patho sheet # 16 - Fadi Salameh

Dr. starts finishing about the adrenocortical neoplasms, and then proceeds to speak about the adrenal medulla.
Adrenocortical adenoma: mostly non-functional, functional adenomas are associated with atrophy of the adrenal cortex, and the contralateral cortex.
Adrenocortical Carcinoma: rare neoplasms, that may occur at any age, they are more likely to be functional than adenomas, and they are highly malignant tumors, they can invade blood vessels especially veins (adrenal vein, and vena cava). Metastases to regional and periaortic nodes, also hematogenous spread to the lungs and other viscera may occur.
The Adrenal Medulla
Is composed of specialized neural crest cells (chromaffin cells), they synthesize and release catecholamines.
Pheochromocytomas:
1-uncommon neoplasms of chromaffin cells that release and synthesize catecholamines
2- it is a surgically correctable form of hypertension, meaning that pheochromocytoma patients’ hypertension may be stabilized by surgically removing the tumor.
3- 85% arise from the adrenal medulla, while the rest arise from extra-adrenal para ganglia
4- 90% are sporadic, 10% are autosomal dominant familial that may arise in situ
5- Rule of 10… 10% are bilateral, 10% are familial, 10% are extra adrenal, 10% are malignant, 10% are non-functional
Hypertension that’s associated with pheochromocytoma is called paroxysmal, which means that it comes in attacks that are associated with tachycardia, palpitations, headache and sweating due to increase catecholamine levels in the body stimulating the sympathetic system.
Paroxysm may be precipitated by stress, exercise changes, posture and even palpations over the tumor.
Tumor may be diagnosed by: increased urinary secretion of catecholamines, and their metabolites such as (VMA) vanillylmandelic acid.
Treatment: we may give adrenergic blocking agents, but surgical excision of the tumor is preferred
Neuroblastoma: is the most common extra cranial solid tumor of childhood, the most common intracranial tumor of childhood is medulloblastoma, and leukemia is more common in children, but it is not solid
20-30% arise from the adrenal medulla, they present as large abdominal masses, infants that are less that 1 year old have a good prognosis, and deletion of the distal …. Arm of chromosome 1 is the most characteristic cytogenetic abnormality of neuroblastoma.
Now we will talk about
Multiple Endocrine Neoplasia Syndromes:
A group of inherited diseases resulting in proliferative lesions (hyperplasias, adenomas or carcinomas) of multiple endocrine organs, tumors arising in MEN setting have distinctive features:
• These tumors occur at a younger age than sporadic cancers
• They arise in multiple endocrine organs, either synchronously or metachronously
Synchronous tumors: same type of tumors occurring at different sites at the same time. eg. Adencarcinomas in multiple sites of the colon.
Metachronous tumors: tumors occur at different times, but it is the same tumor
• Even in one organ the tumors are often multifocal
• The tumors are usually preceded by an asymptomatic stage of endocrine hyperplasia involving the cell of origin of the tumor, eg. Patients with MEN1 syndrome develop varying degrees of islet cells hyperplasia, some of which progress to pancreatic tumors
• These tumors are usually more aggressive and recur in a higher proportion of cases than similar endocrine tumors that occur sporadically
Multiple Endocrine Neoplasia Type 1 (MEN 1)
3 p’s: parathyroid hyperplasia(95%) or multiple adenomas are seen in 90-95% of cases appearing at the age 40-45 years
Pancreatic lesions which include endocrine tumors which may secrete a variety of peptide hormones, most commonly pancreatic polypeptide, while gastrin and insulin are the most frequently associated with clinical symptoms.
Pituitary adenomas: are present in 10-15% of cases frequently as prolactinomas
Additional tumors include duodenal gastrinomas, thyroid and adrenocortical adenomas.
The etiology involves a germ line mutation in the MEN 1 gene, chromosome 11q encoding a 610 amino acid product known as menin, the dominant clinical manifestations of MEN 1 syndrome are usually defined by the peptide hormone and include such abnormalities as recurrent hypoglycemia and insulinomas and recurrent peptic ulcers and gastrinomas such as Zollinger-Ellison syndrome ( multiple ulcers in unusual locations due to increased gastrin secretion)


Multiple Endocrine Neoplasia Type 2 (MEN) 2
Subclassified into 3 distinct syndromes:
• MEN 2A: is clinically and genetically distinct from MEN 1, and is linked to germ line mutations in the RET proto-oncogene on chromosome 10
• Characterized by medullary thyroid carcinoma that arise in 100% of patients and are usually multifocal, C-cell hyperplasia can be found in the adjacent thyroid in addition to calcitonin medullary carcinoma and may elaborate other biologically active peptides.
• Most tumors pursue a malignant course, and prophylactic thyriodectomy is recommended for germ line mutations
• Pheochromocytoma is present in 50% of patients most are upper bilateral and maybe extra-adrenal most lesions are clinically benign
• Parathyroid hyperplasia are found in 10-20% of patients with evidence of hypercalcaemia or renal stones
MEN 2B
Is clinically similar to MEN 2A with the additional feature of mucosal neuromas and ganglioneuromas involving the lips, oral cavity, eyes, Respiratory tract, GIT and urinary bladder, in addition to other sites.
• Develop marfanoid habitus
• Ninety-five percent of MEN 2B cases result from a single amino acid substitution in the RET protein, different from that mutation in MEN 2A
Familial Medullary Thyroid Cancer
A variant from MEN 2A, with a strong predisposition for thyroid malignancy but without other manifestations
** the difference between MEN 2A and MEN 2B, is only the presence of mucosal neuromas and ganglioneuromas in MEN 2B, they bother relate to a mutation in a RET proto-oncogene, but have a different point mutation.
Fadi Salameh 24-4-2011