Pembrolizumab reactivates pulmonary granulomatosis.
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ABSTRACT:
SUBMITTER: Al-Dliw M
PROVIDER: S-EPMC5540828 | biostudies-other | 2017
REPOSITORIES: biostudies-other
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Project description:IntroductionSynthol injection for body contouring has been used by bodybuilders for some time. We report two extremely rare systemic complications; pulmonary granulomatosis and hypercalcemia, in a woman who has received Synthol injections for buttocks augmentation.Presentation of caseThe case discussed in this report is of a 36-year-old lady who presented for severe hypercalcemia and nephrocalcinosis. Subsequent workup revealed granulomas in the buttocks and in the lungs. Upon questioning, it was discovered that she had received Synthol injection for buttocks augmentation a few months earlier. Labs were consistent with calcitriol mediated hypercalcemia, a phenomenon observed in granulomatous diseases. A diagnosis of foreign body granulomatosis with pulmonary migration and secondary hypercalcemia was made. The patient was started on prednisone and showed an initial positive response.DiscussionReported complications of Synthol include pain, muscle deformity, and ulceration at the injection site. Hypercalcemia secondary to foreign body granulomatosis after Synthol injection has been reported only once previously, and here we report a second case. The hypercalcemia is thought to be calcitriol mediated, where overexpression of CYP27B1 in the macrophages forming the granulomas leads to pathological extrarenal calcitriol production. Pulmonary granulomatosis, theorized to be secondary to hematologic migration of the injected material, has never been reported previously with Synthol use.ConclusionSynthol injection for body contouring may be a cause of extensive local and pulmonary foreign body granulomatosis leading to calcitriol mediated hypercalcemia. History of cosmetic injections should not be disregarded during history taking.
| S-EPMC8426527 | biostudies-literature
Project description:The pathologic findings and immunologic mechanisms in eosinophilic granulomatosis with polyangiitis (EGPA) are poorly understood. To characterize pulmonary EGPA’s mechanisms, we examined EGPA paraffin-embedded lung biopsies by immunostaining, RNA sequencing, and reverse transcriptase PCR, compared to normal lung. EGPA lung infiltrates had eosinophils, alveolar macrophages, B and T cells, plasma cells, basophils, and mast cells. Mast cell degranulation was sparse. PhosphoSMAD2 immunostaining suggests TGFβ activity. Using both immunostaining and RNA-sequencing, showed significant increases for both type 2 related genes (CD209, TNFSF14 (induces TGFβ and IL-13)), immunoregulatory genes (FOXP3, CYP27B1 (makes calcitriol), ALOX15 and particularly IGHG4). Regulatory T cells and IgG4 plasma cells with IgG4-containing presumed immune complexes coating macrophages, were strikingly abundant relative to controls. HPGD (metabolizes prostaglandins and other eicosanoids) was substantially decreased. RNA studies also showed increased contents of collagen transcripts, IL13, CCL18, and CCL13. These findings suggest a novel mechanism involving alveolar macrophages, activated by ALOX15-eicosanoid products, making chemokines CCL18 and CCL13 and thus inducing a mixed type 2 plus immunoregulatory immune response. This infiltrate resembles the immune response to an invasive parasite rather than the IgE / mast cell degranulation response to luminal parasites or in asthma and other classic allergies. These findings also suggest new potential treatment targets for EGPA.
2020-01-28 | GSE144302 | GEO
Project description:Granulomatosis with polyangiitis (GPA) is characterized by necrotizing granulomatous lesions and is classified as ANCA-associated vasculitis (AAV). We herein report a case of GPA that was remitted by resection of a pulmonary lesion without immunosuppressive therapy. We detected activated neutrophils and neutrophil extracellular traps (NET) formation in resected lung tissue by immunofluorescence. Activated neutrophils and NETs might be involved in the pathophysiology of AAV and induce the vicious cycle of ANCAs and NETs. In cases of GPA with no other severe lesions, the reevaluation of the disease activity after diagnostic resection is crucial for considering the need for immunosuppressive therapy.
| S-EPMC9556222 | biostudies-literature
Project description:BackgroundPulmonary lymphomatoid granulomatosis (PLG) is a lymphoproliferative disease associated with Epstein-Barr viral infection occurring mainly in adults and rarely in children. It is characterized by multiple pulmonary nodules. Its diagnosis depends on lung biopsy findings. Most patients are immunodeficient, and it commonly presents in children undergoing chemotherapy for leukemia. We report the case of a child with PLG caused by a mutation in the macrophage-expressed gene 1 (MPEG1), suggesting possible PLG occurrence in children undergoing treatment for pulmonary nodular lesions.Case summaryThis study reports a case of PLG without apparent immunodeficiency, suggesting the possibility of this disease occurrence during the treatment of pulmonary nodular lesions in children. Initially, the cause was assumed to be an atypical pathogen. Following conventional anti-infective treatment, chest computed tomography findings revealed that there were still multiple nodules in the lungs. Additionally, the patient was found to be infected with the Epstein-Barr virus. Histopathological examination of the resected lung revealed lymphoproliferative lesions with necrosis. Small lymphocytes, plasma cells, and histiocytes were observed in the background, although Reed-Sternberg cells were absent. Immunohistochemical staining [CD20(+), CD30(+), and CD3(+)] and EBV-encoded small RNA1/2 in situ hybridization of small lymphocytes revealed approximately 200 cells/high-power field. Whole exon sequencing of the patient revealed a mutation in the MPEG1. The patient was eventually diagnosed with PLG and transferred to the Department of Pediatric Oncology for bone marrow transplantation.ConclusionAs PLG is rare and fatal, it should be suspected in clinical settings when treatment of initial diagnosis is ineffective.
| S-EPMC9210899 | biostudies-literature
Project description:The immunologic mechanisms promoting eosinophilic granulomatosis with polyangiitis (EGPA) are unclear. To characterize the mechanisms underlying pulmonary EGPA, we examined and compared EGPA paraffin-embedded lung biopsies with normal lung biopsies, using immunostaining, RNA sequencing, and RT-PCR. The results revealed novel type 2 as well as immuneregulatory features. These features included basophils and increased mast cell contents; increased immunostaining for tumor necrosis factor ligand superfamily member 14; sparse mast cell degranulation; numerous forkhead box protein P3 (FoxP3)+ regulatory T cells and IgG4 plasma cells; and abundant arachidonate 15-lipoxygenase and 25-hydroxyvitamin D-1 α hydroxylase, mitochondrial. Significantly decreased 15-hydroxyprostaglandin dehydrogenase [NAD(+)], which degrades eicosanoids, was observed in EGPA samples. In addition, there was significantly increased mRNA for chemokine (C-C motif) ligands 18 and 13 and major collagen genes, IgG4-rich immune complexes coating alveolar macrophages, and increased immunostaining for phosphorylated mothers against decapentaplegic homolog 2/SMAD2, suggesting transforming growth factor-β activation. These findings suggest a novel self-promoting mechanism of activation of alveolar macrophages by arachidonate 15-lipoxygenase-derived eicosanoids to express chemokines that recruit a combined type 2/immunoregulatory immune response, which produces these eicosanoids. These results suggest that the pulmonary EGPA immune response resembles the immune response to a tissue-invasive parasite infection.
| S-EPMC7322366 | biostudies-literature
Project description:Lymphomatoid granulomatosis is a rare, vascular-centric, and vessel-destroying lymphoproliferative disease that hardly involves the pulmonary arteries. Herein, we report a case with severe right heart failure and pulmonary arterial stenosis caused by pulmonary artery lymphomatoid granulomatosis. This case was diagnosed by percutaneous transluminal pulmonary artery biopsy and was effectively treated with stent implantation and steroid administration.
| S-EPMC7754766 | biostudies-literature
Project description:Expression profiling of 12 Pembrolizumab-treated tumors with CancerImmune Panel
2023-10-01 | E-MTAB-8288 | biostudies-arrayexpress
Project description:Granulomatosis with polyangiitis (GPA, formerly Wegener's granulomatosis) is a multisystem autoimmune condition associated with anti-neutrophil cytoplasm antibodies. Management of GPA can be complex, owing to the sometimes fulminant and multisystem nature of the presentation, the age demographics of the affected population, and a significant incidence of disease relapse. In this paper, we discuss how some of the challenges in the management of GPA have been and continue to be addressed including: reducing the toxicity of induction therapy; developing biomarkers to determine who can safely stop maintenance immunosuppression; improving the efficacy of maintenance therapy for relapsing patients; managing localized disease; and management of disease and treatment-associated comorbidity. Consideration is also given to emerging therapeutics in the treatment of GPA.
| S-EPMC4000246 | biostudies-literature
Project description:We report a case of a 73-year-old man diagnosed with pulmonary pleomorphic carcinoma who showed profound durable response after a single treatment with pembrolizumab. The patient underwent a diagnostic workup in our hospital due to a hoarseness of voice. Chest computed tomography revealed a massive pulmonary tumor in the left upper lobe and multiple nodules in the both lung fields. Histological examination of a transbronchial lung biopsy specimen revealed pulmonary pleomorphic carcinoma. First-line treatment with pembrolizumab was discontinued after a single administration due to treatment-related pneumonitis. However, durable response has been observed over 17 months to date.
| S-EPMC6586952 | biostudies-literature
Project description:BackgroundGranulomatosis with polyangiitis (GPA) is characterised by the main violation of the upper and lower respiratory tract and kidney. GPA is considered a systemic vasculitis of medium-sized and small blood vessels where aortic involvement is extremely rare.Case presentationA 28-year-old male was admitted to the hospital due to 4 h of chest pain. Computed tomography scan of the aorta showed a thickened aortic wall, pulmonary lesions, bilateral pleural effusion and pericardial effusion. The aortic dissection should be considered. An emergency operation was performed on the patient. Surgical biopsies obtained from the aortic wall showed destructive changes, visible necrosis, granulation tissue hyperplasia and a large number of acute and chronic inflammatory cells. Nearly a year later, the patient was re-examined for significant pulmonary lesions. His laboratory studies were significantly positive for anti-neutrophilic antibody directed against proteinase 3. Finally, the diagnosis of GPA was obviously established.ConclusionsAlthough GPA rarely involves the aorta, we did not ignore the fact that GPA may involve large blood vessels. In addition, GPA should be included in the systemic vasculitis that can give rise to aortitis and even aortic dissection.
| S-EPMC6615146 | biostudies-literature