Non-small Cell Carcinoma Research Articles

Surgical resection of lung cancer inhibits mRNA expression of GOT2 gene encoding kynurenine aminotransferase in leukocytes.

Lung cancer is the most common malignant tumour. More than 80% of all diagnosed cases are non-small cell carcinoma which can be effectively treated by radical resection. Despite significant progress in the field of diagnostic and therapeutic methods, the results of lung cancer treatment are still unsatisfactory. Lung cancer is detected relatively late, which leads to an unfavourable prognosis. Kynurenine aminotransferases are an important element of the kynurenine pathway of tryptophan metabolism, which has recently aroused great interest from the aspect of possible use as a target point of personalized therapies in malignant tumours.The aim of the study was to analyze the expression of the selected gene of kynurenine aminotransferases GOT 2 at the mRNA level in peripheral blood leukocytes of patients with lung cancer. The mRNA expression of the GOT 2 gene was tested on blood samples from 50 patients treated surgically for non-small cell lung cancer.The control group consisted of 15 healthy individuals.The determination of mRNA expression of the GOT 2 gene was performed using the real-time PCR method.The GAPDH gene was used as the endogenous reference level. The mRNA expression of the GOT2 gene on the 6th day after surgery was statistically significantly lower than before surgery (p = 0,05). In the study group, the average LogRQ mRNA expression of the GOT2 gene before the procedure was 0.192082±0.292174 in woman. This was statistically significantly higher than in men whose average LogRQ mRNA expression of the GOT2 gene before the procedure was 0.004210±0.235065 (p=0.0183). Surgical resection of lung cancer results in inhibition of GOT2 mRNA expression in leukocytes. Further studies are expected to show whether it may be used as a target point for personalized therapies in lung cancer.

Overview of Lung Cancer

The two main types of lung cancer are small cell carcinoma and non-small cell carcinoma. Lung cancer is a primary bronchogenic carcinoma. Patients who are diagnosed with lung cancer typically exhibit symptoms like hemoptysis, dyspnea, chronic cough, chest pain, or weight loss. Since the onset of symptoms typically indicates that a patient's stage has already progressed, screening with low-dose chest CT (LDCT) exams is advised for high-risk patients. Cytology and core biopsy specimens are the main sources of the diagnosis for these patients. Staging, histology, genetic, and immunotherapy biomarker tests form the basis of the treatment. The most often used pharmacological therapies include radiotherapy, adjuvant platinum-based chemotherapy, surgery, which might involve mediastinal lymph node dissection or lymph node sampling, as well as total removal of the tumor (typically stages I and II). Currently, meanwhile, immunotherapy is the most advanced form of treatment for NSCLC that is oncogenic driver negative

Sclerosing epithelioid fibrosarcoma associated with WRN gene variant presenting as chronic dyspnea and pathologic cervical fracture: a case report and review of the literature

BackgroundSclerosing epithelioid fibrosarcoma is an aggressive sarcoma subtype with poor prognosis and limited response to conventional chemotherapy regimens. Diagnosis can be difficult owing to its variable presentation, and cases of sclerosing epithelioid fibrosarcoma are rare. Sclerosing epithelioid fibrosarcoma typically affects middle-aged individuals, with studies inconsistently citing gender predominance. Sclerosing epithelioid fibrosarcoma typically arises from the bones and soft tissues and often has local recurrence after resection and late metastases. Immunohistochemical staining typically is positive for mucin-4. Werner syndrome is due to an autosomal recessive mutation in the WRN gene and predisposes patients to malignancy.Case presentationA 37-year-old Caucasian female presented to the emergency department with 4 months of dyspnea and back pain. She had been treated for pneumonia but had persistent symptoms. A chest, abdomen, and pelvis computed tomography showed near-complete right upper lobe collapse and consolidation, mediastinal lymphadenopathy, lytic spinal lesions, and a single 15-mm hypodense liver nodule. The patient underwent a transthoracic right upper lobe biopsy, bronchoscopy, endobronchial ultrasound with transbronchial lymph node sampling, and bronchoalveolar lavage of the right upper lobe. The bronchoalveolar lavage cytology was positive for malignant cells compatible with poorly differentiated non-small cell carcinoma; however, the cell block materials were insufficient to run immunostains for further investigation of the bronchoalveolar lavage results. Consequently, the patient also underwent a liver biopsy of the liver nodule, which later confirmed a diagnosis of sclerosing epithelioid fibrosarcoma. Next-generation sequencing revealed a variant of unknown significance in the WRN gene. She was subsequently started on doxorubicin.ConclusionSclerosing epithelioid fibrosarcoma is a very rare entity, only cited approximately 100 times in literature to date. Physicians should be aware of this disease entity and consider it in their differential diagnosis. Though pulmonary involvement has been described in the context of sclerosing epithelioid fibrosarcoma, this malignancy may affect many organ systems, warranting extensive investigation. Through our diagnostic workup, we suggest a possible link between sclerosing epithelioid fibrosarcoma and the WRN gene. Further study is needed to advance our understanding of sclerosing epithelioid fibrosarcoma and its clinical associations as it is an exceedingly rare diagnosis.

Optimization of media components for enhanced carotenoid production by Paracoccus marcusii RSPO1 and assessment of their cytotoxicity against A549 and vero cells

In this study, we tried to explore the influence of various tricarboxylic acid (TCA) cycle intermediates on carotenoid production and with a focus on enhancing pigment biosynthesis, we conducted two statistical analysis. In case of TCA intermediates influence on pigment production by Paracoccus marcusii RSPO1; fumaric acid, and malic acid were observed as potent enhancers of pigment biosynthesis. Further, to optimize key media components for enhanced carotenoid production, the Plackett–Burman design was employed encompassing carbon, nitrogen sources, TCA cycle intermediates, and metal salts. The selected factors after Plackett Burman were fine-tuned through Response Surface Methodology and the optimal concentrations that have remarkably elevated carotenoid production were starch-2.24 g/l, MgSO4-0.416 g/l, ZnSO4-0.0157 g/l, and fumaric Acid-16 mM. Further, evaluation of pigment cytotoxicity against normal (Vero) and Non-Small Cell Carcinoma (A549) cells was performed. The resultant IC50 values were quantified as 161.3 µg/ml and 7.623 µg/ml for Vero and A549 cells, respectively. Moreover, a reactive oxygen species (ROS) determination study in A549 cells was done which have shown a noteworthy threefold ROS production in A549 cells through fluorescence spectroscopic observation. This implies that the bacterial carotenoids can act as potent pro-oxidants against cancerous cells while being nontoxic toward normal cells.

Karsinoma Sel Skuamosa Paru Kanan Dengan PPOK Dan Atelektasis Paru Kiri

Lung cancer is one of the most common causes of death today. One case of right lung squamous cell carcinoma with COPD and atelectasis has been reported in a 44 year old male patient. Based on the history, the patient said he had experienced chest pain for 1 week before entering the hospital and had a cough without phlegm or blood. Physical examination revealed dull chest wall percussion at the apex of the right lung and dullness in the left lung field, vesicular breathing sounds in both lung fields and rhonchi in the left lung field. The results of the supporting examination found a mass in the left lung on a chest x-ray and a bronchoscopy examination found a right lung tumor (type?) T3N1M0 Stage IIIA and the results of the anatomical pathology examination showed a picture of non-small cell carcinoma type squamous cell carcinoma. Patients are treated with chemotherapy and symptomatic therapy.

Comparative studies on the cytotoxic effects induced by iron oxide nanoparticles in cancerous and noncancerous human lung cells subjected to an alternating magnetic field

The cytotoxic effects of water-based ferrofluids composed of iron oxide nanoparticles, including magnetite (Fe3O4) and maghemite (γ-Fe2O3), ranging from 15 to 100 nm, were examined on various lung cancer cells including adenocarcinomic human alveolar basal epithelial cells (A549), nonsmall lung squamous cell carcinoma (H1703), small cell lung cancer cells (DMS 114), and normal bronchial epithelial cells (BEAS-2B). The cytotoxic effect was evaluated both with and without exposure to an alternating magnetic field (AMF). The studies revealed that neither AMF nor iron oxide nanoparticles when tested individually, produced cytotoxic effects on either cancerous or noncancerous cells. However, when applied together, they led to a significant decrease in cell viability and proliferative capacity due to the enhanced effects of magnetic fluid hyperthermia (MFH). The most pronounced effects were found for maghemite (<50 nm) when subjected to an AMF. Notably, A549 cells exhibited the highest resistance to the proposed hyperthermia treatment. BEAS-2B cells demonstrated susceptibility to magnetized iron oxide nanoparticles, similar to the response observed in lung cancer cells. The studies provide evidence that MFH is a promising strategy as a standalone treatment for different types of lung cancer cells. Nevertheless, to prevent any MFH-triggered adverse effects on normal lung cells, targeted magnetic ferrofluids should be designed.

Molecular and Pathologic Characterization of YAP1-Expressing Small Cell Lung Cancer Cell Lines Leads to Reclassification as SMARCA4-Deficient Malignancies.

The classification of small cell lung cancer (SCLC) into distinct molecular subtypes defined by ASCL1, NEUROD1, POU2F3, or YAP1 (SCLC-A, -N, -P, or -Y) expression, paves the way for a personalized treatment approach. However, the existence of a distinct YAP1-expressing SCLC subtype remains controversial. To better understand YAP1-expressing SCLC, the mutational landscape of human SCLC cell lines was interrogated to identify pathogenic alterations unique to SCLC-Y. Xenograft tumors, generated from cell lines representing the four SCLC molecular subtypes, were evaluated by a panel of pathologists who routinely diagnose thoracic malignancies. Diagnoses were complemented by transcriptomic analysis of primary tumors and human cell line datasets. Protein expression profiles were validated in patient tumor tissue. Unexpectedly, pathogenic mutations in SMARCA4 were identified in six of eight SCLC-Y cell lines and correlated with reduced SMARCA4 mRNA and protein expression. Pathologist evaluations revealed that SMARCA4-deficient SCLC-Y tumors exhibited features consistent with thoracic SMARCA4-deficient undifferentiated tumors (SMARCA4-UT). Similarly, the transcriptional profile SMARCA4-mutant SCLC-Y lines more closely resembled primary SMARCA4-UT, or SMARCA4-deficient non-small cell carcinoma, than SCLC. Furthermore, SMARCA4-UT patient samples were associated with a YAP1 transcriptional signature and exhibited strong YAP1 protein expression. Together, we found little evidence to support a diagnosis of SCLC for any of the YAP1-expressing cell lines originally used to define the SCLC-Y subtype. SMARCA4-mutant SCLC-Y cell lines exhibit characteristics consistent with SMARCA4-deficient malignancies rather than SCLC. Our findings suggest that, unlike ASCL1, NEUROD1, and POU2F3, YAP1 is not a subtype defining transcription factor in SCLC. See related commentary by Rekhtman, p. 1708.

Comprehensive analysis and immunohistochemistry localization of NRP1 expression in pancancer and normal individual tissues in relation to SARS‑CoV‑2 susceptibility.

Neuropilin 1 (NRP1/CD304) is a typical membrane-bound co-receptor for vascular endothelial growth factor, semaphorin family members and viral severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, NRP1 expression levels across cancer types and the potential role of SARS-CoV-2 infection in patients with cancer are not clear. Online databases, such as The Cancer Genome Atlas database of Human Protein Atlas, Gene Expression Profiling Interactive Analysis and cBioPortal were used for the expression analysis in this study. Immunohistochemical (IHC) staining for NRP1 was performed in the tissues of patients with non-small cell carcinoma. As a result, it was found that NRP1 mRNA and protein expression levels were highest in the female reproductive tissues and the respiratory system, specifically in the nasopharynx, bronchus and fallopian tube, as well as in adipocytes, hepatic stellate cells, Sertoli cells, endothelial cells and dendritic cells. IHC showed that the NRP1 protein was mainly localized to the cytoplasm and membrane in the tissues of patients with non-small cell carcinoma, demonstrating its role in lung infection by SARS-CoV-2, due to invasion of cell membranes by the virus. Levels of NRP1 mRNA were significantly increased in lymphoid neoplasm diffuse large B-cell lymphoma, esophageal carcinoma, glioblastoma multiforme, head and neck squamous cell carcinoma, kidney renal clear cell carcinoma (KIRC), pancreatic adenocarcinoma, stomach adenocarcinoma and thymoma, and significantly decreased in cervical squamous cell carcinoma and endocervical adenocarcinoma, kidney chromophobe, lung squamous cell carcinoma, ovarian serous cystadenocarcinoma, uterine corpus endometrial carcinoma and uterine carcinosarcoma, compared with corresponding healthy tissues in pancancer, indicating roles for viral invasion in most cancer types. Moreover, low NRP1 expression was significantly associated with long overall survival (OS) time in adrenocortical carcinoma, brain lower grade glioma, stomach adenocarcinoma and uveal melanoma, but with short OS time in KIRC only. The ENST00000374867.6 (NRP1-202) isoform is most highly expressed in most cancer types and thus could be involved in tumorigenesis and SARS-CoV-2 invasion in cancer patients. NRP1 may be involved in SARS-CoV-2 invasion in patients with cancer, including those with lung cancer.

Case of Metastatic Atypical Meningioma to Lung: Utility of Cytological Preparations for Intraoperative Diagnosis

Abstract Introduction/Objective Meningiomas are the most common primary intracranial and intraspinal tumors. They are typically benign with an indolent behavior but can metastasize extracranially to the skin, bone, lymph node and liver. Lung metastasis is exceptionally rare, and the diagnosis can be challenging, especially during intraoperative diagnosis without ancillary studies. We describe a metastatic atypical meningioma to the lung for which intraoperative cytology facilitated the diagnosis and guided management. Methods/Case Report A 53-year-old woman with a history of left frontal atypical meningioma and multiple surgical resections for recurrences at outside hospitals, presented with an incidental left lung nodule. A lung wedge resection was performed and submitted for intraoperative diagnosis. Gross examination revealed a well-circumscribed, tan- white, and rubbery subpleural nodule. Cytological preparations— Diff-Quik and H&amp;E stains—and frozen section were prepared. Cytologically, the nodule displayed cohesive distinctive papillary whorls of uniform eosinophilic cells with indistinct cell membranes, round to oval nuclei with central nucleoli and intranuclear pseudoinclusions. The frozen section exhibited similar cytological features, few identifiable whorls and predominantly solid sheets of tumor cells typical of non-small cell carcinoma. Based primarily on the cytological findings, the intraoperative diagnosis was a neoplasm with papillary growth pattern, and a metastasis was favored based on the whorled pattern and clinical history; no further resection was performed. Permanent sections displayed mitoses and no necrosis. Immunohistochemical analysis revealed positivity for somatostatin receptor 2a, progesterone receptor, and EMA (focal); no staining was seen with pancytokeratin, TTF-1, or p40. A diagnosis of atypical meningioma, WHO grade 2, was rendered. Subsequently, an atypical cranial and temporalis muscle meningioma at the site of the prior craniotomy bone flap was resected and had an identical molecular profile (1p36 deletion) to that in the lung, further supporting metastasis to the lung. Results (if a Case Study enter NA) NA Conclusion This case illustrates a rare presentation of metastatic atypical meningioma and highlights the distinctive intraoperative utility of cytology preparations—architectural and cytological details—for diagnosis and appropriate management. Cytology preparations can be a valuable tool and complement frozen sections, in which certain morphological features may be less obvious or confounded by freezing artifact.

Epidermal growth factor receptor inhibitor Geftinib-induced erosive pustular dermatosis of the scalp – A report with a brief review of the literature

Gefitinib is an epidermal growth factor receptor inhibitor used in the treatment of non-small cell carcinoma of the lungs, adenocarcinoma of the lungs, and solid malignancies of the head and neck region. A 65-year-old female patient with non-small cell carcinoma lung with bone metastasis was started on gefitinib monotherapy after which the patient noticed papulo-pustular lesions on the scalp, later leading to loss of hair. Dermatological examination revealed erythema, pustules with crusting, along with matting of the hair on the frontoparietal area with some areas of hair loss. Trichoscopic examination showed the absence of follicular openings indicating scarring alopecia. Skin biopsy showed perivascular mixed infiltrate of lymphocytes and neutrophils and absent hair follicles, consistent with gefitinib-induced erosive pustular dermatosis of the scalp, a rare entity.

A quantitative evaluation method utilizing the homology concept to assess the state of chromatin within the nucleus of lung cancer

Homology is a mathematical tool to quantify "the contact degree", which can be expressed in terms of Betti numbers. The Betti numbers used in this study consisted of two numbers, b0 (a zero-dimensional Betti number) and b1 (a one-dimensional Betti number). We developed a chromatin homology profile (CHP) method to quantify the chromatin contact degree based on this mathematical tool. Using the CHP method we analyzed the number of holes (surrounded areas = b1 value) formed by the chromatin contact and calculated the maximum value of b1 (b1MAX), the value of b1 exceeding 5 for the first time or Homology Value (HV), and the chromatin density (b1MAX/ns2). We attempted to detect differences in chromatin patterns and differentiate histological types of lung cancer from respiratory cytology using these three features. The HV of cancer cells was significantly lower than that of non-cancerous cells. Furthermore, b1MAX and b1MAX/ns2 showed significant differences between small cell and non-small cell carcinomas and between adenocarcinomas and squamous cell carcinomas, respectively. We quantitatively analyzed the chromatin patterns using homology and showed that the CHP method may be a useful tool for differentiating histological types of lung cancer in respiratory cytology.

Molecular pathology of non-small cell carcinoma.

Currently, lung cancer is treated by the highest number of therapeutic options and the benefits are based on multiple large-scale sequencing studies, translational research and new drug development, which has promoted our understanding of the molecular pathology of lung cancer. According to the driver alterations, different characteristics have been revealed, such as differences in ethnic prevalence, median age and alteration patterns. Consequently, beyond traditional chemoradiotherapy, molecular-targeted therapy and treatment with immune check-point inhibitors (ICI) also became available major therapeutic options. Interestingly, clinical results suggest that the recently established therapies target distinct lung cancer proportions, particularly between the EGFR/ALK and PD-1/PD-L1-positive subsets, e.g. the kinase inhibitors target driver mutation-positive tumours, whereas driver mutation-negative tumours respond to ICI treatment. These therapeutic efficacy-related differences might be explained by the molecular pathogenesis of lung cancer. Addictive driver mutations promote tumour formation with powerful transformation performance, resulting in a low tumour mutation burden, reduced immune surveillance, and subsequent poor response to ICIs. In contrast, regular tobacco smoke exposure repeatedly injures the proximal airway epithelium, leading to accumulated genetic alterations. In the latter pathway, overgrowth due to alteration and immunological exclusion against neoantigens is initially balanced. However, tumours could be generated from certain clones that outcompete immunological exclusion and outgrow the others. Consequently, this cancer type responds to immune check-point treatment. These pathogenic differences are explained well by the two-compartment model, focusing upon the anatomical and functional composition of distinct cellular components between the terminal respiratory unit and the air-conducting system.

Reconstruction of Complex Anterior Chest Wall Defects: The Lasagna Technique.

Sternal tumors are rare, comprising only 0.94% of all bone tumors, with the majority being sarcomas. An extensive composite defect is often the result of surgical resection. Reconstruction of this anatomical area is a challenge for plastic surgeons. Reconstruction must fulfil two different tasks: restoration of soft tissues and stabilization of the chest wall. Both are well defined, and many techniques have been historically proposed. We present the case of a 66-year-old man affected by sternal metastasis of lung non-small cell carcinoma with sarcomatoid features. After wide tumor resection, a large defect was created. The patient underwent a complex multilayer reconstruction that combined multiple techniques: Gore DualMesh to reconstruct the pericardial plane and protect the heart muscle, omental flap to facilitate integration of the mesh, titanium bars to recreate chest wall stability, and bilateral pectoralis muscle flaps to cover hardware. This multilayer reconstruction was named the "lasagna technique." Due to the rarity of primary malignancies of the sternum, it is difficult to standardize a therapeutic approach. For this reason, it is necessary to customize the surgical treatment by combining several techniques and materials. Our lasagna technique may be considered a valuable option in treating these complex reconstructive cases.

A novel risk score for venous thromboembolism in lung cancer patients: a retrospective cohort study

Background: Venous thromboembolism (VTE) is a common and potentially fatal complication in patients with lung cancer. This study aimed to develop and validate a risk score for early prediction of VTE in these patients. Methods: Four hundred and one patients with lung cancer from three pulmonology departments hospitalized between January 2011 and December 2021 were retrospectively assessed. The population was divided into two groups: a Development Group (182 patients) and a validation group (199 patients). In the development group, the risk score system was developed, via univariate and multivariate analyses, based on demographic and clinicopathological variables; it was then validated in the validation group. Results: The incidence of VTE was 26.8% in the development group. It was 25.8%, and 27.6% in the internal and external validation groups, respectively. Hemoglobin level &lt;10g/l, metastasis, histological type poorly or undifferentiated non-small cell carcinoma, and active smoking were the items of the risk score system. This score allowed proper stratification of patients with either high or low risk of VTE in the development group (c statistic =0.703). The patients in the development group were classified into 3 risk groups: low risk (scores 0-1), moderate risk (scores 2-3), and high risk (scores 4-5). When validated in the validation group, there was a moderate loss of predictive power of the score (c statistic=0.641), but the categorization of the patients by the score remained clinically useful. Conclusions: This risk score requires prospective validation studies on a nationwide scale in order to use it as a valid tool for the prevention of VTE in lung cancer.

Grey zones in respiratory cytology: Atypical or suspicious for malignancy and neoplasms of unknown malignant potential.

The purpose of pulmonary cytology is two-fold. First, to establish whether a pulmonary nodule is benign or malignant. Second, pulmonary cytology should classify the type of pathologic process present. When a pulmonary nodule is characterized as malignant, it is of high importance to further classify the malignancy as to type, with non-small cell carcinomas being sub-divided into adenocarcinomas, squamous cell carcinomas, and other types of non-small cell carcinoma. The World Health Organization Reporting System for Lung Cytopathology (WHORSLC) provides an important framework for reporting and classifying material obtained by cytologic techniques, including sputum analysis, bronchial brushings, bronchial washings, and fine-needle aspiration. The system contains five categories for specimen reporting. Clinicians prefer definitive diagnoses separating specimens into definitively benign or definitively malignant categories. The WHORSLC recognizes that it is not invariably possible for cytopathologists to separate specimens into definitively benign or definitively malignant categories. The five categories of the WHORSLC recognize the spectrum of cytologic changes running from clearly benign to clearly malignant, which cytopathologists must place into diagnostically useful and reproduceable categories. The intermediate categories of "atypical" and "suspicious for malignancy" provide structured categories with stringent definitions, estimated malignancy risks, and suggested management and follow-up recommendations. In this way, the categories "atypical" and "suspicious for malignancy" aid in maintaining the high diagnostic accuracy of the "benign" and "malignant" categories.

THU503 An Unusual Case Of Ectopic ACTH Syndrome Secondary To Non-small Cell Lung Cancer

Abstract Disclosure: N. Hernandez: None. E. Askar: None. J.R. Fredrick: None. R.C. Schulman-Rosenbaum: None. Background: Cushing syndrome (CS) is a clinical entity characterized by HTN, DM, peripheral edema, hypokalemia, metabolic alkalosis, and myopathy. CS can be clinically classified into Corticotropin-dependent vs Corticotropin-independent processes. Those categorized as corticotropin dependent can further be subclassified into Eutopic CS (i.e. from the pituitary) vs Ectopic CS (i.e. extra-pituitary). The extra-pituitary source of ACTH most often comes from intra-thoracic neoplasms, of which small cell lung cancer (SCLC) is the most prevalent. However, here we present a case of a patient with Ectopic ACHT Syndrome (EAS) due to non-small cell lung cancer. Clinical Case: 87-year-old woman with pmhx of RA and HTN was admitted for 2-week history of constipation and lower abdominal pain. Physical exam was notable for hypertension and tachycardia, along with lower abdominal tenderness. Laboratory results showed WBCs of 32,000 (3,800-10,500), K of 2.7 mmol/L (3.5-5.5 mmol/L) and HCO3 was 38 mmol/L (22-29 mmol/L). CT chest and abdomen showed a left perihilar necrotic mass 6.6 X 6.0cm, with loco-regional lymphadenopathy with destructive osseous lesion on the right pedicle of L1 and metastatic disease to the liver and adrenal glands. Paraneoplastic ACTH production was suspected in the setting of metastatic lung cancer. Serum ACTH level was 105 pg/mL (7.2-63.6 pg/mL). Initial 8AM cortisol was 41 ug/dL (6.8-18.4 ug/dL) and 24 hr urine cortisol was 2327 mcg/24 h (3.5-45 mcg/24 h) which proved the diagnosis of ACTH-dependent hypercortisolemia. The AM cortisol was 62.3 ug/dL (6.0-18.4 ug/dL) after the 1mg dexamethasone test consistent with hypercortisolemia secondary to ectopic ACTH. IR biopsy of the right axillary LN showed poorly differentiated non-small cell carcinoma with squamous differentiation. The patient was started on chemotherapy, as well as, mifepristone 300 mg daily and ketoconazole 200 TID for hypercortisolism. She was also considered for Metyrapone. However, cortisol levels did not improve despite optimized therapy due to the aggressive nature of the cancer. Later chemotherapy was discontinued and was discharged on hospice with ketoconazole and mifepristone. Conclusion: EAS is associated with neuroendocrine tumors of which up to 50% are caused by SCLC and rarely with adenocarcinoma. However, our case is novel as the source of ACTH was a lung tumor of squamous cell origin. Treatment strategies for ACTH secreting tumors combine chemotherapy as well as medications that target the hormonal imbalance such as steroidogenesis inhibitors and cortisol receptor blockers. Unfortunately, patients with ACTH producing tumors tend to have low median survival rates which limits our ability as clinicians to determine the effectiveness of such interventions. Given the uniqueness of her case, it would be even harder to predict the type of clinical response obtained from such treatment. Presentation: Thursday, June 15, 2023

SAT531 Thyroid Metastasis From Non-small Cell Lung Cancer: An Unusual Case Presentation

Abstract Disclosure: E.Y. Ibrahim: None. I. Guillen Alvarez: None. I. Hulinsky: None. D. Regelmann: None. C. Janowiecki: None. Background: Cases of thyroid tumors metastasizing from the lungs are rare, and their diagnosis is often challenging and can be mistaken for primary thyroid tumors or subacute thyroiditis. Thyroid function tests are typically normal and not helpful in establishing the diagnosis. Ultrasonography commonly shows focal or diffuse hypoechoic lesions. Correspondingly, heterogeneous hypodense areas with mild contrast enhancement are seen on CT scans. Clinical Case: Our patient is a 61-year-old male with a history of diabetes mellitus and 40 years tobacco use, who presented with a 1-week history of right-sided weakness and 3-weeks of dry cough. The weakness of his leg progressed to the point he could not ambulate. Initially, he was evaluated for a stroke and underwent CT imaging showing extensive lesions of the bilateral frontal, temporal, and parietal lobes. These findings were suspicious, and confirmed by MRI, to reflect multifocal metastatic lesions with vasogenic edema. Initial physical examination revealed a palpable thyroid nodule in the right lobe with bilateral cervical lymphadenopathy. CT of the neck demonstrated lymphadenopathy as well as multiple bilateral hypoechoic thyroid nodules, the largest of which measured 0.8 cm in the right thyroid lobe. TSH was 0.34 (0.48-4.17mU/L) with Free T4 at 1.39 (0.8-1.90ng/dL). The patient had denied symptoms of heat intolerance, tremor, or palpitations. A CT chest with contrast found a 3.5 cm cavitary lesion in the right upper lobe concerning for a primary lung neoplasm, as well as multiple bilateral lung nodules, mediastinal and hilar lymphadenopathy, and bilateral adrenal masses. Subsequent ultrasound-guided biopsy of the thyroid tumor revealed histologic features of a poorly differentiated non-small cell carcinoma, with features of a primary lung origin. These features were also present on a concurrent fine needle biopsy of an enlarged cervical lymph node. Immunohistochemistry staining showed the tumor was highly expressive for PDL1, focally positive for p40, pancytokeratin AE1/AE3, and negative for TTF-1 and thyroglobulinDue to the vasogenic cerebral edema, he was given dexamethasone with good response, and his weakness improved to the point that patient was able to ambulate. Treatment also included radiation therapy with subsequent pembrolizumab upon completion of radiotherapy. Conclusion: Several thyroid lesions representing metastases may go unnoticed because the physician’s attention toward lesions at other, more common sites, and detailed thyroid examination can be commonly overlooked. Patients with newly diagnosed malignancies should also be screened for thyroid involvement, including detailed physical, radiographic, and histologic examination of pathologic findings. Presentation Date: Saturday, June 17, 2023

A rare case of pulmonary endobronchial spindle cell carcinoma with liver metastasis along with concurrent cutaneous neurofibroma

Spindle cell carcinoma is one of the histological variants of pulmonary sarcomatoid carcinoma. It is a rare, poorly differentiated, highly malignant, and rapidly growing non-small cell carcinoma of the lung. Information about pulmonary spindle carcinoma incidence, clinical features, and immunohistochemical markers are not well known compared to other variants of sarcomatoid carcinoma. Most sarcomatoid carcinoma features mimic non-small cell carcinoma, so it is easily misdiagnosed. Cutaneous neurofibroma with primary lung spindle cell carcinoma has not been reported in any previous literature. Here we report a rare endobronchial sarcoma with liver metastasis and concurrent skin neurofibroma.

Selected-Lesion Stereotactic Radiosurgery in Treatment of Patients with Multiple Brain Metastases: A Single Institution Retrospective Study

Stereotactic Radiosurgery (SRS) has been increasingly used as first and subsequent-line treatments for brain metastases. While the appropriate cut-off number of lesions for SRS is still being debated nationally in patients with multiple brain metastases, some institutions use an alternate approach particularly for patients with >10-15 lesions. Selected-lesion SRS (SL-SRS) is where only a subset of lesions are chosen for initial SRS treatment leaving small and clinically inconsequential lesions for treatment using alternate or delayed treatments. This study aims to investigate the patient selection criteria, patient and tumor characteristics and analyze the outcomes in patients receiving SL-SRS for brain metastases at our institution. Clinical data from patients treated using the SL-SRS approach from 2012-2022 at our institution were retrospectively reviewed. Patients were divided into cohorts based on overall survival from time of SL-SRS treatment and indications for using SL-SRS. We compared the patient characteristics (age, histology, KPS, dsGPA), tumor characteristics (cumulative tumor volumes, tumor dose, number of brain metastases found, number of metastases treated), treatment characteristics (chemotherapy, immunotherapy, previous SRS/ radiation, previous WBRT) and the reason for decision to recommend SL-SRS across these cohort. A total of 102 patients were treated using the SL-SRS approach. Indications for using SL-SRS were immunotherapy trial (n = 40), CNS penetrating drug options available (n = 18), patient refusing WBRT (n = 6), palliative after prior WBRT/SRS (n = 28), WBRT planned to follow SRS (n = 9). 31 patients were alive at 12 months and 21 patients at 24 months. In patients surviving <12 months - the most common indications for SL-SRS were CNS palliation in the setting of progressive disease after prior WBRT or SRS. Patients in this group had median KPS< = 60 and had predominantly non-small cell carcinoma primary diagnosis. In those patients surviving >12 months - the most common indication for SL-SRS was participation in CNS-penetrant agent clinical trials without WBRT. Patients in this group were more likely to be female, had a median KPS of 90, had predominantly diagnoses of melanoma. Following the SL-SRS treatment, 14 patients required further SRS and 4 patients went on to WBRT in the >12-month survival group. No patients died of CNS progression alone. 10 patients survived 24 months without requiring further CNS radiation. In our institution, SL-SRS has predominantly been used either as palliative treatment at time of disease progression or to facilitate entry onto clinical trial with immunotherapy or potentially CNS-penetrant agents. The latter indication resulted in 47.6% patients surviving >24 month without the need for additional radiation to the CNS and therefore SL-SRS should be considered a feasible, safe and effective alternative to either WBRT or SRS treatment of all radiographically visible brain metastases.

Pathologic Nodal Staging Before SBRT for Early-stage NSCLC Does Not Impact Overall Survival: A Propensity Score-matched NCDB Analysis.

Stereotactic body radiation therapy (SBRT) for early-stage non-small cell carcinoma of the lung (NSCLC) is increasingly utilized. We sought to assess overall survival (OS) for early-stage NSCLC patients receiving SBRT depending on staging method. Early-stage NSCLC patients treated with definitive SBRT were identified in the National Cancer Database (NCDB), and OS was determined based on method of staging. Patient, disease, and treatment characteristics were also analyzed. A total of 12,106 patients were included; 865 (7%) received invasive staging (nodal sampling, NS) and 11,241 (93%) had no nodal sampling (NNS). From this larger dataset, a propensity score matching (1:1 without replacement) was performed, which yielded 839 patients for each group (NNS and NS). With a median follow-up time of 3.12 years, median survival for all patients included in the matched dataset was 2.75 years (95% CI: 2.55-2.93y), with 2- and 5-year OS estimated at 63.9% and 25.7%, respectively. In a multivariable analysis on matched data, there was no difference in mortality risk between the NNS and NS groups (hazard ratio=1.08, 95% CI: 0.94-1.24, P =0.25). Negative prognostic factors identified in the multivariable analysis of the matched data included: age more than 65, male sex, Charlson-Deyo Score ≥1, and tumor size ≥3cm. SBRT use in early-stage NSCLC steadily increased over the study period. Most patients proceeded to SBRT without nodal staging, conflicting with National Comprehensive Cancer Network (NCCN) guidelines which recommend pathologic mediastinal lymph node evaluation for all early-stage NSCLC cases, except stage IA. Our findings suggest similar OS in patients with early-stage NSCLC treated with SBRT irrespective of nodal staging. Furthermore, we highlight patient-related, disease-related, and treatment-related prognostic factors to consider when planning therapy for these patients.