Endocrine https://doi.org/10.1007/s12020-020-02229-0 ORIGINAL ARTICLE Outcome of classical (CVPTC) and follicular (FVPTC) variants of papillary thyroid cancer: 15 years of follow-up C. Giani 1 ● L. Torregrossa 2 ● P. Piaggi 3 ● A. Matrone 1 ● D. Viola 1 ● E. Molinaro 1 ● L. Agate 1 ● C. Romei 1 ● C. Ugolini 2 ● L. De Napoli 4 ● G. Materazzi 4 ● F. Basolo 2 ● R. Elisei 1 Received: 7 January 2020 / Accepted: 12 February 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020 Abstract Purpose To compare the epidemiological, clinical, and pathological features of follicular (FVPTC) and classical (CVPTC) variants of papillary thyroid cancer and to correlate their outcomes according to different features. Methods Retrospective analysis of FVPTC and CVPTC patients selected at the moment of surgical treatment from 1999 to 2004, with a median follow-up of 15 years. Results Several significant differences were found between FVPTC and CVPTC such as the mean age at diagnosis, the presence of tumor capsule, the presence of thyroid capsule invasion, the presence of perithyroid soft tissue invasion, the lymph node metastases, the multifocality and bilaterality. At the end of follow-up only 9% (77/879) patients were not cured. However, a statistically significant lower percentage of persistent disease was found in the FVPTC than in the CVPTC group (3% vs. 14.5%, respectively, p < 0.0001). In multivariate analysis, the absence of the tumor capsule (OR = 6.75) or its invasion (OR = 7.89), the tumor size ≥4 cm (OR = 4.29), the variant CVPTC (OR = 3.35), and the presence of lymph node metastases (OR = 3.16) were all independent risk factors for the persistence of the disease. Conclusions Despite an overall excellent prognosis of both variants, a higher percentage of CVPTC than FVPTC patients had a persistent disease. The absence of tumor capsule or its invasion, the tumor size ≥4 cm and the presence of lymph node metastases are other prognostic factors for the persistence of the disease. In contrast, the presence of an intact tumor capsule is the only good prognostic factor for their outcome. Keywords Follicular variant ● Classical variant ● Papillary thyroid cancer ● Tumor capsule ● Tumor dimension Introduction Differentiated thyroid cancer (DTC) is the most common thyroid cancer and accounts for more than 90% of all his- totypes. DTC is classified as papillary thyroid carcinoma (PTC) or follicular thyroid carcinoma (FTC) according to the predominant histology [1]. Many histological variants of PTC have been described and the most common are the classical (CVPTC) and follicular (FVPTC) variants of PTC which account for more than 50% and 23–41%, respec- tively [2–7]. FVPTC was first described by Crile and Hazard in 1953 as the alveolar variant of papillary thyroid carcinoma [8]. In 1960, Lindsay confirmed this entity and used the term “follicular variant” of PTC to describe a thyroid tumor with nuclear features of PTC (e.g., nuclear clearing, grooves, and pseudoinclusions) but with a follicular growth pattern [9]. With the dramatic increase of the incidence of thyroid cancer, FVPTC has been the PTC variant with the highest rate of increase in recent years [10, 11]. Despite its high incidence, the malignant biological behavior of FVPTC, and in particular its degree of aggressiveness, still remains controversial. Some authors demonstrated that FVPTC has a greater tendency to spread to the lung and bone compared * R. Elisei rossella.elisei@med.unipi.it 1 Endocrine Unit, Department of Clinical and Experimental Medicine, University Hospital of Pisa, 56124 Pisa, Italy 2 Pathology Unit, Department of Surgical, Medical, Molecular Pathology and Critical Area, University Hospital of Pisa, 56124 Pisa, Italy 3 Department of Information Engineering, University of Pisa, 56122 Pisa, Italy 4 Surgery Unit, Department of Surgical, Medical, Molecular Pathology and Critical Area, University Hospital of Pisa, 56124 Pisa, Italy 1234567890();,: 1234567890();,: