Adrenocortic

al neoplasm
Dr:Eman Khammas
Alsadi
Pathology lecturer

Adrenocortical neoplasms

functional adenomas
are most commonly associated
with hyperaldosteronism and
with Cushing syndrome

a virilizing neoplasm is more

likely to be a carcinoma

functional and nonfunctional

adrenocortical neoplasms
cannot be differentiated on
clinical evaluation only but
need the measurement of the
hormone or its metabolites in
the laboratory

Morphology
1. Adrenocortical adenomas
Most adenomas are non
functioning and are usually
encountered as incidental findings

.gross appearance:
they are small, averaging 1 to 2 cm
. in diameter
On cut surface, :adenomas are usually yellow
to
yellow-brown, owing to the presence of lipid
.within the neoplastic cells

Microscopically,
adenomas are composed of
cells
similar to those of normal
adrenal
cortex.
1.The nuclei tend to be small,
2. some degree of
pleomorphism may be
encountered even in benign
lesions ("endocrine atypia") .
3.The cytoplasm of the
neoplastic cells ranges from
eosinophilic to vacuolated,
depending on their lipid
content;
4. mitotic activity is generally
inconspicuous.

 This high power microscopic appearance of an adrenal

cortical carcinoma demonstrates that the neoplasm closely
resembles normal adrenal cortex. It is difficult to
determine malignancy in endocrine neoplasms based upon
cytology alone. Thus, invasion ( as seen here in a vein

and metastases are the most reliable indicators.

Luckily, most endocrine neoplasms are benign adenomas .

2.Adrenocortical carcinomas
1. are rare neoplasms
2. may occur at any age, including in childhood.
3. Two rare inherited causes of adrenal cortical
carcinomas include
1. the Li-Fraumeni syndrome
2. the Beckwith-Wiedemann syndrome
4. adrenocortical carcinomas are large, invasive
lesions

,On cut surface

adrenocortical carcinomas are typically

variegated, poorly demarcated lesions
containing areas of necrosis, hemorrhage and
. cystic change

,Microscopically
adrenocortical carcinomas
1. may be composed of well-differentiated
cells resembling those seen in cortical
adenomas
2. or bizarre, pleomorphic cells, which may
be difficult to distinguish from those of
an undifferentiated carcinoma metastatic
to the adrenal

Adrenal cancers
1. have a strong tendency to invade
the adrenal vein, vena cava, and
lymphatics.
2. Metastases to regional and
periaortic nodes are common, as
are distant hematogenous spread
to the lungs and other viscera.
3. Bone metastases are unusual.
4. The median patient survival is
about 2 years

ADRENAL MEDULLA
It is populated by cells derived from the neural crest
(chromaffincells) and their supporting
(sustentacular) cells.

The chromaffin cells,:

1) synthesize and secrete catecholamines in
response to signals from preganglionic nerve
fibers in the sympathetic nervous system.
2) Similar collections of cells are distributed
throughout the body in the extra-adrenal
paraganglion system.
The most important diseases of the adrenal medulla are
neoplasms, which include both
1. neuronal neoplasms (including neuroblastomas
and more mature ganglion cell tumors)
2. chromaffin cells neoplasms (pheochromocytomas).

Pheochromocytomas
usually subscribe to a convenient "rule of 10s":
of pheochromocytomas arise in association with 10%( 1
one of several familial syndromes.These include
A. the MEN-2A and MEN-2B syndromes ,
B. type 1 neurofibromatosis ,
C. von Hippel-Lindau disease
D. ,and Sturge-Weber syndrome .
of pheochromocytomas are extra- 10%( 2
adrenal,occurring in sites such as the organ of
Zuckerkandl and the carotid body, where they are usually
.calledparagangliomasrather than pheochromocytomas
.of adrenal pheochromocytomas are bilateral 10%( 3
of adrenal pheochromocytomas are biologically 10% (4
malignant,although the associated hypertension
represents a serious and potentially lethal complication
of even "benign" tumors. Frank malignancy is somewhat
.more common in tumors arising in extra-adrenal sites

Morphology
Pheochromocytomas range from small
circumscribed lesions confined to the
adrenal to large, hemorrhagic masses
weighing several kilograms

. On cut surface,
1. smaller pheochromocytomas are yellow-tan, welldefined lesions that compress the adjacent adrenal .
2. Larger lesions tend to be hemorrhagic, necrotic, and
cystic and typically efface the adrenal gland.
3. Incubation of the fresh tissue with potassium
dichromate solutions turns the tumor a dark brown
color.

, Microscopically
1. pheochromocytomas are
composed of polygonal to
spindle-shaped chromaffin cells
and their supporting cells,
forming small nests, by a rich
vascular network .
2. The cytoplasm of the
neoplastic cells often has a
finely granular appearance,
highlighted by a variety of
silver stains, because of the
presence of granules
containing catecholamines
Seen by the Electron
microscopy.

 4- The nuclei of the neoplastic cells are

often quite pleomorphic.
5- Both capsular and vascular invasion may
be encountered in benign lesions, and the
presence of mitotic figures per se does not
imply malignancy.
6-the definitive diagnosis of malignancy in
pheochromocytomas is based exclusively
on the presence of metastases.
7-These may involve regional lymph nodes
& more distant sites, including liver, lung,
and bone.

clinical manifestation
The dominant clinical manifestation of
pheochromocytoma ishypertension.

Classically, this is described as an abrupt, precipitous elevation in

blood pressure, associated with tachycardia, palpitations,
headache, sweating, tremor, and a sense of apprehension.
with pain in the abdomen or chest, nausea, and vomiting.
In practice,isolated, paroxysmal episodes of hypertension occur
infewer than half of individualswith pheochromocytoma
In about two-thirds of patients the hypertension occurs in the
form of a chronic, sustained elevation in blood pressure, although
an element of labile hypertension is often present as well.
Whether sustained or episodic, the hypertension is associated
with an increased risk of myocardial ischemia, heart failure, renal
injury, and cerebrovascular accidents.
Sudden cardiac death may occur, probably secondary to
catecholamine-induced myocardial irritability and ventricular
arrhythmias.

In some cases, pheochromocytomas secrete other

hormones such as ACTH and somatostatin and may
therefore be associated with clinical features related
to the secretion of these and other peptide hormones.
The laboratory diagnosis of pheochromocytoma is
based on demonstration of increased urinary
excretion of free catecholamines and their
metabolites, such as vanillylmandelic acid and
metanephrines.
Isolated benign pheochromocytomas are treated
with surgical excision, after pre- and intraoperative
medication of patients with adrenergic-blocking
agents.
Multifocal lesions may require long-term medical
treatment for hypertension.

Neuroblastoma
1. extra-cranial solid tumor of childhood.
(common)
2. These neoplasms occur most commonly
during the first 5 years of life and may
arise during infancy.
3. Neuroblastomas may occur anywhere in
the sympathetic nervous system and
occasionally within the brain, but they
are most common in the abdomen;
4. most cases arise in either the adrenal
medulla or the retroperitoneal
sympathetic ganglia.
5. Most neuroblastomas are sporadic,
although familial cases also occur.

MULTIPLE ENDOCRINE NEOPLASIA

SYNDROMES
inherited diseases resulting in
proliferative lesions (hyperplasias,
adenomas, and carcinomas) of multiple
endocrine organs.
These tumors occur at ayounger
agethan sporadic cancers.
oftenmultifocal.
usually preceded by anasymptomatic
stage of endocrine hyperplasiainvolving
the cell of origin of the tumor
usuallymore aggressiveandrecurin a
higher proportion of cases than similar
endocrine tumors that occur sporadically.

MULTIPLE ENDOCRINE NEOPLASIA TYPE 1

inherited in an autosomal dominant pattern.
Organs commonly involved include the
1. parathyroid (95%),
2. pancreas (40%),
3. and pituitary (30%)the "3 Ps."
Parathyroid:Primary hyperparathyroidism, arising from
multiglandular parathyroid hyperplasia, is the most consistent
feature of MEN-1.

Pancreas:
tumors of the pancreas are the leading cause of death in MEN-1.
These tumors are usually aggressive and present with metastatic
disease or multifocality.
are often functional (i.e., they secrete hormones). Zollinger-Ellison
syndrome, associated with gastrinomas, and hypoglycemia,
related to insulinomas, are common endocrine manifestations.
Pituitary:The most frequent pituitary tumor in MEN-1 patients is a
prolactin-secreting macroadenoma. Some individuals develop
acromegaly from somatotrophin-secreting tumors.

MULTIPLE ENDOCRINE NEOPLASIA TYPE 2

is inherited in an autosomal dominant pattern.
Organs commonly involved include:
Thyroid:
Medullary carcinoma of the thyroid develops in virtually
all untreated cases, and the tumors usually occur in the
first 2 decades of
Adrenal medulla
:50% of patients develop adrenal pheochromocytomas;
fortunately, no more than 10% are malignant.
Parathyroid:
Approximately a third of patients develop parathyroid
gland hyperplasia with primary hyperparathyroidism.


Multiple Endocrine Neoplasia,
Type 2B
Organs commonly involved include the
1. thyroid
2. adrenal medulla.

unlike MEN-2A, patients with

:MEN-2B
3. Do not develop primary

hyperparathyroidism
4. Develop extraendocrine manifestations:ganglioneuromas of
mucosal sites (gastrointestinal tract, lips, tongue) and marfanoid
habitus

Now, routine genetic testing identifiesRETmutation carriers earlier

and more
reliably in MEN-2 kindreds;all persons carrying germ-line RET
mutations are advised to have prophylactic thyroidectomy to
prevent
the inevitable development of medullary
.carcinomas

Thank
you