CASE REPORT |
https://doi.org/10.5005/jp-journals-10002-1450 |
A Rare Case of Giant Malignant Pheochromocytoma
1,2,4,5Department of General Surgery, Saint Georges Hospital University Medical Center, University of Balamand, Beirut, Lebanon
3Faculty of Medicine, University of Balamand, Beirut, Lebanon
6Department of Laboratory, Lebanese American University Medical Center, Beirut, Lebanon
7Department of General Surgery, Saint Georges Hospital University Medical Center, Beirut, Lebanon
Corresponding Author: Ziad El Rassi, Department of General Surgery, Saint Georges Hospital University Medical Center, Beirut, Lebanon, e-mail: Ziadelrassi@gmail.com
Received on: 23 July 2023; Accepted on: 20 August 2023; Published on: 30 October 2023
ABSTRACT
A pheochromocytoma (PCC) is a tumor that arises from an embryonic neural crest and produces catecholamines at high levels. The mean size of these tumors is approximated to be around 7.2 cm, with an average weight of 222 g. In this case, a 61-year-old female patient was referred to our medical center to investigate multiple episodes of hypertensive crisis associated with a huge 18 cm right adrenal mass identified on a computed tomography (CT) scan and magnetic resonance imaging (MRI). Twenty-four-hour urine analysis and blood level exhibited elevated total metanephrine and normetanephrine levels. Mass resection was performed via laparotomy en bloc. Histopathological analysis of the resected specimen confirmed PCC of the right adrenal gland weighing 1900 g. The Adrenal gland Scaled Score (PASS) was 13. PCC may reach sizes much larger than the average observed in the literature and size tends to be positively correlated to malignancy.
How to cite this article: Younes A, Ghattas S, Semaan S, et al. A Rare Case of Giant Malignant Pheochromocytoma. World J Endoc Surg 2023;15(2):46–49.
Source of support: Nil
Conflict of interest: None
Patient consent statement: The author(s) have obtained written informed consent from the patient for publication of the case report details and related images.
Keywords: Case report, Giant, Malignant, Pheochromocytoma
INTRODUCTION
Pheochromocytomas (PCC) are tumors of the neuroendocrine type, most commonly arising in the adrenal medulla, and being labeled as adrenal paragangliomas.1,2 This tumor originates from the embryonic neural crest cells and is known for secreting catecholamines in large quantities.3 Symptoms of PCC are not limited to hypertension, headaches, palpitations, and sweating. Hypertension most often presents as sudden onset episodes, but may range in severity to sustained hypertension, and may be complicated by myocardial infarcts, strokes, and hypertensive crises if left untreated.4,5 It is widely agreed upon in the literature that PCC can be fatal, regardless of malignancy status. A study conducted in 2002 on 100 different cases of PCC estimated the average tumor size to be around 7.2 cm, with an average weight of 222 g, however, a smaller average size is more commonly reported, ranging between 3 and 5 cm.3-6 General consensus is that the percentage of malignant PCC is around 10% of the total, keeping in mind that more recent studies estimate that percentage to be a bit higher.7,8 In this case report, we will dissect the case of a malignant PCC, with a size larger than 16 cm, an uncommon finding in practice.
CASE DESCRIPTION
A 61-year-old female patient was referred to our medical institution in March 2023 with a multiple-year history of hypertensive crisis. The patient’s medical and surgical history included hypertension, open cholecystectomy, and total abdominal hysterectomy for benign fibroid, and the patient reported no family history of PCC and paraganglioma. An abdominal ultrasound performed when the patient initially presented 10 years ago showed a 3 cm mass in the right upper quadrant. The patient did not follow up on this mass, and no further evaluation was performed. Over the years, she reported occasional (1–2 times/week) spontaneous hypertensive crises, associated with headaches, palpitations, diaphoresis, and pallor. These crises worsened in December 2021. A physical examination of the patient revealed a right upper quadrant bulky mass on palpation. Initial laboratory workup comprising blood electrolytes, blood glucose level, hemogram, and multiple biochemical parameters were ordered and came back unremarkable. The patient’s vital signs upon examination showed no pertinent findings: blood pressure was 110/70 mm Hg, heart rate was 70 bpm, and temperature was 36.8˚C, all of which are within normal range. A computed tomography (CT) scan of the abdomen with contrast was ordered and came back showing an ill-defined, heterogeneous, solid and cystic infiltrative tumoral process occupying the right retroperitoneal space, extending to the right hepatic lobe and reaching the hepatic dome, with the invasion of the superior pole of the right kidney. The mass measured 16.6 × 16 cm in transaxial diameter and 14.6 cm in craniocaudal diameter. The lesion contained linear lobulated calcifications exerting mass effect over the inferior vena cava. No enlarged retroperitoneal or mesenteric lymph nodes were seen. A biopsy of this mass was performed and showed trabeculo-sinusoidal tumor pathology with nondiagnostic immunophenotyping. The patient was directed to our hospital for further assessment and treatment (Fig. 1). T2 weighted magnetic resonance imaging (MRI) of the abdomen and pelvis was done for further workup, and showed a right 15 × 16.5 retroperitoneal mass of mixed solid and liquid components, in close contact with, but not invading the liver and the right kidney. The liver was displaced superiorly and the right kidney inferiorly. No lymphadenopathy was seen on MRI as well (Fig. 2). PCC or adrenocortical carcinoma was initially suspected. Serum metanephrine and normetanephrine, aldosterone, 3-methoxytyramine, and AM cortisol were ordered, as well as 24-hour urine samples of metanephrine, normetanephrine, 3-methoxytyramine, and cortisol were ordered (Table 1). Results showed elevated blood and urine metanephrine, normetanephrine, and 3-methoxytyramine levels. After reviewing the case, we opted for an open adrenalectomy as recommended by the 2014 Endocrine Society Guidelines for a large PCC (>6 cm) or invasive PCC.9 Prior to surgery, the patient underwent 2 weeks of α-blockade treatment, alongside increased oral fluid and salt intake as preoperative surgical preparation.
| Serum | 24-hour urine collection | |||
|---|---|---|---|---|
| Result | Normal range | Result | Normal range | |
| Metanephrine | >5000 ng/L | <70 ng/L | 3641 mcg/24 hour | 29–158 mcg/24 hour |
| Normetanephrine | >5000 ng/L | <120 ng/L | 10241 mcg/24 hour | 56–659 mcg/24 hour |
| 3-methoxytyramine | 165 ng/L | <18 ng/L | 3046 mcg/24 hour | <222 mcg/24 hour |
| Aldosterone | 7.5 ng/mL | <2.5–39.2 ng/mL | ||
| AM cortisol | 128.7 ng/mL | 60–285 ng/mL | ||
| Cortisol | 157 mcg/24 hour | 21–292 mcg/24 hour | ||
Figs 1A and B: Computed tomography (CT) scan of abdomen pelvis with IV contrast showing a 16.6 × 16 × 14 cm mass occupying the right retroperitoneal space. (A) Coronal view; (B) Axial view
Figs 2: T2 weighted MRI of the abdomen and pelvis showing a right 15 × 16.5 cm retroperitoneal mass (axial view)
The surgery was done through a right subcostal incision. The mass was in close relation with the liver, right kidney, and IVC, with no invasion. The mass was fully resected using a lateral to medial approach; starting with dissection of the tumor of the kidney and liver, followed by medial control of the suprarenal vein from the inferior vena cava (IVC) (Fig. 3). The IVC was controlled via endovascular stapler. Intraoperative systolic blood pressure fluctuations occurred, with variations between 20 and 290 mm Hg. The patient lost around 3 L of blood. Six units of packed red blood cells and two fresh frozen plasma were transfused. The patient was started on vasopressors intraoperatively. Postoperatively, the patient was placed in the intensive care unit, intubated, and on vasopressors for hypotension and low urine output. The patient was extubated on the day 1 postoperative and transferred to the floor on day 2 postoperative. Complications occurred on day 3 postoperative, at which point the patient presented with left eye diplopia. An urgent MRI of the brain was ordered, which showed a focus of ischemia in the thalamus, most probably due to the rapid change in blood pressure experienced intraoperatively. The neurology team was consulted, and the patient was started on antiplatelets. The remaining hospital course was otherwise uncomplicated, the diet was started on day 3 postoperative, drains were removed and the patient was discharged home on day 7 postoperative. In the pathological evaluation done on the specimen, the PCC weighed 1900 g and was 18 × 17 × 12 cm in size. The core of the lesion was fibrotic and had clusters of hemosiderin-laden macrophages, inflammatory cells, and extensive hemorrhage with hematoma formation. No lymphovascular invasion was present. The periadrenal fat was invaded, with negative margins. p TNM staging was the following: p T3N x Mx. Immunostaining was strongly positive for chromogranin A, synaptophysin, and PS 100 sustentacular cells. Negative PS 100 tumoral cells, melan A, and keratin AE 1–3. Ki 67: 7%. Morphology and immunostains were consistent with PCC. The Adrenal gland Scaled Score (PASS) was 13, detailed in (Table 2).
| Adrenal gland Scaled Score (PASS) | |
|---|---|
| Periadrenal adipose invasion | +2 |
| >3 mitoses—10 HPF | +2 |
| Atypical mitoses | 0 |
| Necrosis | +2 |
| Cellular spindling | 0 |
| Marked nuclear pleomorphism | +1 |
| Cellular monotony | 0 |
| Large nests or diffuse growth | +2 |
| High cellularity | +2 |
| Capsular invasion | +1 |
| Vascular invasion | 0 |
| Hyperchromasia | +1 |
Figs 3A to C: (A) Dissection of the mass of the right kidney; (B) Specimen removed; (C) Specimen opened
DISCUSSION
Pheochromocytomas (PCC) are a rare tumor, with an incidence of 0.005–0.1% in the general population, and a higher prevalence in the hypertensive population, ranging from 0.1 to 0.2%.10 While most of these tumors fall within the same pool of benign adrenal paragangliomas, a subset deviates from the normal variation, following what is commonly referred to in the literature as the “rule of 10s”: 10% of PCC are bilateral, 10% are malignant, 10% are familial, 10% present in nonhypertensive patients, and 10% are extraadrenal (of which 10% are intraabdominal).11,12 Nevertheless, research has shown that the classic epidemiology attributed to PCC can be challenged, with the percentage of malignancy increasing in the extraadrenal and hereditary cases (specifically the succinate dehydrogenase complex—subunit B SDHB mutation), and the extent of PCCs in the normotensive population well surpassing 10%.12 Familial PCC is found in a multitude of syndromes, the main ones being multiple endocrine neoplasia type 2 and Von Hippel-Lindau (VHL), with rare cases reported in neurofibromatosis 1.13 Nonsyndromic mutations have also been linked to PCC, all of which increase susceptibility via the mitochondrial complex two—these mutations include succinate dehydrogenase complex subunit D (SDHD), succinate dehydrogenase complex subunit B (SDHB), and succinate dehydrogenase complex subunit C genes.13 VHL, RET proto-oncogene, SDHB, and SDHD mutation analysis is generally encouraged in all cases of PCC.13 Among PCC, only a few cases have been reported with very large parameters. While no clear cutoff has been made as to what is considered “large” or “giant,” a case series compiled by Pan et al. In 2008 15 cases with a size larger than 10 cm, of which 9 cases are 15 cm or larger.11 Based on this, the PCC discussed in this case, determined on histopathology to be 18 × 17 × 12 cm, would be considered much larger than average. The probability of PCC malignancy increases with increasing tumor size; the benign-to-malignant tumor ratio becomes ⅛ once the lesion surpasses 6 cm.14 Malignancy profile of PCC is not clearly defined in terms of histology, but rather based on multiple criteria at presentation, which include extraadrenal location, spread beyond the original tumor location, invasion of the capsule or neighboring vasculature, high mitotic index, intraabdominal free fluid with malignant features, and recurrence at the site of resection.4 Not all of the previously mentioned features have to be present to make the diagnosis of malignancy, and some of these characteristics, such as recurrence and metastasis, present more commonly than others. Predicting the clinical course of adrenal tumors, and the likelihood of malignancy, may be achieved using the PASS, which relies on histologic analysis. Thompson et al. showed in their study of 100 patients with PCC that an PASS of ≥4 is accurate in the identification of histologically malignant tumors.6 As malignant PCC are extremely rare tumors, not enough reports and studies are available to assess prognosis and survival. Malignant PCC usually has a poor prognosis and resistance to chemotherapy and radiotherapy.4 Most PCC leads to symptomatic manifestations, however, it is important to note that an estimated 8% are entirely asymptomatic.15 While PCC size is positively correlated with a higher incidence of tachycardia, hypertension, and diaphoresis, few cases of larger PCC have been reported with no symptoms at or before presentation.4 PCC poses major mortality risks, and so do other adrenal secretory adrenal tumors. Adrenal incidentalomas should be investigated regardless of symptoms and manifestations: PCC is estimated to make up 5–6.5% of this category.15 Traditionally, biochemical PCC diagnosis is based on 24-hour urinary metanephrine collection and fractionated catecholamines—urine total metanephrine specificity is 99%.16 Other laboratory testing includes urine and plasma catecholamines. Plasma metanephrines are the preferred screening test in high-risk populations.16 Resection is the mainstay of treatment, and is usually curative, to be preceded by increasing doses of α-blockade, followed by a β-blockade for both blood pressure optimization.17
CONCLUSION
Pheochromocytomas (PCC) may reach sizes much larger than the average observed in the literature. Size and malignancy tend to be positively correlated, but cases, where PCC have reached sizes beyond 15 cm with no malignancy, have been observed.
ORCID
Ahmad Younes https://orcid.org/0000-0001-8110-4028
Souad Ghattas https://orcid.org/0000-0003-0328-3555
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