Path Lab

Name: Onyedika Egbujo

No: #671
Topic: Pheochromocytoma

Identify the Tissue
with reason



This large adrenal neoplasm has been sectioned in half. Note the grey-tan color of
the tumor compared to the yellow cortex stretched around it and a small remnant of
remaining adrenal at the lower right. This patient had episodic hypertension. This is
a tumor arising in the adrenal medulla--a pheochromocytoma.
Describe gross
morphology changes
Varies from small, circumscribed to large, hemorrhagic and necrotic (1g to 4 kg)
Mean 7 cm / 200 g
Small tumors have rim of compressed adrenal gland
Lobulated, yellow-red-brown
Familial tumors are bilateral and multicentric, and adjacent medulla may appear
hyperplastic
Chromaffin reaction: Fresh tumor turns dark brown if add potassium dichromate
at pH 5-6 (Zenkers)

Describe
histopathology
changes
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.
May have marked pleomorphism
Capsular and vascular invasion common in benign behaving tumors
Nests outlined by sustentacular cells (cannot see in H&E but S100+)


Amyloid also common.
Rare / no mitotic figures
May be mixed with neuroblastoma, ganglioneuroma, ganglioneuroblastoma,
cortical adenoma, spindle cell sarcoma
Unusual morphological features:
o Coexisting cortical hyperplasia, vacuolar degeneration of tumor cells,
presence of pheochromoblasts (small cells), ganglion-like cells,
calcospherites, melanin pigmentation, insular growth pattern, brown fat

List possible
etiology/ risk factors
Probably >10% of cases; usually younger age of onset (10-20 years vs. 40-
60 years), bilateral (70% vs. 10% in sporadic), multicentric, associated with
other neoplasms, male gender
MEN 1:
o Pituitary tumors, parathyroid hyperplasia or adenoma, pancreatic
hyperplasia or adenoma and carcinoid tumors
MEN 2a/2:
o Sipple first described in 1961
o Autosomal dominant with high penetrance, 30-50% have
pheochromocytoma, all have medullary thyroid carcinoma and 10-
15% have parathyroid hyperplasia
o Due to mutation in RET proto-oncogene
MEN 2b/3:
o MEN2a signs / symptoms plus mucosal neuromas and
ganglioneuromas
o Autosomal dominant or sporadic
o May lack parathyroid hyperplasia
Sturge-Weber:
o Cavernous hemangiomas (port-wine spots) of trigeminal nerve
(cranial nerve V), pheochromocytoma
von Hippel Lindau:
o 10-20% of patients
o Cysts of kidney, liver and epididymis
o Renal cell carcinoma (clear cell type), pheochromocytoma,
angiomas and cerebellar hemangioblastoma
von Recklinghausen (neurofibromatosis type 1):
o 1-5% of patients
o Neurofibromatosis, schwannoma, meningioma, glioma and
pheochromocytoma


o Composite tumors with neuroblastoma, ganglioneuroma or
ganglioneuroblastoma may be associated with neurofibromatosis 1
Describe the
pathogenic
mechanism
The clinical manifestations of a pheochromocytoma result from excessive
catecholamine secretion by the tumor. Secretion may occur either intermittently or
continuously. Catecholamines typically secreted are norepinephrine and epinephrine;
some tumors produce dopamine.
What is the
pathology or
diagnosis
Episodic hypertension
Causes surgically correctable hypertension (also aldosterone-secreting tumors,
renal artery stenosis)
Called 10% tumor: 10% bilateral (probably higher), 10% outside adrenal
medulla, 10% metastasize (probably higher), 10% in children
Extra-adrenal tumors secrete only norepinephrine, have 20% malignancy rate
In children, usually extra-adrenal, bilateral and associated with MEN 2a/2b
Metastases usually to lymph nodes, bone (ribs, spine), liver and lung; occasionally
to brain, diaphragm, ileum, kidney, pancreas, peritoneum, pleura, spleen, stomach
Catecholamine cardiomyopathy:
o Myocardial instability, ventricular arrhythmias
o Due to ischemic damage from vasoconstriction of coronaries or direct
toxicity
o Cardiac biopsy shows myocytolysis, interstitial fibrosis and mononuclear
inflammation
Diagnosis:
o Increased urinary excretion of catecholamines or metabolites
(vanilllylmandelic acid-VMA or total metanephrines)
o Elevated serum chromogranin A levels
o Clonidine test
List symptoms/signs The symptoms of phaeochromocytoma tend to be unpredictable you may
suddenly get an attack lasting 15-20 minutes. The three typical symptoms are:
severe headaches
sweating
heart palpitations
Other possible symptoms are:
high blood pressure
feeling irritable, nervous or anxious
having problems sleeping
tremors
stomach pains
weakness
weight loss
The attacks may become more frequent, longer and more severe as the tumour
grows.


However, some people with phaeochromocytoma never develop symptoms,
and their condition is only discovered during tests for another problem.
List other systems
affected/complicatio
ns
Hypertension
Hypertensive encephalopathy
Myocarditis
Signs and symptoms of myocardial infarction
Dilated cardiomyopathy
Pulmonary edema: Either of cardiac or noncardiac origin
In pregnancy: maternal and fetal mortality rates of 48% and 55%, respectively.
List
relevant/additional
info
Criteria for malignancy
Most reliable is presence of metastases (lymph nodes, liver, lung, bone)
Malignant cases have MIB1 positive cell rate of 2-3% or more.
PASS score (Pheochromocytoma of the Adrenal gland Scaled Score):
o Benign if 0-3 points, potential for malignancy if 4+ points; each feature
present gets points added.
o 1 point: vascular invasion, capsular invasion, profound nuclear
pleomorphism or hyperchromasia
o 2 points: invasion of periadrenal adipose tissue, large nests or diffuse
growth, focal or confluent necrosis, high cellularity, tumor cell spindling,
cellular monotony, 4+ mitotic figures per 10 high power fields, atypical
mitotic figures
Write a clinical
vignette
A 50-year-old man has episodic headaches for 3 months. On physical
examination his blood pressure is 185/110 mm Hg, with no other
remarkable findings. Laboratory studies show sodium 145 mmol/L,
potassium 4.3 mmol/L, chloride 103 mmol/L, C02 26 mmol/L, glucose
91 mg/dL, and creatinine 1.3 mg/dL. An abdominal CT scan shows a 7
cm left adrenal mass. During surgery, as the left adrenal gland is
removed, there a marked rise in blood pressure. Which of the following
laboratory test findings most likely explains his findings?
A Decreased serum cortisol
B Decreased urinary homovanillic acid
C Increased serum ACTH
D Increased urinary free catecholamines
E Elevated serum ANCA
List 3 important
features that might
be tested
Risk factors, pathologic mechanism and morphological features.