Application of endobronchial ultrasound-guided transbronchial needle aspiration in the diagnosis and treatment of mediastinal lymph node tuberculous abscess: a case report and literature review.

BACKGROUND: This study aimed to report the experience of diagnosis and treatment of one rare case of mediastinal lymph node tuberculous abscess (MLNTA) using endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). CASE PRESENTATION: An 18-year-old female patient was hospitalized in the Affiliated Hospital of Xuzhou Medical University in November 2017, due to intermittent left chest pain. She was suspected of infecting tuberculosis (TB) and thus received anti-TB treatment. Since April 1, 2018, she began to exhibit symptoms of chest distress. The patient was then admitted to Shanghai Pulmonary Hospital and continued receiving systemic anti-TB treatment during the whole course. On April 11, 2018, she received EBUS-TBNA to puncture pus and inject isoniazid. Simultaneously, the pus was sent for cytopathological and bacteriological examination, both supporting the diagnosis of TB in the patient. On April 24 and May 10, she received two times of EBUS-TBNA treatment. The symptoms of chest distress were relieved, but granulomatous neoplasm occurred at the EBUS-TBNA site on the trachea wall. The patient then received local clamp removal and cryotherapy on May 29 and Jul 19, respectively. Chest computed tomography (CT) reexamination on September 28 revealed that the MLNTA lesion had been completely absorbed, and electronic bronchoscopic reexamination on September 30 demonstrated that the granulomatous neoplasm on the trachea wall was entirely invisible. CONCLUSIONS: Using EBUS-TBNA to puncture and aspirate pus and inject drugs can be effectively used to diagnose and treat MLNTA, which provides a new, less invasive, safe and reliable method for diagnosis and treatment of MLNTA.

A 52-Year-Old Man Presented With Cough, Chest Pain, and a Mass in the Right Lung.

CASE PRESENTATION: A 52-year-old man, current smoker with a 50 pack-year history, presented to our department with cough, yellow sputum, and localized right chest pain. Chest radiograph revealed a large mass in the right upper lobe. He denied the presence of fever, night sweats, or weight loss. He has a medical history of COPD and anxiety disorder. He was receiving long-acting beta agonists/long-acting muscarinic antagonists as a treatment for COPD and quetiapine 100 mg for anxiety disorder.

The first case of multiple pulmonary granulomas with amyloid deposition in a dental technician; a rare manifestation as an occupational lung disease.

BACKGROUND: Occupational lung diseases, such as pneumoconiosis, are one of the health problems of dental workers that have been receiving increasing interest. Pulmonary amyloidosis is a heterogenous group of diseases, and can be classified into primary (idiopathic) and secondary (associated with various inflammatory diseases, hereditary, or neoplastic). To date, the development of pulmonary amyloidosis in dental workers has not been reported. CASE PRESENTATION: A 58-year-old Japanese female presented with chest discomfort and low-grade fever that has persisted for 2 months. She was a dental technician but did not regularly wear a dust mask in the workplace. Chest X ray and computed tomography revealed multiple well-defined nodules in both lungs and fluorodeoxyglucose (FDG)-positron emission tomography revealed abnormal FDG uptake in the same lesions with a maximal standardized uptake value (SUV [max]) of 5.6. We next performed thoracoscopic partial resection of the lesions in the right upper and middle lobes. The histological examination of the specimens revealed granuloma formation with foreign body-type giant cells and amyloid deposition that was confirmed by Congo red staining and direct fast scarlet (DFS) staining that produce apple-green birefringence under crossed polarized light. Because there were no other causes underlying the pulmonary amyloidosis, we performed electron probe X-ray microanalysis (EPMA) of the specimens and the result showed silica deposition in the lesions. Based on these results, we finally diagnosed the patient with pulmonary granulomas with amyloid deposition caused by chronic silica exposure. Afterward, her symptoms were improved and the disease has not progressed for 2 years since proper measures against additional occupational exposure were implemented. CONCLUSIONS: Our case presented three important clinical insights: First, occupational exposure to silica in a dental workplace could be associated with the development of amyloid deposition in lung. Second, EPMA was useful to reveal the etiology of amyloid deposition in the lungs. Last, proper protection against silica is important to prevent further progression of the disease. In conclusion, our case suggested that occupational exposure to silica should be considered when amyloid deposition of unknown etiology is found in the lungs of working or retired adults.

Use of a leukocyte-targeted peptide probe as a potential tracer for imaging the tuberculosis granuloma.

Granulomas are the histopathologic hallmark of tuberculosis (TB), both in latency and active disease. Diagnostic and therapeutic strategies that specifically target granulomas have not been developed. Our objective is to develop a probe for imaging relevant immune cell populations infiltrating the granuloma. We report the binding specificity of Cyanine 3 (Cy3)-labeled cFLFLFK-PEG12 to human leukocytes and cellular constituents within a human in vitro granuloma model. We also report use of the probe in in vivo studies using a mouse model of lung granulomatous inflammation. We found that the probe preferentially binds human neutrophils and macrophages in human granuloma structures. Inhibition studies showed that peptide binding to human neutrophils is mediated by the receptor formyl peptide receptor 1 (FPR1). Imaging the distribution of intravenously administered cFLFLFK-PEG12-Cy3 in the mouse model revealed probe accumulation within granulomatous inflammatory responses in the lung. Further characterization revealed that the probe preferentially associated with neutrophils and cells of the monocyte/macrophage lineage. As there is no current clinical diagnostic imaging tool that specifically targets granulomas, the use of this probe in the context of latent and active TB may provide a unique advantage over current clinical imaging probes. We anticipate that utilizing a FPR1-targeted radiopharmaceutical analog of cFLFLFK in preclinical imaging studies may greatly contribute to our understanding of granuloma influx patterns and the biological roles and consequences of FPR1-expressing cells in contributing to disease pathogenesis.

Granulomatous-Lymphocytic Interstitial Lung Disease in a Patient With Common Variable Immunodeficiency.

Common variable immunodeficiency is the most common primary immunodeficiency and consists of impaired immunoglobulin production causing recurrent sinopulmonary infections. The most common cause of mortality for this disorder, however, is from the development of malignancy and autoimmune disorders. One common entity that develops is a systemic granulomatous and lymphoproliferative disorder that can cause an interstitial lung disease more formally referred to as granulomatous-lymphocytic interstitial lung disease (GL-ILD). We discuss a case of a 25-year-old woman with common variable immunodeficiency and GL-ILD and review the literature to summarize the most common radiological findings to raise the suspicion for GL-ILD on high-resolution computed tomography and delineate this from infection and other mimickers. We will also review key histopathological characteristics for diagnosis and the clinical approach and treatment options for this rare disease.

Transesophageal Echocardiogram-Guided Stent Placement in Superior Vena Cava Syndrome Secondary to Granulomatous Lung Disease: A Case Series and Literature Review.

Obstruction of the superior vena cava (SVC) is an uncommon, but potentially life-threatening condition due to likely development of edema in the head and neck and potential respiratory compromise. Less than half of those affected by SVC syndrome survive more than a year. Obstruction can be from neoplasms or secondary to benign disease. Treatment for most cases of symptomatic SVC syndrome involves placement of a stent to relieve the stenosis. Serious complications such as stent migration, pulmonary embolism, and cardiac tamponade can occur in 5% to 10% of cases, and inadequate imaging of the SVC-atrial junction by fluoroscopy contributes to these problems. The overlapping contrast in the atrium makes it difficult to precisely place the distal end of the stent, potentially allowing for embolization of the stent to occur. We present a case series of 3 patients wherein transesophageal echocardiography was used for guidance of stent placement in the SVC and significantly aided in placement.

Pulmonary hyalinizing granuloma presenting with dysphagia: a rare presentation.

A 25-year-old man presented with a 2-month history of dysphagia and past history of pulmonary and intestinal tuberculosis. A barium swallow showed a point of constriction 42 mm above the gastroesophageal junction. Computed tomography revealed large opacities in bilateral lung fields, encroaching more on the esophagus. The lesion progressively compressed the esophagus as it moved inferiorly. A right posterolateral thoracotomy was performed for sub-anatomical resection of the mass. A biopsy revealed homogenous whirling hyalinized collagen fibers, highly suggestive of pulmonary hyalinizing granuloma, with no evidence of malignancy. Pulmonary hyalinizing granuloma should be considered in the differential diagnosis of longstanding dysphagia.

FDG PET-CT imaging of therapeutic response in granulomatous lymphocytic interstitial lung disease (GLILD) in common variable immunodeficiency (CVID).

Common variable immunodeficiency (CVID) is the most common severe adult primary immunodeficiency and is characterized by a failure to produce antibodies leading to recurrent predominantly sinopulmonary infections. Improvements in the prevention and treatment of infection with immunoglobulin replacement and antibiotics have resulted in malignancy, autoimmune, inflammatory and lymphoproliferative disorders emerging as major clinical challenges in the management of patients who have CVID. In a proportion of CVID patients, inflammation manifests as granulomas that frequently involve the lungs, lymph nodes, spleen and liver and may affect almost any organ. Granulomatous lymphocytic interstitial lung disease (GLILD) is associated with a worse outcome. Its underlying pathogenic mechanisms are poorly understood and there is limited evidence to inform how best to monitor, treat or select patients to treat. We describe the use of combined 2-[(18)F]-fluoro-2-deoxy-d-glucose positron emission tomography and computed tomography (FDG PET-CT) scanning for the assessment and monitoring of response to treatment in a patient with GLILD. This enabled a synergistic combination of functional and anatomical imaging in GLILD and demonstrated a widespread and high level of metabolic activity in the lungs and lymph nodes. Following treatment with rituximab and mycophenolate there was almost complete resolution of the previously identified high metabolic activity alongside significant normalization in lymph node size and lung architecture. The results support the view that GLILD represents one facet of a multi-systemic metabolically highly active lymphoproliferative disorder and suggests potential utility of this imaging modality in this subset of patients with CVID.

Pulmonary manifestation of immunoglobulin G4-related disease in a 7-year-old immunodeficient boy with Epstein-Barr virus infection: a case report.

BACKGROUND: Immunoglobulin G4-related disease (IgG4-RD) is a multiorgan fibroinflammatory condition with lymphoplasmacytic infiltrates containing abundant IgG4-positive plasma cells. The immunopathogenesis of the disease and the potential role of triggering autoantigens or infectious factors have not been clearly defined. Immunoglobulin G4-related lung disease is a new and emerging condition in pediatric patients and to date, there have been only two reports regarding pulmonary manifestation of IgG4-RD in children recently published. This is the first report of IgG4-related lung disease in an immunodeficient child with Epstein-Barr virus infection. CASE PRESENTATION: We report on the case of a 7-year old atopic boy who was hospitalized with an initial clinical and radiological diagnosis of pneumonia, positive Epstein-Barr virus (EBV)-DNA in the blood and defective adaptive immunity. The lung CT showed a consolidated mass lesion adjacent to the posterior wall of the chest and the diaphragm. The child underwent surgical resection of the tumor, and the histologic examination of the lung specimens revealed lymphoplasmacytic infiltrates with fibrosis and vasculitis correlating with IgG4-related lung disease. Subsequent monitoring of the patient with lung CT, pulmonary function tests and IgG4 levels did not show signs of active disease. CONCLUSIONS: The diagnosis of IgG4-related lung disease in children is challenging because of its rarity, nonspecific symptomatology and heterogeneous morphological manifestations. Further studies are required in children with pulmonary presentation of IgG4-RD to better understand pathogenesis of this condition, possible immunological or infectious triggering factors, and finally, to determine pediatric patient-targeted therapeutic interventions.

[Pulmonary hyalinizing granuloma]. / Pulmonale hyaline Granulomatose.

Benign lesions as pulmonary hyalinizing granuloma may mimic a malign disease. A 63-year old patient complained dyspnea and a weight loss of 30 kg. CT-thorax scans showed a destructive and infiltrative pulmonary process with pleural thickening. Histologic examination of transbronchial and transthoracic biopsies as well as of biopsies taken by minithoracotomy was not conclusive. Due to further progression the patient underwent a left-sided pleuropneumonectomy despite a VO2 peak of 9 ml/kg/min. Histology revealed DIP-like infiltrations, a histiocytic reaction and hyaline granulomas. Among less than 100 published cases of pulmonary hyaline granuloma a comparable rapid progression with a total functional loss of the affected lung is not reported. Mostly hyalinizing granuloma presents with infiltrations, which may mimic lung cancer, or nodular lesions, partly with cavitations or calcifications. The etiology is unknown, a persistent immunologic response to an antigenic stimulus is discussed. Associations with infections, lymphomas, amyloidosis or IgG4-related disease are reported. Some cases have features of multifocal fibrosis. In the case reported none of these associations could be found. The prognosis of pulmonary hyaline granuloma is regarded as benign. There is no effective treatment yet. Once the diagnosis has been established a conservative approach as well as a resection of nodules and a therapeutic attempt with steroids are an option. Extensive resections as pleuropneumonectomy are an exception.

Etanercept-induced sarcoidosis in rheumatoid arthritis: FDG PET findings.

We report the F-FDG PET/CT findings of an etanercept-induced sarcoidosis in a patient with rheumatoid arthritis. A 68-year-old woman with rheumatoid arthritis who had been treated with etanercept and methotrexate showed multiple lung nodules and hilar lymph node swellings on CT. She underwent FDG PET/CT for cancer screening. Intense FDG uptakes were found in the multiple lung nodules, bilateral hilar lymph nodes, a periurethral masslike lesion, and cranial meningeal nodules. A histopathological examination revealed epithelioid granuloma with multinucleated giant cells, which was compatible with sarcoidosis.

Clinical and pathological features of adult pulmonary tuberculosis with reversed halo sign.

OBJECTIVE: To understand the pathological correlation of the reversed halo sign (RHS) in adult pulmonary tuberculosis (PTB) patients, and to compare the clinical characteristics of PTB patients with RHS with those without RHS. MATERIALS AND METHODS: The study included 80 patients consecutively diagnosed with PTB by pathology or smear-positive sputum or bronchoalveolar lavage fluid from 1 January to 31 August 2012. All patients underwent high-resolution computed tomography (HRCT) scan, and were divided into two groups based on HRCT findings: RHS and non-RHS. All patients in the RHS group underwent CT-guided transthoracic lung biopsy to evaluate histopathological abnormalities. Clinical features such as smoking history, TB-related symptoms and comorbidities were compared. RESULTS: The 'ring' in the RHS corresponded to granulomata, with or without acid-fast stain positivity, and with or without caseating necrosis. Compared with the non-RHS group, patients in the RHS group were significantly younger, were less likely to have a smoking history and had fewer TB-related symptoms and comorbidities. CONCLUSIONS: Our study shows that younger PTB patients with relatively better baseline status tended to present with RHS on HRCT, have fewer TB-related symptoms and present atypically.

[A man with a 'galaxy sign']. / Een man met het 'galaxy sign'.

This brief report describes the radiographic images of a 29-year-old man with asymptomatic sarcoidosis. On a CT-scan a coalescent granuloma with a central core and peripheral nodules mimics a globular cluster galaxy; therefore it is called 'galaxy sign'. This is a classic finding in a granulomatous disease like sarcoidosis.

Pulmonary hyalinising granuloma: a rare pulmonary disorder.

Pulmonary hyalinising granulomas are rare, noninfectious fibrosclerosing lesions of the lung which can mimic metastatic disease. It was first described in literature by Engleman et al in the year 1977. Its etiology is unknown but they may be caused by an exaggerated immune response. The patient typically presents with cough, chest pain. dyspnoea or haemoptysis in association with multiple bilateral parenchymal nodules. We report the case of a 20 years old male who presented with a 12-month history of worsening dry cough. His plain chest radiograph and subsequent CT scan revealed bilateral pulmonary nodules. A CT guided biopsy of the pulmonary lesions was consistent with Pulmonary Hyalinising Granuloma [PHG].

Granulomatous mediastinal adenopathy: can endoscopic ultrasound-guided fine-needle aspiration differentiate between tuberculosis and sarcoidosis?

BACKGROUND AND STUDY AIMS: Mediastinal lymphadenopathy may indicate diseases such as tuberculosis or sarcoidosis, and it is often difficult to establish a diagnosis when standard medical work-up is inconclusive. In this study we investigated the diagnostic yield of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) in the differentiation between tuberculosis and sarcoidosis. PATIENTS AND METHODS: In this prospective study, 72 consecutive patients with mediastinal lymphadenopathy, negative endoscopic investigations including bronchoscopic procedures, and no radiological evidence of lung cancer or other malignancies on computed tomography were enrolled. EUS-FNA and subsequent cytology, microscopy for acid-fast bacilli, and culture were performed. At least 12 months' follow-up including further investigations was included to exclude tuberculosis. RESULTS: Adequate samples were obtained from 71/72 patients (36 male; mean age 50.2 years). No complications occurred. The final diagnosis included 30 cases of sarcoidosis, 28 of tuberculosis, four malignancies, one abscess, and nine benign lymphadenopathies. The size of lymph nodes on EUS varied from 0.5 cm to 4.2 cm. Tuberculosis nodes were significantly smaller than those in sarcoidosis. Unrelated nodes were significantly smaller than in either tuberculosis or sarcoidosis. The sensitivity, specificity, and positive and negative predictive values of EUS - FNA for tuberculosis were 86 %, 100 %, 100 %, and 91 %, respectively; those for sarcoidosis were 100 %, 93 %, 91 %, and 100 %, respectively. For culture of tuberculosis, they were 71 %, 100 %, 100 %, and 84 %, respectively. EUS - FNA led to a definite diagnosis in 64/72 cases (89 %) that had not been previously diagnosed by routine methods. CONCLUSION: EUS - FNA offers a high diagnostic yield for the differential diagnosis of tuberculosis and sarcoidosis that have not been diagnosed by conventional methods.

Granulomatous reaction to pneumocystis jirovecii: clinicopathologic review of 20 cases.

To better characterize the clinical and pathologic features of granulomatous reaction to Pneumocystis jirovecii, we reviewed 20 cases of this uncommon response. Patients included 15 males and 5 females (mean age 52 y). The most common symptom was dyspnea (5 of 14). Primary medical diagnoses included human immunodeficiency virus/acquired immunodeficiency syndrome (7 of 20), hematopoietic (6 of 20), and solid malignancies (4 of 20). Radiology findings included nodular (8 of 16) and diffuse (5 of 16) infiltrates and solitary nodules (3 of 16). Diagnostic procedures with the highest yield were open lung biopsy (13 of 20) and autopsy (5 of 20); false-negative results were most common on bronchial washings/brushings, bronchoalveolar lavage, fine needle aspiration, and transbronchial biopsy. Follow-up showed resolution of disease (6 of 13), death from disease (6 of 13), and death from unknown cause (1 of 13). Histologically, clusters of Gomori methenamine silver-positive (20 of 20) Pneumocystis organisms were identified in all cases. Organisms were identified within well (16 of 20) and poorly (4 of 20) formed necrotizing (16 of 20) and non-necrotizing (4 of 20) granulomas ranging in size from 0.1 to 2.5 cm (mean 0.5 cm); granulomas were multiple (18 of 20) or single (2 of 20). Giant cells (11 of 20), a fibrous rim (8 of 20), and eosinophils (6 of 20) were seen. Foamy eosinophilic exudates were present centrally within some granulomas (5 of 20). Cystic spaces (1 of 20) and calcification (1 of 20) were rare. Only one case demonstrated classic intra-alveolar foamy exudates containing Pneumocystis. Granulomatous P. jirovecii pneumonia occurs most commonly in males with human immunodeficiency virus/acquired immunodeficiency syndrome, hematopoietic, and solid malignancies. The diagnosis may be overlooked as conventional radiologic and pathologic features are absent. When suspected, open lung biopsy is most likely to yield diagnostic material. Attention to organism morphology avoids misdiagnosis as Histoplasma.

Pulmonary hyalinizing granuloma mimicking multiple lung metastases: report of fluorodeoxyglucose positron emission findings.

Pulmonary hyalinizing granuloma (PHG) is a rare disease characterized by multiple bilateral pulmonary nodules of uncertain etiology. We describe a 71-year-old female patient with thyroid papillary carcinoma in whom bilateral pulmonary nodules were found during a routine chest radiography examination. Subsequent fluorodeoxyglucose positron emission tomography/computed tomography scan gave the impression of multiple pulmonary metastases based on high maximum standardized uptake value. She underwent video-assisted thoracoscopic surgery with wedge resection, and PHG was diagnosed on the basis of histopathologic findings. To our knowledge, this is the first report of PHG developing in a patient as a solid cancer, mimicking multiple pulmonary metastases. We also present the first description of positron emission tomography in PHG, according to a Medline search.