Reasons Associated with Total Thyroidectomy as Initial Surgical Management of an Indeterminate Thyroid Nodule.

BACKGROUND: Diagnostic hemithyroidectomy (HT) is the most widely recommended surgical procedure for a nodule with indeterminate cytology; however, additional details may make initial total thyroidectomy (TT) preferable. We sought to identify patient-specific factors (PSFs) associated with initial TT in patients with indeterminate thyroid nodules. METHODS: Retrospective analysis of all patients with a thyroid nodule ≥ 1 cm and initial cytology of atypia of undetermined significance or suspicious for follicular neoplasm between 2012 and 2015 who underwent thyroidectomy. Medical records were reviewed for patient demographics, neck symptoms, nodule size, cytology, molecular test results, final histopathology, and additional PSFs influencing surgical management. Variables were analyzed to determine associations with the use of initial TT. Logistic regression analyses were performed to identify independent associations. RESULTS: Of 325 included patients, 182/325 (56.0%) had HT and 143/325 (44.0%) had TT. While patient age and sex, nodule size, and cytology result were not associated with initial treatment, five PSFs were associated with initial TT (p < 0.0001). These included contralateral nodules, hypothyroidism, fluorodeoxyglucose avidity on positron emission tomography scan, family history of thyroid cancer, and increased surgical risk. At least one PSF was present in 126/143 (88.1%) TT patients versus 47/182 (25.8%) HT patients (p < 0.0001). Multivariate logistic regression analysis demonstrated that these variables were the strongest independent predictor of TT (odds ratio 45.93, 95% confidence interval 18.80-112.23, p < 0.001). CONCLUSIONS: When surgical management of an indeterminate cytology thyroid nodule was performed, several PSFs were associated with a preference by surgeons and patients for initial TT, which may be useful to consider in making decisions on initial operative extent.

Recurrent IDH2 R172X mutations in sinonasal undifferentiated carcinoma.

Sinonasal undifferentiated carcinoma is a rare and aggressive malignancy. Sinonasal undifferentiated carcinoma has long been considered a diagnosis of exclusion; to date, the molecular pathogenetic basis for sinonasal undifferentiated carcinoma is unknown. To identify potential oncogenic drivers in sinonasal undifferentiated carcinoma, targeted next-generation sequencing of 300 cancer-related genes was performed on 11 cases of sinonasal undifferentiated carcinoma. We identified IDH2 R172X mutations in 55% of sinonasal undifferentiated carcinomas including R172S, R172T, and R172M. Multispecific mutant IDH1/2 immunohistochemistry was performed and identified mutant-specific protein expression in all cases with available tissue: 3/3 sinonasal undifferentiated carcinomas with R172 mutations were positive and 4/4 wild-type cases were negative. Review of sequencing data for our institutional head and neck cohorts (n=412) confirmed the absence of IDH-activating mutations in other tumor types. Alterations in the IDH2-wild-type sinonasal undifferentiated carcinomas included SMARCA4 loss-of-function with confirmed loss of immunohistochemical expression, NOTCH1 gain-of-function, and TET2 loss-of-function. We demonstrate that the majority of histologically defined sinonasal undifferentiated carcinomas are characterized by IDH2 R172X mutations and overexpression of mutant protein. IDH2 R172X mutations are specific to sinonasal undifferentiated carcinoma among carcinomas of the head and neck, confirming this tumor type as a distinct clinicopathologic entity. These findings have significant implications for diagnosis and therapy with IDH inhibitors for patients with this rare and poorly understood tumor.

HMGA2 is a specific immunohistochemical marker for pleomorphic adenoma and carcinoma ex-pleomorphic adenoma.

AIMS: Accurate classification of salivary gland neoplasms may be challenging, owing to morphological overlap, particularly in small biopsies. Recurrent translocations involving the high-mobility group AT-hook 2 (HMGA2) gene are present in a subset of pleomorphic adenomas (PAs) and carcinoma ex-pleomorphic adenomas (CA ex-PAs). The aim of this study was to evaluate immunohistochemical HMGA2 expression in 225 salivary gland tumours, including 56 PAs, 37 CA ex-PAs, and 132 potential histological mimics, to determine its diagnostic utility. METHODS AND RESULTS: HMGA2 expression was identified in 19 PAs (33.9%) and nine CA ex-PAs (24.3%). Expression was strong and diffuse throughout all PAs, and in four of nine positive CA ex-PAs. In five CA ex-PAs, HMGA2 showed weak-to-strong multifocal staining within the carcinomatous component, and strong diffuse HMGA2 expression in the residual PA. Among histological mimics, six de-novo salivary duct carcinomas (28.5%), three epithelial-myoepithelial carcinomas (33.3%) and one case each of myoepithelioma and basal cell adenoma expressed HMGA2. Fluorescence in-situ hybridization for HMGA2 rearrangement performed on a subset of tumours that showed diffuse HMGA2 expression in PAs and CA ex-PAs was frequently associated with rearrangement of the HMGA2 locus, whereas cases of de-novo salivary duct carcinoma, or CA ex-PA with limited or no HMGA2 expression, had an intact HMGA2 locus. CONCLUSIONS: HMGA2 expression is a highly specific (96.2%), but low-sensitivity (29.8%), marker for PA and CA ex-PA when compared with histological mimics, and is frequently associated with rearrangement of the HMGA2 locus.

The variable phenotype and low-risk nature of RAS-positive thyroid nodules.

BACKGROUND: Oncogenic mutations are common in thyroid cancers. While the frequently detected RAS-oncogene mutations have been studied for diagnostic use in cytologically indeterminate thyroid nodules, no investigation has studied such mutations in an unselected population of thyroid nodules. No long-term study of RAS-positive thyroid nodules has been performed. METHODS: We performed a prospective, blinded cohort study in 362 consecutive patients presenting with clinically relevant (>1 cm) thyroid nodules. Fine needle aspiration cytology and mutational testing were obtained for all nodules. Post-operative histopathology was obtained for malignant or indeterminate nodules, and benign nodules were sonographically followed. Histopathological features were compared between RAS- and BRAF-positive malignancies. RAS-positive benign nodules were analyzed for growth or cellular change from prior aspirations. RESULTS: Overall, 17 of 362 nodules were RAS-positive. Nine separate nodules were BRAF-positive, of which eight underwent surgery and all proved malignant (100%). Out of the 17 RAS-positive nodules, ten underwent surgery, of which eight proved malignant (47%). All RAS-positive malignancies were low risk - all follicular variants of papillary carcinoma, without extrathyroidal extension, metastases, or lymphovascular invasion. RAS-positivity was associated with malignancy in younger patients (P = 0.028). Of the nine RAS-positive benign nodules, five had long-term prospective sonographic follow-up (mean 8.3 years) showing no growth or signs of malignancy. Four of these nodules also had previous aspirations (mean 5.8 years prior), all with similar benign results. CONCLUSIONS: While RAS-oncogene mutations increase malignancy risk, these data demonstrate a low-risk phenotype for most RAS-positive cancers. Furthermore, cytologically benign, yet RAS-positive nodules behave in an indolent fashion over years. RAS-positivity alone should therefore not dictate clinical decisions.

Pure Apocrine Intraductal Carcinoma of Salivary Glands: Reassessment of Molecular Underpinnings and Behavior.

BACKGROUND: Intraductal carcinoma (IDC) of the salivary glands is a confounding entity, our understanding of which continues to evolve. At least four forms have been elucidated based on histomorphology, immunophenotype, and molecular profile: (1) intercalated duct-like, S100/SOX10+ with frequent NCOA4::RET fusions; (2) oncocytic, S100/SOX10+ with TRIM33::RET, NCOA4::RET, and BRAF V600E; (3) apocrine, AR+ with PI3 kinase pathway mutations; and (4) mixed/hybrid intercalated duct-like/apocrine, with S100/SOX10+ and AR+ areas and frequent TRIM27::RET. The revelation that myoepithelial cells harbor the same fusion as luminal cells suggested that fusion-positive cases are not in situ carcinomas as previously believed. To this point, purely apocrine IDC with entirely intraductal growth has not been found to harbor fusions, but very few cases have been tested. METHODS: IDCs with pure apocrine morphology, entirely intraductal growth, and no precursor lesion (pleomorphic adenoma or sclerosing polycystic adenoma) were retrieved from the authors' archives. Several immunostains (S100, SOX10, GCDFP-15, AR, p40/SMA) and targeted next generation sequencing (NGS) panel including 1425 cancer-related genes were performed. RESULTS: Seven entirely IDC with pure apocrine type were collected. The cases arose in the parotid glands (mean, 1.9 cm) of 5 men and 2 women ranging from 51 to 84 years (mean, 69.7 years). Histologically, tumors consisted of rounded to angulated ductal cysts lined by epithelial cells with abundant finely granular eosinophilic cytoplasm and large nuclei with prominent nucleoli. Pleomorphism was mild to moderate, the mitotic rate was low, and necrosis was absent. Conventionally invasive foci or areas of intercalated duct-like morphology were not identified. In all cases, luminal cells were diffusely positive for AR and GCDFP-15 while negative for S100/SOX10, and the ducts were completely surrounded by myoepithelial cells highlighted by p40 and SMA. Molecular analysis was successful in 6 cases. Three harbored fusions: one with NCOA4::RET, another with STRN::ALK and one with both CDKN2A::CNTRL and TANC1::YY1AP1. The three fusion-negative cases all harbored HRAS mutations; additional mutations (PIK3CA, SPEN, ATM) were found in 2 of 3 cases. All patients were treated by surgery alone. Six of them are currently free of disease (follow up 12-190 months), but the case harboring NCOA4::RET developed lymph nodes metastasis in the form of a fusion-positive invasive salivary duct carcinoma. CONCLUSIONS: Purely apocrine IDC is a heterogeneous disease. A subset seems to be genetically similar to salivary duct carcinoma and may indeed represent carcinoma in situ. The other group harbors fusions, similar to other forms of IDC. Moreover, the occurrence of lymph node metastasis discredits the idea that any fusion-positive IDC with a complete myoepithelial cell layer has no metastatic potential. With the wide use of RET-and ALK-based targeted therapies, our findings further underscore the importance of fusion analysis for IDC.

Trastuzumab for the treatment of salivary duct carcinoma.

OBJECTIVE: Salivary duct carcinoma (SDC) is a rare and aggressive malignancy with high mortality and poor response to treatment. A significant fraction of SDCs are HER2 positive. This retrospective review examines HER2 testing in SDC and the outcome of trastuzumab-based therapy in adjuvant and palliative settings. METHODS: A total of 13 patients with SDC and HER2/neu expression by immunohistochemistry of 1-3+ were treated with trastuzumab in adjuvant (n = 8) or palliative (n = 5) setting. Adjuvant therapy consisted of concurrent radiation and chemotherapy with weekly paclitaxel, carboplatin, and trastuzumab (TCH) for 6 weeks followed by TCH for 12 weeks and trastuzumab alone for 1 year. Palliative treatment for metastatic disease consisted of TCH every 3 weeks for 6 cycles followed by trastuzumab for variable time periods with or without second-line chemotherapy for progression. All patients had fluorescence in situ hybridization testing for HER2/neu gene amplification. RESULTS: The median duration of follow-up was 27 months (range: 8-48 months). In all, 62% of adjuvant patients (5/8) had no evidence of disease more than 2 years from completion of therapy. All patients with metastatic disease (5/5 patients) responded to treatment with TCH. One patient achieved a complete response and remains with no evidence of disease 52 months after initiation of TCH. The median duration of response was 18 months (range: 8-52 months). CONCLUSION: HER2/neu positivity and treatment with trastuzumab correlated well with long-term survival and response in our patients. Based on this data, we propose that HER2/neu status be examined routinely in all patients with SDCs and the treatment be directed accordingly.

Role of cytology in the diagnosis and management of HPV-associated head and neck carcinoma.

Human papillomavirus (HPV)-associated head and neck squamous cell carcinoma (HNSCC) accounts for up to 25% of all HNSCCs. These tumors largely arise from the oropharynx, particularly the tonsil and base of tongue. The first manifestation of HPV-associated HNSCC is frequently as metastasis to cervical lymph nodes that can be documented by fine-needle aspiration. These metastases are often cystic with a predominantly non-keratinizing, basaloid morphology. Knowledge of the HPV status of metastatic HNSCC has significant treatment and prognostic implications as HPV-associated tumors have a more favorable prognosis than conventional HNSCC. Accordingly, HPV testing should be performed on any squamous cell carcinoma of unknown primary identified in neck lymph nodes. HPV detection may be performed using a variety of methods including p16 as a surrogate immunohistochemical marker, in situ hybridization and/or polymerase chain reaction detection of viral DNA or RNA. Further investigation is needed to determine the optimal method for HPV detection in fine-needle aspiration specimens. Cytology screening for HPV-associated HNSCC does not appear to be effective. Greater understanding of the natural history of oral HPV infections is needed before knowing if oral HPV testing may be useful as a screening test.

A subset of cutaneous and soft tissue mixed tumors are genetically linked to their salivary gland counterpart.

Neoplasms morphologically similar to mixed tumors and myoepitheliomas of the salivary glands, under the broad concept of myoepithelial neoplasia, have recently been defined in the skin and soft tissue; however, to date, no data have supported a shared genetic background with their salivary gland counterpart. From a large body of research, it has been well established that rearrangement of pleomorphic adenoma gene 1 (PLAG1) leads to aberrant expression of its protein and is pathogenically relevant in the development of salivary mixed tumors. On the other hand, in soft tissue lesions, compelling evidence suggests that EWSR1 is involved in a significant subset. To examine the hypothesis that there is a genetic link between these histologically similar tumors at different sites, we randomly selected 20 benign myoepitheliomas/mixed tumors of skin and soft tissue (10 cases each). Nineteen cases could be immunostained for PLAG1, of which 11 cases showed distinct nuclear staining with moderate or strong intensity in a significant number of cells. Interphase fluorescence in situ hybridization for PLAG1 was successfully performed in 11 cases (seven in skin and four in soft tissue) and was positive for gene rearrangement in eight cases (five in skin and three in soft tissue). All PLAG1-rearranged tumors, except one, had clear-cut ductal structures and were immunoreactive for PLAG1. In our series, tumors with PLAG1 alteration shared a common morphologic phenotype characterized by prominent tubuloductal differentiation, suggesting that myoepithelial neoplasms with genuine salivary gland-like morphology, so-called soft tissue/cutaneous mixed tumors, are genetically related to their salivary gland counterpart.

The evolution of "atypia" in thyroid fine-needle aspiration specimens.

The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) provided a standardized framework for resulting thyroid fine-needle aspiration (FNA) specimens and introduced the low-risk category of atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS). This indeterminate category has significantly evolved over time with the incorporation of molecular testing, reclassification of noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP), and a shift toward more conservative management. Despite these refinements, AUS/FLUS remains a challenge, at both the diagnostic and therapeutic level. We review the criteria for AUS/FLUS and the associated controversies in rendering this diagnosis, while highlighting the importance of a multidisciplinary approach to managing atypical thyroid nodules.

Ex vivo hypercellular parathyroid gland differentiation using dynamic optical contrast imaging (DOCI).

Primary hyperparathyroidism, often caused by a single adenoma (80-85%) or four-gland hyperplasia (10-15%), can lead to elevated parathyroid hormone (PTH) levels and resultant hypercalcemia. Surgical excision of offending lesions is the standard of care, as the removal of pathologic adenomas reduces PTH and calcium values to baseline. The small size, variable location, and indistinct external features of parathyroid glands can make their identification quite challenging intraoperatively. Our group has developed the dynamic optical contrast imaging (DOCI) technique, a novel realization of dynamic temporally dependent measurements of tissue autofluorescence. In this study, we evaluated the efficacy of using the DOCI technique and normalized steady-state fluorescence intensity data for differentiating types of human parathyroid and thyroid tissues. We demonstrate that the DOCI technique has the capability to distinguish normal parathyroid tissue from diseased parathyroid glands as well as from adjacent healthy thyroid and adipose tissue across 8 different spectral channels between 405nm-600nm (p<0.05). Patient tissue DOCI data was further analyzed with a logistic regression classifier trained across the 8 spectral channels. After computer training, the computer-aided identification was able to accurately locate hypercellular parathyroid tissue with 100% sensitivity and 98.8% specificity within the captured DOCI image.

Modular polymer platform as a novel approach to head and neck cancer therapy.

Head and neck cancer is the sixth most common cancer in the world, with more than 300,000 deaths attributed to the disease annually. Aggressive surgical resection often with adjuvant chemoradiation is the cornerstone of treatment. However, the necessary chemoradiation treatment can result in collateral damage to adjacent vital structures causing a profound impact on quality of life. Here, we present a novel polymer of poly(lactic-co-glycolic) acid and polyvinyl alcohol that can serve as a versatile multidrug delivery platform as well as for detection on cross-sectional imaging while functioning as a fiduciary marker for postoperative radiotherapy and radiotherapeutic dosing. In a mouse xenograft model, the dual-layered polymer composed of calcium carbonate/thymoquinone was used for both polymer localization and narrow-field infusion of a natural therapeutic compound. A similar approach can be applied in the treatment of head and neck cancer patients, where immunotherapy and traditional chemotherapy can be delivered simultaneously with independent release kinetics.

Application of the Milan System for Reporting Salivary Gland Cytopathology in pediatric patients: An international, multi-institutional study.

BACKGROUND: Pediatric salivary gland fine-needle aspiration (FNA) is uncommon with a higher frequency of inflammatory lesions and a small proportion of malignancies. This international, multi-institutional cohort evaluated the application of the Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) and the risk of malignancy (ROM) for each diagnostic category. METHODS: Pediatric (0- to 21-year-old) salivary gland FNA specimens from 22 international institutions of 7 countries, including the United States, England, Italy, Greece, Finland, Brazil, and France, were retrospectively assigned to an MSRSGC diagnostic category as follows: nondiagnostic, nonneoplastic, atypia of undetermined significance (AUS), benign neoplasm, salivary gland neoplasm of uncertain malignant potential (SUMP), suspicious for malignancy (SM), or malignant. Cytology-histology correlation was performed where available, and the ROM was calculated for each MSRSGC diagnostic category. RESULTS: The cohort of 477 aspirates was reclassified according to the MSRSGC as follows: nondiagnostic, 10.3%; nonneoplastic, 34.6%; AUS, 5.2%; benign neoplasm, 27.5%; SUMP, 7.5%; SM, 2.5%; and malignant, 12.4%. Histopathologic follow-up was available for 237 cases (49.7%). The ROMs were as follows: nondiagnostic, 5.9%; nonneoplastic, 9.1%; AUS, 35.7%; benign neoplasm, 3.3%; SUMP, 31.8%; SM, 100%; and malignant, 100%. Mucoepidermoid carcinoma was the most common malignancy (18 of 237; 7.6%), and it was followed by acinic cell carcinoma (16 of 237; 6.8%). Pleomorphic adenoma was the most common benign neoplasm (95 of 237; 40.1%). CONCLUSIONS: The MSRSGC can be reliably applied to pediatric salivary gland FNA. The ROM of each MSRSGC category in pediatric salivary gland FNA is relatively similar to the ROM of each category in adult salivary gland FNA, although the reported rates for the different MSRSGC categories are variable across institutions.

The frequency of 'atypia of undetermined significance' interpretations for thyroid fine-needle aspirations is negatively correlated with histologically proven malignant outcomes.

OBJECTIVE: Cytopathologists' usage patterns for 'atypia of undetermined significance' (AUS) in thyroid fine-needle aspiration (FNA) are not well understood. AUS rates over a 5-year period were analyzed to quantify variability and identify correlations with experience and histologic outcomes. STUDY DESIGN: A retrospective review of thyroid FNAs from a tertiary-care hospital from 2005 to 2009 was performed. Results were compiled for individual cytopathologists, stratified by year, and correlated with histologic outcomes. RESULTS: Thyroid FNAs (5,327) were evaluated by 7 cytopathologists, with an overall AUS rate of 11.2%. The annual AUS rate remained relatively constant over this time period, though notable inter- and intrapathologist variability was seen. The AUS rate was significantly lower for those with cytopathology boards (10.3%) compared to those without (14.0%). There was no correlation between the AUS rate and cytopathologist experience or thyroid FNA volume. The AUS rate and malignant outcome were inversely related: the higher an individual's AUS rate was, the lower the rate of malignancy for that AUS cohort was. CONCLUSIONS: Individual cytopathologist AUS rates were variable and often exceeded the recommended target of 7%. The application of recently published defined diagnostic criteria, along with directed cytopathologist feedback, may reduce observer variability and appropriately lower AUS utilization.

Repeatedly nondiagnostic thyroid fine-needle aspirations do not modify malignancy risk.

OBJECTIVE: Thyroid nodules with nondiagnostic (ND) fine-needle aspirations (FNA) typically undergo repeat sampling. While repeat FNA is often diagnostic, little is known regarding the significance of repeatedly ND aspirates. Limited data suggest there is very low, if any, risk of malignancy for repeatedly ND FNAs. STUDY DESIGN: We performed a retrospective analysis of ND thyroid FNAs over a nearly 6-year period at our institution to further address this question. RESULTS: There were 834 ND thyroid FNAs, representing 694 distinct thyroid nodules. Repeat FNA was performed after an initial ND aspirate in 52% of cases (363/694); 19% (70/363) had at least one additional ND diagnosis on repeat FNA. Surgical follow-up was available for 57 cases. Malignancy was identified histologically in 21% (9/42) of nodules after a single ND FNA and in 20% (3/15) of nodules with 2 or more repeatedly ND aspirates. Accounting for all benign cytologic follow-up, the overall risk of malignancy was 4% [12/303; 3.5% (9/255) following a single ND FNA and 6.3% (3/48) after repeated ND FNAs]. CONCLUSION: We observed no modification of malignancy risk when repeated FNAs were ND. Clinical management for an ND aspirate should remain repeat aspiration along with clinical and sonographic correlation.

Applications of Computational Pathology in Head and Neck Cytopathology.

BACKGROUND: The application of computational technology to head and neck cytology material has been explored experimentally in several areas with a variety of potential applications. SUMMARY: This review summarizes the application of these techniques to the diagnosis of thyroid, salivary gland, and other head and neck fine-needle aspiration specimens. Current limitations and potential future applications in diagnosis are discussed along with the possibilities for therapeutic applications of computational methodology. Key Message: Particularly promising applications include resolving diagnostic uncertainty in indeterminate thyroid aspirates and assessing the tumor microenvironment in response to immunotherapy for squamous cell carcinoma.

Should "suspicious for high-grade urothelial carcinoma" and "positive for high-grade urothelial carcinoma" remain separate categories?

BACKGROUND: The Paris System (TPS) for Reporting Urinary Cytology aims to standardize urine cytology reporting. Per TPS, the diagnosis of "suspicious for high-grade urothelial carcinoma (SHGUC)" is applied in cases that have few urothelial cells with severe atypia but are quantitatively insufficient for a diagnosis of "high-grade urothelial carcinoma (HGUC)." In our study, we compared the diagnostic accuracy and risk of malignancy (ROM) of these 2 categories to assess whether they could be combined in clinical practice to perhaps improve overall interobserver variability. METHODS: All urine specimens with a diagnosis of either SHGUC or HGUC from January 2016 to July 2019 were retrieved from the pathology database of 2 large academic institutions. Only cases with follow-up biopsies within 6 months were included. RESULTS: One hundred eighty-nine cases met the study criteria. Of these, 122 had a cytologic diagnosis of SHGUC, and 67 had a diagnosis of HGUC. Ninety-five (78%) cases from the SHGUC group and 64 (96%) cases from the HGUC group had biopsy-proven HGUC. The majority of cases with discordance had a history of treatment with either intravesical bacillus Calmette-Guérin or mitomycin. The difference in the rate of biopsy-proven HGUC between the SHGUC category and the HGUC category (95/122 vs 64/67, respectively) was statistically significant (P < .001). CONCLUSIONS: The difference in ROM between SHGUC and HGUC was statistically significant in our study cohort. Intravesical chemotherapy was frequently observed in negative biopsy cases in both groups. Our preliminary findings suggest that the 2 TPS categories should remain separate.

Hürthle cell lesions of the thyroid: Progress made and challenges remaining.

Hürthle cell-predominant thyroid fine needle aspirations (FNA) are encountered frequently in routine practice, yet they are often challenging to diagnose accurately and are associated with significant interobserver variability. This is largely due to the ubiquity of Hürthle cells in thyroid pathology, ranging from nonneoplastic conditions to aggressive malignancies. Although limitations in cytomorphologic diagnoses likely will remain for the foreseeable future, our knowledge of the molecular pathogenesis of Hürthle cell neoplasia and application of molecular testing to cytologic material have increased dramatically within the past decade. This review provides context behind the challenges in diagnosis of Hürthle cell lesions and summarizes the more recent advances in diagnostic tools.

A Tool to Locate Parathyroid Glands Using Dynamic Optical Contrast Imaging.

OBJECTIVES/HYPOTHESIS: Identification of parathyroid glands and adjacent tissues intraoperatively can be quite challenging because of their small size, variable locations, and indistinct external features. The objective of this study is to test the efficacy of the dynamic optical contrast imaging (DOCI) technique as a tool in specifically differentiating parathyroid tissue and adjacent structures, facilitating efficient and reliable tissue differentiation. STUDY DESIGN: Prospective study. METHODS: Both animal and human tissues were included in this study. Fresh specimens were imaged with DOCI and subsequently processed for hematoxylin and eosin (H&E) stain. The DOCI images were analyzed and compared to the H&E results as ground truth. RESULTS: In both animal and human experiments, significant DOCI contrast was observed between parathyroid glands and adjacent tissue of all types. Region of interest analysis revealed most distinct DOCI values for each tissue when using 494 and 572 nm-specific band pass filter for signal detection (P < .005 for porcine tissues, and P = .02 for human specimens). Linear discriminant classifier for tissue type prediction based on DOCI also matched the underlying histology. CONCLUSIONS: We demonstrate that the DOCI technique reliably facilitates specific parathyroid gland localization. The DOCI technique constitutes important groundwork for in vivo precision endocrine surgery. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:2391-2397, 2021.