Pheochromocytoma / Paraganglioma
Epidemiology:
- 40-60y
- Children
(10%)
- High
altitudes:
- Higher
incidence of paraganglionic hyperplasia and neoplasia
Common sites:
- extra-adrenal
sites (10%) (paraganglioma):
- branchiomeric
(near major arteries and cranial nerves of head and neck, ex. Carotid
bodies)
- intravagal
- aorticosympathetic
- urinary
bladder
Gross features:
- range
in size (must be >1cm by definition in adrenal – otherwise medullary
hyperplasia)
- weight
> 300g – suspicious for malignancy
- well
demarcated
- lobular
pattern due to richly vascularized fibrous trabeculae
- adrenal
remnant stretched around the edge often
- yellow-tan
cut surface
- larger
lesions hemorrhagic, necrotic, cystic
Histologic features:
- chromaffin
cell differentiation
- variable
- nests
or alveoli (zellballen) of chromaffin cells or chief cells with
sustentacular cells
- rich
vascular network between nests
- chromaffin
cells:
- polygonal
to spindle-shaped
- abundant
cytoplasm with fine catecholamine granules (silver stains bring them
out)
- nuclei
round to ovoid
- stippled
“salt and pepper” chromatin
- sometimes
dominant cell type is spindle or small
- nuclear
pleomorphism is not uncommon and is not a criterion for malignancy
- malignancy criteria:
- solely
based on presence of metastasis
- lymph
nodes
- liver,
lung, bone
- other
features are soft and practically not useful:
- LVI
(can be seen in benign pheo)
- cellular
monotony is paradoxically associated with aggressive behaviour
- mitosis count
(>3/10HPF)
- confluent
tumour necrosis
- spindle
cell morphology
- absent
hyaline globules
- capsular
and vascular invasion may be seen in benign lesions
- MEN 2:
- medullary
hyperplasia
- extension
of medulla to the tips of the wings
- extension
of medulla into the tail
- vHL:
- vaculolated
cytoplasm (lipid)
- stromal
degeneration (lipid accumulation)
Immunophenotype:
Marker:
|
Sensitivity:
|
Specificity:
|
Chromogranin
|
|
|
Synaptophysin
|
|
|
S-100
(sustentacular)
|
|
|
Tyrosine
hydroxylase
|
|
Excellent
|
RB (loss
associated with malignancy in one study)
|
|
|
Molecular features:
- CGH:
- chromosome
11 alterations more frequent in malignant in one study
- losses
on chromosomes 6q and 17p more common in malignant in another study
- somatic
VHL mutations more frequent in malignant
- TP53
mutations higher frequency in malignant
Other features:
- vanillylmandelic
acid (VMA) in urine
- metanephrines
in urine
- EM –
membrane0-bound, electron-dense granules (catecholamines and other
peptides)
- Clinical
features:
- Generally
they are functional
- Head
and neck paragangliomas are only rarely functional
- Hypertension
(chronic, sustained)
- May
have abrupt onset of attacks/paroxysms:
- Hypertension
(can be fatal)
- Tachycardia
- Palpitations
- Headache
- Sweating
- Tremor
- Sense
of apprehension
- Chest
or abdomen pain
- Nausea/vomiting
- Rule
of 10’s is WRONG:
- 50%
are familial
- MEN 2
- MEN
2A and MEN 2B
- more
likely benign
- NF1
- vHL
- Sturge-Weber
syndrome
- Mitochondrial
complex II genes:
- SDHD
genes
- SDHB
- SDHC
- 10%
are extra-adrenal
- 10%
are bilateral (70% in familial)
- 10%
are malignant
- 3-13%
overall
- 23-44%
5y survival (97% for benign)
- intra-abdominal
extra-adrenal have highest rate of malignancy
- intra-adrenal
unilateral solitary have lowest rate of malignancy
- SDHD
mutations greater chance of malignancy
- 10%
arise in childhood (usually familial)
- potassium
chromate turns the tumour brown
References:
- Robbins
2005
- WHO
Tumours of Endocrine Organs (2004)