Sentinel lymph node biopsy in medullary thyroid microcarcinomas

Abstract

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. In addition to total thyroidectomy and central neck dissection, all patients had bilateral sentinel biopsy of jugulo-carotid regions after methylene blue injection to decide upon necessity for lateral dissection. If sentinels were benign on frozen section, additional nonsentinels were extirpated, with no further lateral dissection. If sentinels were malignant, one-time lateral dissection was performed. 20 patients were included in this study. Hereditary disease form was observed in 3/20 (15%) of patients with RET proto-oncogene mutation C634F; remaining 17/20 (85%) were negative for germline mutations. There were no allergic reactions to methylene blue and identification rate of sentinels was 100%. In total, 2/20 (10%) cN0 patients had lymphonodal metastases, thus were reclassified as pN1b. Remaining 18/20 (90%) were classified pN0 based on standard pathohistology. Frozen section findings on sentinels were 100% match with standard pathohistology, and there were no skip metastases in lateral compartments. Sensitivity, specificity and accuracy of sentinel biopsy method with methylene dye and frozen section were 100%. Dzodic's sentinel lymph node biopsy method can be used for intraoperative assessment of lateral compartments and optimization of initial surgery of medullary microcarcinomas with calcitonin <1,000 pg/mL. This way, cN0 patients with sentinel metastases can receive one-time lateral dissection, and those without benefit from less extensive surgery. MEDULLARY THYROID CARCINOMA (MTC)is a rare thyroid malignancy of C cell origin, characterized by the secretion of a peptide hormone calcitonin (CT). It is accounting for 3% (adults) to 10% (children) of thyroid cancers [1]. MTC appears in two forms: sporadic (75%) and hereditary (25%), with similar gender distribution [1]. MTCs have more aggressive behavior than differentiated thyroid carcinomas, and tend to spread relatively early into regional lymph nodes (LN) [2]. It has been reported that 80% of patients with palpable MTCs have central compartment LN metastases at the time of diagnosis, while 75% and 47% (respectively) have LN metastases in ipsilateral and contralateral jugulo-carotid regions [3].

Sentinel lymph node detection in thyroid carcinoma using [68Ga]Ga-tilmanocept PET/CT: a proof-of-concept study

“…For MTC patients, adjuvant therapy is of limited value. Surgical resection is the cornerstone of treatment and aims to achieve loco-regional control and, if possible, curation [ 20 , 32 ]. Patients who are biochemically cured with normal basal calcitonin levels after intended curative dissection have a 10-year survival rate of 97.7% [ 20 , 33 ].…”

“…SLN biopsy in MTC has been investigated in a few studies [ 25 – 27 , 32 ]. Puccini et al performed the SLN procedure using preoperative lymphoscintigraphy and intraoperative gamma probe and found micrometastases in 3 of 4 cT1N0 patients.…”

Sentinel lymph node mapping: current applications and future perspectives in thyroid carcinoma

“…Focussing on those papers on SLN detection with the highest number of patients, in 2010 Cunningham et al examined 211 PTC patients using 1% isosulphan blue with a detection rate (DR) of 91%; in 2006 Rubello et al used patent blue V in 153 PTC cases with a DR of 69%; in 2020 I. Markovic et al used methylene blue in 153 PTC patients with a DR of 91.8% ( 62–64 ). Using methylene blue in 20 MTC patients, in Santrac et al ( 65 ) achieved a DR of 100%, with 10% positive for metastasis. In Wang et al ( 66 ) described the use of indocyanine green (ICG) with methylene blue for detecting SLN in 45 micro-PTC patients with a longer operative time but a lower rate of hypoparathyroidism: the authors concluded that for SLN in TC ICG in combination with methylene blue is feasible, safe and also clinically significant for protection of the parathyroids.…”

“…With the VD method at surgery, the vital blue dye intra-or peritumoral injection is performed generally utilizing a tuberculin syringe (24,62,(64)(65)(66)(67). The authors recommend not mobilizing the thyroid before injection to ensure intact lymphatic drainage.…”

Fluorescence Polarization Imaging of Methylene Blue Facilitates Quantitative Detection of Thyroid Cancer in Single Cells

“…Methylene blue (MB) is cytological stain that has demonstrated affinity to cancer [ 25 , 26 ]. It is approved for several clinical applications by the United States Food and Drug Administration [ 27 , 28 ] and there is a progressively increasing number of publications focused on MB in the context of thyroid oncology-based problems [ 29 , 30 , 31 , 32 ]. Recent reports have demonstrated that fluorescence polarization (Fpol) of MB is significantly elevated in cancerous human breast ductal carcinoma and glioblastoma cell lines [ 33 , 34 ], and in malignant renal FNAC specimens [ 35 ].…”