Lung Nodules Research Articles

MA08.12 Semi-Sold Lung Nodule Growth Rates, Need for Treatment, and Cancer-Specific Verses All-Cause Mortality in a Large North American Population

MA08.12 Semi-Sold Lung Nodule Growth Rates, Need for Treatment, and Cancer-Specific Verses All-Cause Mortality in a Large North American Population

OA17.04 Implementation of a Natural Language Processing (NLP) Model to Detect Incidental Lung Nodules in a Nationwide Health Care Network

OA17.04 Implementation of a Natural Language Processing (NLP) Model to Detect Incidental Lung Nodules in a Nationwide Health Care Network

Editorial Comment: Computer-Aided Detection of Lung Nodules on Low-Dose Pediatric Chest CT-A Cautionary Tale.

Editorial Comment: Computer-Aided Detection of Lung Nodules on Low-Dose Pediatric Chest CT-A Cautionary Tale.

Second generation stationary chest tomosynthesis with faster scan time and wider angular span.

Digital tomosynthesis has shown potential for increasing specificity and sensitivity compared to radiography for low-dose chest imaging. Prior investigation of the s-DCT system indicated potential, but additional iteration with improved scan speed, power, and angular span was necessary for translation. The study aims to demonstrate and characterize a second-generation stationary digital chest tomosynthesis (s-DCT) scanner with increased x-ray energy, tube current, and larger angular span. The second-generation s-DCT system employed a meter-long linear carbon nanotube (CNT) source array integrated with a digital detector and patient imaging table. Tube output, focal spot size, modulation transfer function (MTF), artifact spread function (ASF), and imaging performance were evaluated. A lung phantom with simulated nodules was imaged for clinical task-based demonstration. The scanner achieved a 6s scan time, significantly improved from the prior generation's 16s. The x-ray tube exhibited good current stability, with 20.4±0.6mA tube current and focal spot size aligned with specifications (IEC 0.8). The MTF confirmed enhanced spatial resolution of 2.4lp/mm, comparable to commercial chest tomosynthesis systems. The ASF indicated improved depth resolution (5.2mm, previously 9.5mm). Phantom imaging showcased visualization of both high and low-attenuation lung nodules. The second-generation s-DCT system exhibited improved performance in terms of tube power, scan time, and image quality. Enhanced in-plane and depth resolution, along with faster imaging, suggest potential clinical benefits for improved diagnoses. Further clinical validation is warranted to ascertain the system's clinical utility.

P4.04C.05 AI-Assisted CXR Analysis in the Detection of Lung Nodules and Incidental Lung Cancers

P4.04C.05 AI-Assisted CXR Analysis in the Detection of Lung Nodules and Incidental Lung Cancers

CRTC1::TRIM11-fusion tumor with rare sinonasal presentation and locally aggressive disease course

Abstract Introduction/Objective Cutaneous melanocytic tumor with CRTC1::TRIM11 fusion (CMTCT) is a rare dermatological neoplasm that has not yet been formally recognized by the World Health Organization. At present, our knowledge of this disease is limited to single reports and a series 41 cases with limited follow-up information. It is typically described as a skin lesion expressing melanocytic makers, often leading to its misdiagnosis as melanoma or clear cell sarcoma. CMTCT is regarded as an indolent tumor with infrequent recurrence after complete surgical excision. However, we present a case with uncommon sinonasal presentation and metastasis after multiple resections. Methods/Case Report A 23-year-old woman presented with a right nasal vestibule mass, requiring partial rhinectomy in a foreign country, where she subsequently received chemoradiation. Her tumor at the time was diagnosed as a mucosal melanoma. Eleven years following initial presentation, she demonstrated a recurrent right nasal tumor, as well as neck mass, cervical lymphadenopathy, and lung nodules. The patient then underwent a nasal endoscopic resection and modified neck dissection, which demonstrated a high-grade neoplasm with intersecting fascicles of medium-to-large monomorphic cells; whole exome and whole transcriptome sequencing performed on the resected neck mass identified a pathogenic TERT c.-146C>T alteration and CRTC1 exon 1::TRIM11 exon 2 fusion. The patient is currently alive and undergoing post-surgical chemoradiation. Results (if a Case Study enter NA) NA Conclusion This case expands our understanding of CMTCT and emphasizes its potentially aggressive behavior. The sinonasal presentation contrasts the tumor’s typical appearance on the skin and could mimic mucosal melanoma. Of note, our patient developed recurrent disease and distant metastases, thereby emphasizing the possible role of systemic therapy and suggesting that simple surgical excision may not be curative in all cases. Our case illustrates that CMTCT is an uncommon and potentially misidentified neoplasm, but that its proper diagnosis is essential for treatment selection and follow up.

Is there value in the routine inclusion of chest computed tomography for patients with gastrointestinal stromal tumor?

PurposeNational Comprehensive Cancer Network guidelines suggest chest CT when gastrointestinal stromal tumors are larger than 2 cm. We evaluate the value of screening the chest region during initial and follow-up CT. MethodSingle institution retrospective analysis of GIST cancer registry for patients diagnosed between May 2010 and November 2019 with tumor > 2 cm. We collected the patient demographics and clinical data; reviewed all CT scans of the chest region and recorded the lung nodules. Patients were grouped into lung nodule group and non-nodule group. Categorical variables were compared with the Chi square test and continuous variables with the Mann-Whitney U test. The survival probability was determined from Kaplan-Meier survival analysis and log-rank test for comparing differences. ResultsThe final cohort included 382 patients (median age 61 years-old [interquartile range: 52–71]) and grouped into non-nodule group (n = 284) and lung nodule group (n = 98). The frequency of the CT scan was more in lung nodule group (8 [5–12]) than in non-nodule group (4 [2–9], p < 0.001). The lung nodule group had more CT including the chest region (6 [3–10] vs 3 [1–7], p < 0.001). In progressive lung nodules (8/98 [8 %]), only one patient had confirmed lung metastasis from GIST (1/382 [3 %]). There was no difference in overall survival between nodule groups (p = 0.12). ConclusionsGIST patients with tumors larger than 2 cm have extremely low risk for lung metastasis. Routine inclusion of chest CT scan in staging and follow up is unnecessary.

Prediction of Malignancy and Pathological Types of Solid Lung Nodules on CT Scans Using a Volumetric SWIN Transformer.

Lung adenocarcinoma and squamous cell carcinoma are the two most common pathological lung cancer subtypes. Accurate diagnosis and pathological subtyping are crucial for lung cancer treatment. Solitary solid lung nodules with lobulation and spiculation signs are often indicative of lung cancer; however, in some cases, postoperative pathology finds benign solid lung nodules. It is critical to accurately identify solid lung nodules with lobulation and spiculation signs before surgery; however, traditional diagnostic imaging is prone to misdiagnosis, and studies on artificial intelligence-assisted diagnosis are few. Therefore, we introduce a volumetric SWIN Transformer-based method. It is a multi-scale, multi-task, and highly interpretable model for distinguishing between benign solid lung nodules with lobulation and spiculation signs, lung adenocarcinomas, and lung squamous cell carcinoma. The technique's effectiveness was improved by using 3-dimensional (3D) computed tomography (CT) images instead of conventional 2-dimensional (2D) images to combine as much information as possible. The model was trained using 352 of the 441 CT image sequences and validated using the rest. The experimental results showed that our model could accurately differentiate between benign lung nodules with lobulation and spiculation signs, lung adenocarcinoma, and squamous cell carcinoma. On the test set, our model achieves an accuracy of 0.9888, precision of 0.9892, recall of 0.9888, and an F1-score of 0.9888, along with a class activation mapping (CAM) visualization of the 3D model. Consequently, our method could be used as a preoperative tool to assist in diagnosing solitary solid lung nodules with lobulation and spiculation signs accurately and provide a theoretical basis for developing appropriate clinical diagnosis and treatment plans for the patients.

Multi-View Soft Attention-Based Model for the Classification of Lung Cancer-Associated Disabilities.

Background: The detection of lung nodules at their early stages may significantly enhance the survival rate and prevent progression to severe disability caused by advanced lung cancer, but it often requires manual and laborious efforts for radiologists, with limited success. To alleviate it, we propose a Multi-View Soft Attention-Based Convolutional Neural Network (MVSA-CNN) model for multi-class lung nodular classifications in three stages (benign, primary, and metastatic). Methods: Initially, patches from each nodule are extracted into three different views, each fed to our model to classify the malignancy. A dataset, namely the Lung Image Database Consortium Image Database Resource Initiative (LIDC-IDRI), is used for training and testing. The 10-fold cross-validation approach was used on the database to assess the model's performance. Results: The experimental results suggest that MVSA-CNN outperforms other competing methods with 97.10% accuracy, 96.31% sensitivity, and 97.45% specificity. Conclusions: We hope the highly predictive performance of MVSA-CNN in lung nodule classification from lung Computed Tomography (CT) scans may facilitate more reliable diagnosis, thereby improving outcomes for individuals with disabilities who may experience disparities in healthcare access and quality.

Assessment of solitary pulmonary nodules using dual-layer spectral detector computed tomography.

We aim to quantitatively investigate the difference between benign and malignant solid pulmonary nodules that appeared on dual-energy spectral computed tomography, and assess the diagnostic accuracy of several parameters derived from computed tomography in differentiating malignant from benign pulmonary nodules. Between September 2021 and December 2022, spectral images of 71 patients (male:female = 44:27, mean age = 71.0 years) confirmed by pathology were retrospectively analyzed in the venous phase. Patients were classified into the malignant group and the benign group. The iodine concentration values of the nodules, normalized iodine concentration of the nodules to the neighboring vessels, virtual monochromatic images of 40 and 80 keV, and slope of the spectral curve were calculated and compared between the benign and malignant groups. Receiver operating characteristic curves and the area under the curve were performed to assess the diagnostic performance of the above parameters. Both virtual monochromatic images and iodine concentration maps prove to be highly useful in differentiating benign and malignant pulmonary nodules. The malignant pulmonary nodules have higher iodine density and slope of the spectral curve than the benign lesions. The combined model of iodine density and curve slope with an optimal cutoff of 0.39 (area under the curve = 0.82) yielded a sensitivity of 95% and a specificity of 63%. Contrast-enhanced dual-energy spectral computed tomography allows promising capability of distinguishing malignant from benign lesions, potential for avoiding unnecessary invasive procedure or surgery.

An anthropomorphic diagnosis system of pulmonary nodules using weak annotation-based deep learning

The accurate categorization of lung nodules in CT scans is an essential aspect in the prompt detection and diagnosis of lung cancer. The categorization of grade and texture for nodules is particularly significant since it can aid radiologists and clinicians to make better-informed decisions concerning the management of nodules. However, currently existing nodule classification techniques have a singular function of nodule classification and rely on an extensive amount of high-quality annotation data, which does not meet the requirements of clinical practice. To address this issue, we develop an anthropomorphic diagnosis system of pulmonary nodules (PN) based on deep learning (DL) that is trained by weak annotation data and has comparable performance to full-annotation based diagnosis systems. The proposed system uses DL models to classify PNs (benign vs. malignant) with weak annotations, which eliminates the need for time-consuming and labor-intensive manual annotations of PNs. Moreover, the PN classification networks, augmented with handcrafted shape features acquired through the ball-scale transform technique, demonstrate capability to differentiate PNs with diverse labels, including pure ground-glass opacities, part-solid nodules, and solid nodules. Through 5-fold cross-validation on two datasets, the system achieved the following results: (1) an Area Under Curve (AUC) of 0.938 for PN localization and an AUC of 0.912 for PN differential diagnosis on the LIDC-IDRI dataset of 814 testing cases, (2) an AUC of 0.943 for PN localization and an AUC of 0.815 for PN differential diagnosis on the in-house dataset of 822 testing cases. In summary, our system demonstrates efficient localization and differential diagnosis of PNs in a resource limited environment, and thus could be translated into clinical use in the future.

Performance of Lung-Nodule Computer-Aided Detection Systems on Standard-Dose and Low-Dose Pediatric CT Scans: An Intraindividual Comparison.

Background: When applying lung-nodule computer-aided detection (CAD) systems for pediatric CT, performance may be degraded on low-dose scans due to increased image noise. Objective: To conduct an intraindividual comparison of the performance for lung nodule detection of two CAD systems trained using adult data between low-dose and standard-dose pediatric chest CT scans. Methods: This retrospective study included 73 patients (32 female, 41 male; mean age, 14.7 years; age range, 4-20 years) who underwent both clinical standard-dose and investigational low-dose chest CT examinations within the same encounter from November 30, 2018 to August 31, 2020 as part of an earlier prospective study. Fellowship-trained pediatric radiologists annotated lung nodules to serve as the reference standard. Both CT scans were processed using two publicly available lung-nodule CAD systems previously trained using adult data: FlyerScan and Medical Open Network for Artificial Intelligence (MONAI). The systems' sensitivities for nodules measuring 3-30 mm (n=247) were calculated when operating at a fixed frequency of two false-positives per scan. Results: FlyerScan exhibited detection sensitivities of 76.9% (190/247; 95% CI: 73.3-80.8%) on standard-dose scans and 66.8% (165/247; 95% CI: 62.6-71.5) on low-dose scans. MONAI exhibited detection sensitivities of 67.6% (167/247, 95% CI: 61.5-72.1) on standard-dose scans and 62.3% (154/247, 95% CI: 56.1-66.5%) on low-dose scans. The number of detected nodules for standard-dose versus low-dose scans for 3-mm nodules was 33 versus 24 (FlyerScan) and 16 versus 13 (MONAI), 4-mm nodules was 46 versus 42 (FlyerScan) and 39 versus 30 (MONAI), 5-mm nodules was 38 versus 33 (FlyerScan) and 32 versus 31 (MONAI), and 6-mm nodules was 27 versus 20 (FlyerScan) and 24 versus 24 (MONAI). For nodules measuring ≥7 mm, detection did not show a consistent pattern between standard-dose and low-dose scans for either system. Conclusions: Two lung-nodule CAD systems demonstrated decreased sensitivity on low-dose versus standard-dose pediatric CT scans performed in the same patients. The reduced detection at low dose was overall more pronounced for nodules measuring less than 5 mm. Clinical Impact: Caution is needed when using low-dose CT protocols in combination with CAD systems to help detect small lung nodules in pediatric patients.

Combination of Renal Cell Carcinoma and Organizing Pneumonia

Solitary pulmonary nodule is a difficult case for differential diagnosis. The list of pathological processes manifested by pulmonary nodule is quite large, including organizing pneumonia, which has non-specific CT picture. A correct diagnosis requires comparing the radiation examination data with anamnesis, the results of invasive and morphological studies. The presented clinical case shows the difficulties of diagnosing a combination of pulmonary nodule and extensive renal mass.

Deep Learning Enhanced CNN with Bio-Inspired Techniques and BCE For Effective Lung Nodules Detection &amp; Classification For Accurate Diagnosis

Objectives: To propose a new hybrid deep learning model to boost lung nodule detection and classification in combination with a bioinspired method for efficient hyper-parameter optimization to maximize true positive and nodule discrimination rates. Methods: In order to extract the intrinsic and complex features from different lung nodules, deep learning-based enhanced CNN (ECNN) is used. Segmentation masks are generated using Mask-RCNN to isolate and capture the ROIs, which serve as input to CNN. Prior to segmentation and extraction, data cleaning, transformation, and augmentation is done. Hyper-parameter optimization is done using a bio-inspired differential evolution method, which helps to identify the learning rate and number of layers to achieve optimal performance. We utilize BCE to quantify the performance of classification tasks. A large-scale CT-DICOM image dataset with 25,1135 images is used for this research work, collected from the cancer imaging archive, which has a clinically proven record of 355 instances with detailed image analysis, tumor location, and bounding boxes with a resolution of 512x512 pixels. 175794 images are used for training, and 75341 images are used for testing and validation. The performance of the new system is assessed using MATLAB, where results are compared with existing models such as SVM-WSS, GCPSO-PNN, and 3D-DLCNN models. Findings: The newly suggested ECNN with DE Bio-inspired model boosts the performance of lung nodule detection and classification with 94.7% accuracy, 93.8% sensitivity, 94.5% specificity, 93.4% F1 score, 92.4% dice coefficient, 0.1 Log Loss and AUC-ROC with 0.93 TPR and 0.07 FPR. Novelty: The novel method presents an advanced computational model using deep learning and bio-inspired algorithms for robust classification of lung nodules, which significantly improves the early diagnosis. This CAD model overcomes the limitations of the existing approaches SVM-WSS, GCPSO-PNN, and 3D-DLCNN in terms of segmentation, classification, error detection, and hyper-parameter tuning. Keywords: Lung Nodules, Deep Learning, Disease Classification, Image Processing, ECNN- DE Classifier, CT-DICOM Dataset

8014 Cushing’s Syndrome: Two Sides of The Spectrum

Abstract Disclosure: M. Aguilera: None. A. Vu: None. J. Shakil: None. R. Al-Ward: None. Introduction: Cushing’s syndrome (CS) is a rare condition with an annual incidence of 2-8 per million. Endogenous CS is mainly due to corticotroph adenoma of the pituitary followed by excessive glucocorticoid production from adrenal and ectopic sources. CS has significant morbidity and mortality hence the need for timely diagnosis. The varied presentations often pose great challenges in identifying the source of hypercortisolism. We present two unusual cases of CS with distinct clinical presentations and atypical laboratory profiles. Case 1: 25-year-old male with no medical history presented with 9 months of facial puffiness, weight gain, fluid retention, hypertension and blurred vision. Physical examination revealed round facies, bilateral supraclavicular fat pads and wide abdominal striae. Laboratory workup showed markedly elevated ACTH 537 pg/mL [7.2-63 pg/mL], serum cortisol 8.5 ug/dL [6.2-19.4 ug/dl], 24-hour urine free cortisol (UFC) 30 [5-62 ug/24H] and normal late-night salivary cortisol (LNSC). Repeat workup a month later showed serum cortisol of 56ug/dL, ACTH 874 pg/dL, 24-hour UFC of 11880ug/24H and elevated LNSC. Pituitary MRI showed a large heterogenous 3.1 cm partially cystic sellar mass with suprasellar extension. Due to significantly elevated ACTH and short duration of symptoms, we suspected an ectopic source. Due to initial negative testing, except for high ACTH level, a silent corticotroph adenoma was also considered. The patient underwent transsphenoidal resection resulting in significant decrease of cortisol and ACTH postoperatively. Pathology showed a corticotroph adenoma with Ki-67 index of &amp;lt;1%. Case 2: 47-year-old woman with medical history of obesity, polycystic ovary syndrome and a stable 1 cm lung nodule since 2020, presented with fluid retention, worsening acne and resistant hypertension over a 1-year period. She required hospitalization for hypertensive emergency and hypokalemia. Laboratory data showed morning serum cortisol 28 ug/dL, ACTH of 90.1 pg/mL, 24-hour UFC 346 ug/24H, elevated LNSC on two occasions and cortisol 24.3 ug/dl after a 1mg dexamethasone suppression. MRI did not show a pituitary mass. PET dotatate scan revealed a tracer avid 1 cm right upper lobe pulmonary nodule. She underwent a right upper lobe lobectomy, resulting in a significant decrease in cortisol and ACTH levels on postoperative day 1. Pathology confirmed a typical carcinoid tumor. Discussion: High ACTH levels and a short symptom duration often point to ectopic production, paraneoplastic syndromes or corticotroph carcinomas. Cushing's disease typically exhibits mildly elevated ACTH levels, but our cases deviate from this norm, complicating source identification. This atypical presentation highlights the complexity of Cushing's syndrome, challenging conventional diagnostic paradigms. Presentation: 6/1/2024

6918 A Unique Case of Oncocytic Thyroid Cancer with an NBN Gene Pathogenic Variant

Abstract Disclosure: A. Grover: None. S. Jhawar: None. S. Shekhar: None. S.A. Avadhanula: None. G. Al-Naqeeb: None. G. Thota: None. P. Veeraraghavan: None. C. Cochran: None. M.Y. Kao-Hsieh: None. A. Gharib: None. F.E. Escorcia: None. J. Del Rivero: None. J. Klubo-Gwiezdzinska: None. S. Gubbi: None. Introduction: Oncocytic thyroid carcinoma (OTC), previously known as “Hürthle cell” carcinoma, makes up less than 5% of all thyroid cancers. OTCs are often aggressive with a high risk of metastasis, and a poorer prognosis compared to other forms of differentiated thyroid carcinoma (DTC). Molecular drivers of OTC include pathogenic variants (PVs) in NRAS, DAXX, CDKN1A, the mitochondrial genome and chromosomal alterations. PVs in the NBN gene in OTC have not been previously reported. Case: A 53-year-old male was noted to have a thyroid nodule on a routine physical examination. Patient denied any hyper/hypothyroid or compressive symptoms, and family history was unremarkable. Cytopathologic analysis of the fine needle aspiration biopsy of the nodule was consistent with a thyroid follicular neoplasm (Bethesda IV). A total thyroidectomy with central compartment neck dissection was performed. Histopathologic examination demonstrated a 7 cm x 4 cm x 4 cm OTC with capsular and lymphovascular invasion, but without extra-thyroidal extension or lymph node metastasis (pT3aN0Mx). Subsequently, adjuvant radioiodine (RAI) I131 therapy with 165 mCi was administered and post-therapy scan revealed neck uptake. One-year post-therapy RAI diagnostic scan was negative. Three years following the initial thyroid surgery, elevated serum thyroglobulin (Tg) levels were noted. A computed tomogram of the chest revealed multiple bilateral lung nodules. Further imaging ruled out involvement of other distant sites. A diagnostic lower lung wedge resection demonstrated metastatic OTC. The tumor stained positive for CK7, PAX8, TG, TTF-1 and negative for CK20 on immunohistochemistry. Next-generation sequencing of the tumor tissue (Oncomine Comprehensive Assay v3) revealed a PV in the NBN gene (c.2166_2167delGCinsAT; p.Trp722Ter). A year later, the serum Tg levels continued to rise, and the lung nodules had increased in size. Due to disease progression, lenvatinib was initiated. A [F18]-fluorodeoxyglucose positron emission tomography performed one year later demonstrated persistent pulmonary tumor burden with new osseous metastasis in the right scapula, left acetabulum, and the sternum. Zoledronic acid was initiated for the treatment of the skeletal metastases, and palliative external beam radiation (2000 cGy in 5 fractions) was administered to the sternal lesion to alleviate the bone pain. Conclusion: The NBN gene encodes for the protein nibrin, a member of the MRE11/RAD50 complex that is involved in DNA repair. PVs in NBN are commonly identified in non-thyroidal malignancies such as breast and lung carcinomas. While NBN PVs are rarely reported in DTCs, as per our knowledge, this is the first described case of OTC with a PV in NBN as the molecular driver, manifesting with an aggressive disease course. Identification of this novel PV therefore adds to the current knowledge of the molecular landscape of OTC. Presentation: 6/3/2024

7911 High Dose Serial Radioactive Iodine Therapies Facilitated byAutologous Stem Cell Cryopreservation in a Patient with Exceptionally Avid Metastatic FTC

Abstract Disclosure: S. Paknikar: None. D. Toro Tobon: None. J. Durski: None. H. Alkhateeb: None. M.M. Ryder: None. Introduction: Radioactive iodine (RAI) therapy-induced myelosuppression is a dose-limiting toxicity for RAI avid metastatic differentiated thyroid cancers. We describe a patient with exceptionally RAI avid metastatic follicular thyroid cancer (FTC) who underwent autologous stem cell cryopreservation (ASCC) to enable high dose I-131 treatments. Case: A 60-year-old woman with T1bN0M0 FTC underwent two-stage thyroidectomy and three doses of I-131 between 2002-2007 (434 mCi cumulative activity) due to incomplete biochemical response. She presented to our institution in 2015 with rising thyroglobulin (Tg) levels and lung nodules that were intensely RAI avid. She enrolled in a clinical trial of selumetinib versus placebo (for 1 month) followed by 150 mci I-131. She had a profound response with an 80% reduction in Tg and 50% tumor shrinkage. The following year her Tg rose to 8381 ng/mL and she developed biopsy proven, well differentiated metastatic FTC in the hip and liver. Lenvatinib treatment resulted in partial tumor and Tg response but was halted due to grade 3/4 toxicities. Tumor genomic interrogation revealed NRAS, PIK3CA, and TSH-R activating mutations, providing a causal explanation of her intensely RAI avid and responsive disease. Repeat I-131 therapy was facilitated by GM-CSF stimulated ASCC (8.57 x10(6) CD34+ cells/kg for two cycles) as a tool to help mitigate future potential RAI-induced myelosuppression. The patient received 295 mci I-131 followed by a 98% decrease in Tg and 20-25% shrinkage of liver metastases. Transient pancytopenia ensued but did not require autologous stem cell transplantation (ASCT). Due to insurance issues, the patient was lost to follow-up for two years. She returned with cachexia from severe, untreated thyrotoxicosis due to widespread functional, thyroxine producing metastatic disease. Anti-thyroid drug therapy (ATD) restored euthyroid status with significant clinical improvement. A non-stimulated I-123 whole body scan showed diffuse RAI avid disease with 88% whole body radioiodine retention at 48h. She received 125 mci I-131 with initial tumor response but with progression of bone marrow, calvaria, and retinal metastases. Six months later, a final dose of 253 mCi I-131 (cumulative activity 1,370 mCi) resulted in mixed tumor responses. Unfortunately, resection of a RAI refractory calvaria lesion postoperatively resulted in serious complications. ASCT and salvage treatments could not be pursued due to her impaired functional status. The patient pursued hospice care and passed away 20 years after her diagnosis. Conclusion: We characterize a patient with NRAS, PIK3CA and TSH-R mutant metastatic, thyroxine-producing FTC whose recurrences over 20 years retained intense RAI avidity and response to I-131 therapy. In cases with potential benefit from multiple high dose RAI therapies, ASCT may be a tool to mitigate I-131-induced myelosuppression. Presentation: 6/1/2024

8282 A Diagnostically Challenging Case of Ectopic ACTH Secreting Pancreatic Neuroendocrine Tumor Presenting with Cushing’s Syndrome

Abstract Disclosure: O.A. Aluko: None. S. Patel: None. S.V. Silparshetty: None. T. Gallagher: None. Introduction: Ectopic ACTH mediated Cushing’s syndrome is an uncommon but treatable condition that poses time constrained diagnostic and therapeutic challenge due to severe morbidity as illustrated by our case below. Clinical case:A 65-year-old male was admitted with profound generalized weakness. He became restricted to wheelchair from being able to hike a trail at Yosemite national park 8 weeks prior. Recent history included hospitalization with uncontrolled diabetes and hypertension, new vertebral compression fractures, AKI, hypokalemia, proximal myopathy, anasarca, upper GI bleed and acute upper extremity DVT. Initial testing there revealed hypercortisolemia, elevated ACTH and a normal pituitary MRI. Further workup at our center revealed elevated 24hr urinary cortisol 2598 (n = 5 - 64 μg/24hr), random cortisol 55 (n= 4.2 -22.4 μg/dL) with elevated ACTH 194 (n= 7.2 - 63.3 pg/mL) consistent with ACTH dependent hypercortisolism. IPSS deferred due to AKI, underlying comorbidities and severe cervical stenosis with myelopathy. ACTH and cortisol remained elevated with an 8mg dexamethasone suppression test suggesting ectopic source ACTH. CT with contrast of chest, abdomen and pelvis showed 5mm right lower lobe lung nodule and bilateral adrenal nodularity. Bronchoscopic FNAC was negative for NET.Ketoconazole 400 mg twice daily was started pending localization of culprit lesion with improvement in 24 hr urinary cortisol to 554μg/24 hr however this was stopped within 4 weeks due to acute transaminasemia. Repeat imaging with Gallium-68 dotatate PET CT showed a 1.8 X 2.4 X 1.7 cm pancreatic mass. He underwent distal pancreatectomy with splenectomy. Pathology confirmed a 2.2cm well differentiated neuroendocrine tumor limited to the pancreas with immunohistochemistry strongly for ACTH and weakly for Gastrin. Postoperatively, patient was given hydrocortisone replacement. ACTH was 14.3 pg/mL and cortisol 6.2μg/dL a few weeks later. His diabetes, hypertension, hypokalemia, transaminasemia and proximal myopathy improved. Discussion:Ectopic ACTH mediated Cushing’s syndrome is responsible for about 5 - 20% of all Cushing’s syndrome cases. Pancreatic neuroendocrine tumor secreting Ectopic ACTH is rarer but can be aggressive. Clinical presentation can be confounding due to secretion of &amp;gt;1 neurohormone i.e ACTH and Gastrin in our patient. Gallium-DOTATATE PET/CT tracer has a very high sensitivity and specificity. Early use of this imaging may prevent comorbidity and mortality as surgical resection of ectopic ACTH secreting neuroendocrine tumor is first line therapy. Other diagnostic principles to consider are that severely elevated ACTH levels correlate only with a pituitary macroadenoma, IPSS is invasive and has relative contraindication in sick patients and Desmopressin stimulation test is not widely available. Presentation: 6/1/2024

7639 A Rare Cause of Lung Adenocarcinoma with Metastasis to the Thyroid

Abstract Disclosure: E. Echevarria-Torres: None. C.G. Yap: None. K.E. Izuora: None. A rare cause of lung adenocarcinoma with metastasis to the thyroid. Metastasis to the thyroid gland from non-thyroid malignancies is rare. When metastasis occurs, presenting symptoms are typically nonspecific, representing a diagnostic challenge. With the goal of raising awareness, we present a case of lung adenocarcinoma with metastasis to the thyroid. An 85-year-old man with a history of hypertension, hyperlipidemia and 60 years smoking history presented to the endocrine clinic for evaluation of subclinical hyperthyroidism. On the physical exam, there was fullness in the right thyroid area which on ultrasound showing a large right thyroid nodule occupying the entire lobe. There was also a solid 4.5 cm x 3.4 cm x 4.6 cm nodule in the mid-anterior left thyroid lobe. Fine needle aspiration cytology of right nodule revealed malignant cells and cell block material positive for TTF-1 (Thyroid Transcription Factor 1) concerning for malignancy. The left thyroid nodule cytology was consistent with benign follicular nodule. Chest CT ordered for surgical planning showed right upper lobe pleural-based lung opacity measuring 3.7 cm x 2.9 cm with supra clavicular lymphadenopathy. Biopsy of lung mass and supra clavicular lymph nodes revealed primary lung adenocarcinoma involving the lymph nodes consistent with stage Iva (cT3NxM1b). The patient was referred to oncology for further management. Discussion: Metastatic lesions to the thyroid gland account for less than 1 % of all malignant thyroid tumors with most cases found on autopsy. This is hypothesized to be due to the rich blood supply and high iodine content of the thyroid gland. Thyroid metastasis usually presents several years after initial diagnosis and treatment of non- thyroid malignancy. Patients can present with enlarging thyroid nodules, neck swelling, dysphagia and, in rare instances, upper airway obstruction. We present a rare case of lung cancer with metastasis into the thyroid. The thyroid nodule initially palpated upon physical exam led to eventual thyroid ultrasound and subsequently to his diagnosis of lung adenocarcinoma after findings of lung nodule which was biopsied and showed primary lung adenocarcinoma. TTF-1 was also positive which is typically expressed by lung adenocarcinomas. Treatment for thyroid metastasis is surgery, along with treatment of primary malignancy. The earlier the diagnosis and treatment the more favorable the prognosis. Radiotherapy and chemotherapy are other means to reduce the recurrence. Thyroid hormone replacement will be warranted post operatively for hypothyroidism. We present this uncommon case to raise awareness about the presentation of thyroid metastasis to enhance timely diagnosis and intervention. Presentation: 6/1/2024

8078 TERT Positive Thyroid Nodule in the Setting of Metastatic Melanoma

Abstract Disclosure: E. Langnas: None. S. Chao: None. K.M. Gomes: None. A. Bhan: None. Metastatic disease to the thyroid gland is uncommon with a reported incidence of up to 4% in post-surgical specimens. Lung cancer is the most common primary tumor site in autopsy series. Clinically, renal cell carcinoma is the most common primary tumor site. Metastatic melanoma to the thyroid gland is clinically rare, however, in autopsy series, it has been reported with incidence of up to 39%. A 61-year-old man presented to the endocrinology clinic for an incidentally detected thyroid nodule. He had recently presented with a chronic cough, prompting a chest x-ray that revealed pulmonary nodules. Subsequent computed tomography (CT) showed numerous bilateral lung nodules measuring up to 2.5 cm and an incidental thyroid nodule. Ultrasound of the thyroid identified a 2.7 cm mixed cystic-solid right thyroid nodule. No risk factors for thyroid cancer were identified. His TSH was 3.51uIU (0.45 - 5.33 uIU/mL). The thyroid nodule was biopsied, and pathology revealed atypical spindle cells with irregular nuclear membranes and scattered histiocytes. A further review with cytopathology suggested non-thyroidal origin of the cells. Molecular testing with AFIRMA reported a telomerase reverse transcriptase (TERT) promoter mutation at C228T. The sequencing was negative for TERT C250T, BRAF, RET, PETC1, PTC3 and MTC. Due to concerns about metastatic disease, a positron-emission tomography (PET)-CT was conducted, revealing hypermetabolic lesions in numerous bilateral lung nodules, right thyroid nodule, porta hepatis lymph node, and a soft tissue nodule within the greater curvature of the gastric body. Subsequent biopsies of the right lung and gastric body confirmed the diagnosis of metastatic melanoma. On further questioning, it was found that the patient had a history of a skin lesion on his back that was excised several years ago with pathology reporting tumoral melanosis. Malignant melanoma has a poor prognosis due to high recurrence and metastatic rates. In melanoma, TERT promoter mutations are the most common mutations in noncoding regulatory regions. TERT C228T mutations and C250T mutations are seen in malignant melanoma and studies have shown that TERT promoter mutations are associated with aggressive clinical behavior. These TERT promoter mutations can also be seen in various other cancers including primary thyroid cancers with a similar association with more aggressive thyroid tumor characteristics. Our case describes a patient with a thyroid nodule and molecular testing noting a TERT promoter mutation. Both primary thyroid cancer and metastatic disease to the thyroid should be considered in these cases. This case also highlights the importance of obtaining a thorough history of prior malignancy in patients with thyroid nodules to assess the risk of metastatic disease. Presentation: 6/1/2024