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Background While ultrasound-guided fine-needle aspiration cell block (FNACB) is a cost-effective, expeditious, and reliable procedure used routinely in the initial evaluation of head and neck masses, it has limited efficacy in diagnosing lymphoproliferative disorders such as non-Hodgkin lymphoma (NHL). Flow cytometry performed on an fine-needle aspiration (FNA) sample [ultrasound-guided fine-needle aspirate flow cytometry or flow cytometry performed on an FNA sample (FNAFC)], has been shown to be a valuable adjunct to FNACB in the diagnosis of lymphoproliferative disorders of the spleen, kidney, and thyroid. The objective of this study was to appraise FNAFC’s utility as an ancillary tool to detect NHL arising in the head and neck region in adult patients.Methods This is a retrospective study involving 52 adult patients with head and neck lymphadenopathies and masses suspicious for lymphoproliferative disorders, who underwent ultrasound-guided FNACB and ultrasound-guided FNAFC between January 2017 and November 2022. Patient demographics, FNACB histopathological and immunophenotypic results, postoperative histopathology results (when available), and follow-up information until May 2023 were reviewed.Results Of the 52 FNACB samples, 23 samples (44.2%) yielded a diagnosis negative for carcinoma, 20 samples (38.5%) were nondiagnostic on account of scant cellularity, 8 samples (15.4%) were suspicious for malignancy, and a single sample (1.9%) was compatible with malignancy. Regarding FNAFC samples, 37 samples (71.2%) were diagnosed as showing no evidence for a lymphoproliferative disorder, 4 samples (7.7%) as nondiagnostic because of insufficient cell count, 4 samples (7.7%) as suspicious for a lymphoproliferative neoplasm, and 7 samples (13.5%) as compatible with a lymphoproliferative neoplasm, most frequently a B-cell lymphoma. 7 of the 11 patients (63.6%) with a suspicious/positive FNAFC result underwent excisional biopsy for additional work up. Postoperative histopathology reports corroborated FNAFC’s findings in 6 patients (85.7%), while the remaining patient’s (14.3%) suspicious FNAFC result was discordant with postoperative histopathology results. The other 4 patients (36.4%) did not require excisional biopsy as the hemato-oncologist deemed the information provided by the FNAFC as sufficient for the diagnosis and treatment of an NHL in the specific clinical contexts of those patients. All patients with nondiagnostic (due to insufficient cell count), inconclusive, or negative FNAFC (ie, nondiagnostic of a lymphoproliferative disorder) were followed up for a mean follow-up period of 11.9?months (range: 61.2?months; SD: 10.2?months), during which no new lymphadenopathies/masses nor progression was observed.Conclusions FNAFC is a useful and practical supplementary tool in the diagnosis of lymphoproliferative disorders in the head and neck region, principally B-cell lymphoma. While conventional FNACB offers a valuable insight into the initial work up of head and neck masses, FNAFC can routinely detect small abnormal cell populations. Furthermore, in specific clinical contexts, it can reliably diagnose NHL, thereby averting the need for an excisional biopsy in a subset of patients.

Background: This study aims to develop and validate, a clinically useful modified index of fragility (mIFG) to identify patients at risk of fragility and to predict postoperative adverse events. Method: An observational study was performed using the American College of Surgeons National Surgical Quality Improvement Program database, from 2006 to 2018. All patients undergoing nonemergency head and neck cancer surgery were included. A seven-item index (mIFG) was developed using variables associated with frailty, cachexia, and sarcopenia, drawn from the literature (weight loss, low body mass index, dyspnea, diabetes, serum albumin, hematocrit, and creatinine). Multivariable logistic regression was used to model the association between mIFG, postoperative adverse events and death. A validation cohort was then used to ascertain the diagnostic accuracy of the mIFG. Results: A total of 23,438 cases were included (16,407 in the derivation group and 7031 in the validation group). There was a total of 4273 postoperative major adverse events (AE) and deaths, 1023 postoperative pulmonary complications and 1721 wound complications. Using the derivation cohort, the 7-item mIFG was independently associated with death, major AEs, pulmonary and wound complications, when controlling for significant covariates. The mIFG predicted death and major adverse events using the validation cohort with an accuracy of 0.70 (95% CI: 0.63–0.76) and 0.64 (95% CI: 0.63–0.66), respectively. The mIFG outperformed the modified Frailty index. Conclusion: The modified index of fragility is a reliable and easily accessible tool to predict risk of postoperative adverse events and death in patients undergoing head and neck cancer surgery. Graphical Abstract:

Medullary thyroid cancer (MTC) cells are capable of secreting various tumor markers including calcitonin and carcinoembyronic antigen (CEA). The purpose of this study is to determine whether abnormal CEA levels may be used as a tumor marker to predict the severity of disease in MTC. A retrospective analysis was completed for 33 patients with MTC who had preoperative serum CEA levels. Univariate and multivariate analyses were used to quantify the relationship between serum CEA levels and tumor stage and prognosis. On multivariate analysis, elevated preoperative CEA levels were significantly associated with the size and stage of tumor, distant metastasis, decreased biochemical cure, and mortality. There was a significant association between tumor size greater than 37 mm and elevated CEA levels (> 271 ng/ml). There was also a positive correlation with increased cancer stage (> 377 ng/ml), distant metastasis (> 405 ng/ml), and contralateral compartment location of lymph node metastasis (> 162 ng/ml). When pre-operative CEA levels are > 500 ng/ml, patient mortality was 67%. In this study, both pre-operative calcitonin and CEA levels were significantly correlated with the extent of disease in MTC. While calcitonin has a linear relationship with disease progression, abnormal CEA levels were a better indicator of advanced disease. CEA levels > 271 ng/ml are significant for advanced tumor size and staging, metastasis to the central compartment, and decreased chance of biochemical cure. CEA levels greater than 500 ng/ml are associated with significant patient mortality.

Management decisions are not straightforward when the Ultrasound Guided Fine Needle Aspiration (USFNA) demonstrates a Bethesda score of either category III or IV, and a diagnostic hemi-thyroidectomy or a repeat USFNA (r-USFNA) could be performed. The aim of this study is to assess the effectiveness of r-USFNA in the management of indeterminate thyroid nodules by evaluating the likelihood of obtaining a definite diagnosis. We reviewed the medical records of all patients with thyroid nodules between 2011 and 2015 at the Jewish General Hospital (Montreal, Canada). Three hundred fifty-one patients who had undergone a surgical procedure (hemi or total thyroidectomy) and a diagnosis of B3 or B4 on the primary USFNA (p-USFNA) were included in the study. Ninety-six of the included patients also had a repeat USFNA prior to the surgery. Demographic data, type of procedure, and McGill Thyroid Nodule Score (MTNS) were obtained from the medical records. Malignancy rates were calculated based on the final surgical histopathology report. Upon r-USFNA, an average 76 % of patients did not change Bethesda categories, 7.4 % downgraded to a benign category. The results showed that, on an average 17.3 % of patients with p-USFNA of B3 and 20 % of patients with p-USFNA of B4, upgraded to a malignant or suspicious for malignancy category, thus changing the clinical management to total thyroidectomy. Our data demonstrates that r-USFNA facilitates choosing the correct surgery of total thyroidectomy in about 20 % of nodules that have upgraded from B3/B4 to a more definite malignant category. r-USFNA in patients with indeterminate diagnoses (B3 or B4) increases categorization into more definite categories. Approximately 20 % of patients are found to have malignant thyroid nodules and suspicious for malignancy thyroid nodules upon repeating the biopsy, hence a diagnostic hemi-thyroidectomy was avoided and a more definitive surgery could be performed. Furthermore, repeat USFNA results in a fewer number of hemi-thyroidectomy and completion thyroidectomy procedures.

Background: In clinical practice, thyroid tumor size plays a critical role in the staging of thyroid malignancies and in the selection of nodules that should undergo ultrasound-guided fine-needle aspiration. Thyroid tumor size is influenced by the elapsed time since the beginning of oncogenesis and by the presence of somatic mutations driving growth, such as BRAFV600Emutations, associated with aggressive phenotypes, and RAS-like mutations, associated with more indolent behavior. Although large nodules are often considered to be more alarming, the true impact of tumor size on prognosis remains controversial. The aim of this study was to assess the relationship between mutational status, tumor size and aggressiveness, with emphasis on BRAFV600Eand RAS-like mutations. Method: We conducted a multicentric retrospective chart review in Montréal, Canada, of all patients who underwent thyroid surgery between January 2016 and December 2020, with well-differentiated thyroid cancer on final pathology, and who had undergone molecular testing revealing the presence of BRAFV600Emutations or RAS-like mutations (NRAS, HRASor KRAS). Results: We included 214 cases. There were 117 (54.7%) cases of BRAFV600Eand 97 (45.3%) cases of RAS-like mutations. The BRAFV600Egroup was statistically associated with a smaller mean tumor size when compared with the RASgroup of 1.55 cm and 2.04 cm, respectively. In a multivariate model, tumors with BRAFV600Emutations were also more likely to display aggressive pathological features, including extra-thyroidal extension, lymph node metastasis, columnar cell features, tall cell histology, or hobnail histology (OR 26.69; 95% CI 11.15–70.81). In contrast, tumor size was not associated with pathologic aggressive features on multivariate analysis (OR 0.81; 95% CI 0.54–1.22). Conclusion: This study demonstrates that thyroid tumors expressing BRAFV600Emutations correlate with aggressive pathologic features more than tumors expressing RAS-like mutations. When comparing tumors with BRAFV600Eand RAS-like mutations, the former were found to be smaller. As a result of this finding, this study suggests that molecular alterations may better predict aggressive pathologic features than the size of the tumor. Graphical abstract:

Background: The EIF1AXmutation has been identified in various benign and malignant thyroid lesions, with a higher prevalence in poorly differentiated thyroid carcinoma (PDTC) and anaplastic thyroid carcinoma, especially when combined with RASor TP53mutation. However, data and clinical significance of EIF1AXmutations in thyroid nodules is still limited. We investigated the prevalence of EIF1AXmutations and co-mutations in cytologically indeterminate thyroid nodules at our institution. Methods: A 5-year retrospective analysis was performed on surgically resected thyroid nodules with identified EIF1AXmutations on molecular testing with ThyroseqV3®. Mutation type and presence of co-mutations were correlated with histopathologic diagnosis and clinical characteristics. Histopathology diagnoses were subsequently categorized as benign, borderline, malignant or aggressive malignant (≥ 10% PDTC component). Chi-square test was used to compare the malignancy associations of the: 1) A113_splice mutation compared to non-A113_splice mutations 2) singular A113_splice mutations compared to singular non-A113_splice mutations. Fisher’s Exact Test was used to determine the association of A113_splice mutation with aggressive malignancies compared to non-A113_splice mutations. A pvalue of 0.05 or less was considered statistically significant. Results: Out of 1583 patients who underwent FNA, 621 had further molecular testing. 31 cases (5%) harbored EIF1AXmutations. Of these cases, 12 (38.7%) were malignant, 2 (6.5%) were borderline, and 17 (55%) were benign. 4/31 cases (13%) were aggressive malignant (≥ 10% PDTC component). The most prevalent mutation was the A113_splice mutation at the junction of intron 5 and exon 6 (48%). All other mutations, except one, were located at the N-terminal in exon 2. 7/31 cases (22.6%) harbored ≥ 1 co-mutation(s), including 4 RAS, 3 TP53, 1 TERT and 1 PIK3CA,with 86% of them being malignant. All 4 nodules with RASco-mutations were malignant including one PDTC. Conclusion: Our study reports the largest cohort of EIF1AXmutations in Bethesda III/IV FNA samples with surgical follow-up to our knowledge. The presence of the EIF1AXmutation confers a 45.2% risk of malignancy (ROM) or borderline after surgery. However, the coexistence of EIF1AXmutations with other driver mutations such as RAS, TERTor TP53conferred an 86% ROM. While 55% of thyroid nodules were benign at the time of surgery, the possible malignant transformation of these nodules, had they not been resected, is unknown. Finally, 13% of the nodules with EIF1AXmutations were aggressive with a significant PDTC component. These findings can further aid in clinical decisions for patients with thyroid nodules. Graphic Abstract:

Vocal cord paralysis (VCP) is found in both benign and malignant thyroid disease. This study was performed to determine if the presence of preoperative VCP predicts malignancy. A retrospective analysis was performed on a cohort of 1923 consecutive patients undergoing thyroid surgery. The incidence of preoperative VCP was recorded. Patient and nodule characteristics were correlated with final pathology. 1.3 % of our cohort was found to have preoperative VCP. Malignant pathology was discovered in 76 % of patients with preoperative VCP. Among these patients, 72 % had a left sided paralysis. 10.5 % of patients with preoperative VCP had perineural invasion (PNI) on final pathology, compared to 1.1 % of patients with normal VC function. Preoperative VCP appears to be a strong, though not an absolute, indicator of malignancy. Most VCP were on the left side. Assessing for preoperative VCP is crucial in all patients who need thyroid surgery, as even benign nodules can be accompanied by preoperative vocal cord paralysis.

It is not uncommon for patients with indeterminate thyroid nodules to undergo diagnostic hemithyroidectomy. When the final pathology determines that the nodule is in fact malignant, patients require counseling as to the whether a completion thyroidectomy is necessary. 1.Determine the incidence of well differentiated thyroid cancer (WDTC) in the contralateral thyroid lobe in patients undergoing completion thyroidectomy.2.Identify features of the malignant tumor in the initial resection that increase the likelihood of malignancy in the contralateral lobe. Retrospective chart review of 97 patients who underwent hemithyroidectomy and completion thyroidectomy in a university’s teaching hospital network between 2006 and 2012. Pathology reports from both surgeries as well as patient and thyroid nodule characteristics were reviewed. Of the 97 patients, 47 (48 %) had a malignancy in the contralateral lobe. In the contralateral lobe, 42/47 (89 %) of malignancies were papillary microcarcinomas (PMC) and 15/42 (36 %) of the PMC were multifocal. Multifocal malignancies in the initial specimen had a 60 % rate of contralateral malignancy and were found to be a predictor of bilateral disease (p= 0.04) with OR= 2.74 (95 % CI: 1.11–6.79; p= 0.003) in WDTC and OR= 3.59 (95 % CI:1.35 9.48; p= 0.01) in papillary cancer specifically. There was no statistical significant correlation established for the following variables: presence of positive cervical nodes, extrathyroidal extension, positive resection margins, size and angio-lymphatic invasion. Moreover, there was no statistical correlation between any of the variants of papillary thyroid cancer and bilateral disease, even though most aggressive subtypes were found to be bilateral. In this study, the rate of malignancy in the contralateral lobe was 48 %. Multifocality and presence of an aggressive subtype of papillary thyroid cancer in the initial specimen were found to be more important variables to consider in decision-making regarding completion thyroidectomy than size of the initial tumor alone.

We sought to determine the ability of the endoscopic Mueller maneuver (MM) to predict the severity of OSAS based on upper airway (UA) collapse. This chart review retrospectively analyzed the results of endoscopic Mueller maneuvers examining the UA on 506 patients suspected of having OSAS. There were 3 areas of UA collapse that were evaluated: velopharynx (VP), base of tongue (BOT), and lateral pharyngeal walls (LPW). A sleep study was done after the examination to assess the severity of OSAS based on the apnea-hypopnea index (AHI). A total of 506 patients met criteria for OSAS, with 194 mild cases (5 ≤ AHI < 15), 163 moderate cases (15 ≤ AHI < 30) and 149 severe cases (30 ≤ AHI). At the VP, 30 patients had minimal collapse (mean AHI = 17); 41 patients had moderate VP collapse (mean AHI = 25); 392 patients had severe VP collapse (mean AHI = 27). At the BOT, 144 patients had minimal collapse (mean AHI = 19); 187 patients had moderate BOT collapse (mean AHI = 24); 175 patients had severe BOT collapse (mean AHI = 33). At the LPW, 158 patients had minimal collapse (mean AHI = 20); 109 patients had moderate LPW collapse (mean AHI = 25); 120 patients had severe LPW collapse (mean AHI =33). The correlations found between VP collapse, BOT collapse, and LPW collapse and OSAS severity were: r= 0.069 (95 % CI; −0.022, 0.16), r= 0.26 (95 % CI; 0.18, 0.34) and r= 0.22 (95 % CI; 0.12, 0.31), respectively. In this study, the degree of collapse of the UA at all levels, especially at the BOT and LPW levels, correlate significantly with the severity of OSAS. The Mueller maneuver helped identify patients with severe sleep apnea based on UA collapse. The MM cannot be used to diagnose OSAS, but can be a valuable tool to help the physician estimate the severity of sleep apnea and the urgency to obtain a sleep study.

Background: While some studies suggest that the BRAF V600Emutation correlates with a high-risk phenotype in papillary thyroid microcarcinoma (PTMC), more evidence is necessary before this mutation can be used to help guide decision making in the management of small thyroid nodules. This study investigated whether BRAF V600Emutation is associated with aggressive features in PTMC (≤ 1 cm) and small PTC (1–1.5 cm). Methods: Retrospective chart review was performed on 121 patient cases. Patients who underwent thyroid surgery for PTMC (≤ 1 cm) or small PTC (1–1.5 cm) were included if molecular testing was done for BRAF V600Emutation. Two study groups were created based on tumour size: PTMC (n = 55) and small PTC (n = 66). The groups were analysed for the presence of a BRAF V600Emutation and aggressive features, including macroscopic extrathyroidal extension (ETE), lymph node metastasis (LNM), and high-risk histological features (tall cell, columnar cell, hobnail, solid/trabecular, and diffuse sclerosing). The Fischer exact test was used to calculate statistical significance. Results: BRAF V600Emutations were detected in 43.6% of PTMC and 42.4% of small PTC. Of the mutated PTMC nodules, 54.1% demonstrated aggressive characteristics as compared to 19.4% of the non-mutated PTMCs (p= 0.010). Of the mutated small PTC tumours, 82.1% had aggressive features. In contrast, 28.9% of the non-mutated small PTCs showed aggressive features (p&lt; 0.001). Conclusions: Our findings demonstrate an association between a BRAF V600Emutation and aggressive features in PTMC (≤ 1 cm) and small PTC (1–1.5 cm). Therefore, determining the molecular status of these thyroid nodules for the presence of BRAF V600Ecan help guide patient management. Graphical Abstract:

The aim of this study is to prospectively review the role of sentinel lymph node (SLN) biopsy in the management of well differentiated thyroid carcinoma (WDTC), and to determine the efficacy of intraoperative frozen section analysis at detecting SLN metastasis and central compartment involvement.