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A universal recommendation does not exist for thyroid FNA suspicious for malignancy (SFM). In this context, the guidelines have estimated a risk of malignancy (ROM) from 50 to 80% and both total thyroidectomy and lobectomy may be indicated. This study aimed to (1) retrospectively evaluate the SFM (i.e., TIR4) in a single institution to estimate their cancer prevalence at histology, and (2) systematic review the literature to obtain more robust information. The study period was 2015-2018. As a major inclusion criterion, both cytology and histology had to be performed in our institution. Histological diagnosis was the gold standard. For the systematic review, the online databases of Google Scholar, PubMed/MEDLINE, and Scopus were searched for papers using the same classification for thyroid FNA. A proportion meta-analysis was performed to obtain the pooled histological cancer rate among TIR4 and TIR5 (random-effects model). In the institutional database, there were 271 nodules with both histology and FNA and the cancer rate of TIR4 was 88.9%. By systematic review, five studies were selected for the meta-analysis. The pooled cancer rate was 85% in TIR4 and 99% in TIR5 (I 2  = 0%; no publication bias). In conclusion, these new findings should prompt the guidelines board to fully revise the estimated ROM of SFM category. Clinical thyroidologists and thyroid surgeons should be aware of these data and the patients with SFM should be informed of their ROM.

The revised Italian consensus for the classification and reporting of thyroid cytology (ICCRTC) was published in 2014. Very recently, a high reliability of ICCRTC in classifying low and high risk indeterminate nodules (Tir 3A and Tir 3B, respectively) was demonstrated. This finding prompted us to review our case series of thyroid indeterminate lesions to verify these data. Only lesions undergone FNAC from December 2014 to October 2017 with subsequent histology at our institutions were eligible for the study. All cytologic samples had originally been classified according to ICCRTC in the subcategories of indeterminate lesion, such as Tir 3A and Tir 3B by three cytopathologists and another one with more than 10 years experience, when necessary. Sixty-three indeterminate FNAC were diagnosed during the study period, of which 51 were subsequently surgically treated. Overall, 9 carcinomas (7 follicular and 2 papillary) and 42 benign lesions were found at histology. The cancer rate observed in the Tir 3A category (3/40, 7.5%) was significantly (p = 0.0015) lower than that found in Tir 3B (6/11, 54.5%). No significant differences were found in age and size of the sampled nodules between the two subcategories. We can confirm in our series that the Italian reporting system for thyroid cytology shows high reliability in discriminating low risk indeterminate lesions from those at high risk of malignancy.

Fine needle cytology (FNC) is a crucial procedure in the preoperative diagnosis of thyroid tumors. Papillary thyroid carcinoma (PTC), in its classic variant (cPTC), is the most common malignant neoplasm of the thyroid. Several histological variants of PTC have been described, each one with its own characteristics and prognosis. The ability of FNC to identify the variants represents a challenge even for a skilled pathologist. The aim of this study was to evaluate the diagnostic cytological accuracy of FNC in PTC and to look for specific features that could predict the different variants. This was a single center prospective study on 128 patients who received a diagnosis of PTC on FNC. The smears were blindly reviewed by two cytopathologists to create a frequency score (0, 1, 2, 3) of the features for each variant. The cytological parameters were divided into three groups: architectural, nucleo-cytoplasmic, and background features. Univariate analysis was performed by chi-square test with Yates correction and Fisher exact test as appropriate. Multiple regression analysis was performed among the variables correlated at the linear correlation. The correlation study between cytology and histology showed an accuracy of FNC in classic, follicular, and oncocytic PTC variants of 63.5, 87.5, and 87% respectively. Familiarity with cytological features may allow an early diagnosis of a given PTC variant on FNC samples. This is fundamental in a preoperative evaluation for the best surgical approach and subsequent treatment.

Merkel cell carcinoma (MCC) is an uncommon neuroendocrine small cell tumor derived from the transformation of the homonymous cells in the basal layer of the epidermis. MCC has a generally aggressive course, with a high tendency for local recurrence, lymph node involvement, and distant metastasis. Fine needle cytology (FNC) and immunocytochemistry were used as diagnostic procedures for 22 cases of MCC presented at our institute. All cases of MCC were successfully diagnosed on FNC. Among all of the monoclonal antisera used (CD56, CK20, CK MNF116, neuron-specific enolase (NSE), synaptophysin, and chromogranin), NSE and CD56 showed the highest frequency of positivity. The accuracy of the cytological diagnosis was 100% compared to the corresponding previous or subsequent pathological diagnoses. FNC and immunocytochemistry represent excellent and accurate diagnostic methods to distinguish MCC from other small-cell malignant entities.

Fine-needle cytology (FNC) is frequently used to diagnose thyroid nodules discovered by palpation or imaging studies. Molecular tests on FNC material may increase its diagnostic accuracy. We report a case of a classic papillary thyroid carcinoma combined with a mucoepidermoid carcinoma correctly identified on FNC. The papillary component had a classic immunophenotype (CK19+, TTF1+), while the mucoepidermoid one was only focally CK19+. Point mutations (BRAF and RAS) and rearrangements (RET/PTC) of the papillary component have been also investigated on FNC samples, with resulting concurrent rearrangements of RET/PTC1 and RET/PTC3, but no point mutations. The histogenesis of combined papillary and mucoepidermoid carcinoma of the thyroid still remains partly unsettled, and further genomic studies are needed to shed some more light on this peculiar neoplasm.