Pulmonary Granulomas Research Articles

Pulmonary hyalinizing granuloma: literature review and case presentation

Pulmonary hyalinizing granuloma (PHG) is an extremely rare condition. Only 170-200 cases have been described until now all over the world. There have been no reports in the Russian medical literature. Etiology of the disease is unknown. The X-ray picture is very unspecific. Tumors of lungs and pleura and infectious diseases are included in the differential line. Patients with pulmonary hyalinizing granuloma have long stabile progression of the disease, and the treatment with glucocorticoids can lead to the long lasting remission.The aim of the review was to inform pulmonologists, general practitioners, infectious disease specialists, thoracic surgeons, and oncologists about the existence of pulmonary hyalinizing granuloma, its diagnosis, clinical course, and treatment. Also we present one clinical case of patient with pulmonary hyalinizing granuloma.Conclusion. Because of very low incidence of PHG, an internist or a pulmonologist can never encounter it in their professional life. However it is worth keeping this condition in mind and including it into the diagnostic process when focal and focused shadows are identified in the lungs during chest X-ray. Probably, the disease is caused by different immune-mediatory processes, but the exact pathogenesis is still unknown. Biopsy of the lung tissue by means of lung resection is crucial for the morphological verification of the diagnosis. The prognosis of the disease is favorable. The timely initiation of treatment can sufficiently prolong the remission.

Pulmonary Hyalinizing Granuloma: Case Report and Discussion of Diagnostic Challenges and Terminology.

Pulmonary hyalinizing granuloma (PHG) is a rare, benign condition characterized by slow-growing pulmonary nodules, often mimicking malignant lesions radiologically. Its pathogenesis is unclear but is thought to result from an exaggerated immune response to persistent antigenic stimuli. This report presents a case of a 71-year-old male with PHG, incidentally detected during imaging for acute appendicitis. Diagnostic challenges arose due to the radiological resemblance to metastatic disease, and inadequate biopsy samples. Surgical resection revealed fibrocollagenous nodules with perivascular inflammatory infiltrates. Immunohistochemistry and special stains excluded malignancy and infection. The clinical course of PHG is typically benign, with surgery being the treatment of choice for solitary lesions. However, the current terminology may be misleading, as the lesions are not true granulomas but rather fibrosing lesions. Further research is needed to clarify the underlying pathophysiology and improve diagnostic accuracy.

Idiopathic hyalinizing fibrosclerosis: A systemic steroid-resistant condition distinct from IgG4-related disease

Since the concept of IgG4-related disease (IgG4-RD) was proposed, that diagnosis has been considered in idiopathic fibroinflammatory diseases in various organs, particularly in cases with multi-organ involvement. We have recently encountered three cases of fibrosing disease of uncertain etiology with shared microscopic appearances. Case 1 (56-year-old man) had an irregular mass at the base of mesentery. Case 2 (29-year-old woman) presented with obstructive jaundice due to an ill-defined mass at the hepatic hilum and two lung nodules. Case 3 (53-year-old man) had multiple solid nodules in the mediastinum, peritoneum, retroperitoneum, and mesentery; he also had diffuse irregular narrowing of the intra- and extra-hepatic bile ducts in keeping with sclerosing cholangitis. Serum IgG4 concentrations were not elevated. Biopsies from the nodular lesions showed extensive hyalinizing fibrosis with an only focal lymphoplasmacytic infiltrate. Thick collagenous bundles are arranged in an irregular or partly whorl pattern. Typical storiform fibrosis or obliterative phlebitis was not observed. The number of IgG4-positive plasma cells was <10 cells/high-power field; the ratio of IgG4/IgG-positive plasma cells was <30%. After the histological diagnosis of sclerosing mesenteritis, pulmonary hyalinizing granuloma, and mediastinal fibrosis was made, they were treated with a trial of steroids, but none showed a significant response. In conclusion, a hyalinizing fibrotic condition can occur at various anatomical sites. They have shared microscopic findings, and are steroid-resistant. Although the clinical presentation may mimic IgG4-RD, the two conditions are likely distinct. We would propose a diagnostic term of ‘idiopathic hyalinizing fibrosclerosis’ for this under-recognized, rare, systemic condition.

Peri- and intra-nodular radiomic features based on 18F-FDG PET/CT to distinguish lung adenocarcinomas from pulmonary granulomas.

To compare the effectiveness of radiomic features based on 18F-FDG PET/CT images within (intranodular) and around (perinodular) lung nodules/masses in distinguishing between lung adenocarcinoma and pulmonary granulomas. For this retrospective study, 18F-FDG PET/CT images were collected for 228 patients. Patients diagnosed with lung adenocarcinoma (n = 156) or granulomas (n = 72) were randomly assigned to a training (n = 159) and validation (n = 69) groups. The volume of interest (VOI) of intranodular, perinodular (1-5 voxels, termed Lesion_margin1 to Lesion_margin5) and total area (intra- plus perinodular region, termed Lesion_total1 to Lesion_total5) on PET/CT images were delineated using PETtumor and Marge tool of segmentation editor. A total of 1,037 radiomic features were extracted separately from PET and CT images, and the optimal features were selected to develop radiomic models. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC). Good and acceptable performance was, respectively, observed in the training (AUC = 0.868, p < 0.001) and validation (AUC = 0.715, p = 0.004) sets for the intranodular radiomic model. Among the perinodular models, the Lesion_margin2 model demonstrated the highest AUC in both sets (0.883 and 0.616, p < 0.001 and p = 0.122). Similarly, in terms of total models, Lesion_total2 model was found to outperform others in the training (AUC = 0.879, p < 0.001) and validation (AUC = 0.742, p = 0.001) sets, slightly surpassing the intranodular model. When intra- and perinodular radiomic features extracted from the immediate vicinity of the nodule/mass up to 2 voxels distance on 18F-FDG PET/CT imaging are combined, improved differential diagnostic performance in distinguishing between lung adenocarcinomas and granulomas is achieved compared to the intra- and perinodular radiomic features alone.

Mathematical model of oxygen, nutrient, and drug transport in tuberculosis granulomas.

Physiological abnormalities in pulmonary granulomas-pathological hallmarks of tuberculosis (TB)-compromise the transport of oxygen, nutrients, and drugs. In prior studies, we demonstrated mathematically and experimentally that hypoxia and necrosis emerge in the granuloma microenvironment (GME) as a direct result of limited oxygen availability. Building on our initial model of avascular oxygen diffusion, here we explore additional aspects of oxygen transport, including the roles of granuloma vasculature, transcapillary transport, plasma dilution, and interstitial convection, followed by cellular metabolism. Approximate analytical solutions are provided for oxygen and glucose concentration, interstitial fluid velocity, interstitial fluid pressure, and the thickness of the convective zone. These predictions are in agreement with prior experimental results from rabbit TB granulomas and from rat carcinoma models, which share similar transport limitations. Additional drug delivery predictions for anti-TB-agents (rifampicin and clofazimine) strikingly match recent spatially-resolved experimental results from a mouse model of TB. Finally, an approach to improve molecular transport in granulomas by modulating interstitial hydraulic conductivity is tested in silico.

Schistosoma mansoni co-infection modulates Chagas disease development but does not impair the effect of benznidazole-based chemotherapy

The adequate management of parasite co-infections represents a challenge that has not yet been overcome, especially considering that the pathological outcomes and responses to treatment are poorly understood. Thus, this study aimed to evaluate the impact of Schistosoma mansoni infection on the efficacy of benznidazole (BZN)-based chemotherapy in Trypanosoma cruzi co-infected mice. BALB/c mice were maintained uninfected or co-infected with S. mansoni and T. cruzi, and were untreated or treated with BZN. Body weight, mortality, parasitemia, cardiac parasitism, circulating cytokines (Th1/Th2/Th17); as well as heart, liver and intestine microstructure were analyzed. The parasitemia peak was five times higher and myocarditis was more severe in co-infected than T. cruzi-infected mice. After reaching peak, parasitemia was effectively controlled in co-infected animals. BZN successfully controlled parasitemia in both co-infected and T. cruzi-infected mice and improved body mass, cardiac parasitism, myocarditis and survival in co-infected mice. Co-infection dampened the typical cytokine response to either parasite, and BZN reduced anti-inflammatory cytokines in co-infected mice. Despite BZN normalizing splenomegaly and liver cellular infiltration, it exacerbated hepatomegaly in co-infected mice. Co-infection or BZN exerted no effect on hepatic granulomas, but increased pulmonary and intestinal granulomas. Marked granulomatous inflammation was identified in the small intestine of all schistosomiasis groups. Taken together, our findings indicate that BZN retains its therapeutic efficacy against T. cruzi infection even in the presence of S. mansoni co-infection, but with organ-specific repercussions, especially in the liver.

Spatial transcriptomic sequencing reveals immune microenvironment features of Mycobacterium tuberculosis granulomas in lung and omentum.

Granulomas are a key pathological feature of tuberculosis (TB), characterized by cell heterogeneity, spatial composition, and cellular interactions, which play crucial roles in granuloma progression and host prognosis. This study aims to analyze the transcriptome profiles of cell populations based on their spatial location and to understand the core transcriptome characteristics of granuloma formation and development. Methods In this study, we collected four clinical biopsy samples including Mycobacterium tuberculosis (Mtb) infected lung (MTB-L) and omentum tissues (MTB-O), as well as two lung and omentum biopsies from non-TB patients. The tissues were analyzed by spatial transcriptomics to create a spatial atlas. Utilizing cell enrichment scores and intercellular communication analysis, we investigated the transcriptome signatures of cell populations in various spatial regions and identified genes that may play a decisive role in the formation of pulmonary and omental tuberculosis granulomas. To validate our major findings, an in vitro TB model based on organoid-macrophage co-culture was established. Results Spatial transcriptomics mapped the cell composition and spatial distribution characteristics of tuberculosis granulomas in lung and omental tissues infected with Mtb. The characteristics and evolutionary relationships of major cell populations in granulomas reveal a shift in the immune microenvironment: from a predominance of B cells and fibroblasts in pulmonary granulomas to a predominance of myeloid cells and fibroblasts in omental granulomas. Furthermore, our data identified key differentially expressed genes across cell clusters and regions, showing that upregulation of collagen genes is a common feature of granulomas. Using an organoid-macrophage co-culture model, we demonstrated the notable efficacy of Thrombospondin-1 (THBS1) in reducing protein expression levels related to extracellular matrix remodeling. Conclusion These results provide insights into the pathogenesis and development of tuberculosis, enhancing our understanding of the composition and interactions of tuberculosis granuloma cells from a spatial perspective, and pave the way for novel adjuvant treatments for tuberculosis.

Pulmonary Hyalinizing Granuloma with Radiological Cystic Lesion.

Pulmonary Hyalinizing Granuloma with Radiological Cystic Lesion.

Pathological granuloma fibrosis induced by agar-embedded Mycobacterium abscessus in C57BL/6JNarl mice.

Pulmonary granuloma diseases caused by Mycobacterium abscessus (M. abscessus) have increased in past decades, and drug-resistance in this pathogen is a growing public health concern. Therefore, an animal model of chronic granuloma disease is urgently needed. In this study, M. abscessus embedded within agar beads (agar-AB) was used to develop such a model in C57BL/6JNarl mice. Chronic infection was sustained for at least 3 months after agar-AB infection, visible granulomas spread in the lungs, and giant cells and foamy cells appeared in the granulomas. More importantly, pulmonary fibrosis progressed for 3 months, and collagen fibers were detected by Masson trichrome staining. Further, inducible nitric oxide synthase (iNOS) was highly expressed within the alveolar space, and the fibrosis-mediator transforming growth factor beta (TGF-β) began to be expressed at 1 month. Hypoxia-inducible factor (HIF-1α) expression also increased, which aided in normalizing oxygen partial pressure. Although the transient fibrosis persisted for only 3 months, and the pulmonary structure resolved when the pathogen was cleard, this pulmonary fibrosis model for M. abscessus infection will provide a novel test platform for development of new drugs, regimens, and therapies.

Clinical Observations, Identification, and Antimicrobial Susceptibility of Fungi Isolated from Sea Turtles with Histologically Confirmed Mycotic Infections: 20 Cases, 2005–2020

Abstract Fungal infections were histologically confirmed in 20 stranded sea turtles, including 18 Kemp’s ridley turtles (Lepidochelys kempii), one green turtle (Chelonia mydas), and one leatherback turtle (Dermochelys coriacea). Infection was detected antemortem in 6 cases. Gross external findings in live turtles included carapace lesions (n = 3) and dermatitis (n = 1). Radiographs revealed evidence of pneumonia in 18 animals. Bronchoscopy detected excessive fluid, mucus, clotted blood, or caseous material within the bronchi and lungs of 3 turtles. At necropsy, the most common gross lesions were pulmonary granulomas, consolidation, and, or hemorrhage (n = 18), and the most common histologic lesion was severe heterophilic to granulomatous pneumonia (n = 18). Nine animals had fungal infection at sites outside of the lung. The most commonly identified genera were Purpureocillium, Beauveria, and Fusarium. Other isolates included Metarhizium sp., Trichoderma sp., Clavispora lusitaniae (Candida lusitaniae), Leptospherulina sp., Penicillium chrysogenum, Mucor sp., and Aspergillus section Nigri. Antifungal susceptibility performed for 10 isolates indicated minimum inhibitory concentrations (mg/L) for fluconazole ranging from 8 to &amp;gt;64, often &amp;gt;32; itraconazole 0.06 to 16, often ≤1; voriconazole 0.06 to 2, often ≤0.5; terbinafine 0.06 to &amp;gt;2, often ≤2. These data indicate that fluconazole resistance is common among the fungi that cause infection in sea turtles. Based on susceptibility data, itraconazole, voriconazole, or terbinafine may be appropriate for treatment of such infections, but additional clinical research is needed. Results of this study indicate that fungal infections can be difficult to diagnose antemortem in sea turtles, and more aggressive methods of diagnosis, such as lung biopsy, may be indicated for suspected cases.

Transcriptional profiling of a fungal granuloma reveals a low metabolic activity of Paracoccidioides brasiliensis yeasts and an actively regulated host immune response.

Granulomas are important immunological structures in the host defense against the fungus Paracoccidioides brasiliensis, the main etiologic agent of Paracoccidioidomycosis (PCM), a granulomatous systemic mycosis endemic in Latin America. We have performed transcriptional and proteomic studies of yeasts present in the pulmonary granulomas of PCM aiming to identify relevant genes and proteins that act under stressing conditions. C57BL/6 mice were infected with 1x106 yeasts and after 8- and 12-weeks of infection, granulomatous lesions were obtained for extraction of fungal and murine RNAs and fungal proteins. Dual transcriptional profiling was done comparing lung cells and P. brasiliensis yeasts from granulomas with uninfected lung cells and the original yeast suspension used in the infection, respectively. Mouse transcripts indicated a lung malfunction, with low expression of genes related to muscle contraction and organization. In addition, an increased expression of transcripts related to the activity of neutrophils, eosinophils, macrophages, lymphocytes as well as an elevated expression of IL-1β, TNF-α, IFN-γ, IL-17 transcripts were observed. The increased expression of transcripts for CTLA-4, PD-1 and arginase-1, provided evidence of immune regulatory mechanisms within the granulomatous lesions. Also, our results indicate iron as a key element for the granuloma to function, where a high number of transcripts related to fungal siderophores for iron uptake was observed, a mechanism of fungal virulence not previously described in granulomas. Furthermore, transcriptomics and proteomics analyzes indicated a low fungal activity within the granuloma, as demonstrated by the decreased expression of genes and proteins related to energy metabolism and cell cycle.

An mTORC1-Dependent Mouse Model for Cardiac Sarcoidosis.

Background Sarcoidosis is an inflammatory, granulomatous disease of unknown cause affecting multiple organs, including the heart. Untreated, unresolved granulomatous inflammation can lead to cardiac fibrosis, arrhythmias, and eventually heart failure. Here we characterize the cardiac phenotype of mice with chronic activation of mammalian target of rapamycin (mTOR) complex 1 signaling in myeloid cells known to cause spontaneous pulmonary sarcoid-like granulomas. Methods and Results The cardiac phenotype of mice with conditional deletion of the tuberous sclerosis 2 (TSC2) gene in CD11c+ cells (TSC2fl/flCD11c-Cre; termed TSC2KO) and controls (TSC2fl/fl) was determined by histological and immunological stains. Transthoracic echocardiography and invasive hemodynamic measurements were performed to assess myocardial function. TSC2KO animals were treated with either everolimus, an mTOR inhibitor, or Bay11-7082, a nuclear factor-kB inhibitor. Activation of mTOR signaling was evaluated on myocardial samples from sudden cardiac death victims with a postmortem diagnosis of cardiac sarcoidosis. Chronic activation of mTORC1 signaling in CD11c+ cells was sufficient to initiate progressive accumulation of granulomatous infiltrates in the heart, which was associated with increased fibrosis, impaired cardiac function, decreased plakoglobin expression, and abnormal connexin 43 distribution, a substrate for life-threatening arrhythmias. Mice treated with the mTOR inhibitor everolimus resolved granulomatous infiltrates, prevented fibrosis, and improved cardiac dysfunction. In line, activation of mTOR signaling in CD68+ macrophages was detected in the hearts of sudden cardiac death victims who suffered from cardiac sarcoidosis. Conclusions To our best knowledge this is the first animal model of cardiac sarcoidosis that recapitulates major pathological hallmarks of human disease. mTOR inhibition may be a therapeutic option for patients with cardiac sarcoidosis.

A CT-based radiomics integrated model for discriminating pulmonary cryptococcosis granuloma from lung adenocarcinoma-a diagnostic test.

Chest computed tomography (CT) is a critical tool in the diagnosis of pulmonary cryptococcosis as approximately 30% of normal immunity individuals may not exhibit any significant symptoms or laboratory findings. Pulmonary cryptococcosis granuloma and lung adenocarcinoma can appear similar on noncontrast chest CT. This study evaluates the use of an integrated model that was developed based on radiomic features combined with demographic and radiological features to differentiate pulmonary cryptococcosis nodules from lung adenocarcinomas. Preoperative chest CT images for 215 patients with solid pulmonary nodules with histopathologically confirmed lung adenocarcinoma and cryptococcosis infection were collected from two clinical centers (108 cases in the training set and 107 cases in the test set divided by the different hospitals). Radiomics models were constructed based on nodular lesion volume (LV), 5-mm extended lesion volume (ELV), and perilesion volume (PLV). A demoradiological model was constructed using logistic regression based on demographic information (age, sex) and 12 radiological features (location, number, shape and specific imaging signs). Both models were used to build an integrated model, the performance of which was assessed using the test set. A junior and a senior radiologist evaluated the nodules. Receiver operating characteristic (ROC) curve analysis was conducted, and areas under the curve (AUCs), sensitivity (SEN), and specificity (SPE) of the models were calculated and compared. Among the radiomics models, AUCs of the LV, ELV, and PLV were 0.558, 0.757, and 0.470, respectively. Age, lesion number, and lobular sign were identified as independent discriminative features providing an AUC of 0.77 in the demoradiological model (SEN 0.815, SPE 0.642). The integrated model achieved the highest AUC of 0.801 (SEN 0.759, SPE 0.755), which was significantly higher than that obtained by a junior radiologist (AUC =0.689, P=0.024) but showed no significant difference from that of the senior radiologist (AUC =0.784, P=0.388). An integrated model with radiomics and demoradiological features improves discrimination of cryptococcosis granulomas from solid adenocarcinomas on noncontrast CT. This model may be an effective strategy for machine complementation to discrimination by radiologists, and whole-lung automated recognition methods might dominate in the future.

18 F FDG PET-CT Scan Findings in a Rare Case of Pulmonary Hyalinising Granuloma

Pulmonary hyalinising granuloma (PHG) is a benign lung disease. It is a rare disease of unknown aetiology. Less than 150 cases are reported. Its aetiology has not been established but the underlying cause is thought to be the deposition of an immune complex in lung parenchyma or autoimmune process. It usually presents as solitary or multiple lung nodules. PHG has a good prognosis. Solitary lesions are treated by resection and multiple lesions are treated with immunosuppressive drugs with variable responses. Here, we report a case of a 68-year-old female who presented with two episodes of haemoptysis. On investigation, chest computed tomography (CT) reveals multiple lung nodules on both sides, 18 F fluorodeoxyglucose (FDG) positron emission tomography and CT scan reveal mildly FDG avid and non-FDG avid subpleural and parenchymal nodular lesions of varying sizes with calcification noted scattered diffusely in both lung fields. Pathology findings are suggestive of fibrocollagenous tissue with tiny foci of epithelial cells arranged as papillae, cuboid cells with minimal atypia, mitosis, and necrosis not seen and no lymphoid tissue seen, suggestive of PHG.

CD30 co-stimulation drives differentiation of protective T cells during Mycobacterium tuberculosis infection.

Control of Mycobacterium tuberculosis (Mtb) infection requires generation of T cells that migrate to granulomas, complex immune structures surrounding sites of bacterial replication. Here we compared the gene expression profiles of T cells in pulmonary granulomas, bronchoalveolar lavage, and blood of Mtb-infected rhesus macaques to identify granuloma-enriched T cell genes. TNFRSF8/CD30 was among the top genes upregulated in both CD4 and CD8 T cells from granulomas. In mice, CD30 expression on CD4 T cells is required for survival of Mtb infection, and there is no major role for CD30 in protection by other cell types. Transcriptomic comparison of WT and CD30-/- CD4 T cells from the lungs of Mtb-infected mixed bone marrow chimeric mice showed that CD30 directly promotes CD4 T cell differentiation and the expression of multiple effector molecules. These results demonstrate that the CD30 co-stimulatory axis is highly upregulated on granuloma T cells and is critical for protective T cell responses against Mtb infection.

Inhibition of phosphoinositide‑3 kinases γ/δ ameliorates pulmonary granuloma by rescuing Treg function in a sarcoidosis model.

Sarcoidosis is a multisystem inflammatory disease characterized by the development of Th1/Th17/regulatory T cells (Tregs)-related non-caseating granulomas. Phosphoinositide-3 kinases δ/γ (PI3Kδ/γ) play an important role in the maintenance of effective immunity, especially for Tregs homeostasis and stability. In the present study, superoxide dismutase A (SodA) stimulation was used to establish the sarcoidosis mouse model. The second immune stimulus was accompanied by CAL-101 (PI3Kδ inhibitor) or AS-605240 (PI3Kδ/γ inhibitor) treatment. To detect the effect of the PI3Kδ/γ inhibitor on the morphology of pulmonary granuloma and the activation of the PI3K signaling pathway, hematoxylin and eosin staining and immunofluorescence and western blotting was used, respectively. Fluorescence-activated cell sorting analysis and reverse transcription-quantitative PCR were adopted to detect the effect of the PI3Kδ/γ inhibitor on the SodA-induced sarcoidosis mouse model in respect to immune cell disorder and the function of Treg cells, with CD4+CD25- T cells and CD4+CD25+ T cells sorted by magnetic cell sorting. The results demonstrated that the inhibition of PI3Kδ/γ by transtracheal CAL-101/AS-605240 administration facilitated pulmonary granuloma formation. These therapeutic effects were associated with certain mechanisms, including suppressing the aberrantly activated PI3K/Akt signaling in both pulmonary granuloma and Tregs, particularly rescuing the suppressive function of Tregs. Notably, CAL-101 was more effective in immune modulation compared with AS-605240 and could overcome the aberrantly activated Akt in the lung and Tregs. These results suggest that PI3K/Akt signaling, especially the PI3Kδ subunit, can play a key role in optimal Tregs-mediated protection against pulmonary sarcoidosis. Therefore, transtracheal usage of PI3Kδ/γ inhibitors is an attractive therapy that may be developed into a new immune-therapeutic principle for sarcoidosis in the future.

Multi-Contrast Differentiation by Dual-Energy Spectral CT Angiography in a Patient with Pulmonary Barium Granulomas

Barium inhalation usually relates to accidental aspiration during radiological procedures with an oral contrast agent. When present, barium lung deposits are visible as high-density opacities on chest X-ray or CT scan due to high atomic number, and they may be indistinguishable from calcifications. Dual-layer spectral CT has shown good material differentiation capabilities, due to its increased high-Z element range and smaller spectral separation between low- and high-energy spectral data. We present the case of a 17-year-old female with a history of tracheoesophageal fistula, who underwent chest CT angiography on a dual-layer spectral platform. Despite the close Z numbers and K-edge energy levels of the two different contrast materials, spectral CT was able to identify barium lung deposits from a previous swallowing study and to clearly distinguish them from calcium and the surrounding iodine-containing structures.

Spinal epidural arteriovenous fistula with nerve root enhancement mimicking myeloradiculitis: a case report

BackgroundGadolinium enhancement of spinal nerve roots on magnetic resonance imaging (MRI) has rarely been reported in spinal dural arteriovenous fistula (SDAVF). Nerve root enhancement and cerebrospinal fluid (CSF) pleocytosis can be deceptive and lead to a misdiagnosis of myeloradiculitis. We report a patient who was initially diagnosed with neurosarcoid myeloradiculitis due to spinal nerve root enhancement, mildly inflammatory cerebrospinal fluid, and pulmonary granulomas, who ultimately was found to have an extensive symptomatic SDAVF.Case presentationA 52-year-old woman presented with a longitudinally extensive spinal cord lesion with associated gadolinium enhancement of the cord and cauda equina nerve roots, and mild lymphocytic pleocytosis. Pulmonary lymph node biopsy revealed non-caseating granulomas and neurosarcoid myeloradiculitis was suspected. She had rapid and profound clinical deterioration after a single dose of steroids. Further work-up with spinal angiography revealed a thoracic SDAVF, which was surgically ligated leading to clinical improvement.ConclusionsThis case highlights an unexpected presentation of SDAVF with nerve root enhancement and concurrent pulmonary non-caseating granulomas, leading to an initial misdiagnosis with neurosarcoidosis. Nerve root enhancement has only rarely been described in cases of SDAVF; however, as this case highlights, it is an important consideration in the differential diagnosis of non-inflammatory causes of longitudinally extensive myeloradiculopathy with nerve root enhancement. This point is highly salient due to the importance of avoiding misdiagnosis of SDAVF, as interventions such as steroids or epidural injections used to treat inflammatory or infiltrative mimics may worsen symptoms in SDAVF. We review the presentation, diagnosis, and management of SDAVF as well as a proposed diagnostic approach to differentiating SDAVF from inflammatory myeloradiculitis.

Studying the tumor microenvironment under pressure

Meenal Datta is an assistant professor in the Department of Aerospace and Mechanical Engineering at the University of Notre Dame. Prof Datta received her PhD in Chemical and Biological Engineering from Tufts University in 2018, after which she completed a postdoctoral fellowship at Harvard Medical School and Massachusetts General Hospital. Her research focuses on deciphering the atypical tumor microenvironment that drives disease progression and treatment resistance in incurable cancers. By understanding and overcoming the biological, chemical, electrical, and mechanical abnormalities found in solid tumors, new therapeutic approaches can be discovered. Prof. Datta specializes in multidisciplinary and mechanism-based preclinical research that has the potential to be rapidly translated to improve treatment approaches in the clinic. She has spent her time as a researcher deciphering and reprogramming abnormal tissue microenvironments that present in a variety of diseases ranging from virulent tuberculosis to benign schwannoma to deadly glioblastoma that, surprisingly, share unifying features: abnormal blood vessels, abundant extracellular matrix, immunosuppression, and mechanopathologies. During her PhD, Dr Datta normalized the aberrant blood vasculature found in pulmonary tuberculosis granulomas to improve drug delivery. In her postdoctoral training, Dr Datta re-engineered the immunosuppressive brain tumor microenvironment to improve glioblastoma response to immunotherapy. As the director of the Tumor Immune Microenvironment &amp; Mechanics Lab at Notre Dame (the TIME lab). Prof Datta’s research group is applying engineering fundamentals and problem-solving approaches to explore mechano-immunological phenomena in the tumor microenvironment and discover novel biophysical targets of interest.

Pulmonary Granulomas and Mycobacterial Infection: Concordance between the Results of Special Stains Performed on Lung Tissue Sections and Tissue Cultures.

The most common cause of infectious pulmonary granulomas worldwide is Mycobacterium tuberculosis. The diagnosis is based on clinical presentation, histopathologic findings, detection of acid-fast bacilli (AFB) in tissue or sputum using special stains, and/or isolation of mycobacteria in cultures or via PCR-based methods. Different studies have shown that high levels of discrepancy exist between these diagnostic approaches in lung tissue specimens. To assess the degree of concordance between the results of special stains and cultures on lung tissue specimens in the diagnosis of mycobacterial infections. Eighty-seven patients with a diagnosis of granulomas (necrotizing and non-necrotizing) on lung tissue specimens were identified. Cohen's kappa was used to measure the general concordance between the results of the histopathological examination (special stains) and bacteriological tissue cultures. With Kinyoun acid-fast stains, 8/48 (16.7%) cases were positive for AFB. With FITE stains, 10/57 (17.5%) cases were positive for AFB. There was strong agreement between Kinyoun acid-fast and FITE stains (Kappa = 0.806; p-value &lt; 0.001). Tissue cultures were performed on 38/87 cases (43.7%), and 10/38 (26.3%) of the cultures were positive for mycobacteria. There was no concordance between Kinyoun acid-fast stains or FITE stains and tissue cultures results. Our observations represent an initial step in the process of reviewing the two methods used at our institution to diagnose mycobacterial infections on lung tissue specimens and highlight the need of incorporating more advanced diagnostic methods such as PCR to confirm mycobacterial infections and improve patient management. Importantly, species-level identification of mycobacteria is necessary to guide treatment.