Medullaty Thyroid Cancer Flashcards
(29 cards)
Medullary Thyroid Cancer
- nonfollicular characteristics and amyloid-containing stroma.
- from the neuroendocrine parafollicular C cells which secrete the polypeptide calcitonin
- usually occurs as a sporadic tumor, but 25% of cases, on average, occur in the context of hereditary syndromes
- germline mutations in the RET proto-oncogene, such as MEN types 2A and 2B as well as familial MTC syndrome
Sporadic MTC clinical presentation
- the most common presentation (occurring in up to 50% of cases) is a palpable neck mass
- or from associated lymphadenopathy
- usually unifocal
- arise in the superior lateral thyroid lobes.
- cervical nodal metastases are present in up to over 70% of cases
- distant metastases in 10% to 15% of cases.
- most common locations of distant metastasis are the liver, mediastinum, lungs, and bone.
Hereditary MTC
- familial MTC or MEN2A typically present in the third decade of life
- MEN2B present prior to the second decade.
- hereditary MTC often presents as multifocal disease.
Hormone Secretion
- elevated levels of circulating calcitonin can lead to diarrhea, flushing, and weight loss.
- Uncommonly, MTC also can produce a number of other hormones, such as carcinoembryonic antigen (CEA), adrenocorticotrophic hormone, chromogranin, and somatostatin, which can lead to paraneoplastic syndromes such as Cushing and carcinoid syndromes.
RET and MTC
- RET is located on chromosome 10q11.2 and encodes a transmembrane tyrosine kinase receptor
- Mutations in codon C634 are the most common.
Modified risk classification system for hereditary MTC aggressiveness based of RET mutation
highest-risk category :
- includes patients with MEN2B and the codon M918T mutation in whom macroscopic MTC and nodal metastases can present within the first year of life
in these patients, total thyroidectomy is recommended as soon as possible in the first few months of life
high-risk category
comprises patients with the codon C634 and A883F mutations in whom thyroidectomy is recommended by the age of 5 years or sooner in the presence of elevated serum calcitonin levels
moderate-risk category
includes patients with all other mutations in whom either annual surveillance or thyroidectomy may be pursued.
Genetic Testing
all patients with a diagnosis of MTC or C cell hyperplasia should undergo genetic testing to rule out hereditary disease.
approximately 50% of sporadic MTCs have somatic RET mutations, which are associated with a higher incidence of nodal metastases, persistent disease, and disease-specific mortality.
Therefore, they warrant more aggressive surveillance and treatment
Workup
- diagnosed by FNA biopsy
- presence of stromal amyloid and absence of thyroid follicular
- Measurement of elevated calcitonin levels in the FNA washout fluid increases the accuracy of FNA to 98%
- Measurement of serum calcitonin and CEA is recommended to establish a pretreatment baseline.
ATA guidelines recommend that a serum calcitonin of
- serum calcitonin of at least 100 pg/mL should be considered suspicious for MTC.
- calcitonin value at least 500 pg/mL prior to treatment should raise the suspicion for distant metastases.
CEA ?
CEA is often elevated in more aggressive MTCs that have lost calcitonin secretory function, thus acting as a marker for dedifferentiation.
Recommended management
1
Cont
2
in children, MEN 2B Highest Risk when to screen for Pheo ?
ar 11 years
in children, Men 2A Mod Risk, When To screen Pheo ?
at 16 years
Post Thyroidectomy, Calcitonin elevated but less than 150
Calcitonin and CEA every 3-6 months looking for Doubling times
Post Thyroidectomy, Calcitonin elevated More than 150
Imaging to detect Mets
Workup imaging
US neck
CT IV contrast Neck :
» suspicion for bulky or locally advanced disease
» high-burden cervical disease, symptoms suspicious for distant metastases, or serum calcitonin levels at least 500 pg/mL, radiographic survey for distant metastases should be performed.
» multiphase CT or MRI of the liver, axial MRI, and bone scintigraphy.
Screening and what to manage first
patients with hereditary MTC should be biochemically screened for
» pheochromocytoma
» primary hyperparathyroidism.
If a pheochromocytoma is identified, then treatment for the pheochromocytoma should precede that of MTC in virtually all cases.
Primary hyperparathyroidism can be surgically managed at the time of thyroidectomy for MTC, if present concurrently
Clinically evident MTC is treated with
> > at minimum total thyroidectomy and bilateral central neck dissection, as central nodal metastases are present in more than 70% of cases with palpable tumors regardless of tumor size.
the current ATA guidelines recommend that
> > prophylactic ipsilateral and contralateral lateral neck dissection be considered based on serum calcitonin levels
> > patients with ipsilateral lateral neck metastases noted on preoperative ultrasound, prophylactic contralateral lateral neck dissection should be considered if the basal serum calcitonin level is at least 200 pg/mL
For biochemically diagnosed primary hyperparathyroidism
> > four-gland exploration should be performed at the time of thyroidectomy with intentional resection performed only for enlarged glands.
> > Most cases of primary hyperparathyroidism in MEN2 involve a single parathyroid adenoma.
> > If a normal parathyroid gland is devascularized during surgery, then it should be autotransplanted into a heterotopic site (e.g., the nondominant forearm) for ease of access due to the risk of primary hyperparathyroidism developing in the transplanted tissue later in life.
familial MTC, MEN2B, or sporadic MTC undergoing thyroidectomy
> > devascularized parathyroids may be autotransplanted into the sternocleidomastoid because these patients are not at increased risk for primary hyperparathyroidism.
