Trainee-initiated dictations of endocrine surgeries: Implications for education and reimbursement.

INTRODUCTION: Our university-based surgery department recently transitioned to attending-only authorship of operative reports. We performed a mixed-methods investigation to determine if trainee-initiated endocrine surgical reports were associated with under-coding of specific procedures. METHODS: Endocrine operations performed from July 2020 to June 2022 were identified from billing data. Pre- and post-policy RVU distributions and note modification history were reviewed to determine how often trainees captured billable differentiators over attending note modification. RESULTS: 714 operations and 1138 billed procedures were identified. Parathyroidectomy alone showed greater mean RVUs with attending-only reports attributable to attending practice change in coding for intraoperative parathyroid hormone monitoring. Trainees were more likely to miss coding modifier 22 but RVU losses were prevented by attending note modification. CONCLUSION: Trainee-initiated operative reports were not associated with RVU losses for endocrine operations compared to attending-only reports. Trainee dictation can be improved by emphasizing education on procedural billing differences and surgical reasoning.

Recurrent malignant struma ovarii presenting as peritoneal carcinomatosis in the setting of an intact thyroid: A case report and review of the literature.

Malignant struma ovarii is an exceedingly rare pathology with a paucity of established criteria regarding management and surveillance with recommendations largely based on case reports and retrospective data. Many authors have supported stratification of malignant struma ovarii into low vs high-risk disease with more conservative management reserved for those deemed low-risk. Here we present a unique case of recurrent metastatic malignant struma ovarii after surveillance was undertaken in the setting of initially low-risk disease.

Clinical characteristics and outcomes of adrenal hemorrhage.

BACKGROUND: Although uncommon, adrenal hemorrhage has multiple etiologies. Because clinical characteristics, management, and outcomes of patients with adrenal hemorrhage are inadequately described, we examined the underlying etiology, need for intervention, evolution of imaging characteristics, and adequacy of subsequent evaluation. METHODS: We performed a retrospective review of patients diagnosed with adrenal hemorrhage (radiologist-confirmed density consistent with hemorrhage on computed tomography) from 2005 to 2021 at a university-based institution. Demographic characteristics, hemorrhage etiology, and subsequent follow-up were analyzed. RESULTS: Of 193 adrenal hemorrhage patients, the mean age was 49.2 ± 18.3 years, and 35% were female. Clinical presentations included trauma (47%), abdominal or flank pain (28%), incidental findings on imaging acquired for other reasons (12%), postoperative complication (8%), or shock (3%). Hemorrhage outside of the gland was present in 62% of patients. Unilateral hemorrhage was more frequent (93%) than bilateral (7%). A total of 12% of patients had nodules, but only 70% of these were identified on initial imaging, and only 43% had hormonal evaluation. Of 7 patients who had adrenalectomy or biopsy, pathology was either benign (57%) or nonadrenal malignancy (43%). No adrenocortical carcinomas were identified. Follow-up imaging was performed in 56% of patients and revealed decreased, stable, resolved, or increased adrenal hemorrhage size in 39%, 19%, 30%, and 12% of patients, respectively. CONCLUSION: Adrenal hemorrhage is secondary to multiple etiologies, most commonly trauma. In the setting of adrenal hemorrhage, many adrenal nodules were not identified on initial imaging. Only a minority of patients with nodules underwent "complete" biochemical evaluation. Follow-up imaging may improve the identification of underlying nodules needing hormonal evaluation.

Efficacy and safety of near-infrared fluorescence identification of the thoracic duct during left lateral neck dissection.

BACKGROUND: Thoracic duct leaks occur in up to 5% of left lateral neck dissections. No one imaging modality is routinely used to identify the thoracic duct intraoperatively. The goal of our study was to evaluate the efficacy and safety of indocyanine green lymphangiography for intraoperative identification of the thoracic duct compared to traditional methods using ambient and evaluate the optimal timing of indocyanine green administration. METHODS: We enrolled all patients who underwent left lateral neck dissection at our institution from 2018 to 2022 in this prospective clinical trial. After indocyanine green injection into the dorsum of the foot, we performed intraoperative imaging was performed with a near-infrared fluorescence camera. We reported the data using descriptive statistics. RESULTS: Of the 42 patients we enrolled, 14 had prior neck surgery, and 3 had prior external beam radiation. We visualized the thoracic duct with ambient light in 48% of patients and with near-infrared fluorescence visualization in 64%. In 17% of patients, we could identify the thoracic duct only using near-infrared fluorescence visualization, which occurred within 3 minutes of injection, and were required to re-dose 5 patients. We visualized the thoracic duct with near-infrared fluorescence in all patients with prior neck radiation and 77% of patients with prior neck surgery. One adverse reaction occurred (hypotension), and 5 intraoperative thoracic duct injuries occurred that were ligated. There with no chylous fistulas postoperatively. CONCLUSION: This trial demonstrates that near-infrared fluorescence identification of the thoracic duct is feasible and safe with indocyanine green lymphangiography, even in patients with prior neck surgery or radiation.

Heterogeneous parathyroid near-infrared autofluorescence patterns are associated with single adenomas in primary hyperparathyroidism.

BACKGROUND: Primary adenoma (PA) and multi-gland hyperplasia (MGH) account for 85% and 15% of primary hyperparathyroidism (PHPT) cases, respectively. Near-infrared autofluorescence (NIRAF) enhances intraoperative parathyroid identification. We hypothesized that PA would display a more heterogeneous NIRAF pattern compared to MGH. METHODS: Patients undergoing surgery for sporadic PHPT were categorized based on the presence of PA or MGH. To quantify heterogeneity, we utilized ratios of (1) mean parathyroid gland (PG) NIRAF over background NIRAF (mean ratio), (2) minimum and (3) maximum PG NIRAF over mean PG NIRAF (minimum and maximum ratios). Additionally, a heterogeneity score was quantified using mean ratio (mean PG NIRAF over background NIRAF), and overall NIRAF (mean NIRAF of eight random 15 × 15 pixel areas). A point was assigned to ratios <0.8 or >1.2. Images were quantified by ImageJ software. Mann-Whitney test was performed for all comparisons. RESULTS: Of 78 patients, 63 had a single PA and 15 had MGH, totaling 102 PGs. There was no difference between their mean ratios. PA had a lower minimum ratio compared to that of MGH (0.86 ± 0.01 vs. 0.93 ± 0.01, p = 0.001) and a brighter maximum ratio (1.21 ± 0.02 vs. 1.12 ± 0.01, p = 0.0008). PA also scored higher on their heterogeneity scores compared to MGH (1.27 ± 0.23 vs. 0.33 ± 0.15, p = 0.001). CONCLUSION: Single parathyroid adenomas display a more heterogeneous autofluorescence pattern compared to that of multi-gland hyperplasia. Intraoperative characterization of PGs by real-time NIR imaging patterns may be a beneficial adjunct during parathyroid surgery.

Neoadjuvant dabrafenib and trametinib for functional organ preservation in recurrent BRAF V600E-mutated papillary thyroid cancer.

OBJECTIVES: To describe the first reported use of neoadjuvant dabrafenib and trametinib specifically to permit organ conservation surgery in locally advanced recurrent differentiated thyroid carcinoma. PATIENTS AND METHODS: A patient presented with locally recurrent, radioiodide-resistant DTC with a BRAF V600E mutation invading the laryngotrachea. Definitive treatment would require a total laryngectomy. She was offered neoadjuvant dabrafenib and trametinib prior to surgery. RESULTS: A significant radiographic response permitted partial laryngectomy, enabling preservation of voice, early resumption of oral feeding, and avoidance of permanent tracheostomy. At 9 months, she remained free of disease. CONCLUSION: Neoadjuvant tyrosine kinase inhibitor treatment prior to definitive surgery for locally-invasive recurrent DTC is a potential approach that may limit the degree of surgery and associated morbidity.

Converting a probe-based fluorescence system into an easy-to-use adjunct for the detection of parathyroid glands accidentally resected intraoperatively.

PURPOSE: The reported threshold of a near-infrared fluorescence detection probe (FDP) for judging parathyroid glands (PGs) is based on the autofluorescence intensity relative to other non-PG tissues, making it unreliable when not enough reference tissues are measured. We aim to convert FDP into a more convenient tool for identifying accidentally resected PGs by quantitative measurements of autofluorescence in resected tissues. METHODS: It was a prospective study approved by the Institutional Review Board. The research was divided into two stages: (1) In order to calibrate the novel FDP system, autofluorescence intensity of different in / ex vivo tissues was measured and the optimal threshold was obtained using receiver operating characteristic (ROC) curve. (2) To further validate the effectiveness of the new system, detection rates of incidental resected PGs by pathology in the control group and by FDP in the experimental group were compared. RESULTS: Autofluorescence of PGs was significantly higher than that of non-PG tissue (43 patients, Mann-Whitney U test, p < 0.0001). An optimal threshold of sensitivity / specificity (78.8% and 85.1%) for discriminating PGs was obtained. The detection rates of experimental group (20 patients) and control group (33 patients) are 5.0% and 6.1% respectively (one-tailed Fisher's exact test, p = 0.6837), indicating the novel FDP system can achieve a similar proportion of PG detection compared with pathological examinations. CONCLUSIONS: The novel FDP system can be used as an easy-to-use adjunct for detecting PG accidentally resected intraoperatively before the tissues are sent for frozen sections during thyroidectomy surgeries. TRIAL REGISTRATION: Registration number: ChiCTR2200057957.

Use of fluorescence imaging and indocyanine green during thyroid and parathyroid surgery: Results of an intercontinental, multidisciplinary Delphi survey.

BACKGROUND: In recent years, fluorescence imaging-relying both on parathyroid gland autofluorescence under near-infrared light and angiography using the fluorescent dye indocyanine green-has been used to reduce risk of iatrogenic parathyroid injury during thyroid and parathyroid resections, but no published guidelines exist regarding its use. In this study, orchestrated by the International Society for Fluorescence Guided Surgery, areas of consensus and nonconsensus were examined among international experts to facilitate future drafting of such guidelines. METHODS: A 2-round, online Delphi survey was conducted of 10 international experts in fluorescence imaging use during endocrine surgery, asking them to vote on 75 statements divided into 5 modules: 1 = patient preparation and contraindications to fluorescence imaging (n = 11 statements); 2 = technical logistics (n = 16); 3 = indications (n = 21); 4 = potential advantages and disadvantages of fluorescence imaging (n = 20); and 5 = training and research (n = 7). Several methodological steps were taken to minimize voter bias. RESULTS: Overall, parathyroid autofluorescence was considered better than indocyanine green angiography for localizing parathyroid glands, whereas indocyanine green angiography was deemed superior assessing parathyroid perfusion. Additional surgical scenarios where indocyanine green angiography was thought to facilitate surgery are (1) when >1 parathyroid gland requires resection; (2) during redo surgeries, (3) facilitating parathyroid autoimplantation; and (4) for the predissection visualization of abnormal glands. Both parathyroid autofluorescence and indocyanine green angiography can be used during the same procedure and employing the same imaging equipment. However, further research is needed to optimize the dose and timing of indocyanine green administration. CONCLUSION: Though further research remains necessary, using fluorescence imaging appears to have uses during thyroid and parathyroid surgery.

Adrenal Near-Infrared Autofluorescence.

Context: Parathyroid tissue is one of the few tissues to have strong near-infrared (NIR) autofluorescence, which has been exploited to improve intraoperative parathyroid identification. The US Food and Drug Administration has approved 2 devices for this purpose. Adrenal glands can be difficult to distinguish from surrounding fat, an issue during total adrenalectomy. Objective: We hypothesized adrenal tissue may also possess considerable NIR autofluorescence. Methods: Resected patient adrenal specimens were examined after robotic adrenalectomy with an NIR camera intraoperatively. Patients did not receive fluorescent dye. Images were taken of both gross and sectioned specimens. Post hoc image analysis was performed with ImageJ software. Confocal microscopy was performed on selected tissues using immunofluorescence and hematoxylin-eosin staining. Results: Resected tissue was examined from 22 patients undergoing surgery for pheochromocytomas (6), primary aldosteronism (3), adrenocorticotropin-independent hypercortisolism (10), and a growing or suspicious mass (3). Normal adrenal tissue demonstrated strong NIR autofluorescence. The intensity ratio compared to background (set as 1) for gross images was 2.03 ±â€…0.51 (P < .0001) compared to adjacent adipose of 1.24 ±â€…0.18. Autofluorescence from adrenal tumors was also detected at variable levels of intensity. Cortisol-producing tumors had the highest fluorescence ratio of 3.01 ±â€…0.41. Confocal imaging localized autofluorescence to the cytosol, with the highest intensity in the zona reticularis followed by the zona fasciculata. Conclusion: Normal and abnormal adrenal tissues possess natural NIR autofluorescence. Highest autofluorescence levels were associated with cortisol-producing tumors. Confocal imaging demonstrated the highest intensity in the zona reticularis. NIR cameras may have the potential to improve identification of adrenal tissue during surgery.

Smaller parathyroids have higher near-infrared autofluorescence intensity in hyperparathyroidism.

BACKGROUND: Intraoperative parathyroid gland identification can be challenging. Parathyroid glands have an intrinsic autofluorescence when excited by wavelengths in the near-infrared region. Studies using near-infrared cameras to detect parathyroid gland near-infrared autofluorescence have suggested improved identification. The pathologic parathyroid glands in primary hyperparathyroidism have variable near-infrared autofluorescence intensity, but how this correlates with different characteristics of hyperparathyroidism is unknown. Our objective was to correlate the fluorescent intensity of excited glands with clinical variables to enhance a surgeon's ability to identify parathyroid glands. METHODS: The data on patients undergoing surgery for primary hyperparathyroidism were collected. The images were collected intraoperatively with a handheld near-infrared device and analyzed. The data consisted of the ratio of mean parathyroid gland near-infrared autofluorescence over background (white gauze) near-infrared autofluorescence. The variables assessed for correlation with autofluorescence intensity were gland volume and weight, preoperative serum calcium and parathyroid hormone, age, body mass index, and sex. The images were quantified by Image J software (National Institutes of Health, Bethesda, MD). The lasso regression was analyzed by R version 4.1.3 to calculate adjusted P values (R Foundation for Statistical Computing, Vienna, Austria). RESULTS: From 2017 to 2021, 131 patients with primary hyperparathyroidism underwent parathyroidectomies of 151 parathyroid glands. The mean near-infrared autofluorescence intensity of parathyroid glands had a negative correlation with weight with lighter glands fluorescing more (P = .019) and a positive correlation with age with glands from older patients fluorescing more (P = .013). There were no significant correlations with preoperative serum calcium and parathyroid hormone, body mass index, and sex (P > .05). CONCLUSION: In patients with primary hyperparathyroidism, we found that autofluorescence intensity correlated with parathyroid gland weight and patient age. This suggested that near-infrared camera use may be particularly helpful in identifying smaller adenomas and in older patients.

Near-infrared Autofluorescence Features of Parathyroid Carcinoma.

Introduction: Parathyroid carcinoma is very rare, and intraoperative definitive diagnosis can be elusive with currently available diagnostics. Near-infrared (NIR) autofluorescence is an emerging tool that identifies parathyroid glands in real time. It is not known whether NIR autofluorescence can detect parathyroid carcinoma intraoperatively. Methods: Patients with preoperative suspicion for parathyroid carcinoma were identified from ongoing studies examining parathyroid autofluorescence with a NIR camera and probe. Specimens from these patients were examined intraoperatively to determine their autofluorescence patterns. Results: Three patients with suspected parathyroid carcinoma were identified preoperatively. Intraoperative NIR autofluorescence imaging showed a relative lack of autofluorescence for all cases, in contrast to parathyroid adenomas and normal parathyroid glands, which typically exhibit significant autofluorescence. Final pathology confirmed parathyroid carcinoma in all cases. Conclusion: Parathyroid carcinoma can be difficult to confirm prior to final pathology review. Our 3 cases suggest that absence of NIR autofluorescence may suggest the likelihood of parathyroid carcinoma, but more studies are needed to investigate this experience.

Risk of malignancy in cytologically indeterminate thyroid nodules harboring thyroid stimulating hormone receptor mutations.

Objectives: To evaluate the frequency and risk of malignancy of TSHRpI568T mutations discovered in indeterminate thyroid nodules (ITN) within the Veracyte CLIA laboratory undergoing Afirma® Genomic Sequencing Classifier (GSC) testing, and to evaluate a broader cohort of TSHR variants and their categorization as Afirma GSC benign (GSC-B) or suspicious (GSC-S). Finally, we seek to assess the risk of malignancy (ROM) of this group of TSHR mutated ITN in the GSC-S category. Methods: ITN submitted to Veracyte for Afirma GSC testing between October 2017 and February 2022 were analyzed for TSHR variants and rates of GSC-B and GSC-S were calculated based upon BIII or IV cytology, by TSHR variant codon amino acid (AA) substitution, age, and gender. For GSC-S samples, surgical pathology reports were requested, and the rate of malignancy was calculated. Results: Five percent of the ITN samples harbored an isolated TSHR variant and 5% of those were classified as GSC-S. Among TSHRpI568T samples, 96% were GSC-B and of the GSC-S samples, 21% were malignant. Among an unselected group of TSHR, absent TSHRpI568T mutations, 16.3% of GSC-S samples were malignant, all but one with codon mutations in the transmembrane subdomains of the TSHR. This prompted a dedicated evaluation of transmembrane codons which revealed a malignancy rate of 10.7% among GSC-S nodules. In total, 13/85 (15.3%) TSHR mutated ITN with Afirma GSC-S results were found to be malignant. Conclusions: TSHR variants are rare in ITN, and most are categorized as benign under Afirma GSC testing which carries a < 4% risk of malignancy. For GSC-S ITN with TSHR mutations, the risk of malignancy is ≥= 15%, which is clinically meaningful and may alter treatment or monitoring recommendations for patients.

Comparing intraoperative parathyroid identification based on surgeon experience versus near infrared autofluorescence detection - A surgeon-blinded multi-centric study.

BACKGROUND: Near infrared autofluorescence (NIRAF) detection has previously demonstrated significant potential for real-time parathyroid gland identification. However, the performance of a NIRAF detection device - PTeye® - remains to be evaluated relative to a surgeon's own ability to identify parathyroid glands. METHODS: Patients eligible for thyroidectomy and/or parathyroidectomy were enrolled under 6 endocrine surgeons at 3 high-volume institutions. Participating surgeons were categorized based on years of experience. All surgeons were blinded to output of PTeye® when identifying tissues. The surgeon's performance for parathyroid discrimination was then compared with PTeye®. Histology served as gold standard for excised specimens, while expert surgeon's opinion was used to validate in-situ tissues. RESULTS: PTeye® achieved 92.7% accuracy across 167 patients recruited. Junior surgeons (<5 years of experience) were found to have lower confidence in parathyroid identification and higher tissue misclassification rate per specimen when compared to PTeye® and senior surgeons (>10 years of experience). CONCLUSIONS: NIRAF detection with PTeye® can be a valuable intraoperative adjunct technology to aid in parathyroid identification for surgeons.

Cumulative GRAS Score as a Predictor of Survival After Resection for Adrenocortical Carcinoma: Analysis From the U.S. Adrenocortical Carcinoma Database.

BACKGROUND: Adrenocortical carcinoma (ACC) is a rare but aggressive malignancy, and many prognostic factors that influence survival remain undefined. Individually, the GRAS (Grade, Resection status, Age, and Symptoms of hormone hypersecretion) parameters have demonstrated their prognostic value in ACC. This study aimed to assess the value of a cumulative GRAS score as a prognostic indicator after ACC resection. METHODS: A retrospective cohort study of adult patients who underwent surgical resection for ACC between 1993 and 2014 was performed using the United States Adrenocortical Carcinoma Group (US-ACCG) database. A sum GRAS score was calculated for each patient by adding one point each when the criteria were met for tumor grade (Weiss criteria ≥ 3 or Ki67 ≥ 20%), resection status (micro- or macroscopically positive margin), age (≥ 50 years), and preoperative symptoms of hormone hypersecretion (present). Overall survival (OS) and disease-free survival (DFS) by cumulative GRAS score were analyzed by the Kaplan-Meier method and log-rank test. RESULTS: Of the 265 patients in the US-ACCG database, 243 (92%) had sufficient data available to calculate a cumulative GRAS score and were included in this analysis. The 265 patients comprised 23 patients (10%) with a GRAS of 0, 52 patients (21%) with a GRAS of 1, 92 patients (38%) with a GRAS of 2, 63 patients (26%) with a GRAS of 3, and 13 patients (5%) with a GRAS of 4. An increasing GRAS score was associated with shortened OS (p < 0.01) and DFS (p < 0.01) after index resection. CONCLUSION: In this retrospective analysis, the cumulative GRAS score effectively stratified OS and DFS after index resection for ACC. Further prospective analysis is required to validate the cumulative GRAS score as a prognostic indicator for clinical use.

Prevalence of cancer and the benign call rate of afirma gene classifier in 18 F-Fluorodeoxyglucose positron emission tomography positive cytologically indeterminate thyroid nodules.

BACKGROUND: 18 F-Fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) positive (PET+) cytologically indeterminate thyroid nodules (ITNs) have variable cancer risk in the literature. The benign call rate (BCR) of Afirma Gene Classifier (Gene Expression Classifier, GEC, or Genome Sequence Classifier, GSC) in (PET +) ITNs is unknown. METHODS: This is a retrospective study at our institution of all patients with (PET+) ITNs (Bethesda III/IV) from 1 January 2010 to 21 May 2019 who underwent Afirma testing and/or surgery or repeat FNA with benign cytology. RESULTS: Forty-five (PET+) ITNs were identified: 31 Afirma-tested (GEC = 20, GSC = 11) and 14 either underwent surgery (n = 13) or repeat FNA (Benign cytology) (n = 1) without Afirma. The prevalence of cancer and noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) including only resected nodules and ITN with repeat benign FNA (n = 33) was 36.4% (12/33). Excluding all Afirma "suspicious" non-resected ITNs and assuming all Afirma "benign" ITNs were truly benign, that prevalence was 28.6% (12/42). The BCR with GSC was 64% compared to 25% with GEC (p = 0.056). Combining GSC/GEC-tested ITNs, the BCR was higher in ITNs demonstrating low/very low-risk sonographic pattern by the American Thyroid Association (ATA) classification and ITNs scoring <4 by the American College of Radiology Thyroid Imaging, Reporting and Data System (ACR-TI-RADS) than ITNs with higher sonographic pattern/score (p = 0.025). CONCLUSIONS: The prevalence of cancer/NIFTP in (PET+) ITNs was 28.6-36.4% depending on the method of calculation. The BCR of Afirma GSC was 64%. Combining Afirma GEC/GSC-tested ITNs, BCR was higher in ITNs with a lower risk sonographic pattern.

Prognosis of Macrophage Density in the Absence of Neutrophils in Differentiated Thyroid Cancer.

BACKGROUND: Despite the advances in treatment of differentiated thyroid cancer (DTC), predicting prognosis remains a challenge. Immune cells in the tumor microenvironment may provide an insight to predicting recurrence. Therefore, the objective of this study was to investigate the association of tumor-associated macrophages (TAMs) and tumor-associated neutrophils (TANs) with recurrence in DTC and to identify serum cytokines that correlate with the presence of these immune cells in the tumor. MATERIALS AND METHODS: Forty-two DTC tissues from our institutional neoplasia repository were stained for immunohistochemistry markers for TAMs and TANs. In addition, cytokine levels were analyzed from these patients from preoperative blood samples. TAM and TAN staining were compared with clinical data and serum cytokine levels. RESULTS: Neither TAM nor TAN scores alone correlated with tumor size, the presence of lymph node metastases, multifocal tumors, lymphovascular or capsular invasion, or the presence of BRAFV600E mutation (all P > 0.05). There was no association with recurrence-free survival (RFS) in TAN density (mean RFS, 169.1 versus 148.1 mo, P = 0.23) or TAM density alone (mean RFS, 121.3 versus 205.2 mo, P = 0.54). However, when scoring from both markers were combined, patients with high TAM density and TAN negative scores had significantly lower RFS (mean RFS, 50.7 versus 187.3 mo, P = 0.04) compared with the remaining cohort. Patients with high TAM/negative TAN tumors had significantly lower serum levels of interleukin 12p70, interleukin 8, tumor necrosis factor alpha, and tumor necrosis factor beta. CONCLUSIONS: In DTCs, high density of TAMs in the absence of TANs is associated with worse outcome. Assessment of multiple immune cell types and serum cytokines may predict outcomes in DTC.

Features of Cytologically Indeterminate Molecularly Benign Nodules Treated With Surgery.

BACKGROUND: Most cytologically indeterminate thyroid nodules (ITNs) with benign molecular testing are not surgically removed. The data on clinical outcomes of these nodules are limited. METHODS: We retrospectively analyzed all ITNs where molecular testing was performed either with the Afirma gene expression classifier or Afirma gene sequencing classifier between 2011 and 2018 at a single institution. RESULTS: Thirty-eight out of 289 molecularly benign ITNs were ultimately resected. The most common reason for surgery was compressive symptoms (39%). In multivariable modeling, patients aged <40 years, nodules ≥3 cm, presence of an Afirma suspicious nodule other than the index nodule, and compressive symptoms were associated with higher surgery rates with hazard ratios for surgery of 3.5 (P < 0.001), 3.2 (P < 0.001), 16.8 (P < 0.001), and 7.31 (P < 0.001), respectively. Of resected nodules, 5 were malignant. False-negative rate (FNR) was 1.7%, presuming all unresected nodules were truly benign and 13.2% restricting analysis to resected cases. The FNR was significantly higher in nodules with a high-risk sonographic appearance for cancer (American Thyroid Association high-risk classification and American College of Radiology Thyroid Imaging Reporting and Data Systems score of 5) compared with nodules with all other sonographic categories (11.8% vs 1.1%; P = 0.03 and 11.1% vs 1.1%; P = 0.02, respectively). CONCLUSIONS: Younger age, larger nodule size, presence of an Afirma suspicious nodule other than the index nodule, and compressive symptoms were associated with a higher rate of surgery. The FNR of benign Afirma was significantly higher in nodules with high-risk sonographic features.

Update on Pheochromocytoma and Paraganglioma from the SSO Endocrine/Head and Neck Disease-Site Work Group. Part 1 of 2: Advances in Pathogenesis and Diagnosis of Pheochromocytoma and Paraganglioma.

This first part of a two-part review of pheochromocytoma and paragangliomas (PPGLs) addresses clinical presentation, diagnosis, management, treatment, and outcomes. In this first part, the epidemiology, prevalence, genetic etiology, clinical presentation, and biochemical and radiologic workup are discussed. In particular, recent advances in the genetics underlying PPGLs and the recommendation for genetic testing of all patients with PPGL are emphasized. Finally, the newer imaging methods for evaluating of PPGLs are discussed and highlighted.

Update on Pheochromocytoma and Paraganglioma from the SSO Endocrine and Head and Neck Disease Site Working Group, Part 2 of 2: Perioperative Management and Outcomes of Pheochromocytoma and Paraganglioma.

This is the second part of a two-part review on pheochromocytoma and paragangliomas (PPGLs). In this part, perioperative management, including preoperative preparation, intraoperative, and postoperative interventions are reviewed. Current data on outcomes following resection are presented, including outcomes after cortical-sparing adrenalectomy for bilateral adrenal disease. In addition, pathological features of malignancy, surveillance considerations, and the management of advanced disease are also discussed.

Co-occurrence of multiple endocrine neoplasia type 4 and spinal neurofibromatosis: a case report.

Multiple Endocrine Neoplasia (MEN) type 4 is a rare genetic condition that results from variants of the CDKN1B gene and predisposes individuals to develop endocrine tumors. Spinal neurofibromatosis (SNF) is an uncommon subtype of neurofibromatosis type 1 (NF1) characterized by bilateral neurofibromas of all spinal roots. Here we report a case of the co-occurrence of these syndromes, which has not yet been described in the literature. A male in his 60s presented with Gleason 5 + 4 localized prostate adenocarcinoma treated with radical prostatectomy. Two years later, he developed liver and bone metastasis consistent with trans-differentiation into small cell carcinoma. He developed hypercalcemia due to primary hyperparathyroidism from a parathyroid adenoma treated surgically. His family history was significant for a first-degree relative with a clinical diagnosis of NF1 and several second-degree relatives with multiple café-au-lait macules. Spine MRI showed multiple bilateral neurofibromas. Germline genetic testing showed a pathogenic variant in the CDKN1B gene, a variant in the NF1 gene, and a normal MEN1 gene. In this rare case of MEN4 and SNF, the patient was asymptomatic for much of his life. In addition to parathyroid adenoma and spinal neurofibromas, he had prostate adenocarcinoma with trans-differentiation into metastatic small cell cancer. Whether this diagnosis was coincidental or related to an emerging phenotype remains to be elucidated.