Non-calcified Pulmonary Nodules Research Articles

THU517 Aggressive Cushing’s: A Rare Case Of Pancreatic ACTHoma In A Young Female

Abstract Disclosure: O.C. Reyes: None. A. Sison: None. M. Villa: None. D. Dimayuga: None. Introduction: Adrenocorticotropic hormone-producing pancreatic neuroendocrine neoplasm (ACTHoma) is a rare type of pancreatic neuroendocrine tumor that causes ectopic adrenocorticotropic hormone syndrome. Cushingoid manifestations and metabolic abnormalities can occur rapidly. High index of suspicion is required for early diagnosis. Case: A 31-year-old Filipino female presented with facial and ankle swelling that occurred 6 weeks before the visit. She also had acne, easy bruising, amenorrhea and frequent mood swings. There was reported weight gain of 3 kg a month prior. She had no history of hypertension and diabetes, and had no unusual family history. At the time of admission, vital signs were blood pressure of 130/80mmHg, pulse of 92/min, respiratory rate 20/min and body temperature of 37.2C. Her body mass index was 28kg/m2. She had muscle atrophy of the upper and lower extremities, facial flushing, posterior cervical fat pad, abdominal violaceous striae, and skin pigmentation. Her external genitalia was normal, Tanner Stage 5 consistent with adult pattern. Neurologic exam was unremarkable. She was examined for Cushing’s syndrome. On initial tests, glucose was 406 mg/dl, HbA1C 10.7%, thyroid stimulating hormone 0.122 (NV: 0.55-4.78), Free T3 0.77 (NV: 2.3-4.2), Free T4 0.58 (NV: 0.89-1.76). Creatinine was 0.86 mg/dL, sodium was 140 mEq/L, potassium was 2.1 mEq/L showing hypokalemia. There was leukocytosis on her blood count, white blood cells 15,310/mm3 (neutrophils 94%, lymphocytes 3%). In the low-dose dexamethasone suppression test (DST), the serum cortisol concentration was 991.03nmol/L. Her adrenocorticotrophic hormone (ACTH) level was elevated at 577pg/mL. After high-dose DST, the serum cortisol concentration was > 1750 nmol/L. No tumor was observed on pituitary magnetic resonance imaging. On abdominal computed tomography (CT), a large, lobulated, heterogeneously-enhancing mass arising from the pancreatic body and tail measuring 7.5cm x 10cm x 10.9cm was seen. The mass had infiltrated the gastric fundus, and encased the splenic artery. Multiple non-calcified subcentimeter pulmonary nodules were observed on chest CT. CT-guided biopsy of the pancreatic mass was done. On microscopic examination, numerous atypical cells arranged with small clusters and sheets and scattered singly were found in the tumor. The cells had small to enlarged, hyperchromatic, ovoid to round nuclei and scant to ample delicate cytoplasm. On immunohistochemical staining, the tumor cells were stained positive for synaptophysin and chromogranin A, which are both neuroendocrine markers, as well as ACTH. However, the patient died prior to any definitive management. Conclusion: ACTHoma is a very rare disease that causes hypercortisolemia. Reporting of similar cases will provide insight into its clinical features, immunohistochemical characteristics, diagnosis, therapy, and prognosis. Presentation: Thursday, June 15, 2023

Accurate classification of pulmonary nodules by a combined model of clinical, imaging, and cell-free DNA methylation biomarkers: a model development and external validation study

There is an unmet clinical need for accurate non-invasive tests to facilitate the early diagnosis of lung cancer. We propose a combined model of clinical, imaging, and cell-free DNA methylation biomarkers that aims to improve the classification of pulmonary nodules. We conducted a prospective specimen collection and retrospective masked evaluation study. We recruited participants with a solitary pulmonary nodule sized 5-30 mm from 24 hospitals across 20 cities in China. Participants who were aged 18 years or older and had been referred with 5-30 mm non-calcified and solitary pulmonary nodules, including solid nodules, part solid nodules, and pure ground-glass nodules, were included. We developed a combined clinical and imaging biomarkers (CIBM) model by machine learning for the classification of malignant and benign pulmonary nodules in a cohort (n=839) and validated it in two cohorts (n=258 in the first cohort and n=283 in the second cohort). We then integrated the CIBM model with our previously established circulating tumour DNA methylation model (PulmoSeek) to create a new combined model, PulmoSeek Plus (n=258), and verified it in an independent cohort (n=283). The clinical utility of the models was evaluated using decision curve analysis. A low cutoff (0·65) for high sensitivity and a high cutoff (0·89) for high specificity were applied simultaneously to stratify pulmonary nodules into low-risk, medium-risk, and high-risk groups. The primary outcome was the diagnostic performance of the CIBM, PulmoSeek, and PulmoSeek Plus models. Participants in this study were drawn from two prospective clinical studies that were registered (NCT03181490 and NCT03651986), the first of which was completed, and the second of which is ongoing because 25% of participants have not yet finished the required 3-year follow-up. We recruited a total of 1380 participants. 1097 participants were enrolled from July 7, 2017, to Feb 12, 2019; 839 participants were used for the CIBM model training set, and the rest (n=258) for the first CIBM validation set and the PulmoSeek Plus training set. 283 participants were enrolled from Oct 26, 2018, to March 20, 2020, as an independent validation set for the PulmoSeek Plus model and the second validation set for the CIBM model. The CIBM model validation cohorts had area under the curves (AUCs) of 0·85 (95% CI 0·80-0·89) and 0·85 (0·81-0·89). The PulmoSeek Plus model had better discrimination capacity compared with the CIBM and PulmoSeek models with an increase of 0·05 in AUC (PulmoSeek Plus vs CIBM, 95% CI 0·022-0·087, p=0·001; and PulmoSeek Plus vs PulmoSeek, 0·018-0·083, p=0·002). The overall sensitivity of the PulmoSeek Plus model was 0·98 (0·97-0·99) at a fixed specificity of 0·50 for ruling out lung cancer. A high sensitivity of 0·98 (0·96-0·99) was maintained in early-stage lung cancer (stages 0 and I) and 0·99 (0·96-1·00) in 5-10 mm nodules. The decision curve showed that if an invasive intervention, such as surgical resection or biopsy, was deemed necessary at more than the risk threshold score of 0·54, the PulmoSeek Plus model would provide a standardised net benefit of 82·38% (76·06-86·79%), equivalent to correctly identifying approximately 83 of 100 people with lung cancer. Using the PulmoSeek Plus model to classify pulmonary nodules with two cutoffs (0·65 and 0·89) would have reduced 89% (105/118) of unnecessary surgeries and 73% (308/423) of delayed treatments. The PulmoSeek Plus Model combining clinical, imaging, and cell-free DNA methylation biomarkers aids the early diagnosis of pulmonary nodules, with potential application in clinical decision making for the management of pulmonary nodules. The China National Science Foundation, the Key Project of Guangzhou Scientific Research Project, the High-Level University Construction Project of Guangzhou Medical University, the National Key Research & Development Programme, the Guangdong High Level Hospital Construction "Reaching Peak" Plan, the Guangdong Basic and Applied Basic Research Foundation, the National Natural Science Foundation of China, The Leading Projects of Guangzhou Municipal Health Sciences Foundation, the Key Research and Development Plan of Shaanxi Province of China, the Scheme of Guangzhou Economic and Technological Development District for Leading Talents in Innovation and Entrepreneurship, the Scheme of Guangzhou for Leading Talents in Innovation and Entrepreneurship, the Scheme of Guangzhou for Leading Team in Innovation, the Guangzhou Development Zone International Science and Technology Cooperation Project, and the Science and Technology Planning Project of Guangzhou.

DIPNECH: pragmatic approach, uncertainties, notable associations, and a proposal for an improved definition.

DIPNECH is an increasingly recognized entity that primarily affects middle-aged and elderly women. It is characterized by abnormal proliferation of pulmonary neuroendocrine cells (PNECs) and considered a preinvasive lesion for carcinoid tumorlets/tumors. Sometimes, DIPNECH is accompanied by constrictive bronchiolitis which usually manifests as chronic cough and/or dyspnea, along with airflow limitation on spirometry. The telltale imaging sign of DIPNECH is the presence of multiple noncalcified pulmonary nodules and mosaic attenuation on CT. However, these clinico-radiologic features of DIPNECH are characteristic but nonspecific; thus, histopathologic confirmation is usually necessary. DIPNECH has an indolent course, and only rarely leads to respiratory failure or death; progression to overt neuroendocrine tumor (carcinoid) of the lung occurs in a minority of patients. Of available therapies, somatostatin analogs and mTOR inhibitors are most promising. In this review, we provide an update regarding the diagnosis and management of DIPNECH and describe critical gaps in our understanding of this entity, including the central terms "diffuse" and "idiopathic". We also summarize the inconsistencies in definitions employed by recent studies and discuss the pitfalls of the DIPNECH definitions proposed by the World Health Organization in 2021. In this context, we propose an objective and reproducible radio-pathologic case definition intended for implementation in the research realm and seeks to enhance homogeneity across cohorts. Furthermore, we discuss aspects of PNECs biology which suggest that PNEC hyperplasia may contribute to the pathogenesis of phenotypes of lung disease aside from constrictive bronchiolitis and carcinoid tumorlets/tumors. Finally, we steer attention to some of the most pressing and impactful research questions awaiting to be unraveled.

Immunocyte count combined with CT features for distinguishing pulmonary tuberculoma from malignancy among non-calcified solitary pulmonary solid nodules.

Tuberculoma is the most common type of surgically removed benign solid solitary pulmonary nodule (SPN) and can lead to a high risk of misdiagnoses for clinicians. This study aimed to discuss the value of the immunocyte count combined with computed tomography (CT) features in distinguishing pulmonary tuberculoma from malignancy among non-calcified solid SPNs. Forty-eight patients with pulmonary tuberculoma and 52 patients with lung cancer were retrospectively included in our study. Univariate and multivariate analyses were conducted to screen the independent predictors. Receiver operating characteristic (ROC) analysis was performed to investigate the validity of the predictive model. The univariate and multivariate analyses revealed that a coarse margin, vacuole, lobulation, pleural indentation, cluster of differentiation (CD)3+ T-lymphocyte count, and CD4+ T-lymphocyte count were independent predictors for distinguishing pulmonary tuberculoma from malignancy. The sensitivity, specificity, accuracy, and the area under the ROC curve of the model comprising the CD3+ T-lymphocyte count were 79.2%, 75%, 74.5%, and 0.845 [95% confidence interval (CI), 0.759-0.910], respectively, and those of the model involving the CD4+ T-lymphocyte count were 77.1%, 78.8%, 77.1%, and 0.857 (95% CI, 0.773-0.919), respectively. Immunocyte count combined with CT features is efficient in distinguishing pulmonary tuberculoma from malignancy among non-calcified solid SPNs and has applicable clinical value.

Artificial intelligence assisted discrimination between pulmonary tuberculous nodules and solid lung cancer nodules

The differential diagnosis between pulmonary tuberculous nodules and solid lung cancer nodules is difficult and easy to be misdiagnosed in clinic. The data of clinic and image features of Chest CT with 70 cases of non-calcified pulmonary tuberculous nodules and 198 cases of solid lung cancer nodules confirmed by pathology in the Department of Thoracic Surgery or Respiratory and Critical Care Medicine, the First Affiliated Hospital of Chongqing Medical University from January to September 2020 were collected retrospectively. The characteristics of clinical and chest CT were compared between pulmonary tuberculous nodules and solid lung cancer nodules. The sensitivity, specificity, accuracy and negative predictive value in the two groups were compared between Artificial Intelligence assisted diagnosis system and manual image reading. The results found that the mean age, past tumor history, family history of tumor, CT image features of nodules includes mean diameter, short burr, blood vessel crossing in the pulmonary tuberculous nodules group were lower than those in the solid lung cancer group (p < 0.05). In 35 cases of pulmonary tuberculous nodules group and 63 cases of solid lung cancer nodules group with Dicom format thin-slice chest CT, the sensitivity of AI-assisted diagnosis was 98.98 %. The diagnosis specificity, accuracy and negative predictive value in the AI group (80.61 %, 92.06 %, 60.00 %) were much higher than these in the intermediate respiratory physicians (62.24 %, 76.19 %, 37.14 %, p = 0.004, 0.015, 0.044) respectively, and there was no significant difference between AI and senior radiologists. There are many similarities in clinical and CT image features between pulmonary tuberculous nodules and solid lung cancer nodules. The ability of AI-assisted diagnosis system is better than that of intermediate physicians, reaching the diagnostic level of senior physicians, which is conducive to homogenization and improvement of the differential diagnosis ability of physicians.

S2068 Malignant Colo-Duodenal Fistula in a Rare Anatomic Position

Introduction: The first case of malignant colo-duodenal fistula (MCDF) was reported in 1862 and since then only 70 MCDF cases had been reported. We describe a case of MCDF between the hepatic flexure and second part of the duodenum, a rarely observed anatomic location. Case Description/Methods: A 63-year-old male presented to an outside hospital with lethargy and a weight loss of 30 lbs over 3 months without any overt GI bleed and was found to be anemic. He had RUQ rebound tenderness and a positive stool occult blood test. A large duodenal ulcer was found on EGD that was concerning for malignancy. He was subsequently transferred to our hospital for further evaluation. CT abdomen showed a contrast-filled fistulous communication with associated circumferential wall thickening and luminal narrowing between the duodenum and the colon. Scattered noncalcified pulmonary nodules in both lungs were also observed. A repeat EGD showed a large, partially circumferential, friable ulcer in the first part of the duodenum with a fistulous tract connecting to the colon. A colonoscopy showed a fistulous tract with surrounding ulceration and adenomatous-appearing mucosa in the hepatic flexure of the colon connecting to the duodenum. The endoscope could not be advanced safely beyond the hepatic flexure due to edema around the fistulous tract. Pathology revealed invasive moderately differentiated adenocarcinoma with ulceration and detached fragments of small intestinal and colonic mucosa in the duodenal biopsies and invasive moderately differentiated adenocarcinoma with cells that were CK20+, SATB2+, and CK7− consistent with metastatic colorectal cancer in the colon biopsies. Surgical and medical oncology were consulted for management (Figure 1). Discussion: Most MCDF involve the second portion of the duodenum. In our patient, the fistula connected the first portion of the duodenum to the hepatic flexure of the colon. Although, 20% of hepatic flexure tumors are adherent to the duodenum, very few fistulate into it. Cross-sectional imaging with contrast studies help confirm and stage the primary tumor and fistulous tract by delineating extent of local invasion and evaluating for metastatic spread. Upper and lower endoscopy help demonstrate the fistulous communication and biopsy allows for a pathological diagnosis. Definitive treatment involves a surgical resection of the primary malignancy. However, but once the disease has progressed to point of fistulization or metastases, the overall prognosis is poor.Figure 1.: A, CT Abdomen with contrast showing colo-duodenal fistula (red arrow) B, EGD showing fistula in 2nd part of the duodenum (black arrow) and ulceration. C, Colonoscopy showing fistula (green arrow) in the hepatic flexure with ulceration and edema.

INVASIVE MOLD INFECTION AFTER LUNG TRANSPLANTATION PRESENTING AS A SINGLE PULMONARY NODULE

TYPE: Case Report TOPIC: Transplantation INTRODUCTION: Lung transplant recipients commonly develop invasive fungal infections, particularly in the early postoperative course, despite appropriate antifungal prophylaxis. CASE PRESENTATION: The patient is a 68-year-old woman who received a bilateral lung transplant (09/2020) due to idiopathic pulmonary fibrosis. She received antifungal prophylaxis as deemed appropriate by our transplant center. She presented 10 months after transplant with acute cough. DISCUSSION: The patient had an uncomplicated early postoperative course without evidence of acute cellular rejection or infection leading up to her presentation. At 10 months, she was admitted for acute cough and radiographic imaging concerning for a new pulmonary nodule. Chest CT confirmed a 7 × 7 mm superior segment, left lower lobe, solid, non-calcified pulmonary nodule. Bronchoscopic tissue biopsy revealed Aspergillus spp, and the patient was switched from itraconazole to isavuconazole. In the same admission, mold was identified, which prompted repeat chest CT showing a small cluster of nodules around the initial left lower lobe nodule. Biopsy confirmed acute, granulomatous pneumonitis with fungal elements consistent with Zygomycetes spp. Intravenous amphotericin was initiated, and repeat chest CT four weeks later showed a reduction in the cluster of nodules. Notably, the Cylex ImmuKnow (IK) assay measurements remained low, with values below 100 ng/mL, confirming her high levels of immunosuppression. CONCLUSIONS: A single pulmonary nodule in an immunosuppressed patient requires prompt diagnostic efforts, as fungal airway colonization is common and can progress rapidly despite prophylaxis. IK assays may provide objective evidence of over-immunosuppression, placing patients at higher risk of infection. DISCLOSURE: Nothing to declare. KEYWORD: Lung transplantation

Circulating genetically abnormal cells combined with artificial intelligence for accurate and non-invasive early detection on NSCLC.

3056 Background: Non-small-cell carcinoma (NCSLC) is the most common type of early lung cancer. Early detection of NSCLC is still a diagnostic challenge. Current clinical management of patients with pulmonary nodule is inefficient and may lead to misclassification, thus increasing healthcare expenses. Further, a few previous studies showed liquid biopsy and artificial intelligence (AI) platform on computed tomography (CT) imaging contributes to early NSCLC detection. Still, there is something lacking in a precise and authorized lung nodule classifier to minimize discomfort of patients. This study aims to evaluate the possibility and effectiveness of combining circulating genetically abnormal cells (CACs) with an AI platform on CT imaging to improve the diagnostic route for NSCLC. Methods: A prospective cohort of 101 in-patients was enrolled from Sep. 1, 2020 to Jan. 15, 2021, with non-calcified pulmonary nodules, ranging from 0.5 to 3 cm in diameter, indicated by CT. The participants' pulmonary nodules will be assessed by two evaluation tools: CAC detection on full blood and AI platform on CT imaging. The diagnostic performances of the two tools were evaluated in a blinded validation study respectively and combined in an open-label retrospective analysis. Results: 68 of enrolled patients were confirmed as NSCLC by pathology. The diagnostic performance of CACs for NSCLC detection was 80.9% for sensitivity and 87.3% for positive predictive value (PPV) while overall accuracy reaches 79.2%. AI platform showed a slight disadvantage as 78.6% for PPV and 73.5% for accuracy. 9 false-negative patients on CAC results could be reversed with a combination of AI platform on CT imaging, while sensitivity rises to 94.1%. However, of 33 benign nodules patients, 8 wrong diagnoses by CAC detection could decrease to 2 when combined with the results from the AI platform, which may avoid unnecessary biopsies. Conclusions: Coupling CAC with an AI platform on CT imaging could be a useful strategy to improve the diagnostic route for NSCLC and avoid unnecessary biopsies.[Table: see text]

Malignant Testicular Paraganglioma: The Importance of Adequate Clinical Follow-Up

Background: Paragangliomas (PGL) are rare neuroendocrine tumors derived from neural crest cells. The presence of metastases is the only absolute criterion of malignancy. Clinical Case: A 59 y.o. male patient reports the appearance of a tumor in the right inguinal region operated in 2014 with tumor removal and right orchiectomy, with anatomopathological (AP) outcome spermatic cord adenomathoid tumor and immunohistochemistry (IHC) compatible with PGL: Ki-67 1% (S 100 diffusely positive protein), diffusely positive chromogranin A, weak positive CD99. However, no new tests were performed in the follow-up. After 5 years, the patient started to present sporadic episodes of sweating, palpitations and increased tension levels after doxazosin suspension. Investigation for reoccurrence with Urinary Catecholamines: Noradrenaline (VR< 97 mcg/24h) 112/179, Adrenaline (VR< 27 mcg/24h) 4/4, Dopamine (< 500 mcg/24h) 184/ 342, Plasma Metanephrines: Normetanephrines (VR< 196 pg/ml) 880.7/ 2402 Metanephrines (VR< 65 pg/ml) 44.6/ 53.1. Tests was performed: chest CT Multiple bilateral non-calcified pulmonary nodules with contrast enhancement, measuring 1.2 cm. Abdominal CT: Two retroperitoneal solid lesions located anteriorly to the inferior vena cava and aorta, in a discretely paramedian position on the right, intense arterial enhancement, with a hypoattenuating center. The largest lesion is located just below the emergence of the renal arteries and after the head of the pancreas and third portion of the duodenal. It measures 4.4 x 3.2 x 4.4 cm (LL x AP x CC). The smallest lesion is immediately inferior to the largest and measures 3.1 x 2.6 x 3.6 cm (LL x AP x CC). The lesions have contact with retroperitoneal vascular structures, notably with the inferior vena cava and with the vascular pedicle of the right kidney. Scintigraphy with MIBG: Radiopharmaceutical hyperconcentration in focal areas in the projections of lung fields, in greater number on the left, with intensity of uptake varying from mild to moderate; two contiguous focal areas in the median projection of mesogastrics, in moderate/acentuated degree. Patient was reoperated and removed abdominal lesions with new conclusive AP for PGL whit PASS 3, currently performing therapeutic MIBG for thoracic injury control. Clinical Lesson: Patients with lesions suggestive of PGL but without confirmatory AP should request IHC and clinical follow-up will be according to the findings in it.

Evaluating the diagnostic accuracy of a ctDNA methylation classifier for incidental lung nodules: protocol for a prospective, observational, and multicenter clinical trial of 10,560 cases.

BackgroundLung nodules are a diagnostic challenge. Current clinical management of lung nodule patients is inefficient and therefore causes patient misclassification, which increases healthcare expenses. However, a precise and robust lung nodule classifier to minimize discomfort for patients and healthcare costs is still lacking. The aim of the present protocol is to evaluate the effectiveness of using a liquid biopsy classifier to diagnose nodules compared to physician estimates and whether the classifier can reduce the number of unnecessary biopsies in benign cases.MethodsA prospective cohort of 10,560 patients enrolled at 23 clinical centers in China with non-calcified pulmonary nodules, ranging from 0.5 to 3 cm in diameter, indicated by LDCT or CT will be included. After signed consent forms, the participants’ pulmonary nodules will be assessed using three evaluation tools: (I) physician cancer probability estimates (II) validated lung nodule risk models, including Mayo Clinic and Veteran’s Affairs models (III) ctDNA methylation classifier previously established. Each patient will undergo LDCT/CT follow-ups for 2 to 3 years and their information and one blood sample will be collected at baseline, 3, 6, 12, 24 and 36 months. The primary study outcomes will be the diagnostic accuracy of the methylation classifier in the cohort. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) will be used to compare the diagnostic value of each testing tool in differentiating benign and malignant pulmonary nodules.DiscussionWe are conducting an observational study to explore the accuracy of using a ctDNA methylation classifier for incidental lung nodules diagnosisTrial registrationClinicaltrials.gov NCT03651986.

ATRIAL FIBRILLATION WITH CARDIAC TAMPONADE AS A FIRST SIGN OF UNDERLYING MALIGNANCY

SESSION TITLE: Medical Student/Resident Cardiovascular Disease Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: While cardiac tamponade is unusual as the initial presentation of malignancy, malignant pericardial tamponade presenting as atrial fibrillation is even rarer. We present a case of atrial fibrillation with cardiac tamponade who was subsequently diagnosed with pulmonary adenocarcinoma CASE PRESENTATION: A 65-year-old woman presented with concerns of exertional shortness of breath for 1 week with dry cough, fatigue, and chest tightness, with a sudden worsening of respiratory symptoms and palpitations. She was hypotensive, tachycardic, and afebrile. Auscultation revealed muffled heart sounds and she had jugular venous distension. Her electrocardiogram showed atrial fibrillation with rapid ventricular response and no acute ST-segment changes. Chest x-ray showed blunting of her bilateral costophrenic angles with cardiomegaly, but no acute infiltrate. Computed tomography (CT) revealed moderate bilateral pleural effusions, moderate pericardial effusion (2-cm thickness), and bilateral noncalcified pulmonary nodules, with the largest measuring 1.7 x 2.4 cm at the left upper lobe (Image 1). Transthoracic echocardiogram revealed moderate to large pericardial effusion with early tamponade physiology (Image 2). She received emergent pericardial window surgery with drainage of exudative pericardial fluid. Cytological analysis revealed tumor cells positive for Ber-EP4, CK-7, and TTF-1 and negative for CK-20, PAX-8, and calretinin, consistent with metastatic adenocarcinoma likely from the lung. The patient had marked symptomatic improvement after the procedure, and her cardiac rhythm reverted to sinus rhythm. DISCUSSION: Nearly 18%–20% of autopsies performed on cancer patients show involvement of the heart or pericardium. Malignant pericardial effusions can occur by direct invasion of cancer or by metastatic invasion via the lymphatics or hematogenous spread. Tamponade physiology in patients with malignant pericardial effusion is associated with immediate mortality in up to 85% of cases. The association of atrial arrhythmias with cardiac tamponade is rare in the literature, and the association with malignant pericardial effusion is even rarer. Two cases in the literature report cardiac tamponade with atrial fibrillation as the first manifestation of malignancy—both were lymphoid in origin. This is the first case of newly diagnosed solid pulmonary tumor manifesting as atrial fibrillation with malignant pericardial tamponade. CONCLUSIONS: Despite its rarity, malignant pericardial tamponade with atrial fibrillation and rapid ventricular rate should be recognized and managed promptly to mitigate a potentially life-threating condition. Reference #1: Krisanda TJ. Atrial fibrillation with cardiac tamponade as the initial manifestation of malignant pericarditis. Am J Emerg Med. 1990;8(6):531–533. doi:10.1016/0735-6757(90)90157-u Reference #2: Refaat MM, Katz WE: Neoplastic pericardial effusion. Clin Cardiol. 2011;34:593–598. DISCLOSURES: No relevant relationships by Mohamed Elmassry, source=Web Response No relevant relationships by Amr Ismail, source=Web Response No relevant relationships by John Makram, source=Web Response No relevant relationships by Haneen Mallah, source=Web Response No relevant relationships by Ximena Solis, source=Web Response No relevant relationships by Victor Test, source=Web Response

STRAIGHT TO THE LUNGS: UNUSUAL ETIOLOGY OF BILATERAL PULMONARY OPACITIES

SESSION TITLE: Medical Student/Resident Lung Cancer Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Extraskeletal myxoid chondrosarcoma (EMC) is a rare soft tissue sarcoma of chondroblastic origin by EWSR1-NR4A3 rearrangement. Its insidious nature frequently delays diagnosis. CASE PRESENTATION: 70-year-old male with a past medical history of hypertension presented with dyspnea at rest, fever, malaise, and productive cough without hemoptysis for one week. He is a retired electrical engineer with no recognized employment hazardous material exposure. He had mild recent mold exposure from home woodcutting, tree burning. Physical exam was significant for bilateral posterior lower lobe rhonchi on pulmonary auscultation. Labs revealed highly elevated CRP, mild leukocytosis, lactic acidosis, and elevated procalcitonin. Chest radiographs demonstrated left lower lobe infiltrates and multiple, bilateral soft tissue densities. He was started on broad-spectrum antibiotics for presumptive pneumonia. Chest CT demonstrated numerous bilateral noncalcified pulmonary nodules, the largest in the right lung measuring 3.7 cm, and the largest in the left lung measuring 3.6 cm; no hilar or mediastinal lymphadenopathy. Bronchoscopy and bronchoalveolar lavages showed no endobronchial lesions and were negative for cytological abnormalities or infection with negative bacterial, fungal, and mycobacterial cultures. CT-guided left lower lobe nodule biopsy was suggestive of low-grade myxoid neoplasm. PET-CT demonstrated diffuse pulmonary nodule uptake in addition to a hypermetabolic mass lesion in the left lateral thigh, 3.2 x 2.8 cm, with a maximum uptake value 3.9. Video-assisted thoracoscopy guided wedge resection of left lower lobe was then performed. Immunohistochemical staining from lung tissue was positive for vimentin, CD117, bcl2, p63, CD138. Fluorescence in situ hybridization revealed the presence of a fusion transcript and chromosomal rearrangement involving EWSR1 from t(9;22)(q22;q12), pathognomonic for extraskeletal myxoid chondrosarcoma. Biopsy of the left thigh mass confirmed primary disease origin. Patient followed up with an orthopedic oncologist and is currently on sunitinib, considering future wide local excision. DISCUSSION: Soft tissue sarcomas are rare, comprising 1% of adult malignancies with EMC accountable for <2% of all soft tissue sarcomas. Chromosomal reciprocal translocation of t(9;22)(q22;q12.2) resulting in fusion of EWSR1 to NR4A3 is responsible for carcinogenesis in 70-80% of cases, whereas another fusion gene, RBP56/TEC, is associated with translocation of t(9:17)(q22;q11.2) and comprises 15% of EMC. It has a high propensity to develop pulmonary metastases. Previous published reports have confirmed the therapeutic activity of sunitinib in EMC. Genotype/phenotype analyses support a correlation between chemotherapy response and EWSR1-NR4A3 fusion. CONCLUSIONS: We reported this rare etiology, its pathology and the diagnosis of bilateral pulmonary opacities, found to be metastatic EMC. Reference #1: Stacchiotti S, Pantaleo MA, Astolfi A, et al. Activity of sunitinib in extraskeletal myxoid chondrosarcoma. Eur J Cancer. 2014;50(9):1657–64. Reference #2: Hisaoka M, Hashimoto H. Extraskeletal myxoid chondrosarcoma: Updated clinicopathological and molecular genetic characteristics. Pathol Int. 2005;55:453–63. Reference #3: Oliveira AM, Sebo TJ, McGrory JE, Gaffey TA, Rock MG, Nascimento AG. Extraskeletal myxoid chondrosarcoma: A clinicopathologic, immunohistochemical, and ploidy analysis of 23 cases. Mod Pathol. 2000; 13:900–8. DISCLOSURES: No relevant relationships by Phyo Kyaw, source=Web Response No relevant relationships by Thomas Massutti, source=Web Response No relevant relationships by Peter White, source=Web Response

SUCCESSFUL PALLIATIVE CRYOABLATION AND RECANALIZATION OF INVASIVE FOLLICULAR THYROID CARCINOMA ENCROACHING INTO THE TRACHEA

SESSION TITLE: Fellows Procedures Posters SESSION TYPE: Fellow Case Report Posters PRESENTED ON: October 18-21, 2020 INTRODUCTION: Follicular Thyroid Carcinoma is a rare malignant tumor with an incidence of 5% of all thyroid carcinoma. Demographic profile for follicular thyroid carcinoma is male gender, age over 45 years, iodine deficiency and radiation exposure. Prognosis of follicular carcinoma are affected by tumor size, presence of distant metastases, age, gender, vascular invasion, and rare histologic type. While most thyroid carcinoma has good prognosis, tracheal invasion is an indicator of poor survival. Lesser invasive palliative procedures such as use of cryotherapy for recanalization and ablation are currently available that shortens hospital stay, reduces postsurgical complications, and improves quality of life. CASE PRESENTATION: A 24 year old female was referred to the Lung Center of the Philippines due to a tracheal mass noted on CT scan of the chest and neck which presented as hoarseness of voice and episodes of massive hemoptysis, started 8 months prior. Patient had poor recollection of a thyroid surgery from a surgical mission for enlarging neck mass 2 years preceding the referral. She noted of progressive exertional dyspnea and weight loss, yet denies fever and dysphagia. A repeat CT scan of the neck and chest showed a lobulated enhancing mass of about 2.3 x 2.6 cm at the right thyroidectomy bed encroaching into the trachea with 70% luminal narrowing. There were multiple non-calcified pulmonary nodules on both lungs. Patient underwent rigid bronchoscopic cryotherapy biopsy, ablation and recanalization of the tracheal mass by general anesthesia, total intravenous anesthesia via jet ventilation. On rigid bronchoscopy, there was noted a wide-base smooth mass attached to the anterior surface of the second and third tracheal ring, obstructing 70% the tracheal lumen. Frozen section of mass revealed atypical follicular cells favors thyroid carcinoma. Tracheal mass was signed out as invasive follicular thyroid carcinoma. Thyroid function test showed significant elevation of TSH at 31.927 IU/L, FT3 and T4 were within normal limits. Completion cryoablation was performed after a week. Patient was discharged stable, comfortable and non-oxygen requiring after 10 days of confinement. Patient underwent radioactive iodine treatment as outpatient. As of this writing, 10 months post cryotherapy, patient is still alive, up and about, no report of recurrence of hemoptysis, and non-dyspneic. DISCUSSION: Patient presented wilth metastic invasive follicular thyroid carcinoma. Palliative recanalization done for this patient has severed its purpose of relief of shortness of breath. Cryotherapy has been an adjunct to radioiodine therapy as palliative treatment. CONCLUSIONS: A 24 year old female with advanced invasive follicular thyroid carcinoma enchroaching to the tracheal lumen successfully underwent a palliative coring out and ablation of the tracheal mass using cryotherapy. Reference #1: Ito Y, Miyauchi A. Prognostic factors and therapeutic strategies for differentiated carcinomas of the thyroid. Endocr J 2009; 56(2): 177–9. Reference #2: Filipović A, et al. Invasive Follicular thyroid carcinoma infiltrating the trachea.Vojnosanit Pregl 2011; 68(10): 891–894. DISCLOSURES: no disclosure on file for Joven Gonong; No relevant relationships by Portia Maria Tanyag, source=Web Response

A RARE TWIST: LYMPHANGIOLEIOMYOMATOSIS PLUS DIFFUSE LARGE B-CELL LYMPHOMA

SESSION TITLE: Medical Student/Resident Diffuse Lung Disease SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Lymphangioleiomyomatosis (LAM) is a rare systemic disease resulting in cystic lung destruction, recurrent pneumothoraces, chylous pleural effusions, and abdominal tumors. This multisystem disease most commonly affects women of childbearing age, resulting in stepwise decline in pulmonary function, with clinically apparent hypoxemia developing in most patients within a decade after onset of symptoms. Here we present a rare case of late-onset LAM with concurrent high grade B-cell lymphoma. CASE PRESENTATION: The patient is a 62-year-old female nonsmoker with a remote history of spontaneous pneumothorax who presented due to pleuritic chest pain at rest. Chest CT revealed innumerable pulmonary cysts up to 15 mm, few solid noncalcified pulmonary nodules, multiple complex mediastinal lesions, and a 30% left anterior pneumothorax. Chest tube was placed; the patient was admitted. A nontender swelling was noted on the skull which the patient attributed to a work injury several months prior. MRI showed a 5 cm lytic lesion involving the left frontal bone and subgaleal space with hypercellular diffusion pattern. Craniectomy with resection was performed; pathology revealed high-grade B cell lymphoma. CT abdomen revealed a 4x4 cm right-sided irregular exophytic renal mass. The patient had VEGF-D level of 1382 pg/mL, which, combined with diffuse cystic lung disease, was consistent with a diagnosis of LAM. The patient was discharged and underwent chemotherapy and radiation in the outpatient setting. Two months later, she was readmitted with recurrent left pneumothorax. She failed doxycycline chemical pleurodesis (as there was a nation-wide talc shortage) and went for VATS decortication, pleurectomy, LLL wedge resection, and mechanical pleurodesis. Immunohistochemistry studies on lung pathology confirmed LAM (Table 1). DISCUSSION: LAM may develop sporadically, or may arise in a patient with preexisting tuberous sclerosis complex. The clinical presentation varies and may include cough, dyspnea, recurrent pneumothorax, pleural effusion, or respiratory failure. Overall, the patient’s family history and clinical presentation was not consistent with tuberous sclerosis complex. This is a case of likely sporadic LAM in a patient with recurrent pneumothorax, the first being 5 years prior to this presentation. The concurrent diffuse large B cell lymphoma of the skull adds an interesting twist, as there have only been case reports of LAM occurring with malignant lymphoma. CONCLUSIONS: Although LAM is diagnosed at a median age of 35, more women are being diagnosed at an older age. Pleurodesis after the first occurrence of pneumothorax should be considered due to the high rate of recurrence, as seen in this patient who had multiple pneumothoraces and failed chemical pleurodesis. Sirolimus is also recommended for LAM but this patient’s concurrent treatment for lymphoma complicates her treatment options. Reference #1: McCormack FX, Gupta N, Finlay GR, et al. Official American Thoracic Society/Japanese Respiratory Society Clinical Practice Guidelines: Lymphangioleiomyomatosis Diagnosis and Management. Am J Respir Crit Care Med. 2016;194(6):748-761. doi:10.1164/rccm.201607-1384ST Reference #2: Park S, Lee EJ. Diagnosis and treatment of cystic lung disease. Korean J Intern Med. 2017 Mar;32(2):229-238. doi: 10.3904/kjim.2016.242. Epub 2017 Feb 28. Reference #3: Jawad H, Walker CM, Wu CC, Chung JH. Cystic interstitial lung diseases: recognizing the common and uncommon entities. Curr Probl Diagn Radiol. 2014 May-Jun;43(3):115-27. doi: 10.1067/j.cpradiol.2014.01.001. DISCLOSURES: No relevant relationships by Helen Li Mitchell, source=Web Response No relevant relationships by Sushant Soni, source=Web Response No relevant relationships by Justin Thomas, source=Web Response No relevant relationships by Shawnt Tosonian, source=Web Response

Evaluation of Prediction Models for Identifying Malignancy in Pulmonary Nodules Detected via Low-Dose Computed Tomography

Malignancy prediction models based on participant-related characteristics and imaging parameters from low-dose computed tomography (CT) may improve decision-making regarding nodule management and diagnosis in lung cancer screening. To externally validate 5 malignancy prediction models that were developed in screening settings, compared with 3 models that were developed in clinical settings, in terms of discrimination and absolute risk calibration among participants in the German Lung Cancer Screening Intervention trial. In this population-based diagnostic study, malignancy probabilities were estimated by applying 8 prediction models to data from 1159 participants in the intervention arm of the Lung Cancer Screening Intervention trial, a randomized clinical trial conducted from October 23, 2007, to April 30, 2016, with ongoing follow-up. This analysis considers end points up to 1 year after individuals' last screening visit. Inclusion criteria for participants were at least 1 noncalcified pulmonary nodule detected on any of 5 annual screening visits, receiving a lung cancer diagnosis within the active screening phase of the Lung Cancer Screening Intervention trial, and an unequivocal identification of the malignant nodules. Data analysis was performed from February 1, 2019, through December 5, 2019. Five annual rounds of low-dose multislice CT. Discrimination ability and calibration of malignancy probabilities estimated by 5 models developed in data from screening studies (4 Pan-Canadian Early Detection of Lung Cancer Study [PanCan] models using a parsimonious approach including nodule spiculation [PanCan-1b] or a comprehensive approach including nodule spiculation [PanCan-2b], and PanCan-2b replacing the nodule diameter variable with mean diameter [PanCan-MD] or volume [PanCan-VOL], as well as a model developed by the UK Lung Cancer Screening trial) and 3 models developed in clinical settings (US Department of Veterans Affairs, Mayo Clinic, and Peking University People's Hospital). A total of 1159 participants (median [range] age, 57.63 [50.34-71.89] years; 763 [65.8%] men) with 3903 pulmonary nodules were included in this study. For nodules detected in the prevalence round of CT, the PanCan models showed excellent discrimination (PanCan-1b: area under the curve [AUC], 0.93 [95% CI, 0.87-0.99]; PanCan-2b: AUC, 0.94 [95% CI, 0.89-0.99]; PanCan-MD: AUC, 0.94 [95% CI, 0.91-0.98]; PanCan-VOL: AUC, 0.94 [95% CI, 0.90-0.98]), and all of the screening models except PanCan-MD and PanCan-VOL showed acceptable calibration (PanCan-1b: Spiegelhalter z = -1.081; P = .28; PanCan-2b: Spiegelhalter z = 0.436; P = .67; PanCan-MD: Spiegelhalter z = 3.888; P < .001; PanCan-VOL: Spiegelhalter z = 1.978; P = .05; UK Lung Cancer Screening trial: Spiegelhalter z = -1.076; P = .28), whereas the other models showed worse discrimination and calibration, from an AUC of 0.58 (95% CI, 0.46-0.70) for the UK Lung Cancer Screening trial model to an AUC of 0.89 (95% CI, 0.82-0.97) for the Mayo Clinic model. This diagnostic study found that PanCan models showed excellent discrimination and calibration in prevalence screenings, confirming their ability to improve nodule management in screening settings, although calibration to nodules detected in follow-up scans should be improved. The models developed by the Mayo Clinic, Peking University People's Hospital, Department of Veterans Affairs, and UK Lung Cancer Screening Trial did not perform as well.

Computerized texture analysis of pulmonary nodules in pediatric patients with osteosarcoma: Differentiation of pulmonary metastases from non-metastatic nodules.

ObjectiveTo retrospectively evaluate the value of computerized 3D texture analysis for differentiating pulmonary metastases from non-metastatic lesions in pediatric patients with osteosarcoma.Materials and methodsThis retrospective study was approved by the institutional review board. The study comprised 42 pathologically confirmed pulmonary nodules in 16 children with osteosarcoma who had undergone preoperative computed tomography between January 2009 and December 2014. Texture analysis was performed using an in-house program. Multivariate logistic regression analysis was performed to identify factors for differentiating metastatic nodules from non-metastases. A subgroup analysis was performed to identify differentiating parameters in small non-calcified pulmonary nodules. The receiver operator characteristic curve was created to evaluate the discriminating performance of the established model.ResultsThere were 24 metastatic and 18 non-metastatic lesions. Multivariate analysis revealed that higher mean attenuation (adjusted odds ratio [OR], 1.014, P = 0.003) and larger effective diameter (OR, 1.745, P = 0.012) were significant differentiators. The analysis with small non-calcified pulmonary nodules (7 metastases and 18 non-metastases) revealed significant inter-group differences in various parameters. Logistic regression analysis revealed that higher mean attenuation (OR, 1.007, P = 0.008) was a significant predictor of non-calcified pulmonary metastases. The established logistic regression model of subgroups showed excellent discriminating performance in the ROC analysis (area under the curve, 0.865).ConclusionPulmonary metastases from osteosarcoma could be differentiated from non-metastases by using computerized texture analysis. Higher mean attenuation and larger diameter were significant predictors for pulmonary metastases, while higher mean attenuation was a significant predictor for small non-calcified pulmonary metastases.

Small pulmonary nodules in baseline and incidence screening rounds of low-dose CT lung cancer screening.

Currently, lung cancer screening by low-dose computed tomography (LDCT) is widely recommended for high-risk individuals by US guidelines, but there still is an ongoing debate concerning respective recommendations for European countries. Nevertheless, the available data regarding pulmonary nodules released by lung cancer screening studies could improve future screening guidelines, as well as the clinical practice of incidentally detected pulmonary nodules on routine CT scans. Most lung cancer screening trials present results for baseline and incidence screening rounds separately, clustering pulmonary nodules initially found at baseline screening and newly detected pulmonary nodules after baseline screening together. This approach does not appreciate possible differences among pulmonary nodules detected at baseline and firstly detected at incidence screening rounds and is heavily influenced by methodological differences of the respective screening trials. This review intends to create a basis for assessing non-calcified pulmonary nodules detected during LDCT lung cancer screening in a more clinical relevant manner. The aim is to present data of non-calcified pulmonary baseline nodules and new non-calcified pulmonary incident nodules without clustering them together, thereby also simplifying translation to the clinical practice of incidentally detected pulmonary nodules. Small pulmonary nodules newly detected at incidence screening rounds of LDCT lung cancer screening may possess a greater lung cancer probability than pulmonary baseline nodules at a smaller size, which is essential for the development of new guidelines.

Spectrum of early lung cancer presentation in low-dose screening CT: a pictorial review.

The typical presentation of early stage lung cancers on low-dose CT screening are non-calcified pulmonary nodules. However, there is a wide spectrum of unusual focal abnormalities that can be early presentations of lung cancer. These abnormalities include, for example, cancers associated with ‘cystic airspaces’ or scar-like cancers. The detection of lung cancer with low-dose CT can be affected by the absence of intravenous contrast medium. As a consequence, endobronchial and central lesions can be difficult to recognize, raising the potential for missed cancers. Focal lesions arising within pre-existing lung disease, such as lung fibrosis or apical scars, can also be early lung cancer manifestations and deserve particular consideration as recognition of these lesions may be hindered by the underlying disease. Furthermore, the unpredictable growth rate of lung cancer, which ranges from indolent to aggressive cancers, necessitates attention to the wide spectrum of progression in lung cancer appearance on serial low-dose CT scans. In this pictorial review we discuss the spectrum of early lung cancer presentation in low-dose CT screening, highlighting typical as well as unusual radiological features and the varied growth rates of early lung cancer.Teaching Points• There is a wide spectrum of early presentations of lung cancer on LDCT.• Low radiation dose and the absence of contrast medium injection can affect lung cancer detection.• Lung cancer growth shows various behaviours, ranging from indolent to aggressive cancers.• Familiarity with LDCT technique can improve CT screening effectiveness and avoid missed diagnosis.

Lung cancer screening in high-risk subjects: early detection with LDCT and risk stratification using miRNA-based blood test

Lung cancer still remains a high mortality disease in the face of developments in diagnostic and therapeutic methods that occurred in the last 20 years. The analysis of the experiences from the first studies - in which chest X-ray (CXR) was adopted, associated or not with sputum cytology - has failed to show a reduction in lung cancer specific mortality. Subsequent screening studies that have introduced the use of low-dose computed tomography (LDCT) have revealed a large number of early-stage lung cancers, thus potentially curable; however, this has not allowed us to demonstrate a decrease in lung cancer-specific mortality. With the results of the American study National Lung ScreeningTrial (NLST), published in 2011, for the first time a lung cancer-specific mortality reduction by 20% thanks to the use of LDCT compared to RXT, was highlighted. However, a false discovery rate of 96.4% was also described with an overdiagnosis that can be up to 78.9% for bronchioalveolar lung cancer. Due to the high sensitivity of LDCT, able to identify a non-calcified pulmonary nodule in one subject on two, it becomes necessary to avail instruments to more accurately identify suspicious nodules. Until some time ago, the possible use of lung tumour markers was not viable in view of the poor organ specificity. The study and development was, then, pushed to organ- and tissue-specific markers such as microRNA (miRNA), noncoding RNA sequences involved in many processes and expression of oncogenic activity of the microenvironment. The use of biomarkers such as circulating miRNA implemented in LDCT screening has highlighted a reduction of 5 times for the rate of false positives, going from 19.4% to 3.7%, with a sensitivity of 87%, a specificity of 81%, and a negative predictive value of 99%. The need to appropriately use the available resources commensurate with the disease to treat will push more and more towards the implementation of LDCT biomarkers based screenings, stable and easily reproducible, as circulating miRNAs, obviating to problems such as false positives, unnecessary procedures of invasive surgery for benign lesions, and optimizing the cost benefit ratios.The development of new specific biomarkers appears to offer new promising prospects.

Incidental radiologic findings at breast cancer diagnosis and likelihood of disease recurrence.

Despite guidelines recommending against its routine use, perioperative imaging for distant metastases is frequently performed in newly diagnosed breast cancer patients, uncovering incidental findings of uncertain significance. We assessed the clinical significance of incidental findings by determining if their presence is associated with disease recurrence. A retrospective review of staging imaging was performed in patients with stage II or III invasive breast cancer diagnosed during 2008-2009 at a large academic medical center. Data related to perioperative imaging and disease recurrence were abstracted from the medical record. Kaplan-Meier curves and Cox proportional hazards models were used to assess the association between incidental findings and time to disease recurrence. A total of 169 of 340 patients (49.7 %) underwent staging evaluation for distant metastases (CT chest, abdomen, pelvis, bone scan, and/or PET-CT). Of these, 146 (86.4 %) had at least one suspicious or indeterminate finding. Follow-up studies were performed in 73 (43.2 %) patients. Nineteen patients were diagnosed with metastatic disease at diagnosis, 18 of whom had stage III disease. In patients without metastatic disease at diagnosis, 32 later developed recurrence. Non-calcified pulmonary nodules were associated with shorter time to disease recurrence (hazard ratio 2.51, 95 % CI 1.13-5.57, p = 0.02). Imaging for distant metastases frequently reveals indeterminate findings, most of which are not associated with disease recurrence. The association between pulmonary nodules and recurrence warrants validation in an independent cohort. Overall, these findings support current guidelines recommending against routine extent of disease evaluation in patients with newly diagnosed stage II breast cancer.