Non-small Cell Carcinoma Research Articles

CircCCDC66: Emerging roles and potential clinical values in malignant tumors.

Circular RNAs (circRNAs) are endogenous non-coding RNAs (ncRNAs) with a closed-loop structure. In recent years, circRNAs have become the focus of much research into RNA. CircCCDC66 has been identified as a novel oncogenic circRNA and is up-regulated in a variety of malignant tumors including thyroid cancer, non-small cell carcinoma, gastric cancer, colorectal cancer, renal cancer, cervical cancer, glioma, and osteosarcoma. It mediates cancer progression by regulating epigenetic modifications, variable splicing, transcription, and protein translation. The oncogenicity of circCCDC66 suppresses or promotes the expression of related genes mainly through direct or indirect pathways. This finding suggests that circCCDC66 is a biomarker for cancer diagnosis, prognosis assessment and treatment. However, there is no review on the relationship between circCCDC66 and cancers. Thus, the expression, biological functions, and regulatory mechanisms of circCCDC66 in malignant tumor and non-tumor diseases are summarized. The clinical value and prognostic significance of circCCDC66 are also evaluated, which can provide insights helpful to those exploring new strategies for the early diagnosis and targeted treatment of malignancies.

Whole Mitochondrial Genome Analysis in Non-Small Cell Lung Carcinoma Reveals Unique Tumor-Specific Somatic Mutations.

Mitochondria and mitochondrial DNA have been suggested to play a role in cancer initiation and progression. Knowledge of mitochondrial DNA could provide a breakthrough to advance cancer management. To identify the mitochondrial DNA landscape in non-small cell lung carcinoma. The adenocarcinoma set consisted of 365 pairs of adenocarcinomas and normal lung tissues, whereas the metastasis set included 12 primary non-small cell carcinomas, 15 metastatic tumors, and their normal counterparts. Tumor-specific somatic variants were identified, and if a variant showed heteroplasmy, the proportion of minor alleles was evaluated. Variants with greater than 10% change in allele frequency between tumor and normal pairs were identified as "heteroplasmic shifts." Tumor-specific variants appeared throughout the whole mitochondrial genome, without a common hot spot. Distinct variant profiles were seen in 289 (79.18%) of all individual adenocarcinomas. The presence of a unique profile and the number and loading of heteroplasmic shifts in tumors increased with higher stage or lymph node metastasis, and were related to shorter survival. In the metastasis set, the primary tumor variants were generally found in metastatic tumors. This study shows that somatic mitochondrial DNA mutations present with diverse locations and unique profiles in each individual tumor, implying their clinicopathologic utility.

Safety, feasibility, and effectiveness of a CT-guided transthoracic lung and pleural biopsy - a single-centre experience with own low-dose protocol.

To assess the efficacy and safety of a low-dose, computed tomography (CT)-guided transthoracic biopsy of lung and pleural lesions. A total of 135 low-dose, CT-guided transthoracic lung and pleural lesions biopsies were performed. A cutting needle was utilized in 124 cases, and fine needle aspiration biopsy was performed in 14 cases. In all cases, 14- to 22-gauge biopsy needles were used. Diagnostic material was obtained in 111 (82.2%) patients. In 97 (71.8%) cases neoplastic lesions were found, predominantly adenocarcinoma and non-small cell carcinoma. In 14 (12.6%) cases non atypical cells were reported. Biopsy failed to obtain material suitable for histopathological examination in 24 (17.7%) cases. Complications occurred in 31 patients, including pneumothorax in 28 patients and haematoma in 3 cases. Based on the obtained results, it can be stated that low-dose, CT-guided transthoracic biopsy of lung and pleural tissues is an accurate and safe procedure. Also, it is linked to a low risk of complications such as a small pneumothorax.

Non-Small Cell Lung Cancer Presenting as Anterior Nasal Mass and Epistaxis.

Lung malignancy presentation with an uncommon metastatic site is a diagnostic challenge and often associated with poor prognosis. Nasal cavity is a rare metastatic site for any type of lung cancer. We report an unusual case of poorly differentiated adenosquamous carcinoma of the lung with widespread metastasis presenting as a right vestibular nasal mass with epistaxis. A 76-year-old male patient with chronic obstructive pulmonary disease and 80 pack-year smoking history presented with spontaneous epistaxis. He reported a new rapidly growing right-sided nasal vestibular mass first noticed 2 weeks prior. Physical examination showed fleshy mass with crusting in right nasal vestibule along with a left nasal domus mass. Imaging revealed an ovoid mass in the right anterior nostril and a large mass in the right upper lobe of the lung (RULL) along with thoracic vertebral sclerotic metastasis and large left frontal lobe hemorrhagic lesion with severe vasogenic edema. Positron emission tomography scan showed large right upper lobe mass and suspected to be the primary malignancy along with widespread metastasis. Biopsy of the nasal lesion revealed poorly differentiated non-small cell carcinoma with squamous and glandular features. The diagnosis of very poorly differentiated adenosquamous carcinoma of the lung with widespread metastasis was made. In conclusion, unusual metastatic sites with unknown primary lesions require a thorough diagnostic workup involving biopsy and extensive imaging. Lung cancer with unusual metastatic sites is inherently aggressive and associated with poor prognosis. Multidisciplinary treatment modalities should be employed keeping in view the functional status and comorbidities of the patient.

Endoscopic ultrasound to the rescue of pancoast tumour.

Dear Editor, A 48-year-old male presented with a two-month history of right-sided shoulder pain with right arm radiation and significant weight loss. A radiograph showed an opacity in the right upper zone. A 34 × 45 × 52 mm mass in the apex of the right lung was seen on contrast-enhanced computed tomography (CECT) [Figure 1a]. Magnetic resonance imaging (MRI) for local staging showed involvement of the right subclavian artery and nerve roots [Figure 1b]. A percutaneous biopsy was planned, but no safe window was available due to the clavicle and multiple vessels on the anterior aspect. Because of the proximity of the lesion to the oesophagus, the patient was referred for endoscopic ultrasound (EUS)-guided biopsy. EUS confirmed the findings of prior imaging [Figure 1c]. An initial attempt at EUS-guided fine-needle aspiration (FNA) with 22-G needle failed as the tumour was very hard. Hence, FNA of visualised subcarinal lymph nodes was performed with a 22-G needle followed by FNA of the tumour with a 19-G needle [Figure 2a]. After the procedure, the patient was observed for four hours and was discharged after confirming the absence of pneumothorax on chest radiograph. A final diagnosis of non-small cell carcinoma was made on pathological [Figure 2b] and cytological examination based on visualisation of clusters of large polygonal cells with round-to-oval vesicular pleomorphic nuclei with no evidence of malignancy in the mediastinal nodes. Because of an unresectable lesion, the patient was planned for a combination of induction chemotherapy and radiotherapy.Figure 1: (a) Contrast-enhanced computed tomography (CECT) of thorax showing a mass in the apex of the right lung. (b) Magnetic resonance imaging (MRI) showing involvement of the right subclavian artery (large arrow) and nerve roots of C8, T1, and T2 (small arrows), (c) Transoesophageal endoscopic ultrasound (EUS) showing a hypoechoic irregular lung mass located on top on lung parenchyma (asterisk) and encasing the subclavian artery anteriorly (arrow)Figure 2: (a) Endoscopic ultrasound-guided fine needle aspiration from lung mass, (b) Haematoxylin and eosin (H and E) staining of core lung mass biopsy, suggestive of non-small cell carcinoma of the lung (arrow)EUS has an established role in tissue acquisition from mediastinal lymph nodes, but data on EUS-guided sampling from lung mass remains limited. Transbronchial needle aspiration (TBNA) and endobronchial ultrasound-guided needle aspiration (EBUS-FNA) are the preferred modalities for the diagnosis and staging of lung cancer.[1] However, the tumour’s location at the apex of the lung makes them inaccessible to TBNA or EBUS-FNA. In such cases, tumours close to the oesophagus may be amenable to transoesophageal EUS-guided FNA. It also has the advantage of simultaneous sampling of mediastinal lymph nodes and other organs like the liver and adrenal for assessment of metastasis.[1] The present case highlights the utility of EUS for diagnosing lung tumours at inaccessible sites. A recent multicentric study from Italy reported the efficacy and safety of EUS-guided tissue sampling as a minimally invasive procedure for the diagnosis and staging of peri-oesophageal parenchymal lung lesions.[2] However, transoesophageal FNA from lung mass may be rarely associated with pneumothorax[3] and haemoptysis.[4] Hence, a check X-ray should be done to rule out pneumothorax before discharging the patient. Keeping in mind the possibilities of complications, EUS-FNA of the lung lesions should be done in centres with the availability of pulmonologist to immediately address the adverse events. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.

Relationship of Transforming Growth Factor-Βeta, C-Reactive Protein, and Lactate Dehydrogenase in Bronchial Washing with the Diagnosis of Non-Small Cell Carcinoma Lung Cancer

Background: Most lung cancer cases are diagnosed at an advanced stage. Bronchial washing fluid contains many inflammatory cytokines that play a role in the malignant process. The aim of this study was to analyze the relationship between TGF-β, CRP and LDH in bronchial washing fluid with diagnosis of non-small cell lung carcinoma (NSCLC). Method: This research is an observational analytical study with a cross sectional design at Prof. Ngoerah Hospital, Denpasar (May 2023-August 2023). Descriptive analysis describes subject characteristics and research variables. Normality test with Shapiro Wilk. Bivariate analysis uses the unpaired T test with a normal distribution and the Mann-Whitney test with a non-normal distribution, data in the form of mean and standard deviation. Multivariate analysis with logistic regression. Results: The total research samples were 37 samples. 23 samples were detected as non-small cell lung carcinoma; 14 samples as non-NSCLC. The research results showed a significant relationship between TGF-β levels and diagnosis of non-small cell lung carcinoma (346.11 ± 40.21 pg/mL) vs (290.01 ± 66.22) (p < 0.05) and a significant relationship between LDH levels and diagnosis of non-small cell lung carcinoma (140.38 ± 98.11 U/L) vs (56.62 ± 22.68) (p < 0.05). There was no significant relationship between TGF-β, LDH, CRP and histopathology, bronchoscopy lesions and cancer stage of non-small cell lung carcinoma. Conclusion: There is a significant relationship between TGF-β and LDH levels and diagnosis of non-small cell lung carcinoma. TGF-β and LDH levels are increased in non-small cell lung carcinoma.

Relationship of Tumor Necrosis Factor Alpha, Monocyte-Lymphocyte Ratio, and Neutrophil-Lymphocyte Ratio of Bronchial Washing Fluid with Histopathology, Stage, and Bronchoscopic Lesions of Non-Small Cell Carcinoma Lung Cancer

Background: Chronic inflammation has been shown to be closely associated with immunosuppressive conditions that support the microenvironment for tumorigenesis, tumor progression, and metastasis. The aim of this study was to assess the relationship of inflammatory cytokine levels TNF-a , neutrophil-lymphocyte ratio (NLR), monocyte-lymphocyte ratio (MLR) with histopathology, stage, and bronchoscopic features of non-small cell carcinoma lung cancer (NSCLC). Methods: This study was an analytical observational study with a cross-sectional design at the Prof. Dr. I.G.N.G Ngoerah Central General Hospital in January 2023 – September 2023. Data analysis was performed using the Mann-Whitney, Kruskal-Wallis and 2 independent sample t test. Results: There were 23 samples that met the inclusion criteria. The mean NLR, MLR, and TNF-a in this study were 8.939, 0.095, and 129.46 respectively. NLR was associated with KPKBSK histopathology (p = 0.026), KPKBSK stage (p = 0.003), tumour size classification (T) (p = 0.001) and metastasis (M) (p = 0009). MLR was associated with KPKBSK histopathology (p = 0.035). Smoking status had an influence on the relationship between MLR and KPKBSK histopathology (p = 0.032). TNF-a value was not associated with KPKBSK histopathology, bronchoscopic lesions, and stage. Smoking status had an influence on the bronchoscopic lesions of KPKBSK (p = 0.04). Conclusion: There are associations between MLR and NLR with histopathology of non-small cell carcinoma lung cancer. There is a relationship between NLR and the stage of non-small cell carcinoma lung cancer.

Clinicopathological Evaluation of Endobronchial Ultrasound Guided Transbronchial Needle Aspiration (EBUS-TBNA) in Diagnosis of Mediastinal Lesions

Background: The diagnosis of mediastinal lesions is not easy. Special techniques are indicated for evaluation and confirmation of diagnosis. Objectives: The aim of the study is the endobronchial ultrasound guided transbronchial needle aspiration (EBUS TBNA) is an important tool for clinicopathological evaluation as well as diagnosis of different mediastinal lesions. Materials and Methods: It was an observational study. EBUS-TBNA was done in eighty six patients. All these individuals have mediastinal pathology. Endobronchial aspiration was done from the lesions seen by ultrasonography and its cytomorphological analysis was done. Tissue morphology was also examined from cell block preparation. Immediate post procedure complications were monitored. Results: In the study, total eighty six (86) cases with adequate material were included. Fifty one (51) cases were granulomatous lymphadenitis, necrotizing granulomatous lymphadenitis were identified in 20 cases and 28 had non-necrotizing granulomas and only three cases are granuloma with suppuration. Tuberculosis was diagnosed in 23 patients (26.7% of granulomatous) and sarcoidosis was found in twenty eight cases (32.6% of granulomatous). Seventeen (19.8%) patients had malignant disorders. Out of 17 cases of malignancy, adenocarcinoma was the predominant (07cases), five cases were non-small cell carcinoma, small cell carcinoma was four cases and non-Hodgkin lymphoma was only one. Eighteen cases (20.9%) had cytological features of reactive lymphadenitis. During procedure no complications developed. Conclusions: For diagnosis of different mediastinal pathology and collection of adequate cytological as well as tissue material (cell block), EBUS TBNA is an important diagnostic procedure with minimal invasion.

Programmed Death Ligand 1 (PD-L1) Expression and its Association with Driver Mutations among Patients with Non-Small Cell Lung Cancer in a Private Tertiary Care Setting

Objective. The advent of immunotherapy has significantly changed the treatment and management of patients with advanced non-small cell lung cancer (NSCLC). Prior to initiation of immunotherapy,evaluation of programmed death ligand 1 (PD-L1) expression is required. One factor that affects PD-L1 expression in NSCLC is the presence of oncogenic driver mutations; however, little data on itsassociation is available, especially in the Philippine setting. The study aims to determine the prevalence of PD-L1 expression and its association with driver mutations among patients with non-small cell lung cancer in a private tertiary care hospital in the Philippines.Methodology. The study was undertaken for a period of two years from July 2017-July 2019 at St. Luke’s Medical Center and included 446 NSCLC samples. PD-L1 was evaluated by immunohistochemistry using 22C3 anti-PD-L1 antibody clone, EnVision FLEX visualization system on Autostainer Link 48. Patient demographics and data on driver mutation testing were recorded. Statistical analysis was performed using logistic regression.Results. PD-L1 expression was observed in 273 (61.20%) of 446 cases, 119 (61.20%) of whichdemonstrated high PD-L1 expression while 154 (34.50%) had low PD-L1 expression. There was nosignificant association between PD-L1 expression and EGFR mutation, ALK mutation, age, and gender.For histologic type, high PD-L1 expression was significantly associated with adenocarcinoma and non-small cell carcinoma, NOS.Conclusion. The overall prevalence of PD-L1 expression in non-small cell lung carcinoma is 61.20%based on the cases included. Although we did not find an association between PD-L1 expression andEGFR and ALK mutation, our study observed that ALK-mutated NSCLCs have 4.7 odds of having highPD-L1 expression, however, a higher sample size is warranted to truly determine significant association. The outcome of this study may provide help in the stratification of patients and predict those who will benefit from immunotherapy.

Analysis of Lung Cancer Cases Presenting in Outpatient Department of University Hospital of Nepal

Background Lung cancer is one of the leading cause of cancer related death. Most common histopathology of lung cancer is non-small cell carcinoma of which adenocarcinoma is the most common. There are limited number of studies done in Nepal to know different aspects of lung cancer.
 Objective To know demographic parameters of patients diagnosed as lung cancer in a university hospital. The study also aims to know the different histopathological diagnosis of lung cancer.
 Method All the patients presenting to outpatient department (Cardio Thoracic and Vascular unit) of Dhulikhel Hospital, if are diagnosed as cancer of lung/bronchus will be included in the study. The duration of the study was January 2017 to December 2021. The details on age, gender, presenting symptoms, histopathology of lung cancer, operability will be included in database and will be analyzed.
 Result There were total of 127 patients diagnosed as lung cancer. Male:female ratio was 1.7:1. Overall mean age was 63.23 years (SD 13.5 years, Range 19-89 years). Non small cell carcinoma was the most common type of lung cancer with 83.7%. In non small cell carcinoma, most common type was Squamous cell carcinoma followed by undifferentiated and Adenocarcinoma. Only five (3.93%) cases were in operable stage.
 Conclusion Despite the fact that lung cancer is one of the most common cancer, patients usually present late and mostly are not in operable stage. This study shows that squamous cell carcinoma is the most common histopathology in lung cancer cases.

Lung cancer presenting with central nervous system metastasis: Clinicopathological and molecular analysis of 171 cases

A subset of lung carcinoma presents initially with brain metastasis. Precise subtyping is mandatory for optimized treatment of these advanced aggressive carcinomas. We herein analyzed surgical biopsies from 171 Patients (99 males and 72 females aged 48–96; mean, 72), who presented with brain metastasis of lung cancer. In addition to conventional subtyping, we applied an extended immunohistochemistry (IHC) panel and performed several molecular tests looking for potential therapeutic targets other than EGFR mutations. Non-small cell carcinoma (NSCLC) comprised 157 (91.8 %) of cases: 109 (63.7 %) adenocarcinomas, 27 (15.8 %) squamous cell (SCC), 18 (10.5 %) large cell undifferentiated, 1 (0.6 %) adenosquamous and 2 (1.2 %) unclassified carcinomas. Of the adenocarcinomas, 81.7 % were TTF1+. Notably, 45 % of those TTF1-negative cases expressed HepPar1. SMARCA4 and SMARCA2 loss was observed in 13/171 (7.6 %) and 32/163 (19.6 %) cases, respectively; mainly TTF1- (40.0 %) and HepPar1+ (38.1 %) adenocarcinomas were affected by SMARCA2/4 loss. Loss of at least one mismatch repair (MMR) protein was observed in 3/156 (1.9 %) cases (2 adenocarcinomas and 1 large cell neuroendocrine carcinoma/LCNEC). Limited available data on mutation testing showed a frequency of EGFR mutations of 4.3% and of KRAS mutations of 57%. HER2 expression (2+/3+) was found in 45/166 (27.1 %) of cases with amplification verified by CISH in 18/38 (47.4 % of immunopositive cases and 10.5 % of the whole cohort); all but one were adenocarcinomas. Other genetic abnormalities detected included EML4::ALK rearrangements in 3 (1.8 %; 2 TTF1+ adenocarcinomas and 1 LCNEC) and RET rearrangements in one SCNEC. Variable subsets of tumors revealed amplifications of several potentially therapeutically targetable genes including MYC (30.0 %), MET (10.1 %), HER2 (10 %), FGFR1 (9.6 %), FGFR3 (4.6 %), and FGFR2 (3.4 %). This study highlights a highly heterogeneous molecular background in lung cancer presenting with CNS metastases. These findings highlight the need for individualized tumor testing strategies looking for potential therapeutic targets for this aggressive disease.

Clinical Outcomes, Treatment and Testing Patterns in Patients with Advanced Non-Small Lung Cell Cancer with Epidermal Growth Factor Receptor Mutations: Results of the Romanian Cohort From a Multi-national Retrospective Chart Review (REFLECT)

"Background: REFLECT was a retrospective, non-interventional study conducted in eight countries, including eleven sites from Romania, on patients with advanced stage non-small cell carcinoma (NSCLC). Aim: To characterize clinical outcomes, treatments and the proportion of T790M EGFR mutation testing in patients with advanced non-small cell lung cancer (NSCLC) receiving first- or second-generation (1G/2G) epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs ) as first-line (1L) treatment in the Romanian cohort of an international study. Methods: Comprehensive data were retrieved from the medical records of ninety patients with EGFR-mutated advanced NSCLC treated with 1G/2G EGFR TKIs between January 2015 and June 2018. All analyses are descriptive. Results: The median age at lung cancer diagnosis in the Romanian cohort was 67.5 years, with 68% females. The distribution of EGFR TKIs was 50% erlotinib, 31% afatinib, and 19% gefitinib. First line treatment was stopped in 76 (84%) patients due to progression (79%), toxicities (3%), the patient’s decision (1%) or surgery (1%). The median progression- free survival on 1L treatment was 12.0 months (95% CI 10.3-15.6), and the median overall survival from the start of first line therapy was 26.4 months (95% CI 22.4-34.2). EGFR T790M mutation testing was performed on 69% of patients at the time of progression on 1L therapy, with 57% of patients testing positive. Second-line (2L) therapy was started in 63% of patients discontinuing 1L therapy. Third-line treatment was started in 50% of patients discontinuing 2L treatment. Conclusion: Survival results mirrored those of randomized trials. The suboptimal T790M testing rate (69%) underlines the importance of reflex testing procedures, while attrition rates on 1L (26%) emphasize the need for an upfront selection of the most effective treatments."

Comments on "Clinical, radiological and histopathological profile of patients with endobronchial lesions on fibreoptic bronchoscopy" by Sarma et al.

Dear Editor, The article by Sharma et al. regarding endobronchial biopsy in 120 patients in northern India is an attempt to understand the clinical profile, etiology and pathology of the patients who presented with endobronchial findings.The article concluded that most of the population was middle-aged males with non-small cell carcinoma being the most common diagnosis. However, there are few important points to ponder and understand in the study.

Prognostic and predictive value of YTHDF1 and YTHDF2 and their correlation with tumor-infiltrating immune cells in non-small cell carcinoma.

YTH domain-containing family protein 1 (YTHDF1) or YTHDF2 play crucial roles in cancer immunotherapy. We examine the expression of YTHDF1, YTHDF2, CD8, CD4, and FOXP3 to identify their prognostic or predictive role for PD-1/PD-L1 inhibitor in non-small cell lung cancer (NSCLC). Immunohistochemical expression of YTHDF1, YTHDF2, CD8, CD4, and FOXP3 was investigated in 266 patients not receiving PD-1/PD-L1 inhibitors and in 59 patients receiving PD-1/PD-L1 inhibitors. Immunohistochemical results were verified using mRNA dataset obtained from The Cancer Genome Atlas (TCGA) database. Immunohistochemical expression of YTHDF1 or YTHDF2 was negatively associated with CD8- and CD4-positive T cells; however, the same expression was positively associated with FOXP3-positive T cells. YTHDF1 or YTHDF2 mRNA expression was also negatively associated with CD8- and CD4-positive T cells. Gene set enrichment analysis revealed that low YTHDF1 was related to immune hot tumor gene sets. Expression of YTHDF1 or YTHDF2 was negatively associated with expression of most immune checkpoints. YTHDF1 and YTHDF2 were predictive markers of response to PD-1/PD-L1 inhibitors. YTHDF1 or YTHDF2 expression was associated with better prognosis. YTHDF1 has an immune hot profile in both cell types, whereas YTHDF2 is only seen in adenocarcinoma. Low YTHDF1 or YTHDF2 reflects an immune hot tumor signature and may serve as a predictor or prognostic marker.

Misdiagnosis of Tuberculosis

Introduction: High incidence of tubercular cases in developingcountries, similar clinical presentation of tuberculosis andmalignancy, lack of adequate infrastructure, and lack ofproper follow up are the most common factors associated withmisdiagnosis.Case Summary: A 72 years old male CAME with complainsof cough with expectoration for 2 month, intermittent feverassociated with chills and rigors for 1 month, loss of appetiteand weight, intermittent pain in right side of the chest for1 month. Patient was a known smoker and alcoholic. Onauscultation bilateral air entry was decreased with occasionalrhonchi. Patient’s chest x-ray was suggestive of consolidationin right upper zone of chest. His sputum was negative forAFB from outside, patient started on ATT, 2 months prior todate of admission from private clinic on empirical basis thatwas continued till the date of admission. Patient showed noimprovement, even after 2 months of ATT. His chest X-Ray wassuggestive of right upper zone consolidation, patient had noprior radiography for comparison. He was continued on ATTas he had already taken treatment for 2 months from outside.Patient was tested negative for sputum AFB 1 and 2, CBNAATand culture.Patient presented to emergency after a gap of two monthsin state of drowsiness with complains of breathlessness andsevere right side chest pain. He was intubated in emergencyand managed on ventilator support. Patient recovered and aCECT thorax was done suggestive of likely possibility of rightlung upper lobe neoplasm with metastatic lymphadenopathywith possibility of multiple liver and bilateral adrenal metastasisand changes of chronic airways disease with fibro bullouschanges in bilateral upper lobe apical segments. The FNACwas positive for malignant cells with features suggestive of nonsmallcell carcinoma – (possibly adenocarcinoma). Patient wasfurther managed in the department of Radiation Oncology bychemotherapy. We discuss the radiographical progression andsubsequent investigations required to make a proper diagnosis.Conclusion: It is imperative to form a conclusive diagnosisusing available diagnostic modalities in smear negativetubercular cases to avoid delay in management of otherpossible life-threatening diseases like lung carcinomas.

Petals of rose: Application of rapid on-site evaluation in bronchoscopy

In present day scenario, procedures that are minimally invasive like FNAs and Core needle biopsies are on the rise. Rapid on-site evaluation (ROSE) is a laboratory service that assesses the cytomorphologic features from FNA smears or biopsy contact imprints in the biopsy room and can provide on the spot input and suggestions for the clinician through immediate cytological examination of the biopsy sample. ROSE also allows for a preliminary diagnosis, allowing for the requirement of additional material for ancillary studies. We are presenting two cases which highlights the merits of ROSE in cytological diagnosis. In the first case, a thirty four year old male patient came with complaints of productive cough, breathlessness and fever. Bronchoscopic needle aspiration and biopsy was done with Rapid Onsite Evaluation. ROSE revealed two non-caseating epithelioid granulomas on the 4th pass. Bronchoscopic lymph node biopsy was non- contributory. With other clinical and biochemical parameters, diagnosis of Sarcoidosis was made. This case study underscores the significance of ROSE in arriving at the diagnosis. In the other case, a fifty seven year old male patient came to hospital with productive cough and breathlessness (MMRC grade II). CT chest revealed features suggestive of bronchogenic carcinoma. ROSE was performed along with bronchial brush cytology in which presence of atypical cells with increased nuclear cytoplasmic ratio, nuclear hyperchromatism and nuclear molding was noted. On histopathological examination, it was diagnosed as a case of non-small cell carcinoma of lung – poorly differentiated type. This case proves the advantage of ROSE in avoiding repeated invasive procedures for the patient.

Supernatant Fluid from Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration for Rapid Next-Generation Sequencing

Abstract Introduction/Objective The aims of our study were to optimize the workflow of non-small cell carcinoma (NSCC) endobronchial ultrasound-guided bronchoscopy with transbronchial needle aspiration (EBUS-TBNA) samples to maximize tissue available for next-generation sequencing (NGS), preserve formalin-fixed paraffin-embedded (FFPE) cell blocks (CBs) for future testing, and shorten turnaround time (TAT) of NGS results. We evaluated the performance of supernatant fluid (SNF) processed from a dedicated aspirate for NGS testing. Methods/Case Report 20 EBUS-TBNA samples positive for NSCC on rapid on-site evaluation were collected and processed using a new workflow (Figure 1). Five aspirates were collected in formalin. One additional dedicated pass was collected fresh and centrifuged. The resulting cell pellet was added to the passes in formalin for FFPE CB processing. The SNF was recentrifuged. DNA and RNA were extracted from concentrated SNF for targeted testing using the Oncomine™ Precision Assay (Thermo Scientific™, Waltham, MA). NGS results from the corresponding FFPE CBs were used as “controls” for comparison. Results (if a Case Study enter NA) A total of 31 mutations were detected in SNF (Table 1). The most frequently mutated genes were TP53 (35%), EGFR (23%), KRAS (13%), CTNNB1 (6%), and ERBB2 (6%). EGFR and KRAS amplification, CDKN2A deletion, and SQSTM1-NTRK3 fusion alteration were also detected. There was 100% concordance between the mutations detected in SNF and corresponding FFPE CBs with comparable variant allele frequencies. TAT of NGS results was 1 day for SNF compared to 4 – 10 days for FFPE CB. Conclusion In our study, we were able to demonstrate the usefulness of NGS on SNF to provide reliable, rapid molecular results. This testing strategy was successfully incorporated into the workflow for tissue handling and processing between our clinical, cytopathology, and molecular teams. Molecular results were available at the same time as the cytologic diagnosis, allowing for timely reporting of a comprehensive diagnosis. This approach is particularly useful in patients with advanced disease requiring urgent management.

ODP170 Check Point Inhibitor Associated Multi-Endocrine Dysfunction Presenting With Euglycemic Ketoacidosis

Abstract Introduction Immune check point inhibitors have become breakthrough therapy for many types of cancers. They inhibit one of two immune regulatory pathways, the cytotoxic T-lymphocyte antigen 4 (CTLA-4), and 'programmed death-1' (PD-1) and (PD-L1) pathways. Removing immune regulation allows for anti-cancer immune responses. They also cause immune related endocrine dysfunction such as hypophysitis, thyroiditis, diabetes mellitus (DM) and primary adrenal insufficiency (AI). We describe a patient on Pembrolizumab (PEM) (an anti-PD-1 inhibitor) who presented with new onset DM, euglycemic diabetic ketoacidosis (DKA) with simultaneous secondary AI. Case report 54-year-old woman with stage 4 non-small cell carcinoma of the lung (NSCLC) with known brain metastasis, was under therapy with carboplastin, paclitaxel and PEM, presented with headache, blurry vision and altered mental status. She had past history of Graves’ disease s/p radioactive iodine therapy, currently on levothyroxine. For two weeks, she had decreased oral intake, and generalized weakness. Upon presentation, she was cachectic, BP 152/65, pulse 117 and confabulating. Laboratory evaluation showed: serum glucose 72 mg/dL, Na 139 mmol/L, K 3.2 mmol/L, Cl 113 mmol/L, HCO3 11 mmol/L, anion gap 15 mmol/L, beta-hydroxybutyrate 4.8 mmol/L, lactic acid 0.7 mmol/L, venous pH 7.2 and base excess -16.6 mmol/L. The delta-delta gap was 10 mmol/L, compatible with a mixed anion-gap and hyperchloremic acidosis (HCA). Antibodies to GAD-65, and Zinc transporter-8 were negative. To evaluate euglycemia despite DKA, levels were obtained for serum cortisol 1 mcg/dL, and ACTH <1 pg/mL confirming secondary AI. MRI neuroimaging showed several metastatic brain lesions, a small pituitary gland without stalk enhancement or thickening. Management of euglycemic ketoacidosis required high dose glucose infusion (>10 g/hour), stress doses of hydrocortisone (HC), and infusion of low chloride solute for HCA. Conclusion Awareness of the potential for multi-endocrine dysfunction, directed us towards the urgent institution of therapy for DKA with supplementation of stress dose HC for presumed AI, the latter as a cause of relative "hypoglycemia". Central AI was confirmed with undetectable levels of cortisol and ACTH. Although less frequent than with CTLA-4 inhibitors, PD-1 inhibitors are associated with hypophysitis even without abnormalities on pituitary MRI. The DM (associated with PD-1 inhibitors) although autoimmune is nature, is "antibody" positive approximately 50% of the time. Further therapy for both euglycemic DKA and HCA required adjustment of the conventional management for DKA. To our knowledge this is the first reported case of Euglycemic DKA and secondary AI due to PD-1 inhibitors per literature review. Reference: Walters AGB, BraatvedtG G. Endocrine adverse effects of immune check point inhibitors . Intern Med J. 2021Jul;51(7): 1016-1020. doi: 10.111/imj . 14992. PMID: 34278695. Hattersley R, Nana M,Lansdown AJ. Endocrine complications of immunopathies: a review . ClinMed(Lond).2021 Mar;21(2): e212-e222. doi: 10.7861/clinmed.2020-0827. PMID: 33762389;PMCID: PMC8002767 Presentation: No date and time listed

Changes in glycocalyx-related biochemical parameters during lung resection in non-small cell carcinoma cases : A pilot study

Objective: Non-small cell lung cancer (NSCLC) is one of the most common neoplasms with high mortality rates, and new studies are needed to understand its characteristics better. This study aimed to determine the changes in the glycocalyx structure related to surgery regarding histopathologic subtypes and to evaluate the correlation of these changes on the development of metastasis and mortality. Material and methods: Serum levels of hyaluronan, VEGF-A, FGF-10, BMP-2, and BMP-4 were measured before and after surgery in 42 patients with NSCLC. The alterations in serum levels of studied markers were evaluated as related to metastasis status and mortality in post-operative 18-24 months. Results: Our study included 15 adenocarcinoma and 27 squamous cell carcinoma cases. Pre- and post-operative values of serum hyaluronan, VEGF-A, FGF-10, and BMP-2 showed significant differences for the whole group (p=0.006, p=0.001, p=0.002, and p=0.004, respectively). Post-operative BMP-2 values also correlated with hyaluronan and VEGF-A values. Post-operative values of hyaluronan and VEGF-A values found incorrelation with metastasis and mortality, while BMP-2 with metastasis and FGF-10 with mortality. Serum values of hyaluronan, VEGF-A, FGF-10 and BMP-2 differed significantly in-between the pre- and post-operative measurements in adenocarcinoma cases (p=0.020, p=0.009, p=0.003, and p=0.011, respectively) , but not that of squamous cell carcinoma. Conclusion: Pre- and post-operative changes in serum hyaluronan, VEGF-A, FGF-10 and BMP-2 values may be associated with metastasis and/or mortality in NSCLC. These findings were also more prominent in adenocarcinoma cases, though further extended studies are needed for a better conclusion.

The Relationship Between Clinical Risk Factors and Patient’s Survival Rate in Non-Small Cell Lung Carcinoma Cases: A Cross-Sectional Study

Background: Non-small cell carcinoma (NSCLC) is the most common type of lung cancer. Risk factors for lung cancer include smoking, genetic factors, chronic lung disease, lung infections, radon exposure, air pollution, exposure to carcinogenic substances in the workplace and other risk factors. The significance of each of these risk factors differs by sex, race and region in a given country. Purpose: The study was conducted to assess the analysis of risk factors, treatment response and survival of NSCLC patients. Methods: Cross sectional and survival analysis, patients undergoing diagnostic and treatment at Dr. Wahidin Sudirohusodo Makassar period January 2017-December 2019. Anamnesis of risk factors and survival by telephone and patient medical record data. Results: There are 100 patients who fulfill the inclusion criteria; Subject characteristics were mostly male (64%), age >45 years (84%), Bugis ethnicity (50%), farmer occupation (27%), active smokers (60%), consume filter cigarettes (75%), and has severe brinkman index (BI) (51.6%). About 40% of the subjects were non-smokers, 50% of whom were passive smokers. Severe IB and high-risk occupations by type of KPKBSK were significant (p = 0.02 and p = 0.01). Age <45 years, median survival was better than age 45 years (8 months versus 4 months), p = 0.002. Subjects receiving EGFR-TKI had a better median survival of 7 months, platinum doublet 6 months, did not receive treatment for 2 months, p = <0.05. Conclusion: Brinkman Index (BI) and high-risk occupation based on NSCLC type are significant. Age < 45 years had a good median survival. Subjects who received TKI had a better median survival. Keywords: Non-small cell lung carcinoma, clinical risk factors, survival rate.