medullary thyroid cancer

1. All of the following are true about medullary thyroid cancer except:

a. bilateral tumours appear in 90% of sporadic cases.

b. MTC is typically unilateral in 80 % of cases.

c. C cell hyperplasia is a premalignant lesion.

d.Tumours stain positive for calcitonin gene-related peptide.

2. All of the following are false about medullary thyroid cancer except:

a. FNAB cytology is contraindicated.

b. 50% of patients with MTC have familial disease.

c. All new patients with MTC should be screened for RET point mutations.

d. Calcitonin is a better predictor of prognosis, as compared to CEA.

3. All of the following are true about medullary thyroid cancer except:

a. MTC is operated before pheochromocytoma.

b. pheochromocytoma is operated before MTC.

c. I 131 is ineffective.

d. Total thyroidectomy is recommended for MTC.

4.  All of the following are true about medullary thyroid cancer except:

a. Bilateral central node dissection should be routinely performed.

b. Triple phase liver CT is indicated if palpable lymph nodes are present.

c. Liver metastasis is amenable to resection.

d. Prophylactic thyroidectomy is indicated in RET mutation carrier.

5. All of the following are true about medullary thyroid cancer except:

a. MEN 2A patients with MTC has a better prognosis than sporadic cases.

b. Sporadic cases of MTC has a better prognosis than MEN 2A patients.

c. Prognosis is the worst in patients of MEN 2B.

d. Those with MEN 2B mutation should undergo prophylactic thyroidectomy before 1 year of age.

Answers:

1. (a)

 MTCs typically are unilateral (80%) in patients with sporadic disease and multicentric in familial cases, with bilateral tumors occurring in up to 90% of familial patients. Familial cases also are associated with C-cell hyperplasia, which is considered a premalignant lesion. Microscopically, tumors are composed of sheets of infiltrating neoplastic cells separated by collagen and amyloid. Marked heterogeneity is present; cells may be polygonal or spindle-shaped. The presence of amyloid is a diagnostic finding, but immunohistochemistry for calcitonin is more commonly used as a diagnostic tumor marker. These tumors also stain positively for CEA and calcitonin gene–related peptide.

2. (c)

The diagnosis of MTC is established by history, 

physical examination, raised serum calcitonin, or CEA levels, 

and FNAB cytology of the thyroid mass. Attention to family 

history is important because about 25% of patients with MTC 

have familial disease. Because it is not possible to distinguish, sporadic from a familial disease at initial presentation, all new patients 

with MTC should be screened for RET point mutations, 

pheochromocytoma, and HPT. Screening of patients with famil

ial MTC for RET point mutations has largely replaced using 

provocative testing with pentagastrin or calcium-stimulated 

calcitonin levels to make the diagnosis. Calcitonin and CEA 

are used to identify patients with persistent or recurrent MTC.

Calcitonin is a more sensitive tumor marker, but CEA is a better 

predictor of prognosis.

3 . (a)

 The ATA published guidelines for the management of medullary cancers in 2009. 45 A neck ultrasound is recommended to evaluate the central and lateral neck compartments and superior mediastinum. Serum calcitonin, CEA, and calcium levels should also be measured, and RET proto-oncogene mutation testing should be performed. Pheochromocytomas need to be excluded. If patients are found to have a pheochromocytoma, this must be operated on first. These tumors are generally (>50%) bilateral. Total thyroidectomy is the treatment of choice for patients with MTC because of the high incidence of multicentricity, the more aggressive course, and the fact that  131 I therapy usually is not effective.

4. (C)

Central compartment nodes frequently are involved early in the disease process, so that a bilateral prophylactic central neck node dissection should be routinely performed. In patients with palpable or imaging-detected cervical nodes or calcitonin levels >400 pg/mL, additional imaging to include a neck and chest CT and a triple-phase liver CT or contrast-enhanced MRI is recommended to assess for metastatic disease. 

Liver metastases tend to be multiple and are typically not amenable to resection, percutaneous ethanol ablation, or radiofrequency ablation. However, chemoembolization may be helpful in this setting. There is no effective chemotherapy regimen.

Prophylactic total thyroidectomy is indicated in RET mutation carriers once the mutation is confirmed.

5.  (B)

Survival also is significantly influenced by disease type. It is best in patients with non-MEN familial MTC, followed by those with MEN2A, and then those with sporadic disease. Prognosis is the worst (survival of 35% at 10 years) in patients with MEN2B. Performing prophylactic surgery in RET oncogene mutation carriers not only improves survival rates but also renders most patients calcitonin free.

In general, in patients with less aggressive mutations, thyroidectomy may be delayed >5 years, especially if there is normal annual serum calcitonin, neck ultrasound, less aggressive family history, or family preference. Children with mutations at codon 634 are advised to undergo thyroidectomy at <5 years of age, and those with MEN2B-related mutations should undergo the procedure before age 1. Central neck dissection can be avoided in children who are RET-positive and calcitonin negative with a normal ultrasound examination. When the calcitonin is increased or the ultrasound suggests a thyroid cancer, a prophylactic central neck dissection is indicated.

Reference: Schwartz's Pribciples Of Surgery, 9th Edition.