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Luca Giovanella, Mauro Imperiali, Frederik A Verburg and Pierpaolo Trimboli


To assess the diagnostic performance of three high-sensitive assays in a cohort of TgAb-negative and TgAb-positive differentiated thyroid cancer (DTC) patients.


Retrospective study on prospectively selected DTC patients.


Serum samples from 154 DTC patients were obtained 6–12 months after radioiodine ablation and tested by Beckman, Roche, BRAHMS Tg and TgAb assays, respectively. Receiver operating characteristics curves for Tg were plotted using outcome over time as benchmark and assay-specific Tg thresholds were obtained for TgAb-negative and TgAb-positive patients.


The frequency of positive TgAb was 21, 20 and 20% for Beckman, Roche and BRAHMS, respectively. In TgAb-negative patients, clinical sensitivities and specificities of 100% and 85–95%, respectively, were observed across all assays. In TgAb-positive patients, clinical sensitivities and specificities of 80–100% and 92–96%, respectively, were observed using lower thresholds than in patients without TgAb.


Adopting appropriate thresholds, lower than those for TgAb-negative patients, is possible to reliably follow TgAb-positive patients using highly sensitive Tg assays.

Free access

Luca Giovanella, Giorgio Treglia, Frederik A Verburg, Massimo Salvatori and Luca Ceriani


This study was undertaken to evaluate serum cytokeratin 19 fragment (Cyfra 21.1) expressions in patients with advanced thyroid carcinoma and to explore the relationship between serum Cyfra 21.1 and the degree of radioiodine (131I) avidity of thyroid carcinoma cells.


Enrolled were 76 consecutive patients with advanced thyroid carcinoma submitted to high-activity 131I treatment. In each patient, serum thyroglobulin (Tg) and Cyfra 21.1 were measured before 131I administration and compared with the posttreatment whole-body scan results.


Thirty-one (41%) of 76 patients had iodine-avid and 45 (59%) had iodine-refractory diseases respectively. Significantly higher serum Cyfra 21.1, but not Tg, levels were found in patients with 131I-refractory disease compared with patients with iodine-avid disease (P<0.01).


This is the first report describing the potential role of serum Cyfra 21.1 as marker of dedifferentiation and resistance to 131I therapy in patients with advanced thyroid carcinoma.

Restricted access

Lu Zhang, Marco Castellana, Camilla Virili, Anna Crescenzi, Francesco Giorgino, Emanuele Zucca, Luca Ceriani, Franco Cavalli, Luca Giovanella and Pierpaolo Trimboli

Background: Primary thyroid lymphoma (PTL) is a rare malignancy, and its prognosis depends significantly on its early diagnosis. While fine needle aspiration (FNA) represents the gold standard to identify differentiated thyroid carcinoma, its reliability for the detection of PTL is still unclear. Here we conducted a systematic review and meta-analysis to evaluate the diagnostic performance of FNA in PTL.

Research Design and Methods: A comprehensive literature search of PubMed/MEDLINE and Scopus databases was conducted to retrieve papers reporting histologically proven PTL undergone FNA. The last search was performed in February 2018 without language and time restrictions.

Results: Thirty-two studies describing 593 PTL were included and the pooled FNA sensitivity was 0.48 (95% CI = 0.38 to 0.58). FNA sensitivity was 0.51 in 20 studies published before 2010 and 0.39 in those published later, 0.50 in six articles with at least 20 cases, and 0.44 in nine series enrolled after 2000. This performance was similar in 12 articles including diffuse large B-cell lymphoma (0.54) and those six on marginal zone lymphoma (0.56). Remarkably, FNA sensitivity increased to 0.72 when considering also FNA reports suspicious for PTL reported in 14 articles. Heterogeneity among the series was found. Publication bias was not always detected.

Conclusions: The present meta-analysis demonstrated that FNA has low sensitivity in diagnosing PTL. However, this rate increased when considering also FNA reports suspicious for PTL, which is relevant from a clinical standpoint. This result could support indirectly the use of additional imaging and/or core biopsy when PTL is suspected.

Open access

Luca Giovanella, Penelope M Clark, Luca Chiovato, Leonidas Duntas, Rossella Elisei, Ulla Feldt-Rasmussen, Laurence Leenhardt, Markus Luster, Camilla Schalin-Jäntti, Matthias Schott, Ettore Seregni, Herald Rimmele, Jan Smit and Frederik A Verburg

Differentiated thyroid cancer (DTC) is the most common endocrine cancer and its incidence has increased in recent decades. Initial treatment usually consists of total thyroidectomy followed by ablation of thyroid remnants by iodine-131. As thyroid cells are assumed to be the only source of thyroglobulin (Tg) in the human body, circulating Tg serves as a biochemical marker of persistent or recurrent disease in DTC follow-up. Currently, standard follow-up for DTC comprises Tg measurement and neck ultrasound combined, when indicated, with an additional radioiodine scan. Measurement of Tg after stimulation by endogenous or exogenous TSH is recommended by current clinical guidelines to detect occult disease with a maximum sensitivity due to the suboptimal sensitivity of older Tg assays. However, the development of new highly sensitive Tg assays with improved analytical sensitivity and precision at low concentrations now allows detection of very low Tg concentrations reflecting minimal amounts of thyroid tissue without the need for TSH stimulation. Use of these highly sensitive Tg assays has not yet been incorporated into clinical guidelines but they will, we believe, be used by physicians caring for patients with DTC. The aim of this clinical position paper is, therefore, to offer advice on the various aspects and implications of using these highly sensitive Tg assays in the clinical care of patients with DTC.