Management of surgical diseases of Primary Hyperparathyroidism: indications of the United Italian Society of Endocrine Surgery (SIUEC).

A task force of the United Italian society of Endocrine Surgery (SIUEC) was commissioned to review the position statement on diagnostic, therapeutic and health­care management protocol in parathyroid surgery published in 2014, at the light of new technologies, recent oncological concepts, and tailored approaches. The objective of this publication was to support surgeons with modern rational protocols of treatment that can be shared by health-care professionals, taking into account important clinical, healthcare and therapeutic aspects, as well as potential sequelae and complications. The task force consists of 12 members of the SIUEC highly trained and experienced in thyroid and parathyroid surgery. The main topics concern diagnostic test and localization studies, mode of admission and waiting time, therapeutic pathway (patient preparation for surgery, surgical treatment, postoperative management, management of major complications), hospital discharge and patient information, outpatient care and follow-up, outpatient initial management of patients with pHPT.

Exploring the Link between BMI and Aggressive Histopathological Subtypes in Differentiated Thyroid Carcinoma-Insights from a Multicentre Retrospective Study.

Obesity's role in thyroid cancer development is still debated, as well as its association with aggressive histopathological subtypes (AHSs). To clarify the link between Body Mass Index (BMI) and AHS of differentiated thyroid carcinoma (DTC), we evaluated patients who underwent thyroidectomy for DTC from 2020 to 2022 at four European referral centres for endocrine surgery. Based on BMI, patients were classified as normal-underweight, overweight, or obese. AHSs were defined according to 2022 WHO guidelines. Among 3868 patients included, 34.5% were overweight and 19.6% obese. Histological diagnoses were: 93.6% papillary (PTC), 4.8% follicular (FTC), and 1.6% Hürthle cell (HCC) thyroid carcinoma. Obese and overweight patients with PTC had a higher rate of AHSs (p = 0.03), bilateral, multifocal tumours (p = 0.014, 0.049), and larger nodal metastases (p = 0.017). In a multivariate analysis, BMI was an independent predictor of AHS of PTC, irrespective of gender (p = 0.028). In younger patients (<55 years old) with PTC > 1 cm, BMI predicted a higher ATA risk class (p = 0.036). Overweight and obese patients with FTC had larger tumours (p = 0.036). No difference was found in terms of AHS of FTC and HCC based on BMI category. Overweight and obese patients with PTC appear to be at an increased risk for AHS and aggressive clinico-pathological characteristics.

Identification of a Novel Non-V600E BRAF Mutation in Papillary Thyroid Cancer.

Papillary thyroid cancer (PTC) is a common endocrine malignancy, and its incidence is reported to be constantly increasing. BRAF mutation is detected in approximately 44% of PTCs, and the most common BRAF mutation is thymine (T) to adenine (A) missense mutation in nucleotide 1796 (T1796A, V600E). Although BRAFV600E represents 95% of all BRAF mutations, uncommon BRAF mutations have been reported in thyroid carcinomas and represent an alternative mechanism of BRAF activation with unclear clinical significance. We report a novel non-V600E mutation (c.1799_1812delinsAT, p.V600_W604delinsD), identified preoperatively with next-generation sequencing (NGS) on the material obtained with fine-needle aspiration cytology (FNAC) performed on a thyroid nodule cytologically suspicious for malignancy in a 35-year-old male patient. The presence of this new variant of BRAF mutation was subsequently confirmed in the postoperative phase by direct Sanger sequencing. In conclusion, we report a new non-V600E variant previously undetected in papillary thyroid cancer. In addition, this case report shows that the NGS technique on cytological tissue allows to detect the presence of rare mutations, thus increasing the diagnostic specificity of molecular analysis.

Differences in surgical outcomes between cervical goiter and retrosternal goiter: an international, multicentric evaluation.

Introduction: Goiter is a common problem in clinical practice, representing a large part of clinical evaluations for thyroid disease. It tends to grow slowly and progressively over several years, eventually occupying the thoracic inlet with its lower portion, defining the situation known as retrosternal goiter. Total thyroidectomy is a standardized procedure that represents the treatment of choice for all retrosternal goiters, but when is performed for such disease, a higher risk of postoperative morbidity is variously reported in the literature. The aims of our study were to compare the perioperative and postoperative outcomes in patients with cervical goiters and retrosternal goiters undergoing total thyroidectomy. Methods: In our retrospective, multicentric evaluation we included 4,467 patients, divided into two groups based on the presence of retrosternal goiter (group A) or the presence of a classical cervical goiter (group B). Results: We found statistically significant differences in terms of transient hypoparathyroidism (19.9% in group A vs. 9.4% in group B, p < 0.001) and permanent hypoparathyroidism (3.3% in group A vs. 1.6% in group B, p = 0.035). We found no differences in terms of transient RNLI between group A and group B, while the occurrence of permanent RLNI was higher in group A compared to group B (1.4% in group A vs. 0.4% in group B, p = 0.037). Moreover, no differences in terms of unilateral RLNI were found, while bilateral RLNI rate was higher in group A compared to group B (1.1% in group A vs. 0.1% in group B, p = 0.015). Discussion: Wound infection rate was higher in group A compared to group B (1.4% in group A vs. 0.2% in group B, p = 0.006). Based on our data, thyroid surgery for retrosternal goiter represents a challenging procedure even for highly experienced surgeons, with an increased rate of some classical thyroid surgery complications. Referral of these patients to a high-volume center is mandatory. Also, intraoperative nerve monitoring (IONM) usage in these patients is advisable.

Impact of COVID-19 pandemic on thyroidectomy for malignant diseases in high-volume referral centers.

INTRODUCTION: The COVID-19 pandemic has limited the availability of healthcare resources for non-COVID patients and decreased elective surgeries, including thyroidectomy. Despite the prioritization of surgical procedures, it has been reported that thyroidectomy for thyroid cancer (TCa) was adversely impacted. We assessed the impact of the pandemic on the surgical activities of two high-volume referral centers. MATERIALS AND METHODS: Patients operated at two National Referral Centers for Thyroid Surgery between 03/01/2020 and 02/28/2021 (COVID-19 period) were included (P-Group). The cohort was compared with patients operated at the same Centers between 03/01/2019 and 02/29/2020 (pre-COVID-19 pandemic) (C-Group). RESULTS: Overall, 7017 patients were included: 2782 in the P-Group and 4235 in the C-Group. The absolute number of patients with TCa was not significantly different between the two groups, while the rate of malignant disease was significantly higher in the P-Group (1103/2782 vs 1190/4235) (P < 0.0001). Significantly more patients in the P-Group had central (237/1103 vs 232/1190) and lateral (167/1103 vs 140/1190) neck node metastases (P = 0.001). Overall, the complications rate was significantly lower (11.9% vs 15.1%) and hospital stay was significantly shorter (1.7 ± 1.5 vs 1.9 ± 2.2 days) in the P-Group (P < 0.05). CONCLUSION: The COVID-19 pandemic significantly decreased the overall number of thyroidectomies but did not affect the number of operations for TCa. Optimization of management protocols, due to limited resource availability for non-COVID patients, positively impacted the complication rate and hospital stay.

The impact of obesity on thyroidectomy outcomes: a case-matched study.

Obesity is a well-known public health concern in Western World. Accordingly, an elevated number of obese patients undergo thyroidectomy every year. We aim to assess the impact of obesity on intraoperative and postoperative outcomes of patients who undergo thyroidectomy. 1228 patients underwent thyroidectomy at our department between January 2021 and September 2021. We divided patients into two groups according to body mass index (BMI): non-obese (BMI < 30 kg/m2) and obese (BMI ≥ 30 kg/m2). A propensity score approach was performed to create 1:1 matched pairs (matching according to age, gender, diagnosis, nodule size and type of operation). After matching, the final population included 522 patients, equally divided between each group: non-obese group (Group A; n = 261) and obese group (Group B; n = 261). The primary endpoint of the study was the overall rate of postoperative complications; secondary endpoints of the study were operative time, use of energy device and length of hospital stay. The duration of hospital stay resulted longer in Group B (p = 0.002). No statistically significant differences were documented in terms of operative time (p = 0.206), use of energy devices (p = 0.855) and surgical complications (p = 0.429). Moreover, no statistically significant differences were documented considering each specific complication: transient and permanent hypocalcemia (p = 0.336; p = 0.813, respectively), transient and permanent recurrent laryngeal nerve palsy (p = 0.483; p = 0.523, respectively), hematoma (p = 0.779), bleeding (p = 0.178), wound infection (p = 0.313) and cheloid formation (p = 0.412). Thyroidectomy can safely be performed in obese patients. Outcomes resulted comparable; nonetheless, obesity correlates to longer hospital stay.

BRAF K601E Mutation in Oncocytic Carcinoma of the Thyroid: A Case Report and Literature Review.

BACKGROUND: Thyroid carcinoma (TC) is the most common endocrine cancer, with papillary thyroid carcinoma (PTC) being the most common subtype. BRAF and RAS oncogene were characterized as the most frequently altered genes in PTC, with a strong association between genotype and histotype. The most common mutation in BRAF gene is V600E and is prevalent in classic and aggressive variants of PTC, while BRAF K601E mutation is the most common among the other rare BRAF mutations. BRAF K601E mutated thyroid carcinomas are usually characterized by low aggressiveness, except for anecdotal cases of poorly differentiated TC. CASE PRESENTATION: We described a case of oncocytic carcinoma of the thyroid (OCA) with an aggressive clinical course, including widespread metastasis and resistance to radioiodine treatment. Molecular analysis revealed the exclusive presence of the BRAF K601E mutation in both primary tumor and metastatic lesions. Accordingly, a revision of the literature about aggressive TC cases carrying BRAF K601E mutation was performed. CONCLUSION: Although rare, this case emphasizes the relevance of considering BRAF K601E mutation in advanced non-PTC thyroid carcinomas, since it can be considered an actionable mutation for target therapies.

Risk factors for postoperative cervical haematoma in patients undergoing thyroidectomy: a retrospective, multicenter, international analysis (REDHOT study).

Background: Postoperative cervical haematoma represents an infrequent but potentially life-threatening complication of thyroidectomy. Since this complication is uncommon, the assessment of risk factors associated with its development is challenging. The main aim of this study was to identify the risk factors for its occurrence. Methods: Patients undergoing thyroidectomy in seven high-volume thyroid surgery centers in Europe, between January 2020 and December 2022, were retrospectively analysed. Based on the onset of cervical haematoma, two groups were identified: Cervical Haematoma (CH) Group and No Cervical Haematoma (NoCH) Group. Univariate analysis was performed to compare these two groups. Moreover, employing multivariate analysis, all potential independent risk factors for the development of this complication were assessed. Results: Eight thousand eight hundred and thirty-nine patients were enrolled: 8,561 were included in NoCH Group and 278 in CH Group. Surgical revision of haemostasis was performed in 70 (25.18%) patients. The overall incidence of postoperative cervical haematoma was 3.15% (0.79% for cervical haematomas requiring surgical revision of haemostasis, and 2.35% for those managed conservatively). The timing of onset of cervical haematomas requiring surgical revision of haemostasis was within six hours after the end of the operation in 52 (74.28%) patients. Readmission was necessary in 3 (1.08%) cases. At multivariate analysis, male sex (P < 0.001), older age (P < 0.001), higher BMI (P = 0.021), unilateral lateral neck dissection (P < 0.001), drain placement (P = 0.007), and shorter operative times (P < 0.001) were found to be independent risk factors for cervical haematoma. Conclusions: Based on our findings, we believe that patients with the identified risk factors should be closely monitored in the postoperative period, particularly during the first six hours after the operation, and excluded from outpatient surgery.

Usefulness of second 131I treatment in biochemical persistent differentiated thyroid cancer patients.

Background: Second 131I treatment is commonly performed in clinical practice in patients with differentiated thyroid cancer and biochemical incomplete or indeterminate response (BiR/InR) after initial treatment. Objective: The objective of the is study is to evaluate the clinical impact of the second 131I treatment in BiR/InR patients and analyze the predictive factors for structural incomplete response (SiR). Patients and methods: One hundred fifty-three BiR/InR patients after initial treatment who received a second 131I treatment were included in the study. The clinical response in a short- and medium- long-term follow-up was evaluated. Results: After the second 131I treatment (median 8 months), 11.8% patients showed excellent response (ER), 17% SiR, while BiR/InR persisted in 71.2%. Less than half (38.5%) of SiR patients had radioiodine-avid metastases. Patients who, following the second 131I treatment, experienced SiR had larger tumor size and more frequently aggressive histology and vascular invasion than those experienced BiR/InR and ER. Also, the median values of thyroglobulin on levothyroxine therapy (LT4-Tg), Tg peak after recombinant human TSH stimulation (rhTSH-Tg) and thyroglobulin antibodies (TgAb) were significantly higher in patients who developed SiR. At last evaluation (median: 9.9 years), BiR/InR persisted in 57.5%, while 26.2% and 16.3% of the patients showed ER and SiR, respectively. About half of BiR/InR patients (71/153 (46.4%)) received further treatments after the second 131I treatment. Conclusions: Radioiodine-avid metastatic disease detected by the second 131I is an infrequent finding in patients with BiR/InR after initial treatment. However, specific pathologic and biochemical features allow to better identify those cases with higher probability of developing SiR, thus improving the clinical effectiveness of performing a second 131I treatment.

Parathyroid Retrospective Analysis of Neoplasms Incidence (pTRANI Study): An Italian Multicenter Study on Parathyroid Carcinoma and Atypical Parathyroid Tumour.

BACKGROUND: Parathyroid cancer (PC) is a rare sporadic or hereditary malignancy whose histologic features were redefined with the 2022 WHO classification. A total of 24 Italian institutions designed this multicenter study to specify PC incidence, describe its clinical, functional, and imaging characteristics and improve its differentiation from the atypical parathyroid tumour (APT). METHODS: All relevant information was collected about PC and APT patients treated between 2009 and 2021. RESULTS: Among 8361 parathyroidectomies, 351 patients (mean age 59.0 ± 14.5; F = 210, 59.8%) were divided into the APT (n = 226, 2.8%) and PC group (n = 125, 1.5%). PC showed significantly higher rates (p < 0.05) of bone involvement, abdominal, and neurological symptoms than APT (48.8% vs. 35.0%, 17.6% vs. 7.1%, 13.6% vs. 5.3%, respectively). Ultrasound (US) diameter >3 cm (30.9% vs. 19.3%, p = 0.049) was significantly more common in the PC. A significantly higher frequency of local recurrences was observed in the PC (8.0% vs. 2.7%, p = 0.022). Mortality due to consequences of cancer or uncontrolled hyperparathyroidism was 3.3%. CONCLUSIONS: Symptomatic hyperparathyroidism, high PTH and albumin-corrected serum calcium values, and a US diameter >3 cm may be considered features differentiating PC from APT. 2022 WHO criteria did not impact the diagnosis.

Ultrasound features and risk stratification system in NIFT-P and other follicular-patterned thyroid tumors.

OBJECTIVE: Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFT-P) is an encapsulated follicular variant of papillary thyroid carcinoma (PTC) with nonaggressive clinical behavior. However, since its diagnosis is exclusively possible after surgery, it represents a clinical challenge. Neck ultrasound (US) shows good sensitivity and specificity in suggesting malignancy in thyroid nodules. However, little information is available about its ability in identifying NIFT-P. DESIGN: The aim of this study was to evaluate the US features of NIFT-P, comparing them with other follicular-patterned thyroid tumors, and to test the ability of the main US risk stratification system (RSS) in identifying NIFT-P. METHODS: We retrospectively evaluated 403 consecutive patients submitted to thyroid surgery, with positive histology for at least 1 nodule being NIFT-P, follicular variant of PTC (FV-PTC), follicular thyroid carcinoma (FTC), or follicular adenoma (FA). RESULTS: The US features of NIFT-P (n = 116), FV-PTC (n = 170), FTC (n = 76), and FA (n = 90) were reported. Follicular variant of PTC and FTC more frequently showed irregular margins, presence of calcifications, "taller than wide" shape, and the absence of halo compared with NIFT-P. Furthermore, FTC and also FA were larger and more frequently hypoechoic than NIFT-P. Most cases (77%) showed an indeterminate cytology. Regardless of the US RSS considered, NIFT-P and FA were less frequently classified in the high-suspicious category compared with FV-PTC and FTC. CONCLUSIONS: Ultrasound features of NIFT-P are frequently superimposable to those of nodules with low suspicion of malignancy. The NIFT-P is almost never classified in the high-suspicious category according to the main US RSS. Therefore, although the preoperative identification of NIFT-P remains a challenge, neck US can be integrated in the algorithm of management of nodules with indeterminate cytology, suggesting a possible conservative approach in those with low-suspicious features.

The learning curve on robot-assisted transaxillary thyroidectomy performed by a single endocrine surgeon in a third-level institution in Europe: a cumulative sum (CUSUM) analysis.

Robot-assisted transaxillary thyroidectomy is widely performed in Asian countries, although it is still under discussion in the Western World. However, there have been few studies reporting on the learning curve of robot-assisted transaxillary thyroidectomy. We used the cumulative sum (CUSUM) analysis to assess the learning curve of gasless robot-assisted transaxillary thyroidectomy at a third-level institution in Europe. We included all consecutive patients operated by a single surgeon without previous experience of robotic surgery from February 2012 to January 2023. The primary endpoint of the study was the learning curve extracted from the median operative time using the CUSUM method for the quantitative assessment. Overall, 583 patients were enrolled. The median operative time for thyroid lobectomy and total thyroidectomy was 70 and 90 min, respectively. The CUSUM analysis showed that the learning curve for thyroid lobectomy and total thyroidectomy is 66 and 56 cases, respectively. Moreover, the presence of thyroiditis resulted associated with shorter operative time for total thyroidectomy (p = 0.044), whereas no factors resulted associated with surgical complications. The learning curve for performing robotic transaxillary thyroid lobectomy for a surgeon without previous robotic experience is 66 cases. After that, 56 cases must be performed to acquire proficiency in robotic transaxillary total thyroidectomy. Training programs may reduce the slope of the learning curve.

Robot-assisted transaxillary surgery for thyroid cancer: Oncologic and surgical outcomes in long term follow-up.

BACKGROUND: The use of robot-assisted transaxillary thyroidectomy (RATT) has rapidly spread in the last 2 decades, although it is mostly limited to Asian countries. METHOD: We retrospectively enroled all patients with histologic diagnoses of thyroid cancer who underwent RATT at the University Hospital of Pisa from May 2012 to September 2020. RESULTS: The study included 242 patients; 128 (47%) underwent total thyroidectomy and 114 (53%) underwent thyroid lobectomy, among which 28 patients (24.6%) required completion thyroidectomy. Radioactive iodine ablation therapy was required in 90 patients (37%). The complication rate was 5.3%. After a median follow-up of 38 months, an excellent response to therapy was achieved in 107 patients (74%), whereas the response was indeterminate in 12 (8%) and incomplete in 16 (11%). No local or distant relapses or increases in thyroglobulin or antibody levels were documented. CONCLUSIONS: In experienced hands, RATT represents a valid option for the treatment of thyroid cancer in selected cases.

Sentinel node mapping in thyroid cancer: an overview.

In this paper we describe the current status of sentinel node mapping (SNM) in thyroid tumors and its potential perspectives. SNM in thyroid cancer has been tested since the end of the twentieth century, mainly in papillary thyroid cancer (PTC) and in medullary thyroid cancer (MTC). In PTC, it has been employed to find occult lymph node metastases in the central compartment of the neck as an alternative or indication for prophylactic dissection, by several methods. All of them have proven effective in spotting sentinel nodes, but the results have been somewhat diminished by uncertainty about the clinical significance of occult metastases in differentiated thyroid cancer. SNM in MTC has also been used to find occult lymph node metastases in the lateral compartments of the neck, also with excellent results hindered by a similar doubt about the real clinical significance of MTC micrometastases. Well designed, adequately sized randomized controlled trials are lacking, so SNM in thyroid tumors remains an interesting yet experimental methodology. New technology is emerging that could facilitate such studies, which could add solid information about the clinical significance of occult neck metastases in thyroid cancer.

Cytological and Ultrasound Features of Thyroid Nodules Correlate With Histotypes and Variants of Thyroid Carcinoma.

CONTEXT: Prognosis is excellent for papillary thyroid carcinoma (PTC), noninvasive follicular thyroid neoplasia with papillary-like nuclear features (NIFT-P), and follicular thyroid carcinoma (FTC) but is poor for poorly differentiated thyroid carcinoma (PDTC) and anaplastic thyroid carcinoma (ATC). Among PTCs, the prognosis is more favorable for follicular (FV-PTC) and classic (CV-PTC) than for tall cell (TCV-PTC), and solid (SV-PTC) variants. OBJECTIVE: To associate histotypes and variants of thyroid carcinoma with ultrasound and cytological features. METHODS: Histology of 1018 benign tumors and 514 PTC (249 CV, 167 FV, 49 TC, 34 SV, and 15 other variants), 52 NIFT-P, 50 FTC, 11 PDTC, and 3 ATC was correlated with fine-needle aspiration biopsy categories (Italian classification: TIR1, TIR2, TIR3A, TIR3B, TIR4, and TIR5) and ultrasound features at the Endocrinology Unit, University Hospital of Pisa. In total, 1117 patients with thyroid nodule(s) who underwent thyroidectomy were included. RESULTS: Of PTC, 36.3% had indeterminate cytology (TIR3A or TIR3B), 56.6% were suspicious for malignancy or malignant (TIR4 or TIR5); 84.0% FTC and 69.3% NIFT-P were TIR3A or TIR3B; 72.5% FV-PTC and 73.6% SV-PTC were TIR3A or TIR3B; 79.9% CV-PTC and 95.9% TCV-PTC were TIR4 or TIR5. The association of a hypoechoic pattern, irregular margins, and no microcalcifications was more frequent in TCV-PTC than in CV-PTC (P = .02, positive predictive value = 38.9%; negative predictive value = 85.5%). CONCLUSION: At cytology, most FTC, NIFT-P, FV-PTC, and SV-PTC were indeterminate, most CV-PTC and TCV-PTC were suspicious for malignancy or malignant. Ultrasound can be helpful in ruling out TCV-PTC.

Comparison of surgical completeness in patients operated on conventional open total thyroidectomy (OT) or trans-axillary robot-assisted total thyroidectomy (RATT) by a single axillary approach.

Trans-axillary robot-assisted total thyroidectomy (RATT) is nowadays worldwide accepted but the completeness obtained by RATT is still debated. The Aim of this study was to compare the completeness and safety of RATT with conventional open thyroidectomy (OT). We enrolled patients with nontoxic multinodular goiter, cytologically indeterminate nodules and well differentiated thyroid cancer without local and/or distant metastasis. In all cases the biggest nodule should be < 6 cm. The surgical completeness was evaluated by means of serum thyroglobulin (hs-Tg) and neck ultrasound (nUS) performed three months postoperatively. 100 patients underwent either RATT or OT. The type of surgical procedure was chosen by patients. They were then divided in two subgroups based on benign or malignant histology. There were no significant differences in the postoperatively values of hs-Tg in patients operated with RATT or OT, both in benign and malignant subgroups. The post-operative thyroid remnant volume estimated by nUS was not significantly different between the two groups, both in benign and malignant subgroups. We also analyzed the difference of the volume of the thyroid remnant ipsilateral to the axillary access vs that of the remnant on the contralateral side and there was not significantly difference in both subgroups. RATT was demonstrated to determine a comparable surgical completeness as OT, both in benign and malignant thyroid diseases, with no differences in the prevalence of surgical complications. In our hands the surgical completeness of RATT by a single trans-axillary was satisfying.

NF1 Gene Inactivation Acts as Tumor Driver in RET/RAS Negative Medullary Thyroid Carcinomas.

OBJECTIVE: 20% of sporadic MTC has no RET/RAS somatic alterations or other known gene alterations. Aim of this study was to investigate RET/RAS negative MTC for the presence of NF1 alterations. METHODS: we studied 18 sporadic RET/RAS negative MTC cases: Next generation sequencing of tumoral and blood DNA was performed using a custom panel including the entire coding region of the NF1 gene. The effect of NF1 alterations on the transcripts were characterized by RT-PCR and the loss of heterozygosity of the other NF1 allele was investigated with Multiplex Ligation-dependent Probe Amplification. RESULTS: Two cases showed bi-allelic inactivation of NF1 with a prevalence of about 11% of RET/RAS negative cases. In a patient affected by neurofibromatosis there was a somatic intronic point mutation determining the transcript alteration in one allele and a germline loss of heterozygosity (LOH) in the other. In the other case described both the point mutation and the LOH were somatic events; this latter finding shows, for the first time, a driver role of NF1 inactivation in MTC independent of RET/RAS alterations and the presence of neurofibromatosis. CONCLUSIONS: About 11% of our series of sporadic RET/RAS negative MTC harbor biallelic inactivation of NF1 suppressor gene also regardless neurofibromatosis status. According to our results, NF1 alterations should be searched in all RET/RAS negative MTC as possible driver. Moreover, this finding reduces the number of negative sporadic MTCs and may have important clinical implications in the management of these tumors.

Robotic transaxillary thyroidectomy: time to expand indications?

In 2016, the American Thyroid Association published a statement on remote-access thyroid surgery claiming that it should be reserved to patients with thyroid nodule ≤ 3 cm, thyroid lobe < 6 cm and without thyroiditis. We retrospectively enrolled all patients who underwent robotic transaxillary thyroidectomy between February 2012 and March 2022. We compared surgical outcomes between patients who presented a thyroid gland with a nodule ≤ 3 cm, thyroid lobe < 6 cm and without thyroiditis (Group A) and patients without these features (Group B). The rate of overall complications resulted comparable (p = 0.399), as well as the operative time (p = 0.477) and the hospital stay (p = 0.305). Moreover, bleeding resulted associated to thyroid nodule > 3 cm (p = 0.015), although all bleedings but one occurred in the remote-access site from the axilla to the neck. In experienced hands, robotic transaxillary thyroidectomy is feasible and safe even in patients with large thyroid nodules or thyroiditis.

Outcomes of the Tall-Cell Variant of Papillary Thyroid Carcinoma in Patients with Different Ages: A 17-Year Mono-Institutional Experience.

The tall-cell variant of papillary thyroid carcinoma (TCPTC) is the most common aggressive variant of papillary thyroid carcinoma (PTC) and typically occurs in older patients. In this study, we analyzed retrospectively the largest mono-institutional series of PTCs with tall-cell features (989 patients) over a 17-year period, re-evaluating tumors based on age at presentation and outcomes in different age groups. We divided patients into three age groups following different criteria (the criterion from the American Joint Committee on Cancer Tumor Node Metastasis (AJCC TNM) guidelines, criterion for the statistical division into tertiles and adolescent/post-adolescent criterion) to analyze the clinicopathological characteristics in different age groups, especially in terms of recurrence-free survival (RFS) and distant recurrence-free survival (DRFS). We obtained three main results: 1. the population is distributed among the different age groups, and therefore, this type of cancer is not exclusively found among those of an older age; 2. in the RFS analysis, we can see a higher probability of local recurrence in the younger and older groups and, unexpectedly, a lower probability of local recurrence in the "median age" group; and 3. in the DRFS analysis, we can observe a higher probability of distant recurrence in older patients. From a molecular perspective, no significant differences in the mutational status of BRAF were detected according to different age groups, while mutations in the TERT promoter were exclusively present in older patients of all age groups, highlighting the potential prognostic implications of TERT promoter mutations in PTCs. In conclusion, the results of this series confirm that TC morphology alone in PTCs does not have the same negative prognostic significance in the younger population as in the older population. The reason for these different outcomes remains unclear and needs further studies.

An adrenal cortical adenoma with neuroendocrine-type granules mimicking pheochromocytoma.

Clinical and biochemical presentation of adrenal tumors may rarely conflict with their histologic features. In the present report, we describe a rare case of adrenal neoplasm clinically and biochemically labeled as pheochromocytoma which at histologic examination resulted adrenal cortical tumor. The neoplasm was examined with the electron microscope which revealed the presence of electron-dense neuroendocrine-type granules next to intracytoplasmic lipid droplets. The patient underwent laparoscopic left adrenalectomy which leads to normalization of 24 h urinary metanephrine and normetanephrine. This exceptional entity should be taken into consideration when the clinical and laboratory features conflict with the histological examination. The pathologist can clarify the mixed nature of the tumor by means of the identification of neuroendocrine granules at the electron microscope examination.