Atypical Presentation of Giant Pheochromocytoma Managed With Minimally Invasive Surgery

Abstract

Giant pheochromocytomas are rare tumors, typically exceeding 7 cm in size. Most are noncatecholamine secreting due to tumor necrosis and connective tissue content. Their presentation can range from classic hyperadrenergic symptoms to vague gastrointestinal complaints. Larger tumors are associated with higher risks of metastasis, mortality, and perioperative complications. Our case presents a 31-year-old female who presented with the chief complaint of vomiting, associated with intermittent palpitations and elevated blood pressure, with subsequent imaging revealing an 8.7 cm right adrenal mass. Complete resection of the mass showed a 10 × 7 × 3.9 cm mass that occupied the entire adrenal medulla, consistent with a giant pheochromocytoma. This case contributes to the evidence supporting a minimally invasive approach as well as individualized management of giant pheochromocytomas. Furthermore, it emphasizes the importance of a high clinical suspicion in the context of vague symptoms.

Introduction

Pheochromocytomas are rare tumors, with an incidence rate of around 2 to 8 per million persons annually, often discovered incidentally, with a median size ranging from 4 to 5 cm. ¹ Giant pheochromocytomas have been reported to measure >7 cm.^2-4 Symptoms range from asymptomatic, tremors, palpitations, paroxysmal hypertension to acute heart failure. The Endocrine Society Clinical Practice Guidelines from 2014 recommend minimally invasive adrenalectomy for most adrenal pheochromocytomas and open resection for those >6 cm. ⁵

Case Presentation

A 31-year-old female, weight of 54 kg and height of 1.57 m, presented to the Emergency Department with intermittent vomiting over the past month, increasing in frequency over the last week, with no specific food triggers. The vomiting was preceded by a warm sensation in her right arm and palpitations. Upon arrival, her temperature was 98.6 °F, heart rate 102 bpm, and blood pressure elevated at 168/111 mmHg. She had no history of hypertension but noted sporadic elevated readings at her physician’s office 7 months prior. Physical examination was unremarkable, with no abdominal tenderness to palpation. Laboratory findings showed normal complete blood count, metabolic panel, TSH, T4, and random serum cortisol. Due to persistent vomiting and inability to tolerate oral routes, further imaging was ordered (Figure 1).

Figure 1.

CT abdomen and pelvis with large right adrenal gland mass measuring 8.7 cm. CT, computed tomography.

Computed tomography (CT) abdomen and pelvis with IV contrast showed a large right adrenal gland mass measuring 8.7 cm. The mass was heterogeneous with areas of cystic change versus necrosis. In the setting of hypertension, warmth sensation, and palpitations, pheochromocytoma was suspected. Metanephrine plasma levels were elevated at 7094 pg/ml (n: <57 pg/ml). Urine 24-hour fraction showed epinephrine of 149 µg/24 hours (n: 2-24 µg/24 hours), dopamine of 363 µg/24 hours (n: 52-480 µg/24 hours), norepinephrine of 436 µg/24 hours (n: 15-100 µg/24 hours), renin of 1.77 ng/ml/hour (n: 0.25-5.82 ng/ml/hour), aldosterone of 7 ng/dl (n: <21 ng/dl), and morning cortisol 18.35 (n: 5.27-22.45 µg/dl). Due to the significant size, adrenal cortical carcinoma was also on differential. She was started on Doxazosin 1 mg BID for preoperative management for 14 days and Metoprolol 25 mg starting 5 days prior to surgical intervention. After 10 days of initiation, patients’ blood pressure was reported at an average of 117/80 mmHg from home readings and 117/84 mmHg with a heart rate of 90 bmp in the office. She denied palpitations, dizziness, nausea, vomiting, or flushing.

Laparoscopic approach was chosen over open resection due to patient’s preference and the surgeon’s familiarity with the minimally invasive technique. She underwent laparoscopic adrenalectomy utilizing an umbilical 5-mm port, an epigastric 5-mm port, and 2 right subcostal 5-mm ports. The lateral subcostal port was exchanged for a Nathanson liver retractor. The medial subcostal port was upsized to 12-mm in order to accommodate a laparoscopic stapler. The hepatic flexure of the colon and the right triangular ligament of the liver were mobilized to expose the retroperitoneum, revealing a mass consistent with the patient’s known adrenal tumor. The inferior vena cava was seen displaced to the left by the mass. Dissection began along the inferior and medial side of the mass until identifying an enlarged, solitary adrenal vein at the superior extent of the dissection.

During the half-hour of manipulating the mass prior to ligation of the adrenal vein, the patient experienced transient episodes of hypertension requiring only 20 mg of Labetalol and 5 mg of Nicardipine. The vein was dissected circumferentially and transected with a laparoscopic stapler, after which she required low-dose phenylephrine for the remainder of the operation. A total of 950 µg was administered over the course of an hour to maintain mean arterial pressure >65 mmHg. Just over 2 l of isotonic crystalloid was given with appropriate urine output. The 12-mm port was upsized further to extract the mass in a specimen bag. Estimated blood loss was 100 ml. The patient was maintained on intravenous fluids for 24 hours postoperatively, but she did not require any vasopressors after cessation of general anesthesia.

Macroscopic pathology findings showed an ovoid, tan-pink to red, heterogeneous, soft, centrally friable mass that measured 10 × 7 × 3.9 cm and occupied the entire adrenal medulla (Figure 2). The mass was located at 0.4 cm from the vascular resection margin and 0.2 cm from the external surface.

Figure 2.

10 × 7 × 3.9 cm adrenal mass.

The cell nests (Zellballen) were large, polygonal, with abundant finely granular purple cytoplasm. The nuclei were round to oval, with prominent nucleoli. Capsular and vascular invasion could not be excluded (Figure 3). Synaptophysin and chromogranin exhibited diffuse expression. Succinate dehydrogenase (SDH) staining was not performed (Figure 4). Microscopic diagnosis confirmed a well-differentiated giant pheochromocytoma with a grading of adrenal pheochromocytoma and paraganglioma score of 1. She discharged on postoperative day 2 (POD 2) after an uneventful postoperative course, not requiring any vasopressors and no additional intravenous fluids on POD 2. Preoperative plasma metanephrines were measure at 7084 pg/ml. One month postintervention, repeat serum metanephrines were <25 pg/ml, with patient remaining asymptomatic. Given lack of SDH staining, patient was scheduled to undergo formal genetic counseling and testing.

Figure 3.

High-power microscopy.

Figure 4.

Chromogranin stain.

Discussion

Pheochromocytomas are rare tumors, with an incidence rate of around 2 to 8 per million persons per year, mostly diagnosed incidentally with a median size of 4 to 5 cm.^1-4 Giant pheochromocytomas have been reported to measure >7 cm.^6,7 Symptoms range from asymptomatic to tremors, palpitations, paroxysmal hypertension, and acute heart failure.^2,6,8 Those that are clinically silent or asymptomatic are usually due to tumor necrosis, amount of interstitial tissue, and catecholamine receptor desensitization.^3,6,7 While there is limited data on worldwide prevalence of giant pheochromocytomas, a retrospective cohort study from Mayo Clinic from 2000 to 2003 revealed that 3.7% of 828 patients had giant pheochromocytomas, with a median age of 55 years; 55% were women. ¹ Most of them presented with symptoms; however, while 48% presented with palpitations, only 6% reported gastrointestinal (GI) symptoms.^1,9 The left adrenal gland is anatomically closer to the stomach and pancreas. Large left-sided tumors may compress these organs, whereas right-sided tumors might affect the liver or biliary tract. Left-sided pheochromocytomas can cause GI symptoms through direct compression of stomach, pancreas, or surrounding structures, leading to abdominal pain, early satiety, or vomiting, though such cases are rare and typically occur with larger tumors (≥5 cm).^10,11 While GI symptoms in pheochromocytoma are more commonly attributed to catecholamine excess (eg, nausea, constipation, or pseudo-obstruction due to altered motility), mass effects from tumor size or location may contribute in specific cases. High levels of circulating catecholamines, as seen in conditions like pheochromocytoma, can activate alpha-adrenergic receptors in the area postrema, triggering the emetic (vomiting) cascade. ¹²

The known genetic conditions due to mutations associated with pheochromocytomas include mainly 2 clinically relevant clusters. Cluster 1 includes genes related to the Krebs Cycle like von Hippel-Lindau and SDH enzyme mutations (SDHB, SDHC, and SDHD). Cluster 2 includes genes related to the kinase signaling pathway like RET (seen in MEN2) and neurofibromatosis type 1. ⁵ Around 50% of pheochromocytomas are diagnosed in patients with genetic mutations, and they usually present at a younger age.^2,13 SDH immunohistochemical staining was not performed by pathology in this case. However, the patient is scheduled to undergo comprehensive genetic counseling and testing. Identifying a hereditary syndrome has significant clinical implications, including guiding long-term surveillance strategies, informing prognosis, and facilitating appropriate screening of at-risk family members.

The most commonly produced catecholamine is norepinephrine, while many produce epinephrine as well. The biochemical phenotypes are also mutation-dependent. Initial recommended testing currently includes plasma-free metanephrines or urinary fractionated metanephrines; however, with increasing development of genomic studies, new genetic markers for diagnosis can be considered, for example, the role of SDH enzyme activity.^13,14

Due to variance in genotype and biochemical phenotypes, several imaging modalities are used in the diagnosis and localization of pheochromocytomas, each with its own advantages and limitations. CT of the abdomen and pelvis is the preferred first-line imaging modality for tumor localization following biochemical confirmation. CT has been found to have superior anatomical detail in terms compared with MRI.^1,2,13 When avoiding contrast or radiation, as in children, adolescents, and pregnant women, MRI is a viable alternative with superior tissue contrast resolution though it provides lower spatial resolution.^1,5,13 In presence of clinical symptoms, ultrasound can diagnose up to 90% of pheochromocytomas. ⁶ Imaging modalities for metastatic disease include iodine 123-metaiodobenzylguanidine scintigraphy with CT and gallium 68-DOTATATE PET/CT and fluorine 18-fludeoxyglucose PET/CT.^2,5,13,14

The gold standard for pheochromocytoma resection is minimally invasive via retroperitoneal or transperitoneal approach due to lower postoperative complications. The Endocrine Society Clinical Practice Guidelines from 2014 recommend minimally invasive adrenalectomy for most adrenal pheochromocytomas and open resection for those >6 cm. ⁵ A personalized approach to patient management is also an ungraded recommendation. A 10-year single-centered retrospective study compared laparoscopic approach versus open approach for pheochromocytomas >6 cm. ¹ The study confirmed that the laparoscopic approach was safe, showed less intraoperative hemodynamic instability and faster hospital recovery.^1,15

Giant pheochromocytomas have a higher risk of metastatic disease; hence, close long-term follow-up, including annual biochemical testing is crucial.^1,6 According to the NIH National Cancer Institute, diagnosis of malignancy can only be made by identifying tumor deposits in tissues that do not normally contain chromaffin cells. ² Large tumor size, increased number of mitosis, DNA aneuploidy, extensive tumor necrosis, and vascular or capsular invasion are features associated with malignancy; however, no combination of clinical, histopathological, or biochemical features have been reported to be reliable predictors in pheochromocytoma behavior.^2,3,13 If no definitive malignancy is identified, patients are recommended to undergo lifelong surveillance.^2,9,13

Conclusion

This case report underscores the critical importance of maintaining a high index of suspicion for pheochromocytoma in the emergency department setting. This patient presented with intermittent vomiting as the primary complaint, which deviates from the classic symptoms typically associated with pheochromocytoma, such as episodic hypertension, severe headaches, and sweating. While the patient had not received a formal diagnosis of hypertension, the record of sporadic elevated blood pressure readings may serve as an early indicator of an underlying condition. The surgical intricacies involved in managing this giant pheochromocytoma highlight the significance of expertise in laparoscopic techniques, as a successful laparoscopic adrenalectomy was completed without the need for conversion to open surgery. This achievement not only reflects advancements in minimally invasive surgical methods but also demonstrates the effective management of potential hemodynamic challenges associated with such complex cases. Ultimately, the findings of this case advocate for heightened awareness and timely diagnosis of pheochromocytoma, which can lead to more effective management strategies and long-term health outcomes.