Clinical, Imaging and Biochemical Presentation of Cystic Pheochromocytomas

Prerna Dogra; Patrick J. Navin; Travis J. McKenzie; Trenton Foster; Benzon Dy; Melanie Lyden; William F. Young Jr.; Irina Bancos

Disclosures

Clin Endocrinol. 2023;98(1):32-40.

Abstract and Introduction

Abstract

Objective: Cystic adrenal mass is a rare imaging presentation of pheochromocytoma. We aimed to describe the clinical, biochemical and imaging characteristics of patients with cystic pheochromocytoma.

Design: Single-centre, retrospective study, 2000–2020.

Patients: Consecutive patients with cystic pheochromocytoma were identified from our institutional pathology and adrenal tumour database.

Results: Of the 638 patients with pheochromocytomas, 21 (3.2%) had cystic pheochromocytomas (median age: 57 years, 57% women). Most pheochromocytomas were discovered incidentally (57%) or due to symptoms of catecholamine excess (24%). The median tumour size was 6.4 cm. On imaging, cystic pheochromocytomas were round or oval (90%), heterogeneous lesions (86%) with a thick solid rim (median rim thickness 13.9 mm, unenhanced computed tomography (CT) attenuation 40 Hounsfield units (HU), venous-phase CT attenuation 83 HU), and a median cystic component of 40% (unenhanced CT attenuation 17.6 HU, venous-phase CT attenuation 20.4 HU), and rarely with calcifications (15%). All 20 patients with biochemical testing had functioning tumours (adrenergic in 80%, noradrenergic in 20%). Total urinary metanephrine excretion correlated with the volume of the solid component (R ² = .75, p < .0001) but not the cystic component (R ² = .04, p = .4386). All patients underwent adrenalectomy (48% laparoscopic, 52% open), and the median duration of hospital stay was 4 days.

Conclusions: Cystic pheochromocytomas are rare, large tumours with a phenotypic appearance that can masquerade as other adrenal cystic lesions. The degree of biochemical abnormality in cystic pheochromocytomas is associated with the volume of the solid component. All patients with adrenal cysts that have a solid component or an unenhanced attenuation >10 HU should undergo biochemical testing for pheochromocytoma.

Introduction

Pheochromocytomas are rare catecholamine-secreting neuroendocrine tumours arising from the chromaffin cells in the adrenal medulla. In a population-based study of 1287 patients with adrenal tumours, pheochromocytomas represented 1.1%.^[1] Most pheochromocytomas are discovered incidentally on imaging performed for reasons other than adrenal mass^[2] and are typically solid tumours with unenhanced attenuation on computed tomography (CT) of >20 Hounsfield units (HU).^[3,4] While the presence of focal cystic changes in pheochromocytomas is common,^[5] presentation with a macroscopic cystic component is rare. These cases may pose a diagnostic challenge risking inadequate preparation for surgery due to misdiagnosis as an adrenal cyst. Due to its rarity, evidence regarding cystic pheochromocytomas is limited to case reports or small pathology-based series of up to six patients.^[6–10]

An accurate preoperative diagnosis of pheochromocytoma is important to assure the best perioperative outcomes. Our objectives were to (1) characterize the clinical, biochemical, imaging characteristics and outcomes of patients with cystic pheochromocytoma and (2) determine the association of the solid and cystic component volumes of pheochromocytoma with the degree of catecholamine excess.

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Abstract and Introduction
Methods
Results
Discussion
References

Table 1. Presentation and management of patients with cystic pheochromocytoma
	N = 21
Clinical presentation
Age at diagnosis, years, median (IQR)	57 (51–67)
Women, n (%)	12 (57)
Race, n (%)
White	18 (86)
Native American	1 (5)
Unknown	2 (10)
Mode of discovery, n (%)
Incidental	13 (57)
Hormone excess symptoms	5 (24)
Mass effect symptoms	2 (10)
Genetic surveillance	1 (5)
Post-adrenalectomy	1 (5)
Symptoms and signs of catecholamine excess, n (%)	13 (62)
Symptoms and signs, n (%)
Palpitations	8 (62)
Spells	8 (62)
Paroxysmal hypertension	7 (54)
Sustained hypertension	2 (15)
Genetic testing, n (%)
Not tested	15 (72)
Tested, negative	3 (14)
Tested, positive	3 (14)
Type of pathogenic variant, n (%)
VHL	1 (33)
NF1	1 (33)
MEN 2A	1 (33)
Extra-adrenal malignancy, n (%)	7 (33)
Imaging phenotype
Site, n (%)
Right	15 (71)
Left	6 (29)
Tumour size, cm, median (IQR)	6.4 (5–11.1)
Volume, cm³, median (IQR)
Total	115 (47.4–654.1)
Cystic component	48.7 (15.6–236.3)
Solid component	61.2 (27.3–186.2)
Composition, %, median (IQR)
Cystic component	40 (24–60)
Solid component	60 (40–76)
Unenhanced CT attenuation, HU, median (IQR), available for n = 16
Cystic component	17.6 (14.6–20)
Solid component	40 (32.1–44.3)
Enhanced CT attenuation^a, HU, median (IQR), available for n = 14
Cystic component	20.4 (14.9–26.8)
Solid component	83 (83.3–121)
Other imaging characteristics
Round/oval shape, n (%)	19 (90)
Well defined borders, n (%)	21 (100)
Heterogeneous, n (%)	18 (86)
Rim thickness, mm, median (IQR)	14 (8–22)
Calcification, n (%) available for n = 20	3 (15)
Biochemical evaluation
Preoperative evaluation for catecholamine excess, n (%)	20 (95)
Plasma fractionated metanephrines, nmol/L, median (IQR), available for n = 18
Metanephrine (normal < 0.5 nmol/L)	2.7 (0.9–8.7)
Normetanephrine (normal < 0.9 nmol/L)	13.2 (3.2–23.6)
Urinary fractionated metanephrine, nmol/day, median (IQR), available for n = 16
Metanephrine (normal < 2028 nmol/day)	15,828 (5663–33,731)
Normetanephrine (normal < 4913 nmol/day)	22,957 (9206–84,472)
Urinary fractionated catecholamines, nmol/day, median (IQR), available for n = 15
Epinephrine (normal < 115 nmol/day)	470 (104–1715)
Norepinephrine (normal < 473 nmol/day)	1093 (609–6461)
Dopamine (normal < 2611 nmol/day)	1222 (975–2126)
Tumour type, n (%)
Adrenergic	16 (80)
Noradrenergic	4 (20)
Perioperative details
Preoperative medical therapy, n (%)	20 (95)
Alpha-adrenergic blockade
Number of patients treated, n (%)	20 (100)
Duration, days, median (IQR)	15.5 (10.3–20)
Metyrosine
Number of patients treated, n (%)	4 (20)
Duration, days, median (IQR)	5 (2.8–8)
Beta-adrenergic blockade, n (%)	17 (85)
Adrenalectomy, n (%)
Laparoscopic	10 (48)
Open	11 (52)
Duration of hospital stay, days, median (IQR)	4 (2–6.5)
Postoperative complications, n (%)
Hypotension requiring vasopressors	3 (14)
Pulmonary oedema	1 (5)
Retroperitoneal haemorrhage	1 (5)
Postoperative ileus	1 (5)

Abbreviations: CT, computed tomography; HU, Hounsfield unit; IQR, interquartile range; MEN 2A, multiple endocrine neoplasia type 2 A; NF1, neurofibromatosis type 1; VHL, von-Hippel Lindau.
^aMeasured during portal venous phase.

Table 2. Individual data of patients with cystic pheochromocytoma
Patient indicator	Demographics and presentation			Catecholamine excess	Imaging presentation
Patient indicator	Age	Sex	Symptoms	Fold increment > upper normal range	Maximum tumour size, cm	Cystic volume, %	Solid volume, %	Unenhanced HU cystic component	Unenhanced HU solid component
A	42	F	Yes	>10	11.2	75	25	30	48
B	50	F	No	>10	9.1	77	23	30	50
C	56	M	Yes	>10	11.7	68	32	14	39
D	59	F	Yes	5–10	4.1	26	74	N/A	N/A
E	55	M	Yes	>10	8.2	50	50	20	46
F	63	M	No	<5	2.9	15	85	19	29
G	66	M	No	5–10	3.8	24	76	13	45
H	57	M	Yes	N/A	18.9	40	60	18	35
I	75	M	No	5–10	6.4	53	47	14	34
J	76	F	Yes	>10	5	49	51	17	42
K	69	F	No	<5	12	64	36	N/A	N/A
L	55	F	Yes	>10	8.2	28	72	17	43
M	86	M	No	<5	5.5	44	56	18	28
N	52	F	Yes	>10	6.5	29	71	N/A	N/A
O	65	F	No	5–10	4.4	24	76	17	32
P	4	M	Yes	>10	5	24	76	27	41
Q	49	M	Yes	>10	13.5	23	77	17	34
R	68	F	Yes	5–10	6.3	25	75	N/A	N/A
S	65	F	No	>10	14.9	22	78	20	44
T	54	F	Yes	<5	5.7	56	44	14	22
U	41	F	Yes	>10	6.3	70	30	N/A	N/A

Abbreviations: F, female; HU, Hounsfield unit; M, male; N/A, not available.

Table 3. Comparison between cystic and noncystic pheochromocytoma
	Cystic pheochromocytoma	Noncystic pheochromocytoma^a
Median age, years (range)	57 (51–67)	52 (5–84)
Women (%)	57	52
Mode of discovery (%)
Incidental	60	62
Abdominal mass effect	25	—
Symptoms of hormone excess	10	26
Genetic surveillance	5	12
Symptoms of catecholamine excess regardless of the mode of discovery (%)	62	68
Type of clinical manifestations (%)
Palpitations	62	56
Spells	62	37
Paroxysmal hypertension	54	40
Sustained hypertension	15	—
Headaches	—	43
Tumour laterality (%)	Predominantly unilateral	Predominantly unilateral, bilateral in 8%
Median tumour size, cm (range)	6.4 (3–19)	4.0 (8–26)
Median unenhanced CT attenuation, HU (range)	Cystic component: 18 (13–30)	35 (18–58)
Median unenhanced CT attenuation, HU (range)	Solid component: 40 (22–50)	35 (18–58)
Median contrast enhancement, HU (range)	Cystic component: 20 (15–33)	83 (22–187)
Median contrast enhancement, HU (range)	Solid component: 93 (67–132)	83 (22–187)
Biochemical profile (%)
Adrenergic	80	66
Noradrenergic	20	30
Nonfunctioning	0	4
Median total plasma metanephrines, nmol/L (range)	14.3 (3–223)	Median of 2.2–12.4 (0.4–397)^b
Median total urinary metanephrines, nmol/L	43,000 (10,030–494,681)	Median of 6849–23,176 (221–674,816)^b
Adrenalectomy (%)
Laparoscopic	48%	76%
Open	52%	24%
Median hospital-stay following surgery, days (range)	4 (1–17)	3 (1–32)

Abbreviations: CT, computed tomography; HU, Hounsfield unit.
^aData from Gruber et al.²
^bPreviously reported stratified based on the mode of discovery, lowest in patients discovered based on genetic case detection, and highest in patients presenting with symptoms of catecholamine excess. Presented as a range of medians.