Pheochromocytomas and Paragangliomas
Research Study – A Review
R. G. Wiseman Pinto
Pheochromocytomas and Paragangliomas are related tumors, sometimes referred to as 10% tumors that are known to cause of hypertension that can be corrected. They occur in Adrenal and extra-Adrenal sites and may produce catecholamines like Epinephrine and Norepinephrine. They usually occur in the fourth and fifth decade and have a distinct appearance on gross microscopy & imaging techniques. This review gives the details of these tumors.
This Review deals with Pheochromocytoma and Paraganglioma which arise from the Chromaffin cells and produce Catecholamines like Epinephrine, Norepinephrine and other peptides that lead to Hypertension.The Clinical aspects, Gross features, Microscopic picture, Investigations and various Associated Syndromes are discussed.
Pheochromocytomas and Paragangliomas are rare tumors occuring in Adrenal and extra Adrenal sites, and are an important and curable cause for Hypertension. They are commonly seen in the fourth and fifth decade ,with equal sex incidence and two thirds are functioning. They are referred to as the 10% tumors, implying that 10% are familial, 10% occur in the Pediatric age group, 10% are extra adrenal, 10 % are bilateral and 10% are malignant, Pheochromocytomas can be Pigmented, Composite and associated with Carneys Complex and Carneys triad.
Pheochromocytomas arise from the chromaffin cells in the Adrenal Medulla. They produce catecholamines like Epinephrine, Norepinephrine and other peptides and are an important cause of hypertension which can be corrected. They occur in the fourth and fifth decade and the sex incidence is equal. Two-thirds are functioning as they produce catecholamines. They are referred to as 10% tumors, because 10% are Familial, 10% are bilateral, 10% are malignant, 10% are extra adrenal and 10% occur in paediatric age group.
The extra – adrenal tumors are called Paragangliomas. Paragangliomas are usually non-functioning. Functioning tumors are called Pheochromocytomas. So there are Adrenal and extra-adrenal Pheochromocytomas and Paragangliomas. The Paragangliomas in the carotid body and aortic body are called chemodectomas.
On gross examination they appear as solid, single, encapsulated, 2-10 cms in sized, solid, firm, and circumscribed. They may show large areas of hemorrhage, necrosis, cysts, and may calcify. The cut section is yellow tan, to gray white, or red. If the fresh tissue is incubated with potassium dichromate solution the tumor turns dark brown.
On microscopic examination we see:
- Alveolar (Nested, Organoid, Zellballen) pattern
- Trabecular pattern and
- Solid pattern
There may also be spindle cell and pseudopapillary types.
The individual cells are polygonal and eosinophilic with granular cytoplasm and these groups are supported by the supporting cells with rich vascular network.
The cytoplasmic granules contain catecholamines, which stain with silver.
The nucleus in some areas are pleomorphic, hyperchromatic with mitosis and nuclear pseudoinclusions. These findings are seen in benign pheochromocytoma and are not an indication of malignancy.
Amyloid are seen in 9% of tumors and the surrounding periadrenal fat shows brown fat features.
Immunohistochemistry shows neuron specific enolase positive, chromogranin positive, synaptophysin positive and CD 56 positive. The sustentacular cells are S 100 positive.
With electron microscopy the cells show membrane bound, electron dense granules containing catecholamines.
The patients have hypertension, abrupt rise in blood pressure, tachycardia, palpitations, headache, sweating, tremors, apprehension, pain in abdomen & chest and nausea & vomiting. Sometimes the episodes are paroxysmal and isolated.
There may be sustained rise of blood pressure or labile hypertension. Some patients may have myocardial Infarction, congestive cardiac failure, renal injury, cerebrovascular accident, ventricular arrhythmias and sudden cardiac death.
USG, Color Doppler, CT, MRI, PET – CT, Urinary excretion of catecholamines, VMA, and metanephrine.
Multifocal lesions are familial.
Shows metastasis in non-chromaffin cell containing sites like lymph nodes, liver, lungs, bone marrow. Extra adrenal Tumors are more likely to be malignant.
Occur in younger age in MEN 2A and MEN 3B having type I Neuro fibromatosis, Von- Hippel Lindau disease and Sturge Weber syndrome.
Are black in color and contain melanin pigment. They should not be confused with melamoma.
- Neuroblastoma, Ganglioneuroma, Malignant Schwannomma
- Bilateral Pheochromocytoma with malignant nerve sheath tumor in Von Recklinghausen disease
- Pheochromocytoma with Adrenal Cortical Adenoma
Paragangliomas are extra adrenal, mainly non-functioning.
Chemodectomas occur in the carotid body and aortic body. Persons living in high altitudes have hyperplastic changes in these organs.
When the tumors are familial, they are bilateral, multicentric, and occur in younger age.
Carneys Complex and Carneys Triad
Contains Extra adrenal Paraganalioma, Malignant GIST, Pulmonary Chondroma.
Paragangliomas can also occur in the carotid body, at the bifurcation of common carotid artery, Jugulotympanic site (Glomus jugulare tumor), Vagal (Neck), Mediastinal, Retroperitoneal, and Zuckerkandl’s body.
- Juan Rosai, Surgical Pathology, Tenth Edition, Mosby, Elsevier, India, 2012, pages 1057 -1085.
- Shahid Pervez, Comprehensive Color Atlas of Diagnostic and Predictive Histopathology, 2011, Elite, pages 94 -95.
- Vinay Kumar, Abbas A.K.Fausto N, Mitchell R.N. Robbins Pathology, Saunders, Elsevier, 2007, pages 797-798 10% are bilateral, 10% are malignant, 10% are extra