The aim of this prospective study was to analyze accuracy of sentinel lymph node biopsy with methylene blue dye for intraoperative detection of lateral metastases in clinically N0M0 medullary microcarcinomas with calcitonin <1,000 pg/mL and selection of true-positive patients for one-time therapeutic lateral dissection.
Calcitonin is the specific serum marker; its doubling time is the most important prognostic factor for survival and progression; 30% of MTC patients have distant metastases at diagnosis and, when progressing, systemic therapy with vandetanib or cabozantinib should be considered.
The cut-off values of preoperative calcitonin levels were 226.6 pg/mL (AUC = 0.746) in ipsilateral CLN, 755.0 pg/mL (AUC = 0.840) in contralateral CLN metastases, and 237.0 pg/mL (AUC = 0.775) in ipsilateral LLN metastases.
We describe a case of MTC involving a mass 7 cm in its largest dimension, associated with high Ctn concentrations (> 5,000 pg/mL), but normal carcinoembryonic antigen levels, and with no lymph nodes or distant metastases, in complete remission after thyroid surgery.
With node-positive MTC and preoperative calcitonin levels exceeding 1000 pg/ml, and with more than ten nodal metastases, calcitonin normalization takes longer.
Preoperative calcitonin and carcinoembryonic antigen levels, tumor size (T) > 4 cm, the male sex, clinical and pathological node metastases (N1), distant metastasis (M1), extrathyroid extension (Ex), and a lack of biochemical cure had prognostic impacts on distant recurrence and/or carcinoma-related mortality on univariate analysis.
Sporadic cases had a higher median pre-op calcitonin (969.5 vs. 257.5 pg/ml), greater mean primary tumour size (23.5 vs. 12.5 mm) and more distant metastases (12.8 vs. 10.3%).
In contrast, silencing of CT/CTR expression in highly metastatic PC-3M cells markedly reduces their tumorigenicity and abolishes their ability to form distant metastases in nude mice.
Given these case results, we suggest that screening of RET and pre-surgical Ct levels in the management of MTC patients is essential for earlier diagnosis and more normative initial treatment, that FMTC patients with cervical lymph nodes metastases may be cured by TT with MBiND, and that prophylactic VI compartmental dissection should be avoided when Ct levels are low.
The former patients, being significantly (P < 0.001) younger (means of 5.3 vs 17.6 years) and having lower calcitonin levels (means of 115 vs 25,519 pg/mL), smaller tumors (67% vs 0% were ≤10 mm) and less often extrathyroidal extension (0% vs 81%), lymph node (42% vs 100%), and distant metastases (8% vs 79%), were biochemically cured more often (58% vs 0%).
Conversely, the wild-type (T/T) allele was associated with post-operative calcitonin levels above normal and a higher risk to develop clinical recurrence and distant metastases.
All patient who did not achieve cure had high basal preoperative calcitonin levels, which were related to macroscopic medullary thyroid carcinoma and nodal metastases in 5 of 9 patients.
Group 1 (11 patients) had received no previous surgery; group 2 (13) underwent thyroidectomy before referral and had an elevated calcitonin level without radiologic evidence of local regional or distant metastases; and group 3 (16) underwent thyroidectomy before referral and had an elevated calcitonin level with radiologic evidence of local-regional recurrence.
mRNA isolated from medullary carcinoma of the thyroid (MTC) in six patients with the inherited multiple endocrine neoplasia syndrome type 2 and cervical metastases in two patients with sporadic MTC was screened for the presence of calcitonin and proopiomelanocortin (POMC) related sequences by blot hybridization analysis.
The best chance of cure lies in early diagnosis through the use of immunoreactive calcitonin measurement in family members at risk, and an aggressive surgical attack on the primary tumor and any cervical metastases.