phyochromocytoma

1. FRONT E
I R
Lecture 9. Adrenal
Medulla Diseases:

2. Pheochromocytoma:
• Pheochromocytomas are neoplasms composed of
chromaffin cells, which, like their nonneoplastic
counterparts, synthesize and release catecholamines
and, in some cases, other peptide hormones.
• They are uncommon.
• Pheochromocytomas usually subscribe to a convenient
“rule of 10s”:
• 10% of pheochromocytomas are extraadrenal,
occurring in sites such as the organ of Zuckerkandl and
the carotid body, where they usually are called
paragangliomas, rather than pheochromocytomas.

3. • 10% of adrenal pheochromocytomas are bilateral;
this proportion may rise to 50% in cases that are
associated with familial syndromes.
• 10% of adrenal pheochromocytomas are
malignant, although the associated hypertension
represents a serious and potentially lethal
complication of even benign tumors.
• 10% of adrenal pheochromocytomas are not
associated with hypertension. Of the 90% that
present with hypertension, approximately two-
thirds have “paroxysmal” episodes associated with
sudden rise in blood pressure and palpitations,
which can, on occasion, be fatal.

5. •Pathogenesis:
• 25% of individuals with pheochromocytomas and
paragangliomas harbor a germ line mutation in
one of at least six known genes.
• RET, which causes type 2 MEN syndromes.
• NF1, which causes type 1 neurofibromatosis.
• VHL, which causes von Hippel-Lindau disease.
• Three genes encoding subunits within the succinate
dehydrogenase complex (SDHB, SDHC, and SDHD),
which is involved in mitochondrial electron
transport and oxygen sensing.
• It is postulated that loss of function in one or more
of these subunits leads to stabilization of the
transcription factor hypoxia-inducible factor 1α
(HIF-1α), promoting tumorigenesis.

6. • Morphology:
• Varying size.
• Hemorrhagic masses.
• On cut surface:
• Smaller pheochromocytomas _ are yellow-tan,
well-defined lesions.
• Larger pheochromocytomas _ are hemorrhagic,
necrotic, and cystic.
• On microscopic examination:
• Pheochromocytomas are polygonal to spindle-
shaped chromaffin cells and their supporting cells.

9. • Clinical feature:
1. Hypertension, tachycardia, palpitations.
2. Headache.
3. Sweating.
4. Tremor.
5. Sense of apprehension.
6. Abdominal or chest pain.
7. Nausea, and vomiting.

10. • Diagnosis:
• Vanillylmandelic acid and metanephrines in the
urine and are end product of catecholamines.
• Treatment:
• Small lesion require surgical excision.
• Large with multi focal lesion require long-term
medical treatment for hypertension.
• Phenoxybenzamine ‘nonselective, irreversible
antagonist of the alpha-adrenergic receptors class
of drugs’.
• β-Blocker.
• Metyrosine (catecholamine synthesis inhibitor).

11. Neuroblastoma:
• also called as sympathicoblastoma.
• Is a common malignant tumour of embryonic nerve
cells.
• Most often occurs in children <5 years old.
• Primarily located in the adrenal medulla.
• Occasionally located in the posterior mediastinum
(paraspinal).
• Commonly metastasize to skin and bones.

14. • Clinical feature:
1. Abdominal distension.
2. Fever.
3. Weight loss.
4. Malaise.
5. Carcinoid-like syndrome = watery diarrhoea,
flushing of the skin and hypokalaemia all these
probably due to production of kinins or
prostaglandins by the tumour.
• Diagnosis:
• Foci of calcification observed on radiologic
examination of the abdomen.
• 24-hour urine detection of vanillyl mandelic
acid (VMA) and homovanillic acid (HVA).

15. • Treatment:
• Neuroblastoma Surgery.
• Chemotherapy for Neuroblastoma.
• Radiation Therapy for Neuroblastoma.
• High-dose Chemotherapy and Stem Cell Transplant for
Neuroblastoma.
• Retinoid Therapy for Neuroblastoma.
• Immunotherapy for Neuroblastoma.
Prognosis depends on age.
• Children <1 year old have a
good prognosis

16. Ganglioneuroma:
• A ganglioneuroma is a mature, benign and
uncommon tumour occurring in adults.
• It is derived from ganglion cells, most often in the
posterior mediastinum, and uncommonly in other
peripheral ganglia and brain.
• The tumour produces symptoms because of its size
and location.
• Catecholamines and their metabolites can be
detected in large amounts in the 24-hour urine
specimen of patients with ganglioneuroma.

18. • Diagnosis:
• Magnetic resonance imaging (MRI) and computed
tomography (CT) for evaluating the extension of
spinal tumors.

19. • Treatment:
• Surgery alone.
• However, ganglioneuroblastoma intermixed (GNBI)
is widely seen as a malignant entity and –
depending on stage – treated with multimodal
therapy.