytoma of the adrenal gland, accompanied by bleeding and necrosis, obvious tumor cell atypia, easy to see mitotic images (about 10∼12/10HPF), tumor invasion of the renal hilus ureteral wall muscle layer and protruding into the ureteral lumen, focal invasion of the envelope and surrounding adiposed tissue, intravascular cancer thrombus. No nerve invasion was observed: no tumor violate was observed at the incisal margin of kidney, ureter and hilar vessel. A small number of chronic inflammatory cells infiltrated renal interstitium and focal lymphocyte aggregation. Immunohistochemical results:CKpan Ki67 (+10 %), (−), CD56 (+), CgA (+), Syn (+), according to (+) cells, SDHB (−), P53 expression (negative, wild type), Melan - A (−), Inhibin - A (+),GATA-3 (scattered weak +),PAX-8 (−), CD31 (vascular +), CK7(−), CK20(−).

The patient underwent genetic testing and was found to have a mutation in the SDHB gene.

The patient recovered well after surgery, did not take antihypertensive drugs, and her blood pressure was normal.

3 Discussion

Pheochromocytoma is a rare neuroendocrine tumor derived from pheochromocytoma cells in the adrenal medulla. Its annual incidence ranges from 2 to 8 cases per million people. The incidence was highest between the ages of 30 and 40, with no significant difference between men and women.

Malignant pheochromocytoma is a rare malignant tumor with high recurrence rate and poor prognosis. Pheochromocytomas with distant metastasis, invasion of neighboring organs, large tumors, and lymph node enlargement in imaging examination are generally considered malignant, accounting for about 10 %.1 Ectopic pheochromocytomas are rare but have a higher malignant tendency, accounting for 30 %–40 %.Statistics show that ectopic pheochromocytomas in the genitourinary system are most commonly involved in the bladder, followed by the urethra, renal pelvis and ureter.2 In our case, the primary ectopic pheochromocytoma of the renal pelvis was considered in the examination, but the postoperative pathological analysis suggested that this was a malignant pheochromocytoma of the adrenal gland, which invaded the muscle layer of the ureter wall of the renal hilar.

According to histopathological analysis, benign pheochromocytomas were mostly round or oval in shape, with tumor diameters less than 3cm, clear boundary and relatively complete envelope. Under the microscope, the tumor tissues were arranged as cords or clumps, with large cell bodies and large round nuclei. The appearance of malignant pheochromocytoma is similar to that of benign pheochromocytoma. Occasionally, heterotypic cells and nuclear division can be seen. If there is invasion of the surrounding envelope and blood vessels, the possibility of malignancy is high. In our case, the tumor was large, with obvious heterotypic cells and mitotic signs. Thorough sampling of the specimen indicated that the tumor had invaded the ureteral wall muscle layer, and it was eventually confirmed that this was a malignant pheochromocytoma.

Due to the relatively high familial aggregation of pheochromocytoma patients, genetic counseling and testing should be recommended for each patient after the initial diagnosis of pheochromocytoma.3 Once a susceptibility gene has been identified, other family members should also be screened. Since 1990, susceptibility genes of pheochromocytoma have been reported successively:NF1, RET, VHL, SDHD, SDHC, SDHB, EGLN1/PHD2, KIF1, SDH5/SDHAF2, IDH1, TMEM127, SDHA, MAX, HIF2. Among them, the highest mutation frequency is SDHB(10.3 %), SDHD (8.9 %), VHL (7.3 %), RET (6.3 %) and NF1(3.3 %). Studies have shown that SDHB gene is a tumor suppressor gene, and patients with pheochromocytoma with SDHB gene mutation have a higher risk of malignant transformation and suggest poor prognosis.4

Surgical treatment is the most effective way to treat malignant pheochromocytoma. For single malignant pheochromocytoma, if the tumor is small in size and does not invade the surrounding tissue, endoscopic or robotic surgery can be performed. For malignant pheochromocytoma with large volume, peripheral adhesion, internal bleeding and necrosis, open surgery should be performed. For patients with large surgical scope, contraindications or distant metastases, chemotherapy or radiotherapy is feasible. In addition, there are more and more researches on personalized and gene-guided therapy, and some molecular targeted therapies have played a role in the treatment of malignant pheochromocytoma.5

4 Conclusion

As a rare malignant tumor with high recurrence rate and poor prognosis, malignant pheochromocytoma should be recognized and treated early to improve the prognosis.

CRediT authorship contribution statement

Guang-Jie Li: Writing – review & editing, Writing – original draft. Chao-Hong Zhang: Resources. Li-Xing Jiang: Supervision. Hai-Qing Fan: Supervision. Hui-Long Fang: Investigation. Yu-Ye Wu: Writing – review & editing.
==== Refs
References

1 Jandou I. Moataz A. Dakir M. Debbagh A. Aboutaieb R. Malignant pheochromocytoma: a diagnostic and therapeutic dilemma Int J Surg Case Rep 83 2021 Jun 106009
2 Sharma A.P. Bora G.S. Mavuduru R.S. Panwar V.K. Mittal B.R. Singh S.K. Management of bladder pheochromocytoma by transurethral resection Asian J Urol. 6 3 2019 Jul 298 301 31297323
3 Nölting S. Bechmann N. Taieb D. Personalized management of pheochromocytoma and paraganglioma Endocr Rev 43 2 2022 Mar 9 199 239 34147030
4 Lenders J.W. Duh Q.Y. Eisenhofer G. Pheochromocytoma and paraganglioma:an endocrine society clinical practice guideline J Clin Endocrinol Metab 99 6 2014 1915 1942 24893135
5 Wang K. Crona J. Beuschlein F. Grossman A.B. Pacak K. Nölting S. Targeted therapies in pheochromocytoma and paraganglioma J Clin Endocrinol Metab 107 11 2022 Nov 23 2963 2972 35973976
