Incidental giant cystic pheochromocytoma: a case report and review of the literature

Abstract

Introduction

Pheochromocytoma is a tumour arising from the adrenal medulla, which secretes catecholamines. Approximately 20% of pheochromocytomas are cystic and more likely to be asymptomatic. They should be surgically resected as all have a malignant potential and pose cardiovascular risk.

Case presentation: We report the case of a 61-year-old female patient admitted electively for laparoscopic adrenalectomy for a large cystic pheochromocytoma detected incidentally. Diagnosis was confirmed preoperatively by elevated 24-h urinary metanephrines. The patient was treated preoperatively with alpha and beta blockade. Surgery was without complication; she had an uneventful postoperative recovery and no evidence of recurrence at one-year follow-up.

Conclusion

This case highlights the necessity of investigating for biochemical function in all adrenal lesions by measuring metanephrines, even when entirely cystic on imaging. Given the surgical and anaesthetic risk in resection of pheochromocytoma, attaining a preoperative diagnosis allows for careful preoperative planning and safe surgery.

Keywords

Pheochromocytoma cystic metanephrines adrenalectomy laparoscopic

Introduction

Pheochromocytoma is a rare solid neuroendocrine tumour typically arising from the adrenal medulla. They have an incidence of 2–8 per million.¹ Around 20% are of the cystic variant,² thought to occur when there is haemorrhage into the tumour with liquefaction and fibrous capsule formation or from extensive degeneration and necrosis within the lesion. In solid tumours headaches, sweating and palpitations occur in 80%, 71% and 64%, respectively.³ Cystic pheochromocytoma are usually asymptomatic and incidental, but can be lethal, even when asymptomatic and all have malignant potential. Furthermore, the cystic variant tends to be larger, and size is a predictor of malignant potential.

Approximately 5% of adrenal lesions discovered incidentally prove to be pheochromocytoma and in adrenal cysts of all types, the incidence of malignancy is 7%.^4,5 This has implications for management and follow up of incidentally discovered cystic lesions, which may be both pheochromocytoma and malignant. Cystic pheochromocytoma should be surgically resected, whereas simple adrenal cysts are typically managed conservatively unless large or compressing other structures.⁶ Adrenalectomy is indicated due to the malignant potential and cardiovascular complications secondary to catecholamine secretion. It is important to diagnose pheochromocytoma preoperatively and manage appropriately to reduce the risk of intraoperative haemodynamic instability, which does not occur in non-functioning tumours.

We present the case of a large incidental cystic pheochromocytoma, resected laparoscopically without complication. We also present a review of the English literature on cases of cystic pheochromocytoma measuring 10 cm or greater. To our knowledge, this is the largest reported in the UK to be resected laparoscopically.

Case report

A 61-year-old female was admitted electively for surgery after a right adrenal cystic lesion was found incidentally on an ultrasound scan for investigation of right upper quadrant pain (Figure 1). Initially, the patient reported no other symptoms or signs and was normotensive. Past medical history included supraventricular tachycardia (requiring catheter ablation). Dexamethasone suppression test was normal. Diagnosis of giant cystic pheochromocytoma was confirmed by raised 24-h urinary metanephrines (Table 1) and CT scan showed an 11 × 10×11.5 cm cystic mass adrenal lesion with multiple septations (Figure 2). There was no radiological evidence of nodal or distant metastasis.

Figure 1.

Ultrasound scan of septated cystic pheochromocytoma abutting the liver.

Table 1.

24-h urinary metanephrine values.

	Preoperative (nmol/day)	Postoperative (nmol/day)	Normal range (nmol/day)
Metadrenaline	>22,000	359	<1000
Normetadrenaline	>12,000	855	<3000
3-Methoxytyramine	>5000	618	<2300

Figure 2.

Axial CT section of 11.5 cm cystic pheochromocytoma.

In the weeks preceding surgery, the patient was commenced on alpha and beta blockade (phenoxybenzamine 10 mg three times daily and propranolol 10 mg three times daily). She was admitted to hospital two days preoperatively for blood pressure monitoring, which was 111/70 mmHg on admission, pulse 61/min and ECG showed sinus rhythm. Admission full blood count, urea and electrolytes, liver function and coagulation screen were within normal range.

The patient underwent uneventful laparoscopic right adrenalectomy by transperitoneal approach in the left lateral position. Pneumoperitoneum was achieved using Veress needle insufflation and the first laparoscopic trocar inserted under direct vision. The 11 cm pheochromocytoma was mobilised off the liver. The adrenal vein was secured using 3x Hem-o-lok gold clips and right adrenal gland mobilised using diathermy and LigaSure™. The lateral port site was extended for specimen extraction. There were no intraoperative complications and minimal blood loss (Figure 3). She had a good postoperative recovery, with one planned night in surgical high dependency for cardiovascular monitoring. She was discharged home on day 6.

Figure 3.

Intra-operative photograph of cystic pheochromocytoma with haem-o-lok clips visible on adrenal vein.

Histopathology showed a 10.5 × 9.8 × 7.4 cm cystic, multiloculated lesion weighing 471 g with a fibrotic capsule. Microscopically there was degenerative change with areas of focal calcification, with no profound nuclear pleomorphism. The tumour invaded the adrenal capsule (1 point) extending into the surrounding fat (2 points) with foci of vascular invasion (1 point). Immunohistochemistry was performed with positive stains for chromogranin, synaptophysin and NSE, thereby confirming pheochromocytoma. There was diffuse growth in >10% of the tumour (2 points), high cellularity (2 points) and nuclear hyperchromasia (1 point) giving it a PASS (pheochromocytoma of the adrenal gland scoring system) of 9/20.⁷ Ki67 staining showed a very low proliferative index. At one-year clinic follow-up, the patient was well with no evidence of recurrence. Blood pressure and 24-h urinary metanephrines were within normal range.

Literature search methods

Searches of Medline, Scopus and PubMed databases were conducted. Search terms included “pheochromocytoma” or “phaeochromocytoma”, “cystic” and “case” in the title/abstract/keyword and these were combined to give the final search result. Abstracts were reviewed to detect eligible case reports and where necessary full papers were obtained to further assess suitability for inclusion. The criteria for inclusion were: diagnosis of cystic pheochromocytoma of the adrenal gland, ≥10cm in size, treated by laparoscopic adrenalectomy and reported in English language. Open cases were also reviewed and included if they mentioned when the diagnosis was made in relation to surgery (preoperative, intraoperative, histopathological) and contained information regarding perioperative outcomes.

Discussion

Our case represents a rare presentation of a typically small, solid tumour. This highlights the importance of investigating for pheochromocytoma in adrenal masses even if large and cystic, discovered incidentally or exhibiting atypical symptoms, as there is a risk of malignancy and secondary cardiovascular compromise in these tumours but not in simple cysts.

Minimally invasive adrenalectomy following preoperative alpha blockade is now the gold standard treatment for pheochromocytoma and this procedure was first reported in 1992 by Ganger et al. for a 3.5 cm adrenal mass.⁸ Toniato et al. compared laparoscopic and open adrenalectomy for pheochromocytoma and concluded that laparoscopic surgery resulted in reduced operating time, length of stay, ICU admission, intraoperative hypertension, intraoperative blood loss, duration of postoperative analgesia and faster return to oral nutrition.⁹

To date there are three reports of laparoscopic excision of pheochromocytoma ≥10 cm (Table 2). One used a lateral transperitoneal approach,¹⁰ one used a posterior retroperitoneal approach¹¹ and in the other no technique was specified but bilateral adrenalectomy was performed.¹² The mean age was 38 years and two out of three were females. The largest was 14 cm. Notably all had a preoperative diagnosis, demonstrating elevated urinary or plasma metanephrines. Hence, all were treated with alpha and/or beta blockade preoperatively with no major perioperative complications, good postoperative recovery and no evidence of disease at follow-up.

Table 2.

A summary of the reported cases of pheochromocytoma ≥10 cm resected laparoscopically.

References	Age/ sex	Country	Size/laterality	Presentation	Investigation/ diagnosis	Benign/malignant/metastases	Management/operative details	Outcome/complications
Mishra et al.¹⁰	44/F	India	12.3 × 10.3 × 10 cm, R	Acute abdomen, shock, diabetes	MRI Elevated 24-h urinary metanephrines	Unknown	Preoperative alpha blockade Laparoscopic lateral transperitoneal	Intraoperative hypotension Good postoperative recovery 15 month follow-up: no recurrence, diabetes cured
Costa Almeida et al.¹¹	51/M	Portugal	14 cm, R	Asymptomatic, hypertension	CT/MRI/MIBG Elevated plasma metanephrines	Benign PASS 3	Preoperative alpha blockade Posterior retroperitoneoscopic	Good post-op recovery. Three-month follow-up: asymptomatic, normal plasma metanephrines
Martins et al.¹²	19/F	Portugal	Bilateral R: 11 cm L: 8.5 cm	Palpitations, headache, nausea, abdominal discomfort	USS, CT, MIBG, genetics: MEN2A Elevated metanephrines	Benign	Preoperative alpha and beta blockade Bilateral laparoscopic	No perioperative complications One year follow-up: no recurrence
Current case	61/F	Scotland, UK	10.5x 9.8x 7.4cm, R	Right upper quadrant pain	Incidental finding on USS CT, elevated 24-h urinary metanephrines	Clinically benign PASS 9	Preoperative alpha and beta blockade Laparoscopic lateral transperitoneal	No perioperative complications, One year follow-up: normal 24-h urinary metanephrines

Including both open and laparoscopic cases, a total of 33 cystic pheochromocytoma ≥10 cm had sufficient detail regarding perioperative outcomes for inclusion (including current case). Of all patients, 19 had a preoperative diagnosis^13–27 and 14 had no preoperative diagnosis.^28–40 A summary of characteristics of these two groups is shown in Table 3 and demonstrates a striking difference in number and severity of complications, suggesting that careful anaesthetic and surgical planning can have a positive impact on outcomes. This is supported by an additional report of two patients with acute abdominal pain undergoing emergency operations suspecting pancreatic pseudocyst and hydatid cyst. The initial operations were terminated due to hypertensive crisis. Thereafter raised urinary metanephrines lead to a diagnosis of pheochromocytoma. The patients were commenced on pharmacological treatment with alpha and calcium channel blockade in preparation for resection, which they subsequently underwent without complication.⁴¹

Table 3.

Characteristics of open and laparoscopic cases ≥10 cm.

	Preoperative diagnosis (N = 19)	No preoperative diagnosis (N = 14)
Age
Median – years	55	48
Range – years	17–72	19–85
Gender
Male – no. (%)	8 (42.1)	3 (21.4)
Female – no. (%)	11 (57.9)	11 (78.6)
Maximum diameter
Median – cm	13	15
Range – cm	10–28	10–30
Preoperative α/β blockade – no. (%)	14 (73.7)	0
Laparoscopic – no. (%)	4 (21.1)	0
Perioperative Complications
Hypo/hypertension – no. (%)	7 (36.8)	9 (64.3)
Myocardial infarction – no. (%)	0	2 (14.3)
Bleeding – no. (%)	0	1 (7.1)
Cardiac Arrest – no. (%)	0	1 (7.1)
Unplanned ICU admission – no. (%)	0	1 (7.1)
30-day mortality – no. (%)	0	1 (7.1)
Not specified – no. (%)	1 (5.3)	2 (14.3)
No complications – no. (%)	11 (57.9)	1 (7.1)

The European Society of Endocrinology recommends measuring plasma or urinary metanephrines in adrenal incidentaloma to exclude pheochromocytoma even in clinically silent lesions in normotensive patients but do not comment on cystic pheochromocytoma.⁴² Furthermore, Canadian guidance suggests that cystic lesions can be diagnosed by imaging without further workup and that biochemical analysis is only needed if imaging is indeterminate.⁴³ Here, considering the current case and reviewing the literature, we suggest that every patient with an adrenal incidentaloma, whether cystic or solid should have measurement of plasma or urinary metanephrines to enable diagnosis of pheochromocytoma, appropriate anaesthetic and surgical planning and ultimately to improve patient outcomes.

Conclusion and learning points

Despite atypical symptoms and an entirely cystic lesion on imaging, adrenal lesions may be biochemically functional.

Any patient undergoing adrenal surgery should undergo preoperative functional testing with 24-h urinary or plasma metanephrines.

Resection of pheochromocytoma carries high surgical and anaesthetic risk and such patients require careful surgical and anaesthetic planning as well as preoperative alpha and/or beta blockade.

In this case report, we raise awareness of a rare presentation and add to the evidence that it is possible to laparoscopically resect cystic phaeochromocytoma larger than 10 cm without complication. We also highlight the importance of considering pheochromocytoma as a diagnosis even in entirely cystic adrenal lesions. The importance of preoperative diagnosis and careful preoperative preparation to minimise perioperative complications and improve patient safety is emphasised.

Footnotes

Authors’ contributions

HAC collated case report data from patient records, carried out literature review and drafted the article. MSJW provided patient data and critically revised draft article. DMS was the main contributor to concept and design of the report and revised draft article. All authors critically revised and approved the final manuscript for publication.

Declaration of Conflicting Interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) received no financial support for the research, authorship and publication of this article.

Patient consent

Informed consent has been obtained from the patient for publication of this case.

ORCID iD

Hollie A Clements

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