Pulmonary Granulomas Research Articles

Interaction of antitubercular drug candidates with α1-acid glycoprotein produced in pulmonary granulomas

The intracellular pathogen Mycobacterium tuberculosis can survive and replicate within host macrophages. Among various immunomodulatory substances, macrophages also produce α1-acid glycoprotein (AAG) which is secreted into the extracellular matrix of tuberculosis granulomas that represents a specific binding environment. Employing circular dichroism (CD) and UV/VIS absorption spectroscopic methods, we demonstrated and evaluated the AAG binding properties of novel antitubercular drug candidates developed against sensitive and multidrug-resistant strains of M. tuberculosis. As inferred from the CD spectroscopic data, these chemically diverse organic molecules are engulfed within the β-barrel of the protein either in a monomeric or dimeric form. Molecular docking simulations suggested the importance of H-bonds and ligand-aromatic residue π-π stacking interactions in stabilizing the drug molecules at the protein binding site. Based on the estimated Kd values (7–20 μM), AAG could be considered as the significant binding partner of the antitubercular agents studied herein. As such, it may affect the drug distribution and bioavailability not only in serum but also in macrophages and in the extracellular matrix of tuberculosis granulomas.

Pulmonary granuloma or post-segmentectomy resection stump lung cancer recurrence: Differential diagnosis of two cases

Pulmonary granuloma or post-segmentectomy resection stump lung cancer recurrence: Differential diagnosis of two cases

Aluminium toxicosis: a review of toxic actions and effects.

Aluminium (Al) is frequently accessible to animal and human populations to the extent that intoxications may occur. Intake of Al is by inhalation of aerosols or particles, ingestion of food, water and medicaments, skin contact, vaccination, dialysis and infusions. Toxic actions of Al induce oxidative stress, immunologic alterations, genotoxicity, pro-inflammatory effect, peptide denaturation or transformation, enzymatic dysfunction, metabolic derangement, amyloidogenesis, membrane perturbation, iron dyshomeostasis, apoptosis, necrosis and dysplasia. The pathological conditions associated with Al toxicosis are desquamative interstitial pneumonia, pulmonary alveolar proteinosis, granulomas, granulomatosis and fibrosis, toxic myocarditis, thrombosis and ischemic stroke, granulomatous enteritis, Crohn’s disease, inflammatory bowel diseases, anemia, Alzheimer’s disease, dementia, sclerosis, autism, macrophagic myofasciitis, osteomalacia, oligospermia and infertility, hepatorenal disease, breast cancer and cyst, pancreatitis, pancreatic necrosis and diabetes mellitus. The review provides a broad overview of Al toxicosis as a background for sustained investigations of the toxicology of Al compounds of public health importance.

Alveolar Macrophage ABCG1 Deficiency Promotes Pulmonary Granulomatous Inflammation.

Pulmonary granuloma formation is a complex and poorly understood response to inhaled pathogens and particulate matter. To explore the mechanisms of pulmonary granuloma formation and maintenance, our laboratory has developed a multiwall carbon nanotube (MWCNT)-induced murine model of chronic granulomatous inflammation. We have demonstrated that the MWCNT model closely mimics pulmonary sarcoidosis pathophysiology, including the deficiency of alveolar macrophage ATP-binding cassette (ABC) lipid transporters ABCA1 and ABCG1. We hypothesized that deficiency of alveolar macrophage ABCA1 and ABCG1 would promote pulmonary granuloma formation and inflammation. To test this hypothesis, the effects of MWCNT instillation were evaluated in ABCA1, ABCG1, and ABCA1/ABCG1 myeloid-specific knockout (KO) mice. Histological examination revealed significantly larger pulmonary granulomas in ABCG1-KO and ABCA1/ABCG1 double-KO animals when compared with wild-type animals. Evaluation of BAL cells indicated increased expression of CCL2 and osteopontin, genes shown to be involved in the formation and maintenance of pulmonary granulomas. Single deficiency of alveolar macrophage ABCA1 did not affect MWCNT-induced granuloma formation or proinflammatory gene expression. These observations indicate that the deficiency of alveolar macrophage ABCG1 promotes pulmonary granulomatous inflammation and that this is augmented by additional deletion of ABCA1.

Grouping of carbonaceous nanomaterials based on association of patterns of inflammatory markers in BAL fluid with adverse outcomes in lungs

Carbonaceous nanomaterials (CNMs) are universally being used to make commodities, as they present unique opportunities for development and innovation in the fields of engineering, biotechnology, etc. As technology advances to incorporate CNMs in industry, the potential exposures associated with these particles also increase. CNMs have been found to be associated with substantial pulmonary toxicity, including inflammation, fibrosis, and/or granuloma formation in animal models. This study attempts to categorize the toxicity profiles of various carbon allotropes, in particular, carbon black, different multi-walled carbon nanotubes, graphene-based materials, and their derivatives. Statistical and machine learning-based approaches were used to identify groups of CNMs with similar pulmonary toxicity responses from a panel of proteins measured in bronchoalveolar lavage (BAL) fluid samples and with similar pathological outcomes in the lungs. Thus, grouped particles, based on their pulmonary toxicity profiles, were used to select a small set of proteins that could potentially identify and discriminate between the toxicity profiles associated within each group. Specifically, MDC/CCL22 and MIP-3β/CCL19 were identified as common protein markers associated with both toxicologically distinct groups of CNMs. In addition, the persistent expression of other selected protein markers in BAL fluid from each group suggested their ability to predict toxicity in the lungs, i.e. fibrosis and microgranuloma formation. The advantages of such approaches can have positive implications for further research in toxicity profiling.

STANDING COMPUTED TOMOGRAPHY IN NONANESTHETIZED LITTLE PENGUINS (EUDYPTULA MINOR) TO ASSESS RESPIRATORY SYSTEM ANATOMY AND MONITOR DISEASE.

Multidetector computed tomography (MDCT) scans were performed in clinically healthy, nonanesthetized, standing little penguins (Eudyptula minor) to determine reference ranges for air-sac and lung volumes, as well as lung density. Five of 15 clinically healthy birds were diagnosed with pulmonary granulomas on initial MDCT scans. Granulomas were not readily apparent on radiographs, even in cases where the entire normal pulmonary parenchymal architecture was effaced on the MDCT scan. Serial MDCT scans after antifungal and antimycobacterial therapies demonstrated a response to treatment. MDCT scanning in nonanesthetized little penguins proved to be a well-tolerated, non-invasive imaging modality for respiratory diseases that are otherwise difficult to diagnose, including aspergillosis and mycobacteriosis.

Dendritic Cell-Induced Dissemination of Mycobacterium tuberculosis into the Central Nervous System

Abstract Central nervous system tuberculosis (CNSTB) is the most serious manifestation of extrapulmonary tuberculosis infections representing 5–10% of all cases. Knowledge of CNSTB stems from observations made in 1933 by pathologists Rich and McCordock, who found caseating foci in the brain parenchyma or meninges that rupture into the subarachnoid space leading to diffuse meningeal infection. However, the mechanism of how immobile Mycobacterium tuberculosis, the causative agent of TB crosses the highly regulated blood-brain barrier (BBB) and enters the CNS forming these foci and infection is unknown. We have developed a novel in vitro BBB model that combines Mycobacteria-infected DCs, PBMCs, and primary mouse brain endothelial cells to observe early cellular interaction and aggregate formation at the BBB similar to previous observations by Rich and McCordock. With this model we observed Mycobacteria impedes migration of DCs but increases DC initiation of aggregation on a primary mouse endothelial BBB with a cellular composition similar to pulmonary granulomas. Aggregates induce an inflammatory response by increasing ICAM-1 and VCAM-1 expression and dysregulation of tight junction proteins and mitochondria suggesting barrier damage possibly due to increased iNOS expression observed during within aggregates. Mycobacteria-infected DC transmigration is increased in the presence of aggregation. Previous research from our lab and others have shown DC transmigration across an in vitro BBB rely on MMP-9 secretion while TNF-alpha is necessary for pulmonary granuloma formation and Mtb infection control. Here we will show the role iNOS, MMP-9 and TNF-alpha play in DC-mediated dissemination of Mycobacterium across the BBB.

Tuberculosis caused by Mycobacterium pinnipedii in a wild South American sea lion Otaria flavescens stranded in southern Brazil.

Tuberculosis (TB) in pinnipeds is typically caused by Mycobacterium pinnipedii, which has also been associated with infections in other species, such as cattle and humans. As a result, this pathogen has zoonotic potential and is a public health concern. In 2016, a female South American sea lion Otaria flavescens in southern Brazil presented with emaciation and severe dyspnea and died within 3 h of capture. Gross pathology identified pulmonary granulomas, and Ziehl-Neelsen stain identified acid-fast bacilli. M. tuberculosis complex bacteria were confirmed by a BD BACTEC™ MGIT™ 320 detection system using fibrinous exudate, lung granulomas and thoracic fluid. Molecular characterization by spoligotyping showed a hybridization pattern characteristic of M. pinnipedii (SIT593/PINI1). Currently, there is a paucity of data concerning the transmission and epidemiology of M. pinnipedii in pinniped populations in South America. The case report shows that the disease appeared in a free-ranging beached sea lion on the coast, and further surveillance is needed to determine the origin of this TB because of its potential impact on public health.

Reader response: Lymphoplasmacyte-rich meningioma involving the whole intracranial dura mater.

We read the article by Yang et al.1 that reported lymphoplasmacyte-rich meningioma mimicking the whole intracranial pachymeningitis. We reported immunoglobulin G4 (IgG4) pachymeningitis in a 43-year-old woman who had a history of lymphoplasmacyte-rich meningioma resection in the right middle cranial fossa at age 17, a right orbital granuloma at age 29, and a pulmonary granuloma at age 31.2 She then developed left hearing loss and a hypertrophic dura in the posterior fossa at age 35. Six years later, her MRI showed a left frontal meningioma. The biopsied sample showed dense lymphoplasmatic infiltration and IgG4 was stained immunohistochemically. Recently, pachymeningitis was found to relate to IgG43; so the previously resected samples (meningioma, orbital granuloma, pulmonary granuloma) were restudied and showed positive IgG4 staining. Therefore, our case was a definite IgG4-related pachymeningitis and neurologic symptoms were again improved by steroid therapy. Idiopathic hypertrophic pachymeningitis and lymphoplasmacyte-rich meningioma can be confused on both imaging and histopathologic grounds.4 Lymphoplasmacyte-rich meningioma was occasionally reported to spontaneously regress. Its origin, whether neoplastic or inflammatory, is controversial. The case reported by Yang et al. might be IgG4-related; therefore, steroid therapy might be worth a try.

Formation and Disordered Degradation of Neutrophil Extracellular Traps in Necrotizing Lesions of Anti-Neutrophil Cytoplasmic Antibody–Associated Vasculitis

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is characterized by the production of ANCAs and systemic necrotizing vasculitis in small vessels. Disordered regulation of neutrophil extracellular traps (NETs) is critically involved in the pathogenesis of AAV. NETs are web-like DNA decorated with antimicrobial proteins; they are extruded from activated neutrophils. The principal degradation factor of NETs invivo is DNase I; however, NETs resistant to DNase I can persist in tissues and can lead to the production of ANCAs. Deposition of NETs has been demonstrated in glomerular crescents and necrotizing vasculitis in AAV. Here, the amount of NETs in formalin-fixed, paraffin-embedded tissue sections was examined, and the results for AAV were compared with the results for diseases that should be distinguished from AAV. NETs were more abundant in necrotizing vasculitis of AAV than in non-ANCA-associated vasculitis, or in granulomatous angiitis. Pulmonary granulomas in AAV and non-ANCA-associated diseases were further studied. The amount of NETs was significantly greater in necrotizing granulomas of AAV than in granulomas of sarcoidosis without necrosis. Although NETs were formed in necrotizing granulomas of tuberculosis equivalently to those formed in AAV, they were more susceptible to degradation by DNase I than were NETs in AAV. The formation and disordered degradation of NETs in necrotizing lesions are characteristics of AAV and are possibly related to its pathogenesis.

Programmed genome editing of the omega-1 ribonuclease of the blood fluke, Schistosoma mansoni.

CRISPR/Cas9-based genome editing has yet to be reported in species of the Platyhelminthes. We tested this approach by targeting omega-1 (ω1) of Schistosoma mansoni as proof of principle. This secreted ribonuclease is crucial for Th2 polarization and granuloma formation. Schistosome eggs were exposed to Cas9 complexed with guide RNA complementary to ω1 by electroporation or by transduction with lentiviral particles. Some eggs were also transfected with a single stranded donor template. Sequences of amplicons from gene-edited parasites exhibited Cas9-catalyzed mutations including homology directed repaired alleles, and other analyses revealed depletion of ω1 transcripts and the ribonuclease. Gene-edited eggs failed to polarize Th2 cytokine responses in macrophage/T-cell co-cultures, while the volume of pulmonary granulomas surrounding ω1-mutated eggs following tail-vein injection into mice was vastly reduced. Knock-out of ω1 and the diminished levels of these cytokines following exposure showcase the novel application of programmed gene editing for functional genomics in schistosomes.

1474. Etiology of Pulmonary Granulomas: How Common is Unsuspected Infection?

BackgroundGranulomatous inflammation of the lung may be due to mycobacterial or fungal infections, sarcoidosis or vasculitis. When lung biopsy is performed due to suspicion of neoplasm, cultures may not always be done. In these cases, it is often not possible to order microbiologic testing when the pathology report is completed. The purpose of this study was to investigate how often patients with pulmonary nodules, who underwent biopsy for suspected malignancy, simultaneously have specimens sent for culture to assess for an infectious etiology.MethodsWe retrospectively reviewed the pathology reports of 36 patients from 2014 to 2015 who underwent lung biopsy of pulmonary nodules that showed granulomatous inflammation.ResultsThirty-six patients underwent lung biopsy of pulmonary nodules. One patient was excluded because their pathology report did not reveal any granuloma, resulting in a final sample size of 35 patients. Of these, eight (22.9%) patients simultaneously had specimens sent for mycobacterial and fungal cultures while the other 27 (77.1%) did not. Of the 27 patients who did not have specimens simultaneously sent for mycobacterial and fungal cultures, 17 (48.6% of the sample size) were diagnosed with lung cancer. The remaining 10 (28.6% of the sample size) patients did not have a definitive diagnosis because cultures were not sent for testing (Figure 1). Of the eight patients with cultures sent for testing, two (25%) had pulmonary tuberculosis, four (50%) had nontuberculosis mycobacterium infections, and two (25%) had fungal infections (one was Cryptococcus and one had mixed Aspergillus and Penicillium) (Figure 2).ConclusionWe conclude that pulmonary nodules may have an infectious etiology when biopsy is performed for a suspected malignancy. Specimens should routinely be sent for mycobacterial and fungal cultures regardless of presumptive diagnosis.Figure 1:Figure 2.(MTB, Mycobacterium tuberculosis; NTB, non-Mycobacterium tuberculosis)Disclosures All authors: No reported disclosures.

Role of Macrophage Migration Inhibitory Factor in Granulomatosis With Polyangiitis.

To examine the association between macrophage migration inhibitory factor (MIF) promoter polymorphisms and granulomatosis with polyangiitis (GPA) in human subjects, and to assess the role of MIF in a murine model of granulomatous vasculitis. The human study involved 1,077 patients with GPA and healthy controls whose serum was genotyped by capillary electrophoresis for the MIF -794 CATT5-8 promoter microsatellite (rs5844572). MIF promoter, CATT-length-dependent gene expression in response to β-glucan was assessed by gene reporter assays. In mouse studies, granulomatous disease was induced by injection of Candida albicans β-glucan into wild-type (WT) or Mif-knockout (Mif-KO) C57BL/6 mice and C57BL/6 mice transgenically overexpressing Mif in lung epithelium (Mif lung-Tg2.1). Mice were treated with a neutralizing anti-MIF antibody and analyzed for the density of pulmonary granulomas, expression of inflammatory chemokines, and frequency of mortality. The percentage of human subjects carrying >5 CATT repeats in each MIF allele (high genotypic MIF expressers) was 60.2% among patients with GPA and 53.9% among healthy controls (adjusted P = 0.049). In response to granulomatous stimulation, human MIF gene expression increased proportionally with CATT length. Mif lung-Tg2.1 mice exhibited more pulmonary granulomas than WT mice, which in turn showed more granulomas than Mif-KO mice. A significantly higher percentage of Mif lung-Tg2.1 mice, compared to Mif-KO or WT mice, died when injected with Candida albicans β-glucan, and treatment of these mice with an anti-MIF monoclonal antibody protected against a lethal outcome. Levels of MIF-dependent neutrophil/macrophage chemokines were elevated in the bronchoalveolar lavage fluid or plasma of Mif lung-Tg2.1 mice. Patients with GPA have an increased frequency of high MIF expression CATT alleles. Higher Mif expression increases the incidence of mortality and pulmonary granulomas in Mif lung-Tg2.1 mice, while anti-MIF treatment protects these mice against death. Blockade of MIF in high genotypic MIF expressers may therefore offer a selective pharmacologic therapy for GPA.

Nodular rheumatoid arthritis (RA): A distinct disease subtype, initiated by cadmium inhalation inducing pulmonary nodule formation and subsequent RA–associated autoantibody generation

Nodular rheumatoid arthritis (RA) patients have raised rheumatoid factor (RF) and anti–citrullinated protein antibody (ACPA) levels, and are more likely to smoke than RA patients without nodules. Subcutaneous and pulmonary rheumatoid nodules (granulomas) frequently co–exist. Pulmonary rheumatoid nodules develop prior to RA development and have the immunological machinery to generate RF and ACPAs. Pulmonary granulomas have been observed in animal models exposed to cadmium (Cd) inhalation. Cigarette smoke increases pulmonary Cd exposure. It has been suggested that dust and cigarette smoke co–exposure increases localised pulmonary Cd adsorption. We hypothesise that subcutaneous nodular RA represents a distinct disease subtype induced by pulmonary rheumatoid nodule formation and the generation of high levels of RA associated autoantibodies initiated by Cd inhalation via cigarette smoke.Cohorts of RA patients attending rheumatology clinics in Cornwall, UK (total n = 504) were studied to determine the prevalence of nodular RA, with matched analysis (age, gender and social class) to compare urinary Cd, RF and ACPA levels stratifying for nodular disease and smoking.In cohort 1 45/303 (14.9%) of the RA patients under regular follow up had nodular disease. Of the RA smokers, 30/155 (19%) were nodular and of the RA non–smokers 15/148 (10%) were nodular. Smoking was significantly associated with nodular RA, odds ratio (OR) = 2.48 95% confidence interval (CI) 1.26–4.88, p = 0.008. Raised urinary Cd levels were significantly associated with nodular RA in non–dust exposed individuals, OR 2.26 (95% CI 1.08–4.73), p = 0.03 compared to dust exposed individuals, OR 0.78 (95% CI 0.35–1.76), p = 0.557, despite fewer pack years (py) at diagnosis (16 vs 20 py). Nodular RA smokers had significantly raised RF levels compared to RA smokers without nodular disease (median RF 171.5 (interquartile range (IQR) 48–394) vs median RF 31.7 (IQR 10.3–170.3), p < 0.00001). RF positivity was significantly more prevalent in nodular RA smokers compared to RA smokers without nodular disease (84/89 (94%) vs. 141/199 (71%), OR = 6.9 (95% CI 2.66–17.91), p < 0.00001). ACPA levels were also significantly raised in nodular smokers compared to non–nodular smokers (median ACPA 250 (IQR 145–426) vs 116 (1–257.5), p < 0.00001), as were ACPA positivity rates (83/89 (93%) vs 123/191 (64%), OR = 7.65 (95% CI 3.17–18.4), p < 0.0001).These pilot results support the hypothesis that nodular RA represents a distinct disease subtype initiated by cadmium inhalation, which we suggest induces pulmonary rheumatoid nodule formation and generation of RA–associated autoantibodies.

A CASE OF PULMONARY HYALINIZING GRANULOMA WITH RETROPERITONEAL FIBROSIS

SESSION TITLE: Lung Pathology 2 SESSION TYPE: Fellow Case Report Posters PRESENTED ON: 10/09/2018 01:15 PM - 02:15 PM INTRODUCTION: Pulmonary hyalinizing granuloma (PHG) is a rare benign lung disease characterized by single or multiple lung nodules mimicking lung neoplasm. It is characterized by fibrosing nodules with central concentric deposits of lamellar collagen, surrounded by collections of plasma cells, histiocytes and lymphocytes. Its etiopathogenesis is unknown, although it could be associated with an autoimmune, fibrotic or previous infectious process. CASE PRESENTATION: A 64 year old male with PMH of anemia, renal insufficiency and retroperitoneal fibrosis (RPF diagnosed by imaging study in 2009) presented to pulmonary clinic in September 2013 with dyspnea on exertion, cough with intermittent hemoptysis and chest discomfort. Chest radiograph and CT chest showed RLL (5cm mass) and LLL lesions. Subsequent bronchoscopy with lung biopsy of RLL (TBBx) showed fungal elements felt by pathologist to be Rhizopus. Patient was treated with amphotericin for two weeks but was stopped due to worsening renal function. Slight improvement in lung mases noted on repeat CT chest in 2 months. Infectious disease team recommended resection of the RLL mass since medical therapy of Rhizopus with amphotericin was not clear. Patient refused surgery and lost in follow up. Patient presented to pulmonary clinic for follow up in 6/2017 and CT chest showed increasing size of RLL and LLL masses and new LUL mass. Patient was asymptomatic. Laboratory work up with CBC, BMP, rheumatology work up (including ANA, ENA, RF, CCP), immunoglobulin and fungal serology were unremarkable. PET scan demonstrated increased FDG uptake in RLL, LUL and LLL masses. Subsequent LUL biopsy was consistent with pulmonary hyalinizing granuloma. Patient is asymptomatic and is being followed with serial CT chest to make sure densities do not increase in size. DISCUSSION: PHG represents a hyperfibrotic response to an infectious agent such as histoplasma or associated with mediastinal or retroperitoneal fibrosis. In our case PHG was diagnosed many years after RPF. The association between two disorders is obscure. Abnormal immune response might form a range of conditions common to the two diseases. The prognosis for patients with PHG is generally excellent with no significant impact on longevity. Successful resolution of the nodules with the administration of glucocorticoids has been reported. CONCLUSIONS: PHG is closely associated with fibrotic disease, autoimmune and infectious process. The clinicians should consider the possibility of PHG when encountering a patient with RPF or vice versa. Currently there is no established treatment. Asymptomatic patient can be managed with serial imaging study. Reference #1: 1. Brandao, Viviane, et al. "Hyalinizing granuloma: an unusual case of a pulmonary mass." Case reports in medicine 2010 (2010). Reference #2: 2. Saint-Pierre, Mathieu, et al. "Pulmonary Hyalinizing Granuloma (PHG): An Uncommon Cause of Pulmonary Nodules." Chest 152.4 (2017): A435. Reference #3: 3. Young, Adam S., et al. "Pulmonary hyalinizing granuloma and retroperitoneal fibrosis in an adolescent." Pediatric radiology 37.1 (2007): 91-95. DISCLOSURES: No relevant relationships by James Finley, source=Web Response No relevant relationships by Mohammed Nagori, source=Web Response

Pulmonary fungal granulomas and fibrinous pneumonia caused by different hypocrealean fungi in reptiles

In contrast to fungal dermatitis, fungal glossitis and disseminated visceral mycosis, fungal infection of the lung has so far rarely been described in reptiles. Pulmonary fungal granulomas were diagnosed histopathologically within the scope of post mortem examinations. Fragments of the 18S-internal transcribed spacer1-5.8S rDNA (SSU-ITS1-5.8S) and 28S rDNA (LSU), including domains (D)1 and D2 as well as the protein coding gene translation elongation factor 1 alpha (TEF) were used for phylogenetical analysis after isolation of the fungal pathogen by culturing. Ten reptiles, including lizards (n = 6), snakes (n = 1), crocodilians (n = 2) and tortoises (n = 1) presented with pulmonary fungal granulomas (n = 8) and fibrinous pneumonia (n = 2) caused by different non-clavicipitaceous and clavicipitaceous species of the order Hypocreales. Purpureocillium lavendulum (n = 2) and Metarhizium robertsii (n = 1) as the etiologic agents of pneumonia in reptile species are described for the first time. Fungal pulmonary granulomas caused by clavicipitaceous fungi (n = 6) were all associated with disseminated visceral mycosis as well as oral fungal granulomas (n = 4) and/or fungal dermatitis (n = 1). Differing infection routes being likely for clavicipitaceous and non-clavicipitaceous fungal pathogens. A potential zoonotic health risk should be taken into account during necropsy or lung sampling in live reptiles with pulmonary fungal granulomas, since human infections, mainly keratitis and sclerokeratitis, caused by Beauveria bassiana, Metarhizium robertsii and Purpureocillium lilacinum, have occasionally been described.

Small pulmonary granuloma is often misdiagnosed as lung cancer by positron emission tomography/computer tomography in diabetic patients

A small pulmonary granuloma (SPG) is often misdiagnosed as lung cancer in diabetic patients by positron emission tomography/computed tomography (PET/CT). The present study was conducted to investigate whether diabetes is the influencing factor and to determine other related factors that have an impact on the diagnostic results following PET/CT examination. All clinical, imaging and pathological data of patients diagnosed with pulmonary nodules by PET/CT from January 2004 to December 2017 in our department were collected. Patients with an SPG who were wrongly diagnosed with lung cancer by PET/CT were enrolled (n = 79). The propensity score matching method was used to create a comparable control adenocarcinoma group (n = 395). Maximum standard uptake values, diabetes and fasting blood-glucose (FBG) were determined and analysed. The average maximum standard uptake values in the 2 groups were comparable (P = 0.801). Maximum standard uptake values in 5 subsections were not significantly different between the 2 groups (P = 0.135). The odds ratio (OR) of 3.326 [95% confidence interval (CI) 1.671-6.623] for diabetes favoured misdiagnosis and was statistically significant (P < 0.001). Furthermore, in patients with high FBG levels (≥7.0 mmol/l), the risk of misdiagnosis of SPG increased significantly compared with normal FBG level (OR 2.601, 95% CI 1.174-5.761; P = 0.015). Diabetes and high FBG level were the influencing factors in the false-positive results of lung cancer by PET/CT examination.

Pulmonary Hyalinizing Granuloma Mimicking Primary Lung Cancer

We herein report a case of pulmonary hyalinizing granuloma (PHG), which is a rare pulmonary mass. A 69-year-old man with no symptoms presented to our hospital because of the appearance of an abnormal shadow on chest X-ray. Computed tomography revealed a right middle-lobe mass with spicula and infiltration into the upper lobe. Since a bronchofiberscopic examination showed no malignant cells in the specimen, the patient underwent thoracoscopic surgery, which revealed PHG. Spiculation and interlobar infiltration, which comprise the characteristic features of primary lung cancer, are uncommon presentations of this rare entity.

Pulmonary Hyalinizing Granuloma in the Differential Diagnosis of Pulmonary Carcinoma

Pulmonary hyalinizing granuloma (PHG) which should be considered in the differential diagnosis of pulmonary nodules of unknown origin is a distinct fibrosing lesion of lung that occurs in middle-aged patients. It has been usually reported as case reports in the literature. Patients are usually symptomatic. We present the case which recognized during operation and determined rarely.

PPAR-gamma pathways attenuate pulmonary granuloma formation in a carbon nanotube induced murine model of sarcoidosis

Peroxisome proliferator activated receptor gamma (PPARγ), a ligand activated nuclear transcription factor, is constitutively expressed in alveolar macrophages of healthy individuals. PPARγ deficiencies have been noted in several lung diseases including the alveolar macrophages of pulmonary sarcoidosis patients. We have previously described a murine model of multiwall carbon nanotubes (MWCNT) induced pulmonary granulomatous inflammation which bears striking similarities to pulmonary sarcoidosis, including the deficiency of alveolar macrophage PPARγ. Further studies demonstrate alveolar macrophage PPARγ deficiency exacerbates MWCNT-induced pulmonary granulomas. Based on these observations we hypothesized that activation of PPARγ via administration of the PPARγ-specific ligand rosiglitazone would limit MWCNT-induced granuloma formation and promote PPARγ-dependent pathways. Results presented here show that rosiglitazone significantly limits the frequency and severity of MWCNT-induced pulmonary granulomas. Furthermore, rosiglitazone attenuates alveolar macrophage NF-κB activity and downregulates the expression of the pro-inflammatory mediators, CCL2 and osteopontin. PPARγ activation via rosiglitazone also prevents the MWCNT-induced deficiency of PPARγ-regulated ATP-binding cassette lipid transporter-G1 (ABCG1) expression. ABCG1 is crucial to pulmonary lipid homeostasis. ABCG1 deficiency results in lipid accumulation which promotes pro-inflammatory macrophage activation. Our results indicate that restoration of homeostatic ABCG1 levels by rosiglitazone correlates with both reduced pulmonary lipid accumulation, and decreased alveolar macrophage activation. These data confirm and further support our previous observations that PPARγ pathways are critical in regulating MWCNT-induced pulmonary granulomatous inflammation.