Medullary Thyroid Cancer Flashcards
From where does medullary thyroid cancer originate?
parafollicular (C-cells) -usually upper poles of thyroid lobes/neural crest origin
What % of all thyroid malignancies are medullary thyroid cancer? What is the split between sporadic MTC and familial/genetic MTC?
4-10% of all thyroid malignancies are MTC 80% are sporadic 20% are familial (MEN 2A/2B, familial MTC variant)
Most common genetic mutation on familial MTC?
RET proto-oncogene Chromosome 10 autosomal dominant
What is the most aggressive hereditary form of MTC?
MEN-2B least aggressive- FMTC
MTCs stain positive for _________. Most also make another marker _____. Stains for _______ which is apple green birefringence on this stain.
calcitonin (also have elevated serum levels) CEA amyloid
Work-up for medullary thyroid cancer?
Bloodwork: CEA, calcitonin (serum markers), CBC, LFTs, TSH, free T4, T3
Checking for MEN entities: serum Ca, PTH (looking for hyperparathyroidism), 24 hour urine or plasma catecholamines and metanephrines (for pheochromocytoma)
Imaging: ultrasound lateral neck, CT neck/chest/abdo
Genetic analysis: RET proto-oncogene mutational analysis, genetic counselling
Primary surgical treatment for medullary thyroid cancer?
Total thyroidectomy + central compartment lymph node dissection
Any indications for lateral neck dissection?
Only if positive lymph nodes intra-operatively
Germline and familial MTC
What to do with people with MEN-2A/2B RET mutation?
MEN-2B RET mutation: prophylactic total thyroidectomy within first year of life or at time of diagnosis
MEN-2A RET: <5 years old
can omit Level VI nodal dissection in patients <1 years old with MEN-2B and <5 years old with MEN-2A and FMTC unless nodules >5 mm, elevated calcitonin or gross LN mets
Any external beam radiotherapy (EBRT) required as adjuvant therapy for medullary thyroid cancer?
consider for R1 resection for moderate to high volume disease
consider for R0 resection for moderate to high volume disease with extra-nodal soft tissue extension and detect post-op calcitonin in absence of distant mets
Follow-up required for MTC?
if basal calcitonin not detectable, then annual:
- physical exam
- calcitonin and CEA levels
- neck ultrasound
if basal calcitonin detectable, then:
do calcitonin and CEA every 6 months to determine doubling time
ongoing follow-up should occur at 1/4th the shortest doubling time
Three types of familial MTC? What are the relative proportions of these three entities?
1) MEN-2A (70%)
2) MEN-2B (20%)
3) Familial Non-MEN MTC (10%)
What are the classical MEN-2A manifestations?
Classical variant:
M- medullary thyroid cancer (100% penetrance, other manifestations not full penetrance)
P- pheochromocytoma
H- hyperparathyroidism (usually due to parathyroid hyperplasia)
What are the four variants of MEN-2A?
Four variants of MEN-2A:
1) classical variant
2) MEN-2A with cutaneous lichen amyloidosis (CLA)
3) MEN-2A with Hirschsprung disease
4) Familial MTC (RET germline mutation in families with MTC but don’t develop PHEOs or HPTH)
Surgical treatment for MEN-2A?
As per sporadic MTC, do prophylactic total thyroidectomy
and prophylactic central neck dissection only if clinical/radiological evidence LN mets, nodules >5 mm, calcitonin >40
Follow-up for MEN-2A?
- Annual 24-h urine or plasma catecholamines or metanephrines
- Adrenal imaging with MRI or CT if urine/plasma catecholamines or metanephrines elevated
- annual serum calcium and intact PTH levels
Familial Medullary Thyroid Cancer (FMTC)- work-up, surgical treatment, follow-up
Same as sporadic MTC for everything
MEN-2B- average age of diagnosis?
Remember B for Bad!!
Average age: first year of life
Timing of prophylactic surgery in MEN-2A vs 2B?
Based on ATA guidelines:
MEN-2A:
- low risk ATA level A and B RET mutations: thyroidectomy around age 5
- high risk ATA level C RET mutations: thyroidectomy before age 5
MEN-2B clincal manifestations?
M- medullary thyroid cancer
P- pheochromocytoma
Neuromas- mucosal lip neuromas, ganglioneuromatosis
Patients with MEN2B also have development abnormalities, a decreased upper/lower body ratio, skeletal deformations (kyphoscoliosis or lordosis), joint laxity, Marfanoid habitus, and myelinated corneal nerves. Disturbances of colonic function are common, including chronic constipation and megacolon
What is the most sensitive marker for tumour recurrence in MTC?
(according to SCORE)
pentagastrin stimulated peak plasma levels
identifies recurrence more reliably than basal plasma calcitonin levels (although this latter one is what Toronto Manual recommends)
