definition, presentation ,incidence ,associated syndromes, diagnosis ,imaging ,management

1. Pediatric
Pheochromocytoma
Prof. Dr. Saad S Al Ani
Senior Pediatric Consultant
Head of Pediatric Department
Khorfakkan Hospital
Sharjah ,UAE
anahbaghdad@aol.com

2. Pheochromocytoma
Pheochromocytoma is a rare
catecholamine-secreting tumor
that arises from chromaffin cells
of the sympathetic nervous
system (adrenal medulla and
sympathetic chain)
12/04/2018
PediatricPheochromocytoma
Prof.Dr.SaadSAlAni
2

3. Facts
•The tumor may develop anywhere in
the body.
•Release of catecholamines into the
circulation by these tumors causes
significant hypertension
•Pheochromocytoma may be inherited
as an autosomal dominant trait?
12/04/2018
PediatricPheochromocytoma
Prof.Dr.SaadSAlAni
3

4. Facts (Cont.)
•Adrenal pheochromocytomas are
most often found on the right side
and are sporadic, unilateral, and
intra-adrenal.
•Approximately 6-10% of the
tumors are malignant.
•pheochromocytoma is more
frequently associated with other
familial syndromes
12/04/2018
PediatricPheochromocytoma
Prof.Dr.SaadSAlAni
4

5. Facts (Cont.)
•Extra-adrenal tumors are usually,
located in the abdomen along the
sympathetic chain and constitute
about 10% of sporadic cases.
•Other sites include:
 The neck
 Mediastinum
 Urinary bladder
12/04/2018
PediatricPheochromocytoma
Prof.Dr.SaadSAlAni
5

6. Association with other
familial syndromes
• In children, pheochromocytoma is more
frequently associated with other familial
syndromes, such as:
Neurofibromatosis
von Hippel-Lindau disease
Tuberous sclerosis
Sturge-Weber syndrome
Multiple endocrine neoplasia (MEN)
syndromes
12/04/2018
PediatricPheochromocytoma
Prof.Dr.SaadSAlAni
6

7. Pathophysiology
• Pheochromocytoma is a tumor
of neuroendocrine origin
• The biosynthesis and storage of
catecholamines in chromaffin
cell tumors may differ from the
biosynthesis and storage in the
normal medulla.
12/04/2018
PediatricPheochromocytoma
Prof.Dr.SaadSAlAni
7

8. Pathophysiology(Cont.)
12/04/2018
PediatricPheochromocytoma
Prof.Dr.SaadSAlAni
8
Alteration in the feedback inhibition
of tyrosine hydroxylase
Alteration in the regulation of the
catecholamine biosynthesis

9. Catecholamine biosynthesis
and metabolism
12/04/2018
PediatricPheochromocytoma
Prof.Dr.SaadSAlAni
9
Tyrosine
Dihydroxypheny
lalanine (DOPA)
Dopamine
(DA)
Norepinephrine
+ Epinephrine
Homovanillic
acid (HVA) +
vanillylmandelic
acid (VMA)

10. Catecholamines in
pheochromocytomas
•Pheochromocytomas, unlike the
normal adrenal medulla, are not
innervated, and catecholamine
release is not initiated by neural
impulses
12/04/2018
PediatricPheochromocytoma
Prof.Dr.SaadSAlAni
10

11. Catecholamines in
pheochromocytomas
•Most pheochromocytomas in
children predominantly produce
norepinephrine (unlike the
normal adrenal medulla, which,
in humans, contains 85%
epinephrine)
12/04/2018
PediatricPheochromocytoma
Prof.Dr.SaadSAlAni
11

12. Catecholamines in
pheochromocytomas
•The symptoms associated with
pheochromocytomas are caused by
the physiologic and pharmacologic
effects of large amounts of circulating
norepinephrine and epinephrine.
12/04/2018
PediatricPheochromocytoma
Prof.Dr.SaadSAlAni
12

13. Etiology
Pheochromocytoma occurs wherever
chromaffin tissue is found
• Usually sporadic
• Could be familial
• May be associated with syndromes
12/04/2018
PediatricPheochromocytoma
Prof.Dr.SaadSAlAni
13

14. Epidemiology
12/04/2018
PediatricPheochromocytoma
Prof.Dr.SaadSAlAni
14
Annual incidence rate
• 1 per 100,000 population(in USA)
In children or adolescents
• 10-20%

15. Epidemiology (Cont.)
Frequency of bilateral tumors
• In children >adults(20% vs 5-10%)
Frequency of malignant tumors
• In children <adults (3.5% vs 3-14%)
12/04/2018
PediatricPheochromocytoma
Prof.Dr.SaadSAlAni
15

16. Epidemiology(Cont.)
In affected children:
More than one third have multiple
tumors, most of which are recurrent
70% of cases are confined to adrenal
locations (an increased association with
familial syndromes )
70% of cases are unilateral
12/04/2018
PediatricPheochromocytoma
Prof.Dr.SaadSAlAni
16

17. Epidemiology(Cont.)
In affected children:
In 30-40% tumors : found in both adrenal
and extra-adrenal areas or in only extra-
adrenal areas
In childhood present most frequently
6-14 years (average, 11 y)
Male-to-female ratio is 2:1
12/04/2018
PediatricPheochromocytoma
Prof.Dr.SaadSAlAni
17

18. Clinical Presentation
•Classically, pheochromocytoma
manifests as spells with the following
4 characteristics:
• Headaches
• Palpitations
• Diaphoresis
• Severe hypertension
12/04/2018
PediatricPheochromocytoma
Prof.Dr.SaadSAlAni
18

19. Typical patterns of the spells
•Frequency may vary from monthly
to several times per day
•Duration may vary from seconds
to hours
•Over time, spells tend to occur
more frequently and become more
severe as the tumor grows
12/04/2018
PediatricPheochromocytoma
Prof.Dr.SaadSAlAni
19

20. Other evidence that occur
during spills
•Tremor
•Nausea
•Weakness
•Anxiety, sense of doom
•Epigastric pain
•Flank pain
•Constipation
12/04/2018
PediatricPheochromocytoma
Prof.Dr.SaadSAlAni
20

21. Clinical signs associated with
pheochromocytomas
12/04/2018
PediatricPheochromocytoma
Prof.Dr.SaadSAlAni
21
Hypertension(50% ) Neurofibromas
Postural hypotension Tachyarrhythmias
Hypertensive retinopathy Pulmonary edema
Weight loss Cardiomyopathy
Pallor Ileus
Tremor Café au lait spots

22. Diagnostic tests for
pheochromocytoma
Laboratory tests:
•Plasma metanephrine testing:
96% sensitivity
•24-hour urinary collection for
catecholamines and metanephrines:
87.5% sensitivity
12/04/2018
PediatricPheochromocytoma
Prof.Dr.SaadSAlAni
22

23. Diagnostic tests for
pheochromocytoma (Cont.)
Imaging:
•Abdominal CT scanning:
accuracy of 85-95% for detecting
adrenal masses
•MRI: Preferred over CT scanning in
children
sensitivity of up to 100% in detecting
adrenal pheochromocytomas
12/04/2018
PediatricPheochromocytoma
Prof.Dr.SaadSAlAni
23

24. Contrast-enhanced computed
tomography scan of the abdomen
12/04/2018
PediatricPheochromocytoma
Prof.Dr.SaadSAlAni
24
A cystic-solid mass associated with the left kidney.
https://www.spandidos-publications.com

25. MRI
12/04/2018
PediatricPheochromocytoma
Prof.Dr.SaadSAlAni
25
http://scielo.br/

26. Diagnostic tests for
pheochromocytoma(Cont.)
Imaging:
•Scintigraphy:
Reserved for biochemically confirmed cases in
which CT scanning or MRI does not show a
tumor
•Positron Emission Tomography
(PET)scanning:
A promising technique for detection and
localization of pheochromocytomas
12/04/2018
PediatricPheochromocytoma
Prof.Dr.SaadSAlAni
26

27. Scintigraphy
12/04/2018
PediatricPheochromocytoma
Prof.Dr.SaadSAlAni
27
Whole body 123I
MIBG demonstrating
focal accumulation of
radiopharmaceutical
medially in the left
upper quadrant.
http://ispub.com/IJEN/3/1/3380

28. 18F-FDOPA PET
12/04/2018
PediatricPheochromocytoma
Prof.Dr.SaadSAlAni
28
Right adrenal pheochromocytoma
(A) Anterior view of maximum-
intensity-projection image
demonstrates right adrenal
pheochromocytoma (open arrow)
and adjacent pancreas, gallbladder,
kidneys, and liver.
(B) Transverse cross-section
through tumor.
http://jnm.snmjournals.org/content/50/4/513/F3.expansion.html

29. Pheochromocytoma:
gross pathology
12/04/2018
PediatricPheochromocytoma
Prof.Dr.SaadSAlAni
29
https://radiopaedia.org/cases/pheochromocytoma-gross-pathology-1

30. Pheochromocytoma:
histopathology
12/04/2018
PediatricPheochromocytoma
Prof.Dr.SaadSAlAni
30
• Zellballen (small nests or
alveolar pattern), trabecular
or solid patterns of polygonal /
spindle shaped cells in rich
vascular network
• Cells have finely granular
basophilic or amphophilic
cytoplasm
• Intracytoplasmic hyaline
globules
• Round / oval nuclei with
prominent nucleolus and
variable inclusion-like
structures
http://www.pathologyoutlines.com/topic/adrenalpheochromocytoma.htm

31. Management
•Surgical resection of the tumor is the
treatment of choice and usually cures
the hypertension.
•Careful preoperative treatment with
alpha and beta blockers is required to:
 control blood pressure
 prevent intraoperative hypertensive
crises
12/04/2018
PediatricPheochromocytoma
Prof.Dr.SaadSAlAni
31

32. Preoperative medical stabilization
1st step
• Start alpha blockade with phenoxybenzamine 7-10 days
preoperatively
2nd step
• Provide volume expansion with isotonic sodium chloride
solution
• Encourage liberal salt intake
3rd step
• Initiate a beta blocker only after adequate alpha blockade*
4th step
• Administer the last doses of oral alpha and beta blockers on
the morning of surgery
12/04/2018
PediatricPheochromocytoma
Prof.Dr.SaadSAlAni
32
*to avoid precipitating a hypertensive crisis from unopposed alpha
stimulation

33. Summary
• The gold standard for diagnosis is via:
measurement of plasma free metanephrines
imaging studies performed for:
 localization
 identification of metastatic lesions
 surgical resection.
12/04/2018
PediatricPheochromocytoma
Prof.Dr.SaadSAlAni
33
Review of Pediatric Pheochromocytoma and Paraganglioma.
Front Pediatr. 2017; 5:155 (ISSN: 2296-2360)
Bholah R; Bunchman TE

34. Summary (Cont.)
•Risk factors for intraoperative
hypertensive attack in patients with
pheochromocytoma :
 a large tumor size
 an elevated preoperative urinary
epinephrine level
12/04/2018
PediatricPheochromocytoma
Prof.Dr.SaadSAlAni
34
Risk factors for hypertensive attack during pheochromocytoma resection.
Investig Clin Urol. 2016; 57(3):184-90 (ISSN: 2466-054X)
Kwon SY; Lee KS; Lee JN; Ha YS; Choi SH; Kim HT; Kim TH; Yoo ES; Kwon TG

35. Summary (Cont.)
•Although pheochromocytomas and
paragangliomas (PHEO/PGL) are
rarely diagnosed during childhood,
the pediatric provider should be able
to recognize and screen for such
tumors, particularly in the context of
a known genetic predisposition
12/04/2018
PediatricPheochromocytoma
Prof.Dr.SaadSAlAni
35
A current review of the etiology, diagnosis, and treatment of pediatric
pheochromocytoma and paraganglioma.
J Clin Endocrinol Metab. 2010; 95(5):2023-37 (ISSN: 1945-7197)
Waguespack SG; Rich T; Grubbs E; Ying AK; Perrier ND; Ayala-Ramirez M;
Jimenez C

36. References
• Waguespack SG, Rich T, Grubbs E, Ying AK, Perrier ND, Ayala-Ramirez M, et al. A current review
of the etiology, diagnosis, and treatment of pediatric pheochromocytoma and paraganglioma. J
Clin Endocrinol Metab. 2010 May. 95(5):2023-37.
• Därr R, Lenders JWM, Hofbauer LC, Naumann B, Bornstein SR, Eisenhofer G. Pheochromocytoma:
Update on Disease Management. Ther Adv in Endo and Metab. 2012;3(1):11-26
• Bholah R, Bunchman TE. Review of Pediatric Pheochromocytoma and Paraganglioma. Front
Pediatr. 2017. 5:155
• Kwon SY, Lee KS, Lee JN, et al. Risk factors for hypertensive attack during pheochromocytoma
resection. Investig Clin Urol. 2016 May. 57 (3):184-90
• https://emedicine.medscape.com/article/124059-overview#a3
12/04/2018
PediatricPheochromocytoma
Prof.Dr.SaadSAlAni
36

37. 12/04/2018
PediatricPheochromocytoma
Prof.Dr.SaadSAlAni
37https://www.thebalance.com/business-thank-you-letter-examples-2059676