Is There a Difference Between Minimal and Gross Extension into the Strap Muscles for the Risk of Recurrence in Papillary Thyroid Carcinomas?

Background: The morbidity of papillary thyroid carcinoma (PTC) is primarily related to locoregional recurrences and distant metastases. The definition of minimal extrathyroidal extension (mETE) has been recently revised. The presence of mETE does not impact mortality and is generally not considered to be a predictor for the risk of recurrence. This study aimed at comparing the risk of recurrence and the response to therapy of PTC with mETE and gross extrathyroidal extension (ETE) into the strap muscles (gETE) with low- and intermediate-risk PTC without ETE (low risk w/o ETE and intermediate risk w/o ETE, respectively) to further characterize the impact of ETE on outcomes. Methods: A total of 596 PTCs were analyzed according to the degree of ETE as well as other predictors of recurrence. Four groups of patients were compared, low risk w/o ETE (n = 251), intermediate risk w/o ETE (n = 89), mETE (n = 191), and gETE (n = 65), to determine the risk of recurrence and the response to treatment. Cox proportional hazards models were used to investigate associations between groups and disease-free survival (DFS). Results: The risk of recurrence was 3% in low risk w/o ETE PTC, 14% in intermediate risk w/o ETE, 14% in mETE, and 25% in gETE. The recurrence risk was increased by the presence of ETE (odds ratio [OR] = 2.86, 95% confidence interval [CI] 1.36-5.85, p = 0.005) and lymph node metastases (OR = 2.44 [95% CI 1.25-4.76], p = 0.009). Patients with low-risk carcinomas w/o ETE experienced longer DFS than those with mETE (hazard ratio = 0.08 [95% CI 0.02-0.28], p < 0.001), but no significant difference was observed between intermediate risk w/o ETE, mETE, and gETE. In terms of the response to therapy, patients with gETE had higher rates of biochemical and/or structural incomplete responses within the first year of treatment (OR = 2.68 [95% CI 1.31-5.45], p = 0.007) and at the final follow-up evaluation (OR = 4.35 [95% CI 1.99-9.51], p < 0.001) compared with those with mETE. An analysis of the subgroups of microcarcinomas without lymph node metastases revealed no significant difference in DFS or the response to therapy between the low risk w/o ETE and mETE PTC groups. Conclusions: The results of this study suggest that both mETE and gETE are independent risk factors for the risk of recurrence in PTC. Although gETE has a more pronounced impact on the recurrence risk and is associated with a worse response to therapy, mETE may not be associated with a low risk of recurrence. This observation suggests that patients with PTC and mETE may, in part, have an intermediate risk of recurrence and need to be followed accordingly.

ATR-FTIR spectroscopy and CDKN1C gene expression in the prediction of lymph nodes metastases in papillary thyroid carcinoma.

Thyroid cancer has become in recent years the most common endocrine malignancy. Among its different types, papillary thyroid carcinoma (PTC) has the highest incidence. PTC is slow growing, but shows a high rate of lymph node metastasis. Tissue biochemical characterization and identification of molecular markers can facilitate stratification of patients into those requiring surgical assessment of lymph nodes and patients for whom this surgical procedure is unnecessary; thus, leading to a more accurate prognosis. To this end, the study aimed to predict lymph node metastasis by Attenuated Total Reflectance - Fourier transform infrared (ATR-FTIR) spectroscopy of primary PTC tumors. Another objective of the study was to determine whether CCNA1, CDKN1C, FOS, HSPA5, JUN, KSR1, MAP2K6, MAPK8IP2 and SFN gene expression in primary PTC tumors could be used as predictive markers of lymph node metastasis. Three PTC with lymph node involvement (PTC+), six PTC without lymph node involvement (PTC-), and five normal (N) thyroid tissues were used for FTIR spectroscopy analysis; while 18 PTC+, 17 PTC-, and 6 N samples were used for molecular analysis by real-time quantitative PCR (RT-qPCR). FTIR spectral analysis revealed changes in phosphate groups possibly associated with nucleic acid (1236 cm-1), and protein/lipids (1452, 2924, 3821 cm-1) in PTC + compared to PTC-, and multivariate analysis could distinguish the two groups. Molecular analysis showed significant increase in CDKN1C gene expression in PTC + compared to PTC-. Being a cell growth regulator, increased CDKN1C provides some supporting evidence to the FTIR spectroscopy based finding of increased nucleic acids in PTC+. Thus, the study suggests the possibility of using FTIR spectroscopy and CDKN1C expression for predicting metastasis using primary tumor alone.

Investigação de linfonodos em pacientes em seguimento por carcinoma diferenciado de tiróide / Cervical lymph nodes metastases in patients with differentiated thyroid cancer

Recorrências regionais dos carcinomas diferenciados de tiróide (CDT) são representadas por linfonodos cervicais em 60-75 por cento dos casos. Com a introdução da ultra-sonografia cervical (USC) no seguimento dos pacientes com carcinoma papilífero de tiróide (CPT) tornou-se freqüente o encontro de pequenos linfonodos (LNs) cervicais. Porém, apesar da USC apresentar alta sensibilidade, o estudo citológico obtido por punção aspirativa (PAAF), e nos últimos anos, a dosagem da tiroglobulina (Tg) no lavado da agulha da PAAF (Tg-PAAF), vêm assumindo papel importante no diagnóstico de LNs cervicais. O objetivo deste estudo é revisar a importância do diagnóstico precoce das metástases em linfonodos cervicais no seguimento dos pacientes com carcinoma de tiróide.

Loco-regional recurrences of the differentiated thyroid cancer have been reported to be located in cervical lymph nodes in 60-75 percent of cases. The widespread use of neck ultrasonography (US) during the follow-up of patients with papillary thyroid carcinoma (PTC) has led to the discovery of small cervical lymph nodes (LN). Although US has a high sensitivity for diagnosing LN, fine needle aspiration biopsy (FNA) and measurement of thyroglobulin in fine needle aspirates (FNA-Tg) have proven to be invaluable tools. The aim of this paper is to review the importance of the early diagnosis of lymph node metastases in the follow-up of patients with differentiated thyroid cancer.