The document discusses adrenal medulla and tumors that can arise from it. It notes that adrenal medulla cells are derived from neural crest cells and their supporting cells. The two main tumors are neuroblastomas and pheochromocytomas. Pheochromocytomas arise from chromaffin cells and secrete catecholamines. They can be benign or malignant. Neuroblastomas are the most common extracranial solid tumor in childhood and commonly present with abdominal masses or chest symptoms. The document also discusses multiple endocrine neoplasia syndromes type 1 and 2.

1. Adrenal Medulla
Dr. Reetu Baral MD (Pathology)
Department of Pathology
Nobel medical college

2. Adrenal Medulla
• Adrenal medulla cells derived from:
– Neural crest (chromaffin cells)
– Their supporting (sustentacular) cells
• The chromaffin cells are so named because of their brown-
black color after exposure to potassium dichromate
• They synthesize and secrete catecholamines in response to
signals from preganglionic nerve fibers in the sympathetic
nervous system
• The most important diseases of the adrenal medulla are
neoplasms:
– Neuroblastomas
– Pheochromocytomas

3. Tumors of Adrenal medulla - Pheochromocytoma
• Pheochromocytomas are neoplasms: composed of
chromaffin cells- synthesize and release
catecholamines
• “Rule of 10s”
– 10% are extraadrenal – at organ of Zuckerkandl ,
carotid bodies – called Paragangliomas
– 10% are bilateral
– 10% are malignant
– 10% are not associated with hypertension
• Nearly 2/3rd of the 90% with HTN have Paroxysmal
episode- sudden rise in BP and palpitation – fatal

4. Morphology – Pheochromocytoma
• Small, circumscribed
lesion to large
haemorrhagic masses
weighing several kilos
• Cut section: yellow-tan,
well-defined lesions
that compress the
adjacent adrenal gland
• Incubation of the fresh
tissue with potassium
dichromate solutions
turns the tumor dark
brown

5. Microscopic examination Pheochromocytoma
• Polygonal or spindle cells
arranged in small nests
(Zellballen) surrounded by
sustentacular cells
• The nests are separated by
a delicate fibrovascular
stroma.
• The nuclei are round or
oval and have prominent
nucleoli.
• Definitive diagnosis : based
in presence of metastasis.

6. Pheochromocytoma: Clinical features
• Hypertension: 90% of patients
• 2/3rd patients – Paroxysmal episode-
– Abrupt increase in BP
– Tachycardia
– Palpitations
– Headache
– Sweating
– Tremor
– Sense of apprehension

7. Pheochromocytoma: Clinical features
• Sudden release of catecholamines-
– Precipitate CHF
– Pulmonary Edema
– Myocardial infarction
– Ventricular fibrillation
– Cerebrovascular accidents
• Treatment
– Surgical excision
– Medical treatment for HTN

8. Neuroblastoma
• Most common extracranial solid tumor of
childhood
• First 5 years of life
• May occur anywhere in the sympathetic
nervous system – mostly in abdomen (Adrenal
medulla)
– Sporadic
– Familial 1-2%
• Unique feature - spontaneous regression and
spontaneous or therapy-induced maturation.

9. Neuroblastoma – morphology
• Small, round cells with dark
nuclei, scant cytoplasm,
growing in solid sheets.
• Mitotic activity +
• Nuclear breakdown
“karyorrhexis” +
• Pleomorphism +
• Homer-Wright pseudorosettes:
tumor cells arranged
concentrically around a central
core of neuropil

10. Clinical features
• Neuroblastoma in the abdomen — the
most common form:
– Abdominal pain
– Non tender mass under the skin
– Changes in bowel habits, such as diarrhea or
constipation
• Neuroblastoma in the chest:
– Wheezing
– Chest pain
– Changes to the eyes, including drooping eyelids
and unequal pupil size

11. • Other s/s:
– Lumps of tissue under
the skin
– Eyeballs that seem to
protrude from the
sockets (proptosis)
– Dark circles, similar to
bruises, around the eyes
– Back pain, Fever,
Unexplained weight loss

12. Multiple Endocrine Neoplasia (MEN) syndromes
• The MEN syndromes are a group of inherited
diseases caused by proliferative lesions (hyperplasias,
adenomas, and carcinomas) of multiple endocrine
organs.
• Distinctive features of MEN:
– Younger age
– They arise in multiple endocrine organs: synchronously or
metachronously
– Multifocal – even in one organ
– Aggressive and recur
– Preceded by an asymptomatic stage of endocrine
hyperplasia involving the cell of origin of the tumor (C-cell
hyperplasia followed by medullary thyroid carcinoma)

13. MULTIPLE ENDOCRINE NEOPLASIA TYPE 1
• MEN-1 syndrome is caused by germ line
mutations in the MEN1 tumor suppressor gene,
which encodes a protein called Menin.
• Organs most commonly involved are the
parathyroid, pancreas, pituitary— “3 Ps.”
1. Parathyroid:
– Primary hyperparathyroidism (80%–95% of patients)
– 40 – 50 years
– Hyperplasia and adenomas

14. MULTIPLE ENDOCRINE NEOPLASIA TYPE 1
2. Pancreas:
– Often functional
– Aggressive and metastatic
– Leading cause of death
3. Pituitary:
– Prolactin secreting macroadenoma
– Sometimes acromegaly due to somatotrophin
secreting tumors

15. MULTIPLE ENDOCRINE NEOPLASIA TYPE 2
• Comprises two distinct groups of disorders
that are unified by the occurrence of
activating (gain-of-function) mutations of the
RET proto-oncogene
1. Multiple Endocrine Neoplasia Type 2A
2. Multiple Endocrine Neoplasia Type 2B

16. Multiple Endocrine Neoplasia Type 2A
• Organs commonly involved:
• Thyroid:
– Medullary thyroid carcinoma
– 1st two decade of life
– Multifocal
– Foci of C cell hyperplasia
• Adrenal medulla:
– Adrenal pheochromocytomas develop in 50% cases
– Less than 10% of these tumors are malignant
• Parathyroid:
– 10 – 20% parathyroid hyperplasia

17. Multiple Endocrine Neoplasia Type 2B
• A single amino acid change in RET, distinct
from the mutations that are seen in MEN-2A,
seems to be responsible for virtually all cases
of MEN-2B.
• Patients develop medullary thyroid
carcinomas, which are usually multifocal and
more aggressive than in MEN-2A, and
pheochromocytomas.

18. Multiple Endocrine Neoplasia Type 2B
• Primary hyperparathyroidism does not develop In
patients with MEN-2B
• Extraendocrine manifestations are characteristic in
patients with MEN-2B
• These include ganglioneuromas of mucosal sites
(gastrointestinal tract, lips, tongue)
• Marfanoid habitus, in which overly long bones of the
axial skeleton give an appearance resembling that in
Marfan syndrome

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