Short Telomere Syndrome presenting with pulmonary fibrosis, liver cirrhosis and hepatopulmonary syndrome: a case report.

BACKGROUND: Idiopathic pulmonary fibrosis is thought to result from aberrant post-injury activation of epithelial cells leading to fibroblast proliferation and activation. A number of genetic aetiologies have been implicated in this disease process, including, among others, the short telomere syndromes. Short telomere syndromes follow an autosomal dominant pattern of inheritance resulting in shortened telomere length, which consequently leads to accelerated cell death. Organs with rapid cell turnover are most affected. CASE PRESENTATION: We describe a case of a 53-year-old man with a chief complaint of cough and dyspnea on exertion. His presentation was otherwise significant for features of accelerated aging, including a history of osteoporosis and early greying, and a family history of pulmonary fibrosis in his father. Pulmonary function testing revealed a restrictive pattern with severely reduced diffusion capacity and high resolution CT of the chest showed diffuse lung disease with mild fibrosis, in pattern suggesting an alternative diagnosis to IPF. Biopsy of the lung was in keeping with chronic fibrosing interstitial pneumonia. Imaging of the abdomen showed splenomegaly, hepatic cirrhosis and portal hypertension. Transthoracic contrast echocardiogram showed intrapulmonary shunting consistent with hepatopulmonary syndrome. Given the constellation of early aging, idiopathic pulmonary fibrosis, cryptogenic cirrhosis and a family history of pulmonary fibrosis in this patient, the Short Telomere Syndrome was suspected. Peripheral blood was sent for Flow-cytometry FISH, which demonstrated granulocyte telomere length below the 10th percentile for the patient's age, consistent with a diagnosis of Short Telomere Syndrome in this clinical context. Targeted genetic testing of mutations known to be associated with short telomere was negative though it was acknowledged that the full spectrum of disease-causing mutations remains unknown. Given the extensive fibrosis on biopsy and his progressive hypoxemia he was treated with mycophenolate and prednisone. Ultimately, he developed progressive respiratory failure and underwent double lung and concurrent liver transplant 18 months after the initial diagnosis was made. CONCLUSIONS: Short Telomere Syndrome is a rare cause of end stage organ disease and testing lacks sensitivity making diagnosis challenging. Organ transplant is still the mainstay of treatment. Nevertheless, disease identification is important because of implications for family member screening and the possibility of future treatment options.

Limited Chest Ultrasound to Replace CXR in Diagnosis of Pneumothorax Post Image-Guided Transthoracic Interventions.

PURPOSE: To assess the diagnostic accuracy of limited chest ultrasound in detecting pneumothorax following percutaneous transthoracic needle interventions using chest X-ray (CXR) as the reference standard. METHODS: With IRB approval, after providing consent, asymptomatic patients after percutaneous transthoracic needle interventions were enrolled to undergo limited chest ultrasound in addition to CXR. A chest Radiologist blinded to the patient's prior imaging performed a bedside ultrasound, scanning only the first 3 anterior intercostal spaces. Pneumothorax diagnosed on CXR was categorized as small or large and on ultrasound as grades 1, 2, or 3 when detected in 1, 2, or 3 intercostal spaces, respectively. RESULTS: 38 patients underwent 36 biopsies (34 lungs, 1 pleura, and 1 mediastinum) and 2 coil localizations. CXR showed pneumothorax in 13 patients. Ultrasound was positive in 10 patients, with 9 true-positives, 1 false-positive, 4 false-negatives, and 24 true-negatives. The false positive results were due to apical subpleural bullae. The false-negative results occurred in 2 small apical and 2 focal pneumothoraces at the needle entry sites. Four pneumothoraces were categorized as large on CXR, all of which were categorized as grade 3 on ultrasound. Sensitivity and specificity of US for detection of pneumothorax of any size were 69.23% (95%CI 38.6%, 90.1%) and 96.0% (95%CI 79.6%, 99.9%), and for detection of large pneumothorax were 100% (95%CI 39.8%, 100%) and 100% (95%CI 89.7%, 100%). CONCLUSIONS: Results of this prospective study is promising. Limited chest ultrasound could potentially replace CXR in the management of postpercutaneous transthoracic needle intervention patients.

Aerogenous Metastasis and Spread Through the Air Spaces - Distinct Entities or Spectrum of the Same Process?

Clinicopathological and imaging studies indicate that metastatic spread of cancer cells through the airways may occur in primary lung cancer. The term aerogenous metastasis was been proposed years before the concept of spread through the airspaces (STAS) was introduced in the current World Health Organization classification. The pathogenesis of STAS has not been fully elucidated. The current definition of STAS is controversial and limited to early stage adenocarcinomas. In this article, existing knowledge on the pathogenesis, histology, imaging findings, and clinical and prognostic significance of these 2 entities is presented.

Role of the Thoracic Radiologist in the Evaluation and Management of Solid and Subsolid Lung Nodules.

In this review, the authors describe the imaging characteristics of solid and subsolid nodules as well as their management recommendations including the use of image-guided percutaneous biopsy and preoperative coil localization. Using case presentations, they offer practical management tips for the most commonly encountered nodule nodules in a thoracic surgical practice.

Use of tracheobronchial tree 3-dimensional printed model: does it improve trainees' understanding of segmentation anatomy? A prospective study.

BACKGROUND: This prospective study investigated whether the use of 3D-printed model facilitates novice learning of radiology anatomy on multiplanar computed tomography (CT) when compared to traditional 2D-based learning tools. Specifically, whether the use of a 3D printed model improved interpretation of multiplanar CT tracheobronchial anatomy. METHODS: Thirty-one medical students (10F, 21 M) from years one to three were recruited, matched for gender and level of training and randomized to 2D or 3D group. Students underwent 20-min self-study session using 2D-printed image or 3D-printed model of the tracheobronchial tree. Immediately after, students answered 10 multiple-choice questions (Test 1) to identify tracheobronchial tree branches on multiplanar CT images. Two weeks later, identical test (Test 2) was used to assess retention of information. Mean scores of 2D and 3D groups were calculated. Student's t test was used to compare mean differences in tests scores and analysis of variance (ANOVA) was used to assess the interaction of gender, CT imaging plane and time on test scores between the two groups. RESULTS: For test 1, 2D group had higher mean score than 3D group although not statistically significant (7.69 and 7.43, p = 0.39). Mean scores for Test 2 were significantly lower than for Test 1 (7 and 7.57, p = 0.03) with mean score decline for 2D group (Test 1 = 7.69, Test 2 = 6.63, p = 0.03), and similar score for 3D group (Test 1 and 2 = 7.43). There was no statistically significant interaction of gender and test score over time. Significant interaction between group and time of test was found for axial CT images but not for coronal images. CONCLUSIONS: Use of a 3D-printed model of the tracheobronchial anatomy had no immediate advantage over traditional 2D-printed images for learning CT anatomy. However, use of a 3D model improved students' ability to retain learned information, irrespective of gender.

Imaging-guided Percutaneous Biopsy of Nodules ≤1 cm: Study of Diagnostic Performance and Risk Factors Associated With Biopsy Failure.

OBJECTIVE: Percutaneous biopsy of lung nodules is established as a safe procedure with high diagnostic yield and accuracy. Its role in the diagnosis of subcentimeter nodules is, however, less clear. The goal of this study was to evaluate diagnostic yield, accuracy, and safety of computed tomography (CT)-guided needle biopsy in the diagnosis of subcentimeter lung nodules. MATERIAL AND METHODS: A retrospective review of a prospectively maintained database over a 12-year period identified 133 eligible CT-guided needle biopsies of lesions ≤1 cm. Diagnostic yield and accuracy for the diagnosis of malignancy were calculated. Lesion features and procedure characteristics were assessed using univariate and multivariate logistic regression analysis to identify risk factors associated with biopsy failure and complications. RESULTS: Biopsy specimens were adequate for diagnosis in 116/133(87%) cases; the diagnostic yield for malignant and benign lesions was 93% and 65%, respectively. Final benign diagnosis was the strongest independent risk factor for biopsy failure. In multivariate logistic regression, fine-needle aspiration was an independent risk factor for diagnostic failure. Core needle biopsy was an independent risk factor for pneumothorax, and core needle biopsy, number of passes, and age were independent risk factors for pneumothorax requiring tube drainage. CONCLUSIONS: CT-guided percutaneous needle biopsy had high diagnostic yield for the diagnosis of subcentimeter lung nodules with a similar complication rate to biopsy of larger lesions. Fine-needle aspiration may be an independent factor for diagnostic failure even for malignant lesions.

Metastatic pulmonary calcification: high-resolution computed tomography findings in 23 cases.

OBJECTIVE: The aim of this study was to evaluate the high-resolution computed tomography (HRCT) findings in patients diagnosed with metastatic pulmonary calcification (MPC). MATERIALS AND METHODS: We retrospectively reviewed the HRCT findings from 23 cases of MPC [14 men, 9 women; mean age, 54.3 (range, 26-89) years]. The patients were examined between 2000 and 2014 in nine tertiary hospitals in Brazil, Chile, and Canada. Diagnoses were established by histopathologic study in 18 patients and clinical-radiological correlation in 5 patients. Two chest radiologists analyzed the images and reached decisions by consensus. RESULTS: The predominant HRCT findings were centrilobular ground-glass nodules (n = 14; 60.9%), consolidation with high attenuation (n = 10; 43.5%), small dense nodules (n = 9; 39.1%), peripheral reticular opacities associated with small calcified nodules (n = 5; 21.7%), and ground-glass opacities without centrilobular ground-glass nodular opacity (n = 5; 21.7%). Vascular calcification within the chest wall was found in four cases and pleural effusion was observed in five cases. The abnormalities were bilateral in 21 cases. CONCLUSION: MPC manifested with three main patterns on HRCT, most commonly centrilobular ground-glass nodules, often containing calcifications, followed by dense consolidation and small solid nodules, most of which were calcified. We also described another pattern of peripheral reticular opacities associated with small calcified nodules. These findings should suggest the diagnosis of MPC in the setting of hypercalcemia.

OBJETIVO: O objetivo deste estudo foi avaliar os achados de tomografia computadorizada de alta resolução (TCAR) em pacientes com diagnóstico de calcificação pulmonar metastática (CPM). MATERIAIS E MÉTODOS: Revisamos, retrospectivamente, os achados na TCAR de 23 casos de CPM [14 homens e 9 mulheres; idade média, 54,3 (intervalo, 26-89) anos]. Os pacientes foram examinados entre 2000 e 2014 em nove hospitais terciários no Brasil, Chile e Canadá. O diagnóstico foi estabelecido por estudo histopatológico em 18 pacientes e correlação clinicorradiológica em 5 pacientes. Dois radiologistas de tórax analisaram as imagens e chegaram a decisões por consenso. RESULTADOS: Os achados predominantes na TCAR foram nódulos centrolobulares em vidro fosco (n = 14; 60,9%), consolidação com alta atenuação (n = 10; 43,5%), pequenos nódulos densos (n = 9; 39,1%), opacidades reticulares periféricas associadas com pequenos nódulos calcificados (n = 5; 21,7%) e opacidades em vidro fosco sem nódulos centrolobulares em vidro fosco (n = 5; 21,7%). Calcificação vascular na parede torácica foi encontrada em quatro casos e derrame pleural foi observado em cinco casos. As anormalidades foram bilaterais em 21 casos. CONCLUSÃO: CPM manifestou-se com três padrões principais na TCAR. O aspecto mais comum foram os nódulos centrolobulares em vidro fosco, frequentemente contendo calcificações, seguido de consolidação densa e de pequenos nódulos sólidos, a maioria deles calcificada. Também descrevemos o padrão de opacidades reticulares periféricas associadas a pequenos nódulos calcificados. Esses achados devem sugerir o diagnóstico de CPM no contexto de hipercalcemia.

Metastatic pulmonary calcification: high-resolution computed tomography findings in 23 cases / Calcificação pulmonar metastática: achados na tomografia computadorizada de alta resolução de 23 casos

Abstract Objective: The aim of this study was to evaluate the high-resolution computed tomography (HRCT) findings in patients diagnosed with metastatic pulmonary calcification (MPC). Materials and Methods: We retrospectively reviewed the HRCT findings from 23 cases of MPC [14 men, 9 women; mean age, 54.3 (range, 26-89) years]. The patients were examined between 2000 and 2014 in nine tertiary hospitals in Brazil, Chile, and Canada. Diagnoses were established by histopathologic study in 18 patients and clinical-radiological correlation in 5 patients. Two chest radiologists analyzed the images and reached decisions by consensus. Results: The predominant HRCT findings were centrilobular ground-glass nodules (n = 14; 60.9%), consolidation with high attenuation (n = 10; 43.5%), small dense nodules (n = 9; 39.1%), peripheral reticular opacities associated with small calcified nodules (n = 5; 21.7%), and ground-glass opacities without centrilobular ground-glass nodular opacity (n = 5; 21.7%). Vascular calcification within the chest wall was found in four cases and pleural effusion was observed in five cases. The abnormalities were bilateral in 21 cases. Conclusion: MPC manifested with three main patterns on HRCT, most commonly centrilobular ground-glass nodules, often containing calcifications, followed by dense consolidation and small solid nodules, most of which were calcified. We also described another pattern of peripheral reticular opacities associated with small calcified nodules. These findings should suggest the diagnosis of MPC in the setting of hypercalcemia.

Resumo Objetivo: O objetivo deste estudo foi avaliar os achados de tomografia computadorizada de alta resolução (TCAR) em pacientes com diagnóstico de calcificação pulmonar metastática (CPM). Materiais e Métodos: Revisamos, retrospectivamente, os achados na TCAR de 23 casos de CPM [14 homens e 9 mulheres; idade média, 54,3 (intervalo, 26-89) anos]. Os pacientes foram examinados entre 2000 e 2014 em nove hospitais terciários no Brasil, Chile e Canadá. O diagnóstico foi estabelecido por estudo histopatológico em 18 pacientes e correlação clinicorradiológica em 5 pacientes. Dois radiologistas de tórax analisaram as imagens e chegaram a decisões por consenso. Resultados: Os achados predominantes na TCAR foram nódulos centrolobulares em vidro fosco (n = 14; 60,9%), consolidação com alta atenuação (n = 10; 43,5%), pequenos nódulos densos (n = 9; 39,1%), opacidades reticulares periféricas associadas com pequenos nódulos calcificados (n = 5; 21,7%) e opacidades em vidro fosco sem nódulos centrolobulares em vidro fosco (n = 5; 21,7%). Calcificação vascular na parede torácica foi encontrada em quatro casos e derrame pleural foi observado em cinco casos. As anormalidades foram bilaterais em 21 casos. Conclusão: CPM manifestou-se com três padrões principais na TCAR. O aspecto mais comum foram os nódulos centrolobulares em vidro fosco, frequentemente contendo calcificações, seguido de consolidação densa e de pequenos nódulos sólidos, a maioria deles calcificada. Também descrevemos o padrão de opacidades reticulares periféricas associadas a pequenos nódulos calcificados. Esses achados devem sugerir o diagnóstico de CPM no contexto de hipercalcemia.

Quantitative texture analysis on pre-treatment computed tomography predicts local recurrence in stage I non-small cell lung cancer following stereotactic radiation therapy.

BACKGROUND: The prediction of local recurrence (LR) of stage I non-small cell lung cancer (NSCLC) after definitive stereotactic body radiotherapy (SBRT) remains elusive. The purpose of this study was to assess whether quantitative imaging features on pre-treatment computed tomography (CT) can predict LR beyond 18 (18F) fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/CT maximum standard uptake value (SUVmax). METHODS: This retrospective study evaluated 36 patients with 37 stage I NSCLC who had local tumor control (LC; n=19) and (LR; n=18). Textural features were extracted on pre-treatment CT. Mann-Whitney U tests were used to compare LC and LR groups. Receiver-operating characteristic (ROC) curves were constructed and the area under the curve (AUC) calculated with LR as outcome. RESULTS: Gray-level correlation and sum variance were greater in the LR group, compared with the LC group (P=0.02 and P=0.04, respectively). Gray-level difference variance was lower in the LR group (P=0.004). The logistic regression model generated using gray-level correlation and difference variance features resulted in AUC (SE) 0.77 (0.08) (P=0.0007). The addition of 18F-FDG PET/CT SUVmax did not improve the AUC (P=0.75). CONCLUSIONS: CT textural features were found to be predictors of LR of early stage NSCLC on baseline CT prior to SBRT.

Role of quantitative computed tomography texture analysis in the differentiation of primary lung cancer and granulomatous nodules.

BACKGROUND: Texture analysis is a computer tool that enables quantification of gray-level patterns, pixel interrelationships, and spectral properties of an image. It can enhance visual methods of image analysis. Primary lung cancer and granulomatous nodules have identical CT imaging features. The purpose of this study was to assess the sensitivity and specificity of CT texture analysis in differentiating lung cancer and granulomas. METHODS: This retrospective study evaluated 55 patients with primary lung cancer and granulomatous nodules who had contrast-enhanced (CE) and/or non-contrast-enhanced (NCE) CT within 3 months of biopsy. Textural features were extracted from 61 nodules. Mann-Whitney U tests were used to compare values for nodules. Receiver operating characteristic (ROC) curves were constructed and the area under the curve (AUC) calculated with histopathology as outcome. Combinations of features were entered as predictors in logistic regression models and optimal threshold criteria were used to estimate sensitivity and specificity. RESULTS: The model generated by sum of squares, sum difference, and sum entropy features for NCE CT yielded 88% sensitivity and 92% specificity (AUC =0.90±0.06, P<0.0001). For nodules with fluorodeoxyglucose positron emission tomography (FDG-PET)/CT, sensitivity for detection of lung cancer was 79.2% (CI: 57.8-92.9%), specificity was 38.5% (CI: 13.9-68.4%) and accuracy was 64.8%. CONCLUSIONS: Quantitative CT texture analysis has the potential to differentiate primary lung cancer and granulomatous lesions.

Fat embolism syndrome: State-of-the-art review focused on pulmonary imaging findings.

BACKGROUND: Fat embolism syndrome (FES) is a rare but potentially fatal complication of trauma or orthopedic surgery, which presents predominantly with pulmonary symptoms. Modern intensive care has improved the mortality rates, however diagnosis remains difficult, relying predominantly on a combination of a classic triad of symptoms and non-specific, but characteristic radiological features. The aim of this review is to describe the main clinical and imaging aspects of FES, ranging from pathophysiology to treatment with emphasis on pulmonary involvement. METHODS: We reviewed the currently published literature on the main characteristics of FES. RESULTS: In a hypoxic patient with recent trauma or orthopedic surgery, the presence of diffuse, well-demarcated ground glass opacities or ill-defined centrilobular nodules on computed tomography (CT) of the chest are suggestive of FES. CONCLUSIONS: Combination of the classic clinical syndrome in the appropriate clinical setting, together with the characteristic imaging findings on chest CT, can help to achieve the correct diagnosis. Management remains predominantly supportive care, and the benefit of medical therapies such as corticosteroids and heparin remains unclear.

Fat embolism syndrome: Do the CT findings correlate with clinical course and severity of symptoms? A clinical-radiological study.

OBJECTIVE: Fat embolism syndrome (FES) is rare and diagnosis is challenging. Clinical manifestations are non-specific and no biochemical tests are reliable for diagnosis, highlighting the importance of thoracic CT. Our goal was to describe the CT manifestations of FES and assess whether imaging findings, time of onset of symptoms and time of surgery correlate with clinical course and severity of the disease. METHODS: Retrospective review of 49 patients with respiratory distress after trauma/intramedullary nail fixation over a 10 year period; 12 patients met clinical criteria and were categorized as non-fulminant (NF-FES) or fulminant FES (F-FES). CT images were analyzed and electronic records reviewed for clinical findings, timeline from trauma to surgery and onset of symptoms. Pearson Chi-square and Levene's test were used and results considered significant when p<0.05. RESULTS: All patients were men (18-80 years, mean 38 years), 5 (42%) suffered F-FES and 7 (58%) NF-FES. The most common CT finding was ground-glass opacities (8/12, 67%), often with lobular sparing. Consolidation occurred in 4/12 (33%), all in F-FES patients (p=0.004). In 5/5 F-FES, lung involvement was extensive (>75%) whereas most NF-FES had limited involvement (p<0.01). Centrilobular nodules were the predominant finding in 3/12 (16%). Median time between fracture and onset of symptoms was 43h, in 9/12 patients manifesting after surgery. Mean time between trauma and surgery was 20h in NF-FES and 52h in F-FES (p=0.02). CONCLUSIONS: The most common CT features of FES were ground-glass opacity and consolidation, less commonly, centrilobular nodules. The extent of ground-glass opacities and the presence of consolidation correlated with disease severity. Significant difference was found from time of trauma to surgery in the two groups however is uncertain whether delayed surgery truly increased the risk of F-FES.

Tuberous Sclerosis Complex: State-of-the-Art Review with a Focus on Pulmonary Involvement.

Tuberous sclerosis complex (TSC) is an autosomal-dominant neurocutaneous disease with high phenotypic variability. The incidence is approximately one in 5000-10,000 births. TSC is characterized by widespread hamartomas and benign or rarely malignant neoplasms affecting various organs, most commonly the brain, skin, retinas, kidneys, heart, and lungs. The wide range of organs affected reflects the roles of TSC1 and TSC2 genes in the regulation of cell proliferation and differentiation. Clinical diagnostic criteria are important because genetic testing does not identify the mutation in up to 25% of patients. Imaging is pivotal, as it allows a presumptive diagnosis of TSC and definition of the extent of the disease. Common manifestations of TSC include cortical tubers, subependymal nodules, white matter abnormalities, retinal abnormalities, cardiac rhabdomyoma, lymphangioleiomyomatosis (LAM), renal angiomyolipoma, and skin lesions. Pulmonary involvement consists of LAM and, less commonly, multifocal micronodular pneumocyte hyperplasia (MMPH), which causes cystic and nodular diseases, respectively. Recent reports indicate that pulmonary LAM is found by computed tomography in up to 35% of the female patients with TSC. MMPH is rare and may be associated with LAM or, less frequently, occurs as an isolated pulmonary manifestation in women with TSC. Dyspnea and pneumothorax are common clinical presentations of LAM, whereas MMPH is usually asymptomatic. The aim of this review is to describe the main clinical, imaging, and pathological aspects of TSC, with a focus on pulmonary involvement.

Quantitative CT texture and shape analysis: can it differentiate benign and malignant mediastinal lymph nodes in patients with primary lung cancer?

OBJECTIVE: To assess the accuracy of CT texture and shape analysis in the differentiation of benign and malignant mediastinal nodes in lung cancer. METHODS: Forty-three patients with biopsy-proven primary lung malignancy with pathological mediastinal nodal staging and unenhanced CT of the thorax were studied retrospectively. Grey-level co-occurrence and run-length matrix textural features, as well as morphological features, were extracted from 72 nodes. Differences between benign and malignant features were assessed using Mann-Whitney U tests. Receiver operating characteristic (ROC) curves for each were constructed and the area under the curve (AUC) calculated with histopathology diagnosis as outcome. Combinations of features were also entered as predictors in logistic regression models and optimal threshold criteria were used to estimate sensitivity and specificity. RESULTS: Using optimum-threshold criteria, the combined textural and shape features identified malignant mediastinal nodes with 81% sensitivity and 80% specificity (AUC = 0.87, P < 0.0001). Using this combination, 84% malignant and 71% benign nodes were correctly classified. CONCLUSIONS: Quantitative CT texture and shape analysis has the potential to accurately differentiate malignant and benign mediastinal nodes in lung cancer. KEY POINTS: • Mediastinal nodal staging is crucial in the management of lung cancer • Mediastinal nodal metastasis affects prognosis and suitability for surgical treatment • Computed tomography (CT) is limited for mediastinal nodal staging • Texture analysis measures tissue heterogeneity not perceptible to human vision • CT texture analysis may accurately differentiate malignant and benign mediastinal nodes.