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Pedro Weslley Rosario and Gabriela Franco Mourão

Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) is an encapsulated or clearly delimited, noninvasive neoplasm with a follicular growth pattern and nuclear features of papillary thyroid carcinoma (PTC). It is considered a ‘pre-malignant’ lesion of the RAS-like group. Ultrasonography (US), cytology and molecular tests are useful to suspect thyroid nodules that correspond to NIFTP but there is wide overlap of the results with the encapsulated follicular variant of PTC (E-FVPTC). In these nodules that possibly or likely correspond to NIFTP, if surgery is indicated, lobectomy is favored over total thyroidectomy. The diagnosis of NIFTP is made after complete resection of the lesion by observing well-defined criteria. In the case of patients who received the diagnosis of FVPTC and whose pathology report does not show findings of malignancy (lymph node metastasis, extrathyroidal invasion, vascular/capsular invasion), if the tumor was encapsulated or well delimited, the slides can be revised by an experienced pathologist to determine whether the diagnostic criteria of NIFTP are met, but special attention must be paid to the adequate representativeness of the capsule and tumor. Since NIFTP is not ‘malignant’, tumor staging is not necessary and patients are not submitted to thyroid cancer protocols or guidelines. We believe that patients with NIFTP without associated malignancy and without nodules detected by US of the remnant lobe (if submitted to lobectomy) can be managed like those with follicular adenoma.

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Gabriela Franco Mourão, Pedro Weslley Rosario, and Maria Regina Calsolari

This study evaluated the recurrence rate in patients with papillary thyroid carcinoma (PTC) who had low nonstimulated thyroglobulin (Tg), measured with a second-generation assay, after total thyroidectomy and who were not submitted to ablation with 131I. The objective was to define whether low postoperative nonstimulated Tg can be used as a criterion to spare patients with PTC from therapy with 131I. This was a prospective study including 222 patients with PTC (except for microcarcinoma restricted to the thyroid and tumor with extensive extrathyroid invasion (pT4), aggressive histology, extensive lymph node (LN) involvement, or known residual disease). After thyroidectomy, all patients had nonstimulated Tg<0.3 ng/ml, negative antithyroglobulin antibodies (TgAb) and neck ultrasonography (US) showing no anomalies. Because of this finding, the patients were not submitted to ablation with 131I. The time of follow-up ranged from 15 to 102 months (median 62 months). Of the 222 patients, 217 (97.7%) continued to have nonstimulated Tg <0.3 ng/ml and negative US. Tg was undetectable in the last assessment in 185 of these patients and detectable in 32. Five patients (2.2%) exhibited an increase in Tg, and LN metastases were detected in 4 (structural recurrence). One patient progressed to an increase in Tg, but disease was not detected by the imaging methods (biochemical recurrence). The results obtained here suggest that patients with PTC who have low nonstimulated Tg (measured with a second-generation assay and in the absence of TgAb) and negative neck US after thyroidectomy do not require ablation with 131I.

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Pedro Weslley Rosario, Tiara Grossi Rocha, and Gabriela Franco Mourão

In thyroid nodules (TN) submitted to fine-needle aspiration (FNA), Bethesda categories III and IV are considered ‘indeterminate’ cytology. This result corresponds to 10–25% of all FNAs and the risk of malignancy (RoM) ranges from 10% to 30% for category III and from 15% to 40% for category IV. This review analyzed the practical applicability of accessible imaging method in the management of patients with cytologically indeterminate TN > 1 cm (ITN). When ITN are highly suspicious on ultrasonography (US), the RoM supports surgical indication even in the absence of additional tests. The same can be applied to ITN of intermediate suspicion but with elevated stiffness on elastography. Follow-up without additional tests is acceptable in the case of ITN with low-risk cytology and low-suspicion appearance on US and elastography (if obtained). In the case of ITN without highly suspicious US appearance, 123I scintigraphy may be obtained in patients with TSH < 1–1.5 mIU/L to rule out hyperfunctioning nodules before requesting diagnostic methods that are more expensive and less accessible. In addition, in ITN with not very suspicious US appearance, 18FDG-PET may be obtained. If this method does not reveal nodular uptake, the risk of the nodule corresponding to a macrocarcinoma is sufficiently low in order to allow follow-up. The positive predictive value of focal nodular uptake on 18FDG-PET depends on the pre-test RoM, cytological findings, and maximum SUV. There is currently no evidence for the use of CT, MRI or imaging using 99mTc-MIBI to define the nature of ITN.

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Pedro Weslley Rosario, Gabriela Franco Mourão, Maurício Buzelin Nunes, Marcelo Saldanha Nunes, and Maria Regina Calsolari

Recently, it was proposed that some papillary thyroid carcinomas (PTC) will no longer be termed ‘cancer’ and are christened as ‘noninvasive follicular thyroid neoplasm with papillary-like nuclear features’ (NIFTP). As this is a recent definition, little information is available about NIFTP. The objective of this study was to report the frequency, ultrasonographic appearance, cytology result and long-term evolution of cases of NIFTP seen at our institution. We excluded tumours ≤1 cm. The sample consisted of 129 patients. Sixty-four patients were submitted to total thyroidectomy and 65 to lobectomy. These patients with NIFTP did not receive radioiodine. NIFTP corresponded to 15% of cases diagnosed as PTC >1 cm. An ultrasonographic appearance considered to be of low suspicion for malignancy was common in NIFTP (32.5%), whereas a highly suspicious appearance was uncommon (5%). NIFTP frequently exhibited indeterminate cytology (62%), while malignant cytology was uncommon (4%). The patients were followed up for 12–146 months (median 72 months) after surgery. None of the patients developed structural disease during follow-up. Comparing the concentrations of thyroglobulin (Tg) and anti-Tg antibodies (TgAb) obtained 6–12 months after surgery and in the last assessment, none of the patients exhibited an increase in these markers.

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Pedro Weslley Rosario, Marina Carvalho Souza Côrtes, and Gabriela Franco Mourão

Antithyroglobulin antibodies (TgAb) are present in up to 25% of patients with differentiated thyroid carcinoma on initial postoperative assessment. Detectable concentrations of TgAb even below the manufacturer’s cut-off can interfere with serum thyroglobulin (Tg) determination. When Tg is quantified using an immunometric assay (IMA) (hereafter referred to as Tg-IMA), this interference results in underestimated values of Tg. Although promising, more clinical trials evaluating the capacity of liquid chromatography/tandem mass spectrometry and of new assays to detect elevated Tg in patients with TgAb and structural disease are necessary, particularly when Tg is undetectable by a second-generation IMA (Tg-2GIMA). Neck ultrasonography (US) should be performed in patients submitted to total thyroidectomy and with negative Tg-IMA but with detectable TgAb more than 6 months after initial therapy. In patients treated with 131I, comparison of TgAb concentrations obtained before this treatment is useful to estimate the risk of disease and to guide the investigation. If initial assessment does not reveal any persistent tumor, the repetition of US is recommended while TgAb persist. Significant elevation of TgAb requires extended investigation. On the other hand, patients with negative Tg-IMA and US without abnormalities who exhibit a reduction > 50% in TgAb generally do not require investigation. Although TgAb can interfere with Tg, the management and follow-up of patients submitted to total thyroidectomy with borderline TgAb can probably be the same as those recommended for patients without TgAb if Tg-2GIMA and US indicate an excellent response to therapy. Currently, the presence/absence or the trend of TgAb levels cannot be considered in the follow-up of patients submitted to lobectomy.