Pathology Of The Adrenal Medulla Flashcards
What are the two types of cells in the adrenal medulla
1) chromaffin
- neural crest derived cells that produce catecholamines
- stain brown-black after potassium dichromate
2) sustentacular cells
- supporting cells of the chromaffin cells
Two most important types of neoplasms in the adrenal medulla
Pheochromocytomas = chromaffin cell tumors
- synthesize and release other peptides also. ALWAYS active
- always result in a paradoxical form of correctable HTN, headaches, sweating/flushing, palpitations and irritability. Can be fatal due to arrthymias
Neuroblastomas = neuronal neoplasms
- the most common extracranal solid tumor of childhood and most commonly appear during the first 5 yrs of life
- can occur anywhere in the sympathetic NS but are most common in the adrenal medulla (40%) or the sympathetic trunk (60%). Most common sites along the sympathetic trunk are the Paravertebral abdomen(25%) or retroperitoneal posterior mediastinum sympathetic ganglion (15%)
The rule of 10s for pheochromocytoma
10% of pheochromocytoma are extradrenal
10% of pheochromocytoma are bilateral
10% of pheochromocytoma are malignant
10% of pheochromocytoma are not associated with HTN
What are the rules of 90 for pheochromocytoma’s
The exact opposite of rules of 10
90% are
- in the adrenal gland
- are unilateral
- are benign
- are associated with HTN
Malignant pheochromocytoma
10% of total pheochromocytomas are malignant
- however most people die of uncontrolled HTN that can be found in both malignant and benign
What are gene mutations that are seen in pheochromocytomas
At least 1 of these are found in 25% of all pheochromocytoma
RET = MEN 2A/2B syndrome
NF1 = neurofibromatosis type 1
VHL = Von-hipped-Lindau
SDHD/C/B = Familial paraganglioma 1/3/4 respectively
Morphology of pheochromocytoma
Range in size from small -> large
Usually are yellow-tan well defined unless they are large then they can be red due to hemorrhages
Contain polygonal spindle-shopped chromaffin cells
Also electronic microscopy shows dark/black Catecholamine granules
the definitive diagnosis of malignant pheochromocytoma is NOT histological, only based on the presence of metastasis
Lab diagnosis of pheochromocytoma
Urine analysis shows elevated vanillylmandelic acid and metanephrine metabolites
- 24 hr sample
Treatment = surgical excision if easy, other wise use treatment of HTN on top of it
Neuroblastomas
Most are sporadic, but 1-2 % can be genetic with autosomal dominant transmission
- occurs with a ALK gene mutation
Morphology = very large variance in symptoms.
- 40x more likely to be benign rather than symptomatic
- often spontaneously regress and leave foci of fibrosis or calcification
- can show a fibrous pseudocapsule or no capsule with lots of Mets. Appear gray-tan with “brain like tissues” inside
Histology = show lots of deep staining nucleated immature cells that sometimes appear in a “homer-wright pseudorosette” apperance
What IHC staining will show for neuroblastomas
Neuron specific enolase
Small membrane bound cytoplasmic catecholamine containing secretory granules
Staging of neuroblastoma
More commonly show stage 3-4 (60-80%) than 1-2 (20-40%)
Stage 1 = localized without any residual disease and ipsilateral non adherent lymph nodes negative for tumors
Stage 2A = localized tumor resected incompletely and ipsilateral non adherent lymph nodes negative for tumors
Stage 2B = localized tumor resected incompletely and ipsilateral non adherent lymph nodes are POSITIVE for tumors
Stage 3 = unilateral tumor that is unresectable and infiltrates across the midline. No regional lymph node involvement and show contralateral lymph node involvement. Shows positive for tumors
Stage 4 = any primary tumor that shows dissemination to distant lymph nodes, bone, liver or skin
Outcome for neuroblastoma
Patients who are younger than 18 months are more likely to beat this than older than 18 months
if a patients show MYCN amplification then they always deemed high risk and almost always die with 1 year
Clincial features of neuroblastomas
Protuberant abdomen with fever and weight loss
Also may show signs of metastasis of liver, and bone
- bone pain, hepatomegaly and ascities, elevated AST/ALT, etc.
90% of theses also produce catecholamines similar to pheochromocytoma, however usually DOESNT show paradoxical HTN and assocaited symptoms. Will still show elevated vanillylmandelic and homovanillic acid though
How is pheochromocytoma diagnosed as malignant
ONLY in the presence of metastasis
Histology DOESNT show this
What are ganglioneuromas?
Arise spontaneously from mature neuroblastomas
Are clusters of large ganglion cells with vesicular nuclei and abundant eosinophilic cytoplasm
- often is accompanied by the appearance of Schwann cells
