Dynamic surgical anatomy using 3D reconstruction technology in complex hepato-biliary surgery with vascular involvement. Results from an international multicentric survey.

INTRODUCTION: Three-dimensional liver modeling can lead to substantial changes in choosing the type and extension of liver resection. This study aimed to explore whether 3D reconstruction helps to better understand the relationship between liver tumors and neighboring vascular structures compared to standard 2D CT scan images. METHODS: Contrast-enhanced CT scan images of 11 patients suffering from primary and secondary hepatic tumors were selected. Twenty-three experienced HBP surgeons participated to the survey. A standardized questionnaire outlining 16 different vascular structures (items) having a potential relationship with the tumor was provided. Intraoperative and histopathological findings were used as the reference standard. The proper hypothesis was that 3D accuracy is greater than 2D. As a secondary endpoint, inter-raters' agreement was explored. RESULTS: The mean difference between 3D and 2D, was 2.6 points (SE: 0.40; 95 % CI: 1.7-3.5; p < 0.0001). After sensitivity analysis, the results favored 3D visualization as well (mean difference 1.7 points; SE: 0.32; 95 % CI: 1.0-2.5; p = 0.0004). The inter-raters' agreement was moderate for both methods (2D: W = 0.45; 3D: W = 0.44). CONCLUSION: 3D reconstruction may give a significant contribution to better understanding liver vascular anatomy and the precise relationship between the tumor and the neighboring structures.

Survival benefit of second line therapies for recurrent hepatocellular carcinoma: repeated hepatectomy, thermoablation and second-line transplant referral in a real life national scenario.

BACKGROUND: Despite second-line transplant(SLT) for recurrent hepatocellular carcinoma(rHCC) leads to the longest survival after recurrence(SAR), its real applicability has never been reported. The aim was to compare the SAR of SLT versus repeated hepatectomy and thermoablation(CUR group). METHODS: Patients were enrolled from the Italian register HE.RC.O.LE.S. between 2008 and 2021. Two groups were created: CUR versus SLT. A propensity score matching (PSM) was run to balance the groups. RESULTS: 743 patients were enrolled, CUR = 611 and SLT = 132. Median age at recurrence was 71(IQR 6575) years old and 60(IQR 53-64, p < 0.001) for CUR and SLT respectively. After PSM, median SAR for CUR was 43 months(95%CI = 37 - 93) and not reached for SLT(p < 0.001). SLT patients gained a survival benefit of 9.4 months if compared with CUR. MilanCriteria(MC)-In patients were 82.7% of the CUR group. SLT(HR 0.386, 95%CI = 0.23 - 0.63, p < 0.001) and the MELD score(HR 1.169, 95%CI = 1.07 - 1.27, p < 0.001) were the only predictors of mortality. In case of MC-Out, the only predictor of mortality was the number of nodules at recurrence(HR 1.45, 95%CI= 1.09 - 1.93, p = 0.011). CONCLUSION: It emerged an important transplant under referral in favour of repeated hepatectomy or thermoablation. In patients with MC-Out relapse, the benefit of SLT over CUR was not observed.

The Complex Cyto-Molecular Landscape of Thyroid Nodules in Pediatrics.

Thyroid fine-needle aspiration (FNA) is a commonly used diagnostic cytological procedure in pediatric patients for the evaluation of thyroid nodules, triaging them for the detection of thyroid cancer. In recent years, greater attention has been paid to thyroid FNA in this setting, including the use of updated ultrasound score algorithms to improve accuracy and yield, especially considering the theoretically higher risk of malignancy of these lesions compared with the adult population, as well as to minimize patient discomfort. Moreover, molecular genetic testing for thyroid disease is an expanding field of research that could aid in distinguishing benign from cancerous nodules and assist in determining their clinical management. Finally, artificial intelligence tools can help in this task by performing a comprehensive analysis of all the obtained data. These advancements have led to greater reliance on FNA as a first-line diagnostic tool for pediatric thyroid disease. This review article provides an overview of these recent developments and their impact on the diagnosis and management of thyroid nodules in children.

Non-anatomical liver resection for hepatocellular carcinoma: the SegSubTe classification to overcome the problem of heterogeneity.

BACKGROUND: The superiority of anatomical resection (AR) vs. non-anatomical resection (NAR) in the surgical management of hepatocellular carcinoma (HCC) is debated. ARs are well-defined procedures, whereas the lack of NAR standardization results in heterogeneous outcomes. This study aimed to introduce the SegSubTe classification for NAR detailing the appropriateness of the level of surgical section of the Glissonean pedicles feeding the tumor. METHODS: A single-center retrospective analysis of pre- and postoperative imaging of consecutive patients treated with NAR for single HCC between 2012 and 2020 was conducted. The quality of surgery was assessed classifying the type of vascular supply and the level of surgical section (segmental, subsegmental or terminal next to the tumor) of vascular pedicles feeding the HCCs; then, the population was divided in "SegSubTe-IN" or "SegSubTe-OUT" groups, and the tumor recurrence and survival were analyzed. RESULTS: Ninety-seven patients who underwent NAR were included; 76% were SegSubTe-IN and 24% were SegSubTe-OUT. Total disease recurrence, local recurrence and cut-edge recurrence in the SegSubTe-IN vs. SegSubTe-OUT groups were 50% vs. 83% (P = 0.006), 20% vs. 52% (P = 0.003) and 16% vs. 39% (P = 0.020), respectively. SegSubTe-OUT odds ratio for local recurrence was 4.1 at univariate regression analysis. One-, three-, and five-year disease-free survival rates in the SegSubTe-IN vs. SegSubTe-OUT groups were 81%, 58% and 35% vs. 46%, 21% and 11%, respectively (P < 0.001). CONCLUSIONS: The SegSubTe classification is a useful tool to stratify and standardize NAR for HCC, aiming at improving long-term oncological outcomes and reducing the heterogeneity of quality of NAR for HCC.

Spatially Resolved Molecular Approaches for the Characterisation of Non-Invasive Follicular Tumours with Papillary-like Features (NIFTPs).

Noninvasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTP) are low-risk thyroid lesions most often characterised by RAS-type mutations. The histological diagnosis may be challenging, and even immunohistochemistry and molecular approaches have not yet provided conclusive solutions. This study characterises a set of NIFTPs by Matrix-Assisted Laser Desorption/Ionisation (MALDI)-Mass Spectrometry Imaging (MSI) to highlight the proteomic signatures capable of overcoming histological challenges. Archived formalin-fixed paraffin-embedded samples from 10 NIFTPs (n = 6 RAS-mutated and n = 4 RAS-wild type) were trypsin-digested and analysed by MALDI-MSI, comparing their profiles to normal tissue and synchronous benign nodules. This allowed the definition of a four-peptide signature able to distinguish RAS-mutant from wild-type cases, the latter showing proteomic similarities to hyperplastic nodules. Moreover, among the differentially expressed signals, Peptidylprolyl Isomerase A (PPIA, 1505.8 m/z), which has already demonstrated a role in the development of cancer, was found overexpressed in NIFTP RAS-mutated nodules compared to wild-type lesions. These results underlined that high-throughput proteomic approaches may add a further level of biological comprehension for NIFTPs. In the future, thanks to the powerful single-cell detail achieved by new instruments, the complementary NGS-MALDI imaging sequence might be the correct methodological approach to confirm that the current NIFTP definition encompasses heterogeneous lesions that must be further characterised.

Association of indirect measurement of cell function by bioimpedance analysis with complications in oncologic hepatic surgery.

BACKGROUND: Bioelectric impedance vector analysis (BIVA) is a reliable tool to assess body composition. The aim was to study the association of BIVA-derived phase angle (PA) and standardized PA (SPA) values and the occurrence of surgery-related morbidity. METHODS: Patients undergoing hepatectomy for cancer in two Italian centers were prospectively enrolled. BIVA was performed the morning of surgery. Patients were then stratified for the occurrence or not of postoperative morbidity. RESULTS: Out of 190 enrolled patients, 76 (40%) experienced postoperative complications. Patients with morbidity had a significant lower PA, SPA, body cell mass, and skeletal muscle mass, and higher extracellular water and fat mass. At the multivariate analysis, presence of cirrhosis (OR 7.145, 95% CI:2.712-18.822, p < 0.001), the Charlson comorbidity index (OR 1.236, 95% CI: 1.009-1.515, p = 0.041), the duration of surgery (OR 1.004, 95% CI:1.001-1.008, p = 0.018), blood loss (OR 1.002. 95% CI: 1.001-1.004, p = 0.004), dehydration (OR 10.182, 95% CI: 1.244-83.314, p = 0.030) and SPA < -1.65 (OR 3.954, 95% CI: 1.699-9.202, p = 0.001) were significantly and independently associated with the risk of complications. CONCLUSION: Introducing BIVA before hepatic resections may add valuable and independent information on the risk of morbidity.

An Indeterminate for Malignancy FNA Report Does Not Increase the Surgical Risk of Incidental Thyroid Carcinoma.

Incidental thyroid carcinomas (ITCs) are a fairly frequent finding in daily routine practice, with papillary thyroid microcarcinoma being the most frequent entity. In our work, we isolated incidental cases arising in thyroids removed for other cytologically indeterminate and histologically benign nodules. We retrospectively retrieved cases with available thyroid Fine Needle Aspiration (FNA, 3270 cases), selecting those with an indeterminate cytological diagnosis (Bethesda classes III−IV, 652 cases). Subsequently, we restricted the analysis to surgically treated patients (163 cases) finding an incidental thyroid carcinoma in 22 of them. We found a 13.5% ITC rate, with ITCs representing 46.8% of all cancer histologically diagnosed in this indeterminate setting. Patients received a cytological diagnosis of Bethesda class III and IV in 41% and 59% of cases, respectively. All ITC cases turned out to be papillary thyroid microcarcinomas; 36% of cases were multifocal, with foci bilaterally detected in 50% of cases. We found an overall ITC rate concordant with the literature and with our previous findings. The assignment of an indeterminate category to FNA did not increase the risk of ITCs in our cohort. Rather, a strong statistical significance (p < 0.01) was found comparing the larger size of nodules that underwent FNA and the smaller size of their corresponding ITC nodule.

COVID-19 and Liver Surgery: How the Pandemic Affected an Italian Medium-Volume HBP Center.

Introduction: While the COVID-19 pandemic is still ongoing, it is even more evident that victims of the pandemic are not only those who contract the virus, but also the countless patients suffering from other serious diseases (i.e., tumor) who have undergone delayed potentially life-saving surgery due to a lack of beds. Like many hospitals, ours also initially blocked all elective oncologic surgery, but these operations were "recovered" and reintegrated in a relatively short time, thanks to the establishment of COVID-free wards and operating rooms with staff dedicated to oncological surgery. In tis context, our aim is to assess whether and how the severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2) pandemic has impacted our hepatobiliary surgery unit. Methods: From our prospective database, we retrospectively took data from patients undergoing liver surgery in 2018-2019 (pre-COVID) and 2020-2021 (COVID period). Patients admitted to COVID-free wards must necessarily have a negative nasal swab from the previous 24 h. Results: Between January 1, 2018, and December 31, 2019 (Group 1), 101 patients were treated; during the pandemic [January 1, 2020, and December 31, 2021 (Group 2)], 126 patients were treated. There was no statistical difference between the groups. The median postoperative hospital stay was 7 days for both groups; 7 patients had major complications (Clavien-Dindo > 3) in Group 1 and 11 in Group 2 (p = 0.795). A total of 4 patients died in Group 1 and 6 during the pandemic (p = 0.754). Tumor burden was significantly greater in Group 2 where nodule size, lymphadenectomy, and extrahepatic disease were significantly greater (p = 0.011, p = 0.004, and p = 0.026, respectively). Conclusion: During the COVID pandemic, our HPB unit managed to offer a volume of tertiary-center hepatobiliary surgery without a significant impact in terms of length of stay, morbidity, or mortality despite the increase in tumor burden during the pandemic years.

Lights on HBME-1: the elusive biomarker in thyroid cancer pathology.

Among the different ancillary immunohistochemical tools that pathologists may employ in thyroid nodules, the so-called Hector Battifora's 'MEsothelioma' 1 (HBME-1) staining is one of the most fascinating, since its real identity is currently unknown. In the present review, the different clinical applications of HBME-1 are analysed, with main emphasis on its role in thyroid pathology with overview on less impactful fields, such as haematopathology or mesothelial lesions. Different acceptable or good diagnostic performances were recorded for HBME-1 in thyroid pathology, being used in routine practice as one of the best tools to screen thyroid malignancy both in terms of sensitivity and specificity. From a speculative point of view, after many attempts to hunt the cryptic target antigen of this antibody, its identity still remains elusive. In this setting, the application of high-throughput technologies (mainly in situ proteomics) may be the exact route to improve the knowledge about the pathophysiology of HBME-1 and to finally unveil its true identity.

Cytomolecular Classification of Thyroid Nodules Using Fine-Needle Washes Aspiration Biopsies.

Fine-needle aspiration biopsies (FNA) represent the gold standard to exclude the malignant nature of thyroid nodules. After cytomorphology, 20-30% of cases are deemed "indeterminate for malignancy" and undergo surgery. However, after thyroidectomy, 70-80% of these nodules are benign. The identification of tools for improving FNA's diagnostic performances is explored by matrix-assisted laser-desorption ionization mass spectrometry imaging (MALDI-MSI). A clinical study was conducted in order to build a classification model for the characterization of thyroid nodules on a large cohort of 240 samples, showing that MALDI-MSI can be effective in separating areas with benign/malignant cells. The model had optimal performances in the internal validation set (n = 70), with 100.0% (95% CI = 83.2-100.0%) sensitivity and 96.0% (95% CI = 86.3-99.5%) specificity. The external validation (n = 170) showed a specificity of 82.9% (95% CI = 74.3-89.5%) and a sensitivity of 43.1% (95% CI = 30.9-56.0%). The performance of the model was hampered in the presence of poor and/or noisy spectra. Consequently, restricting the evaluation to the subset of FNAs with adequate cellularity, sensitivity improved up to 76.5% (95% CI = 58.8-89.3). Results also suggest the putative role of MALDI-MSI in routine clinical triage, with a three levels diagnostic classification that accounts for an indeterminate gray zone of nodules requiring a strict follow-up.

Left Anterior Sectorectomy: An Alternative to Left Hepatectomy for Tumors Invading the Distal Part of the Left Portal Vein.

BACKGROUND: Liver tumors invading the distal part of the umbilical portion of the left portal vein usually require left hepatectomy. The recent introduction of the concept of left anterior sector, an independent anatomo-functional unit including the anterior portion of the left liver and supplied by the distal part of the umbilical portion of the left portal vein, could represent the rational for an alternative surgical approach. The aim of this study was to introduce the novel surgical procedure of ultrasound-guided left anterior sectorectomy. METHODS: Among 92 consecutive patients who underwent hepatectomy, 3 patients with tumor invading the distal part of the umbilical portion of the left portal (two with colorectal liver metastases and one with neuroendocrine tumor liver metastases) underwent left anterior sectorectomy alone or in association with liver multiple metastasectomies. RESULTS: Mean operation time was 393 min; post-operative morbidity and mortality were not observed. After a mean FU of 23 months (range 19-28), no local recurrence occurred. CONCLUSIONS: In presence of tumors invading the distal part of the umbilical portion of the left portal, left anterior sectorectomy could be considered as an anatomic radical surgical option that is safe but more conservative than a left hepatectomy.

The uncharted severity of complications after appendectomy for acute appendicitis in children: results from 348 consecutive patients.

Appendectomy is the most frequently performed emergent procedure in paediatric patients. However, there is a wide heterogeneity in outcome definitions and, conversely, a lack of information about complications' severity. This study aims to analyse the outcome of children operated for acute appendicitis, with reference to complications' severity grading. This is a retrospective analysis of a prospectively collected database including all children who underwent emergent appendectomy between September 2013 and March 2020. Postoperative complications were defined according to standardized definitions and graded following Clavien-Dindo classification (CDC). The outcome was analysed in terms of postoperative morbidity, severity of complications, hospital readmission and length of hospital stay (LOS). 348 patients were analysed. Postoperative complications occurred in 18 (5.2%) patients; superficial and organ/space surgical site infections represented the most frequent complications (1.7% and 2.9%, respectively). Major complications (CDC ≥ IIIa) were seen in 4 (1.1%) patients. Median postoperative LOS was 4 (iqr 3-5) days, while hospital readmission was 1.1%. Postoperative complications, preoperative C-reactive protein values and presence of drainage were significantly associated with longer LOS at multivariate analysis. No difference in incidence and severity of complications was found in relation to children's adolescent age. Major complications among paediatric patients undergoing appendectomy for acute appendicitis in a general surgery department are rare. The application of standardized definitions and severity-based grading of complications is crucial for outcome analysis: our results are a useful reference for comparison between forthcoming studies.

Pancreatic Cystic Neoplasms and Pregnancy: A Systematic Review of Surgical Cases and a Case Report of a Fully Laparoscopic Distal Pancreatectomy.

BACKGROUND: Mucinous cystic neoplasms and solid pseudopapillary neoplasms are the most common pancreatic tumors occurring in women of fertile age and in pregnant women. The aim of this study is to provide an updated literature review on this association and to present a fully laparoscopic resection of a pregnancy-associated pancreatic cystic neoplasm. MATERIALS AND METHODS: A systematic literature review was performed using PubMed (MEDLINE), Scopus, Ovid, ISI Web of Science, and Google Scholar for searching. The syntax was (pancr*) AND (cyst*) AND (pregn*) AND (tumor). Only English-language articles describing pancreatic surgical resections were included. RESULTS: Forty-seven case reports were included. The mean age of the patients was 29.6±5.3. Nine patients (20%) required emergency surgery, 4 (9%) due to cyst rupture, and 5 (11%) due to hemorrhage. Four patients (9%) suffered a miscarriage, and 2 (5%) opted for pregnancy termination; the rest of the women delivered a healthy newborn (86%, n=36). Thirty percent (n=14) of the resected neoplasms were malignant, and among mucinous cystic lesions, this raised to 45% (n=11). All patients diagnosed during the third trimester were resected postpartum, whereas 26/34 (76%) of patients diagnosed during the first 2 trimesters underwent surgery before delivery. CONCLUSIONS: The most worrisome complications in pregnancy-associated pancreatic cysts are bleeding or rupture. Mucinous cystic neoplasm has a tendency to grow during pregnancy. A postpartum resection was generally preferred when the cystic neoplasm was diagnosed during the third trimester. This report is the first to describe a fully laparoscopic pancreatic resection.

Rethinking the Barcelona clinic liver cancer guidelines: Intermediate stage and Child-Pugh B patients are suitable for surgery?

According to Barcelona Clinic Liver Cancer recommendations, intermediate stage hepatocellular carcinomas (stage B) are excluded from liver resection and are referred to palliative treatment. Moreover, Child-Pugh B patients are not usually candidates for liver resection. However, many hepatobiliary centers in the world manage patients with intermediate stage hepatocellular carcinoma or Child-Pugh B cirrhosis with liver resection, maintaining that hepatic resection is not contraindicated in selected patients with non-early-stage hepatocellular carcinoma and without normal liver function. Several studies demonstrate that resection provides the best survival benefit for selected patients in very early/early and even in intermediate stages of Barcelona Clinic Liver Cancer classification, and this treatment gives good results in the setting of multinodular, large tumors in patients with portal hypertension and/or Child-Pugh B cirrhosis. In this review we explore this controversial topic, and we show through the literature analysis how liver resection may improve the short- and long-term survival rate of carefully selected Barcelona Clinic Liver Cancer B and Child-Pugh B hepatocellular carcinoma patients. However, other large clinical studies are needed to clarify which patients with intermediate stage hepatocellular carcinoma are most likely to benefit from liver resection.

Is there a role for treatment-oriented surgery in liver metastases from gastric cancer?

BACKGROUND: Distant metastases are found in approximately 35% of patients with gastric cancer at their first clinical observation, and of these, 4%-14% involves the liver. Unfortunately, only 0.4%-2.3% of patients with metastatic gastric cancer are eligible for radical surgery. Although surgical resection for gastric cancer metastases is still debated, there have been changes in recent years, although several clinical issues remain to be defined and that must be taken into account before surgery is proposed. AIM: To analyze the clinicopathological factors related to primary gastric tumor and metastases that impact the survival of patients with liver metastatic gastric cancer. METHODS: We performed a systematic review of the literature from 2000 to 2018 according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. The study protocol was based on identifying studies with clearly defined purpose, eligibility criteria, methodological analysis, and patient outcome. RESULTS: We selected 47 studies pertaining to the purpose of the review, which involved a total of 2304 patients. Median survival was 7-52.3 mo, median disease-free survival was 4.7-18 mo. The 1-, 2-, 3-, and 5-year overall survival (OS) was 33%-90.1%, 10%-60%, 6%-70.4%, and 0%-40.1%, respectively. Only five papers reported the 10-year OS, which was 5.5%-31.5%. The general recurrence rate was between 55.5% and 96%, and that for hepatic recurrence was between 15% and 94%. CONCLUSION: Serous infiltration and lymph node involvement of the primary cancer indicate an unfavorable prognosis, while the presence of single metastasis or ≤ 3 metastases associated with a size of < 5 cm may be considered data that do not contraindicate liver resection.

Analysis of Hashimoto's thyroiditis on fine needle aspiration samples by MALDI-Imaging.

Matrix-Assisted Laser Desorption/Ionization (MALDI)-Mass Spectrometry imaging (MSI) has been applied in various diseases aimed to biomarkers discovery. In this study diagnosis and prognosis of Hashimoto Thyroiditis (HT) in cytopathology by MALDI-MSI has been investigated. Specimens from a routine series of subjects who underwent UltraSound-guided thyroid Fine Needle Aspirations (FNAs) were used. The molecular classifier trained in a previous study was modified to include HT as a separate entity in the group of benign lesions, in the diagnostic proteomic triage of thyroid nodules. The statistical analysis confirmed the existence of signals that HT shares with hyperplastic lesions and others that are specific and characterize this subgroup. Statistically relevant HT-related peaks were included in the model. Then, the discriminatory capability of the classifier was tested in a second validation phase, showing a good agreement with cytological diagnoses. The possibility to overlap the molecular signatures of both the lymphocytes and epithelial cells components (ROIs or pixel-by-pixel analysis) confirmed the composite proteomic background of HT. These results open the way to their possible translation as alternative serum biomarkers of this autoimmune condition.

Creation of a rectal cancer registry in Italy by the Advanced International Mini-Invasive Surgery (AIMS) academy clinical research network.

Background: The management of rectal cancer is multimodal and involves a multidisciplinary team of cancer specialists with expertise in medical oncology, surgical oncology, radiation oncology and radiology. It is crucial for highly specialized centers to collaborate via networks that aim to maintain uniformity in every aspect of treatment and rigorously gather patients' data, from the first clinical evaluation to the last follow-up visit. The Advanced International Mini-Invasive Surgery (AIMS) academy clinical research network aims to create a rectal cancer registry. This will prospectively collect the data of patients operated on for non-metastatic rectal cancer in high volume colorectal surgical units through a well design pre-fashioned database for non-metastatic rectal cancer, in order to take all multidisciplinary aspects into consideration. Methods/Design: The protocol describes a multicenter prospective observational cohort study, investigating demographics, frailty, cancer-related features, surgical and radiological parameters, and oncological outcomes among patients with non-metastatic rectal cancer who are candidates for surgery with curative intent. Patients enrolled in the present registry will be followed up for 5 years after surgery. Discussion: Standardization and centralization of data collection for neoplastic diseases is a virtuous process for patient care. The creation of a register will allow the control of the quality of treatments provided and permit prospective and retrospective studies to be carried out on complete and reliable high quality data. Establishing data collection in a prospective and systematic fashion is the only possibility to preserve the enormous resource that each patient represents.

MALDI-MSI as a Complementary Diagnostic Tool in Cytopathology: A Pilot Study for the Characterization of Thyroid Nodules.

The present study applies for the first time as Matrix-Assisted Laser Desorption/Ionization (MALDI) Mass Spectrometry Imaging (MSI) on real thyroid Fine Needle Aspirations (FNAs) to test its possible complementary role in routine cytology in the diagnosis of thyroid nodules. The primary aim is to evaluate the potential employment of MALDI-MSI in cytopathology, using challenging samples such as needle washes. Firstly, we designed a statistical model based on the analysis of Regions of Interest (ROIs), according to the morphological triage performed by the pathologist. Successively, the capability of the model to predict the classification of the FNAs was validated in a different group of patients on ROI and pixel-by-pixel approach. Results are very promising and highlight the possibility to introduce MALDI-MSI as a complementary tool for the diagnostic characterization of thyroid nodules.

Clinical-pathological issues in thyroid pathology: study on the routine application of NIFTP diagnostic criteria.

In 2017, the WHO classification of tumours of the endocrine organs established the criteria for a NIFTP diagnosis. The present paper considers some aspects that are still debated or unresolved: the real incidence and clinical meaning of multifocal/multinodular lesions, the biological behaviour of micro-NIFTP, the sprinkling phenomenon and the corresponding modifications to the FNA reporting systems based on changes to the ROM. Moreover, the paper suggests possible scenarios for the clinical-pathological management of this entity. From the initial 1470 cases, a group of 68 NIFTPs was recruited in a 9 year-long period. The average age at diagnosis was 55 years. The average diameter of the lesion was 1.7 cm (0.1 cm-10 cm). In 41 cases (60.1%), the lesion was inserted in the context of a multinodular background. In 12 cases, the diagnosis was incidental and the pre- operative FNA was performed on a different target. In 10 out of 68 cases, there was a multifocal NIFTP; in 14.7% of patients, PTC-like nuclear features showed sprinkling phenomenon. The cytological revision allocated 21 cases (49%) to the SIAPEC TIR3 indeterminate class and a nuclear score 2 or 3 were identified in 25 smears. Multifocality is part of the spectrum of NIFTPs, that can arise in a multinodular background with variable sizes from microscopic lesions to very large ones. Cytopathological criteria such as an evaluation of the nuclear score may help the pathologists in promoting a NIFTP diagnosis in the preoperative setting.