Pulmonary Neuroendocrine Tumors Research Articles

Delta-like ligand 3 (DLL3) landscape in pulmonary and extra-pulmonary neuroendocrine neoplasms.

Delta-like Ligand 3 (DLL3) targeting therapies are promising in small cell lung cancer (SCLC) treatment. However, DLL3 expression in SCLC and other neuroendocrine neoplasms (NEN) is heterogeneous and not well characterized. We describe the landscape of DLL3 at the mRNA and protein levels across SCLC, large cell neuroendocrine carcinoma (LCNEC), and non-small cell lung cancer. Additionally, we explore its expression in extra-pulmonary NEN (EP-NEN) using a standardized DLL3 IHC assay. DLL3 expression is enriched in SCLC, LCNEC along with combined histology lung cancers. Moreover, we find a wide range of DLL3 expression in high-grade EP-NEN. We describe heterogenous DLL3 expression not only in SCLC but also in different NEN types. This comprehensive characterization of DLL3 can help guide future clinical trial design targeting DLL3 in NEN including LCNEC and EP-NEN that are lacking standard of care treatment options.

EP.14C.10 Clinical and Pathoanatomical Characteristics of Rare Pulmonary Neuroendocrine Tumors in Greek Population

EP.14C.10 Clinical and Pathoanatomical Characteristics of Rare Pulmonary Neuroendocrine Tumors in Greek Population

Cytomorphologic analysis of pulmonary neuroendocrine tumors – The physical effect of abrasion and aspiration on cytomorphology

Neuroendocrine tumors of the lung display characteristic cytomorphologic features allowing direct diagnosis. The specificity of these features in distinguishing subtypes of neuroendocrine tumors, and their differences among types of cytologic specimen poses as interpretative potential pitfalls. This study reviewed and compared bronchial, effusion fluid and fine-needle aspiration cytology specimens of neuroendocrine tumors of the lung to address these issues. Histology-proven cytology specimens of neuroendocrine tumors were reviewed for cytomorphological parameters focusing on reported specific neuroendocrine nuclear and background features. Totally, 46 cases (26 bronchial, 11 effusion and 9 aspirate specimens), corresponding to 37 small cell carcinomas, 7 neuroendocrine carcinomas and 2 carcinoids were reviewed. Nuclear moulding (n = 35/37, 95 %), naked nuclei (n = 33/37, 89 %) and marked nuclear irregularity (n = 32/37, 86 %) were the three most common features of small cell carcinoma. The only specific feature for small cell carcinoma was the lack of prominent nucleoli (p = 0.004). For pulmonary carcinoids, in addition to the above features, other features associated with neuroendocrine carcinoma reviewed including crush artifact and necrotic material were absent. Compared to bronchial and aspiration cytology, crush artifact (p < 0.001) and necrotic material (p = 0.014) were absent on effusion fluid specimens and naked nuclei were less frequently seen (p = 0.022), while prominent nucleoli were more often observed (p = 0.005). Nuclear moulding, irregularity and naked nuclei are common but not unique features to small cell carcinomas. Effusion fluid specimens have “cleaner” backgrounds while displaying greater nuclear atypia. The type of cytologic preparation/specimen is an important factor which must be considered during diagnostic interpretation.

Metabolomic Profiling of Pulmonary Neuroendocrine Neoplasms.

Pulmonary neuroendocrine neoplasms (NENs) account for 20% of malignant lung tumors. Their management is challenging due to their diverse clinical features and aggressive nature. Currently, metabolomics offers a range of potential cancer biomarkers for diagnosis, monitoring tumor progression, and assessing therapeutic response. However, a specific metabolomic profile for early diagnosis of lung NENs has yet to be identified. This study aims to identify specific metabolomic profiles that can serve as biomarkers for early diagnosis of lung NENs. We measured 153 metabolites using liquid chromatography combined with mass spectrometry (LC-MS) in the plasma of 120 NEN patients and compared them with those of 71 healthy individuals. Additionally, we compared these profiles with those of 466 patients with non-small-cell lung cancers (NSCLCs) to ensure clinical relevance. We identified 21 metabolites with consistently altered plasma concentrations in NENs. Compared to healthy controls, 18 metabolites were specific to carcinoid tumors, 5 to small-cell lung carcinomas (SCLCs), and 10 to large-cell neuroendocrine carcinomas (LCNECs). These findings revealed alterations in various metabolic pathways, such as fatty acid biosynthesis and beta-oxidation, the Warburg effect, and the citric acid cycle. Our study identified biomarker metabolites in the plasma of patients with each subtype of lung NENs and demonstrated significant alterations in several metabolic pathways. These metabolomic profiles could potentially serve as biomarkers for early diagnosis and better management of lung NENs.

Differentiating lung neuroendocrine neoplasms from tumor-like infection using CT in patients with ectopic ACTH syndrome

ObjectivesPulmonary neuroendocrine neoplasms (NENs) are the most frequent cause of ectopic adrenocorticotropic hormone syndrome (EAS); lung infection is common in EAS. An imaging finding of infection in EAS patients can mimic NENs. This retrospective study investigated EAS-associated pulmonary imaging indicators.MethodsForty-five pulmonary NENs and 27 tumor-like infections from 59 EAS patients (45 NEN and 14 infection patients) were included. Clinical manifestations, CT features, 18F-FDG, or 68Ga-DOTATATE-PET/CT images and pathological results were collected.ResultsHigh-sensitivity C-reactive protein (p < 0.001) and expectoration occurrence (p = 0.04) were higher, and finger oxygen saturation (p = 0.01) was lower in the infection group than the NENs group. Higher-grade NENs were underrepresented in our cohort. Pulmonary NENs were solitary primary tumors, 80% of which were peripheral tumors. Overlying vessel sign and airway involvement were more frequent in the NENs group (p < 0.001). Multifocal (p = 0.001) and peripheral (p = 0.02) lesions, cavity (p < 0.001), spiculation (p = 0.01), pleural retraction (p < 0.001), connection to pulmonary veins (p = 0.02), and distal atelectasis or inflammatory exudation (p = 0.001) were more frequent in the infection group. The median CT value increment between the non-contrast and arterial phases was significantly higher in NENs lesions (p < 0.001). Receiver operating characteristic curve analysis indicated a moderate predictive ability at 48.3 HU of delta CT value (sensitivity, 95.0%; specificity, 54.1%).ConclusionChest CT scans are valuable for localizing and characterizing pulmonary lesions in rare EAS, thereby enabling prompt differential diagnosis and treatment.Critical relevance statementThin-slice CT images are valuable for the localization and identification of pulmonary ectopic adrenocorticotropic hormone syndrome lesions, leading to prompt differential diagnosis and effective treatment.Key PointsLung tumor-like infections can mimic neuroendocrine neoplasms (NENs) in ectopic adrenocorticotropic hormone syndrome (EAS) patients.NENs are solitary lesions, whereas infections are multiple peripheral pseudotumors each with identifying imaging findings.Typical CT signs aid in localization and creating an appropriate differential diagnosis.Graphical

Pneumonectomy for broncho-pulmonary carcinoids: a single centre analysis of surgical approaches and patient outcomes.

Pneumonectomy is a radical surgical procedure associated with significant morbidity and mortality. Its application in the context of pulmonary neuroendocrine tumours, including carcinoid tumours, requires meticulous preoperative planning and intraoperative precision. This study aims to assess the safety and efficacy of pneumonectomy in the management of these rare and challenging neoplasms. A retrospective analysis of patients who underwent pneumonectomy for pulmonary carcinoid tumours at our institution over a specified period was conducted. Data regarding patient demographics, tumour characteristics, surgical techniques, intraoperative complications, perioperative management, and long-term outcomes were collected and analysed. Between March 2001 and October 2022, 21 patients (7 male, 14 female) with carcinoid tumours underwent pneumonectomy on a total of 459 surgical operations for carcinoid. Preoperative bronchoscopic procedures were conducted in 90.4% of cases, leading to histological diagnoses for most. The median hospital stay was eight days, with no reported perioperative deaths. Median follow-up after surgery was 73 months, with a five-year overall survival of 65.4 months. Recurrences occurred in 28.6% of cases, primarily in atypical carcinoids. Despite the rarity of bronchial carcinoids, pneumonectomy is effective for low-grade malignancies, demonstrating positive short-and long-term outcomes. Radical lymph node dissection is fundamental in pathological staging and overall survival.

Lung neuroendocrine tumors

Neuroendocrine tumors are a large and heterogeneous group of tumors that develop from neuroendocrine cells. To define this type of tumor, the well-established term “carcinoid” continues to be used in clinical practice for years. In accordance with the characteristics of embryogenesis, three groups of neuroendocrine tumors are distinguished. The source of these tumors are neuroendocrine cells, which are located in almost all organs. The term itself and the concept of “neuroendocrine cell” have historically been repeatedly reassessed. In 1969 A. Pearse, based on the ability of these cells to utilize and decarboxylate amine precursors, introduced the term “APUD system” (aminoprecursor uptake and decarboxylation). Neuroendocrine cells, although they can secrete the same substances as neurons, but, unlike the latter, they participate not in topical, but in paracrine regulation of organs and tissues. They are located in all human organs and are the most important tool for maintaining homeostasis.In recent years, more and more publications have appeared about the frequent localization of neuroendocrine tumors in the lungs, and new approaches to the diagnosis of this pathology. This review presents the diagnostic features and clinical course of pulmonary neuroendocrine tumors.

OTP Expression in Pulmonary and Thymic Neuroendocrine Neoplasms.

OTP Expression in Pulmonary and Thymic Neuroendocrine Neoplasms.

Head-to-head: Should Ki67 proliferation index be included in the formal classification of pulmonary neuroendocrine neoplasms?

The reporting of lung neuroendocrine neoplasms (NENs) according to the 2021 World Health Organisation (WHO) is based on mitotic count per 2 mm2, necrosis assessment and a constellation of cytological and immunohistochemical details. Accordingly, typical carcinoid and atypical carcinoid are low- to intermediate-grade neuroendocrine tumours (NETs), while large-cell neuroendocrine carcinoma (NEC) and small-cell lung carcinoma are high-grade NECs. In small-sized diagnostic material (cytology and biopsy), the noncommittal term of carcinoid tumour/NET not otherwise specified (NOS) and metastatic carcinoid NOS have been introduced with regard to primary and metastatic diagnostic settings, respectively. Ki-67 antigen, a well-known marker of cell proliferation, has been included in the WHO classification as a non-essential but desirable criterion, especially to distinguish NETs from high-grade NECs and to delineate the provisional category of carcinoid tumours/NETs with elevated mitotic counts (> 10 mitoses per mm2) and/or Ki-67 proliferation index (≥ 30%). However, a wider use of this marker in the spectrum of lung NENs continues to be highly reported and debated, thus witnessing a never-subsided attention. Therefore, the arguments for and against incorporating Ki-67 in the classification and clinical practice of these neoplasms are discussed herein in detail.

The impact of primary tumor site on clinical manifestation and prognosis of ectopic Cushing's syndrome (ECS). Do pulmonary neuroendocrine tumors stand out?

The impact of primary tumor site on clinical manifestation and prognosis of ectopic Cushing's syndrome (ECS). Do pulmonary neuroendocrine tumors stand out?

Multi-omic dataset of patient-derived tumor organoids of neuroendocrine neoplasms.

Organoids are 3-dimensional experimental models that summarize the anatomical and functional structure of an organ. Although a promising experimental model for precision medicine, patient-derived tumor organoids (PDTOs) have currently been developed only for a fraction of tumor types. We have generated the first multi-omic dataset (whole-genome sequencing [WGS] and RNA-sequencing [RNA-seq]) of PDTOs from the rare and understudied pulmonary neuroendocrine tumors (n = 12; 6 grade 1, 6 grade 2) and provide data from other rare neuroendocrine neoplasms: small intestine (ileal) neuroendocrine tumors (n = 6; 2 grade 1 and 4 grade 2) and large-cell neuroendocrine carcinoma (n = 5; 1 pancreatic and 4 pulmonary). This dataset includes a matched sample from the parental sample (primary tumor or metastasis) for a majority of samples (21/23) and longitudinal sampling of the PDTOs (1 to 2 time points), for a total of n = 47 RNA-seq and n = 33 WGS. We here provide quality control for each technique and the raw and processed data as well as all scripts for genomic analyses to ensure an optimal reuse of the data. In addition, we report gene expression data and somatic small variant calls and describe how they were generated, in particular how we used WGS somatic calls to train a random forest classifier to detect variants in tumor-only RNA-seq. We also report all histopathological images used for medical diagnosis: hematoxylin and eosin-stained slides, brightfield images, and immunohistochemistry images of protein markers of clinical relevance. This dataset will be critical to future studies relying on this PDTO biobank, such as drug screens for novel therapies and experiments investigating the mechanisms of carcinogenesis in these understudied diseases.

The dark side of T2: central nervous system lesions with low signal intensity on T2-weighted imaging.

The majority of central nervous system diseases show high signal intensity on T2-weighted magnetic resonance imaging. Diseases of the central nervous system with low signal intensity are less common, which makes it a finding that helps narrow the differential diagnosis. This was a retrospective analysis of brain and spine magnetic resonance imaging examinations in which that finding was helpful in the diagnostic investigation. We selected the cases of patients examined between 2015 and 2022. All diagnoses were confirmed on the basis of the clinical-radiological correlation or the histopathological findings. We obtained images of 14 patients with the following central nervous system diseases: arteriovenous malformation; cavernous malformation; metastasis from lymphoma; medulloblastoma; embryonal tumor; metastasis from melanoma; Rathke's cleft cyst; Erdheim-Chester disease; aspergillosis; paracoccidioidomycosis; tuberculosis; syphilis; immunoglobulin G4-related disease; and metastasis from a pulmonary neuroendocrine tumor. We described lesions of different etiologies in which the T2-weighted imaging profile helped narrow the differential diagnosis and facilitated the definitive diagnosis.

68Ga] DOTA-TATE (NETSpot) PET/CT Imaging of Pulmonary Neuroendocrine Tumors

68Ga] DOTA-TATE (NETSpot) PET/CT Imaging of Pulmonary Neuroendocrine Tumors

NEN in a dish: A patient-derived organoid biobank illuminates potential novel therapeutic opportunities for neuroendocrine neoplasms

Neuroendocrine neoplasms are rare cancers with limited treatment options and preclinical models. In this issue of Cancer Cell, Dayton etal. establish a patient-derived tumor organoid biobank encompassing pulmonary low-grade neuroendocrine tumors (LNETs) and high-grade neuroendocrine carcinomas (LCNECs), identifying novel biomarker-dependent therapeutic vulnerabilities using niche perturbation and drug response assays.

EP13.01-10 Mitotic Counts and Phospho-Histone H3 Index in Grading Pulmonary Neuroendocrine Tumors: Assessment of Interobserver Variability and Utility

EP13.01-10 Mitotic Counts and Phospho-Histone H3 Index in Grading Pulmonary Neuroendocrine Tumors: Assessment of Interobserver Variability and Utility

EP13.05-02 Temozolomide-associated Hypermutation and Response to Immunotherapy in Advanced Pulmonary Neuroendocrine Tumors

EP13.05-02 Temozolomide-associated Hypermutation and Response to Immunotherapy in Advanced Pulmonary Neuroendocrine Tumors

Alteration of the immunophenotype and cytokine profiles in patients affected by neuroendocrine neoplasms.

Neuroendocrine neoplasms (NENs) are tumors that arise from cells of the endocrine system and are most common in the gastrointestinal tract, the pancreas, and the lungs. Their incidence is rapidly increasing and the therapeutic options available are limited. Since the immune system can interfere with tumor growth and response to therapy, using flow cytometry we investigated the immunophenotype in samples of peripheral blood leukocytes from patients with pancreatic (Pan-NENs) and pulmonary NENs (Lung-NENs). Moreover, we performed a multiplex analysis of 13 key cytokines and growth factors essential for the immune response in the plasma of NEN patients and controls. Patients presented with a higher percentage of granulocytes, a lower percentage of lymphocytes, and an increase in the granulocytes to lymphocytes ratio compared to healthy donors. These alterations were more marked in patients with metastasis. Somatostatin analogs (SSAs) restored the immunophenotype of patients to that seen in healthy donors. Finally, Pan-NEN patients showed a higher plasma concentration of IP-10, MCP-1, and IL-8 compared to healthy donors, suggesting a potential role for these cytokines as diagnostic biomarkers. This study highlighted differences in the immunophenotype of patients with Pan- and Lung-NENs compared to healthy individuals; these alterations were partially restored by therapy.

THU012 Incidental Pituitary Adenoma In A Patient With Ectopic ACTH Secreting Cushing Syndrome - A Diagnostic Conundrum

Abstract Disclosure: M.S. Nali: None. R.R. Yatavelli: None. Background: Cushing’s syndrome (CS) is a rare condition with an estimated incidence of 2-3 cases/million. Endogenous CS can be divided into ACTH -dependent (80%) and ACTH Independent (20%) with Ectopic Cushing’s syndrome (ECS) accounting for 10-20% of all cases of ACTH-dependent CS. Herein we present a case with indolent onset ACTH-dependent CS who on initial work-up showed a pituitary microadenoma raising the suspicion for Cushing disease, but the source of excess ACTH was found to be from a pulmonary neuroendocrine tumor. Clinical Case: A 44-yr-old female with history of type 1 DM, Obesity, BMI 43.60, Sleep apnea was evaluated elsewhere for suspected Cushing’s due to increased insulin requirements and progressive weight gain. Outside labs showed cortisol of 4.5 ug/dl on 1 mg DST &amp; 8 mg DST cortisol was 3 ug/dl. MRI of the pituitary showed a 3.5x 2.8x 1.8 mm microadenoma &amp; she was initially presumed to have Cushing’s disease secondary to pituitary microadenoma. The patient was seen by neurosurgery who referred to endocrine for localization of cortisol excess by IPSS. Clinically she had moon facies, hirsutism, dorsocervical fat pad, violaceous striae on abdomen. On further laboratory evaluation her ACTH: 88 (0-46) and random cortisol 14 ug/dl with normal rest of pituitary hormones. Her 24-hour urine free Cortisol was 45ug/d (3.5 - 45) and late-night salivary cortisol: 74 &amp;&amp;lt;50 (Ref. range &amp;lt;100 ng/dl) on couple of nights, respectively. Due to non-suppressed cortisol on high dose DST, a CT chest was obtained which showed a 2cms non calcified nodule in the left lower lobe of lung. Transbronchial biopsy was performed, cytopathology showed well differentiated neuroendocrine tumor, likely carcinoid and stained strongly positive for ACTH confirming ectopic ACTH producing tumor. Gallium-68 Dotatate Scan showed abnormal increased uptake in the known left lung nodule. The patient was recommended for surgical removal of neuroendocrine tumor, but she could not tolerate anesthesia and had to undergo stereotactic body radiation therapy (SBRT) for the lung lesion. Repeat ACTH levels 2 months post SBRT showed the ACTH levels were elevated and lesion was still persistent on imaging, however on discussion with rad oncology, the neuroendocrine tumors tend to take longer to show response on imaging and plan is to repeat imaging and biochemical work up in couple of months. Conclusion: The diagnosis of CS and recognizing the source of hormonal excess poses significant challenges Pituitary adenomas are incidentally discovered in up to 10% of the normal population &amp; IPSS is advised for patients with ACTH-dependent Cushing's syndrome and an adenoma smaller than 6 mm, however in patients with equivocal findings, it is important to look for other sources of ACTH prior to any invasive procedure. The source of ectopic ACTH secretion should be established after diagnosis because the excision of an ACTH-producing tumor can be curative. Presentation: Thursday, June 15, 2023

THU538 Use Of Multiple Functional And Structural Imaging Modalities Improves Detection Of Ectopic ACTH Tumors

Abstract Disclosure: H. Elenius: None. R. McGlotten: None. A.M. Gharib: None. L.K. Nieman: None. Introduction: In Ectopic ACTH Syndrome (EAS), Cushing's syndrome (CS) is caused by ACTH secretion from a non-pituitary tumor. Tumor resection reduces CS morbidity and mortality, but up to 38% of tumors remain occult despite repeated structural imaging. We prospectively studied whether functional PET imaging with somatostatin receptor ( 111In-pentetreotide Octreoscan [OCT], vs 68Ga DOTA0-Tyr3 octreotate DOTATATE [DOTA]) or amine precursor (18F-DOPA [F-D]) ligands would improve tumor detection. Methods: From 2014-2022, 22 EAS patients underwent imaging with F-D and DOTA PET/CT and/or MRI (1.5 and/or 3 Tesla, T) of chest/abdomen/pelvis (C/A/P), gated cardiac CT (GC-CT) and/or MRI (GC-MRI), and/or OCT before tumor resection. Pre-surgical imaging results were confirmed by pathology or biochemical cure. Results: Tumors included 16 pulmonary (pulm) neuroendocrine tumors (NET), one thymic NET, one appendiceal NET, one pheochromocytoma and one metastatic NET in mediastinal lymph nodes; two patients had tumorlets. Surgery was done if at least CT or MRI was positive; some lesions were seen only after concurrent PET scan review. Shown in decreasing order, the modalities performed as follows (number of patients = N): Sensitivity (S): CT C/A/P 100%, N 22 ; FDG-PET 100%, N 2 ; 3T MRI C/A/P 93%, N 14 ; F-D 91%, N 22 ; DOTA 86%, N 22 ; 1.5T MRI C/A/P 71%, N 21 ; GC-CT 67%, N 6 ; GC-MRI 50%, N 8 ; OCT 31%, N 13. 95% Confidence intervals (CI) overlapped for all except OCT. Positive predictive value (PPV): GC-MRI 100% ; 3T MRI C/A/P 88% ; 1.5T MRI C/A/P 84% ; DOTA 83% ; CT C/A/P 81% ; GC-CT 80% ; F-D 75% ; OCT 67% ; FDG-PET 67%. All CIs overlapped.1.5T MRI, F-D and DOTA missed a 12 mm pulm NET (false negative, FN) only seen on CT. 1.5T MRI missed three other pulm NET (6, 8 and 10 mm) seen on 3T MRI. 1.5T and 3T MRI missed a 13 mm pulm NET that abutted the heart and was seen on both gated studies - this was the only FN lesion in the 3T MRI cohort. F-D missed the 12 mm pulm NET seen on CT and the retrocardiac NET, which was DOTA +. DOTA missed three other pulm NET (6, 8 and 10 mm); all were positive on F-D. OCT detected 4/10 pulm NET, 6-25 mm, all positive on F-D and DOTA, and missed 9 tumors seen on F-D (N=8) or DOPA (N=8). F-D detected false positive (FP) lesions in seven patients while DOTA detected FP lesions in three, mostly infections or thyroid nodules. All but one patient were localized by DOTA (N=19) and/or F-D (N=20). Conclusions: As reported previously, most EAS tumors were intrathoracic. Among structural modalities, CT was the most sensitive (100%) while cardiac MRI and 3T MRI gave the highest PPV (100% and 88%). Dedicated cardiac imaging found pericardiac lesions missed on routine modalities due to motion artefacts. F-D and DOTA were significantly more sensitive (91% and 86%) than OCT (31%). DOTA detected fewer FP lesions, providing a higher PPV (83%) than F-D (75%), but with lower sensitivity. Use of multiple functional and structural scans improved tumor detection. Presentation: Thursday, June 15, 2023

THU525 Atypical Presentation Of Parathyroid Carcinoma In The Lungs

Abstract Disclosure: J.N. Jacinto: None. O. Reyes: None. M. Cating-Cabral: None. R. Santiago: None. J. Andal: None. A 66-year-old female with a history of parathyroid adenoma underwent partial parathyroidectomy and thyroidectomy of the right lobe in 2006. She has the following comorbidities: pre-diabetes, hypertension, multiple liver cysts, medullary nephrocalcinosis and nephrolithiasis, ureterolithiasis and uterine intramural myoma. She also has a strong familial disposition of endocrine tumors. During the last quarter of 2018, parathyroid hormone and calcium levels were elevated and parathyroid imaging revealed an adenoma on the posteromedial aspect of the left thyroid lobe. Removal of the adenoma was offered but insisted on medical treatment. In 2022, she was admitted for subarachnoid hemorrhage due to fall. There was an incidental finding of a lung mass with minimal pleural effusion on the right lung lobe. PET-scan revealed five FDG-avid nodules (SUV up to 9.6) with the largest in the right middle lobe measuring 2 x 2 x 2 cm. Percutaneous needle biopsy was performed which showed a tumor with fairly uniform cells in organoid nests and solid clusters. By immunohistochemistry (IHC), the tumor cells were diffusely and strongly positive for CK and GATA-3; focally positive for chromogranin and synaptophysin; and negative for TTF-1, Pax-8, and S100. This was signed out as an epithelial tumor with neuroendocrine features; the differential diagnosis includes pulmonary neuroendocrine tumor versus metastasis from the prior parathyroid lesion. She subsequently underwent completion thyroidectomy and video-assisted thoracoscopic surgery. The lung wedge resections both showed tumors with similar morphology and IHC staining pattern as the biopsy. Additional stains were also performed to rule out other entities, which were all negative (CK7, CK20, CD56, mammaglobin, GCDFP-15, TTF-1, S100, ER, Pax-8, HSA, and SALL-4). The Ki-67 proliferation index was 17.26%. Because the overall findings were not definitive, comprehensive genomic profiling by next generation sequencing (NGS) was recommended and subsequently performed. NGS showed gene alteration in CDC73, with a variant allele frequency of 50%; this finding has been documented in parathyroid carcinoma. Pre-operative parathyroid hormone levels remained unchanged (408 to 397 pg/ml) despite surgery. Currently, there is no available targeted therapy to address her genomic alteration. Hyperparathyroidism-jaw tumor syndrome was entertained. The multidisciplinary team advised en-bloc resection of the lung tumor and additional gene testing for family members. She opted for palliative care and is on cinacalcet for her hyperparathyroidism. Presentation: Thursday, June 15, 2023