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Annals of the Rheumatic Diseases Jun 2023Granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) are autoimmune vasculitides associated with antineutrophil cytoplasm antibodies that target...
OBJECTIVES
Granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) are autoimmune vasculitides associated with antineutrophil cytoplasm antibodies that target proteinase 3 (PR3) or myeloperoxidase (MPO) found within neutrophils and monocytes. Granulomas are exclusively found in GPA and form around multinucleated giant cells (MGCs), at sites of microabscesses, containing apoptotic and necrotic neutrophils. Since patients with GPA have augmented neutrophil PR3 expression, and PR3-expressing apoptotic cells frustrate macrophage phagocytosis and cellular clearance, we investigated the role of PR3 in stimulating giant cell and granuloma formation.
METHODS
We stimulated purified monocytes and whole peripheral blood mononuclear cells (PBMCs) from patients with GPA, patients with MPA or healthy controls with PR3 or MPO and visualised MGC and granuloma-like structure formation using light, confocal and electron microscopy, as well as measuring the cell cytokine production. We investigated the expression of PR3 binding partners on monocytes and tested the impact of their inhibition. Finally, we injected zebrafish with PR3 and characterised granuloma formation in a novel animal model.
RESULTS
In vitro, PR3 promoted monocyte-derived MGC formation using cells from patients with GPA but not from patients with MPA, and this was dependent on soluble interleukin 6 (IL-6), as well as monocyte MAC-1 and protease-activated receptor-2, found to be overexpressed in the cells of patients with GPA. PBMCs stimulated by PR3 formed granuloma-like structures with central MGC surrounded by T cells. This effect of PR3 was confirmed in vivo using zebrafish and was inhibited by niclosamide, a IL-6-STAT3 pathway inhibitor.
CONCLUSIONS
These data provide a mechanistic basis for granuloma formation in GPA and a rationale for novel therapeutic approaches.
Topics: Animals; Myeloblastin; Granulomatosis with Polyangiitis; Zebrafish; Interleukin-6; Leukocytes, Mononuclear; Microscopic Polyangiitis; Antibodies, Antineutrophil Cytoplasmic; Granuloma; Giant Cells; Peroxidase
PubMed: 36801813
DOI: 10.1136/ard-2021-221800 -
European Archives of... Mar 2023To evaluate association between clinical and pathological findings and repeated recurrence in sinonasal inverted papilloma.
PURPOSE
To evaluate association between clinical and pathological findings and repeated recurrence in sinonasal inverted papilloma.
METHODS
Retrospective cohort study conducted at a tertiary care teaching hospital included all patients operated for inverted papilloma from January 2010 to December 2019. Patients were categorized as primary and recurrent cases. Based on disease status at follow-up, they were subcategorized into 'primary with no recurrence' (PnR), 'primary with recurrence' (PwR), 'recurrent with no further recurrence' (RnR), and 'recurrent with further recurrence' (RwR) groups. Data including demography, clinical, endoscopic and pathological findings were collected and analyzed.
RESULTS
Increased incidence of pale appearance of lesion in RnR group (p = 0.017), polypoidal appearance in primary group (p = 0.002) and fibrous appearance in the recurrent group (p = 0.002) were statistically significant. Predominant epithelium was combined respiratory and squamous epithelium in primary and recurrent groups and also in RnR group (p = 0.019), while it was squamous (p = 0.024) in RwR group. Epithelial hyperplasia was more common in primary and RnR groups. Oncocytic change, cystic dilatation, microabscess and squamous metaplasia were seen more in recurrent and RnR groups. Cytoplasmic glycogenation was more in recurrent and RwR groups. Stroma was predominantly edematous in all the groups.
CONCLUSIONS
Patients with recurrence are younger and present earlier than those with primary disease. Fleshy appearance and pink/red colour of tumour, lining epithelium being squamous and cytoplasmic glycogenation could be considered as features predicting recurrence. Negative predictors of recurrence of IP include pale appearance of tumour, combined respiratory and squamous epithelium lining and squamous metaplasia.
Topics: Humans; Papilloma, Inverted; Retrospective Studies; Paranasal Sinus Neoplasms; Epithelium; Neoplasm Recurrence, Local; Carcinoma, Squamous Cell; Nose Neoplasms
PubMed: 35932314
DOI: 10.1007/s00405-022-07585-3 -
Anais Brasileiros de Dermatologia 2022A 73-year-old male patient developed a poorly differentiated squamous cell carcinoma in the anal canal nine months ago. He was treated with two cycles of 5-fluorouracil...
A 73-year-old male patient developed a poorly differentiated squamous cell carcinoma in the anal canal nine months ago. He was treated with two cycles of 5-fluorouracil and cisplatin and concomitant radiotherapy (6 MeV linear photon accelerator, total dose of 54 Gy), with complete remission. Since forty-five days he presentes a painful perianal and intergluteal erosion with circinate pustular borders. Light microscopy showed pseudoepitheliomatous hyperplasia of the epidermis with microabscesses of inflammatory cells (neutrophils and eosinophils) and acantholytic keratinocytes . Indirect immunofluorescence was positive for IgG, with an intercellular pattern, 1:80 titer. The diagnosis of radiotherapy-induced pemphigus vegetans was established and there was significant regression with oral prednisone (40 mg) and topical betamethasone.
Topics: Aged; Humans; Hyperplasia; Male; Pemphigus; Suppuration
PubMed: 35300903
DOI: 10.1016/j.abd.2021.09.005 -
Experimental Dermatology Jan 2024Pyodermatitis pyostomatitis vegetans is a rare inflammatory condition, affecting the skin and/or mucous membrane. Some cases include both skin and mucous involvement,... (Review)
Review
Pyodermatitis pyostomatitis vegetans is a rare inflammatory condition, affecting the skin and/or mucous membrane. Some cases include both skin and mucous involvement, whereas others develop either skin or mucous lesions only. The typically affected areas are the scalp, face, trunk and extremities, including the flexural areas and umbilicus. Clinical features show erosive granulomatous plaques, keratotic plaques with overlying crusts and pustular lesions. Among mucous lesions, oral mucosa is most frequently involved, and gingival erythema, shallow erosions, cobblestone-like papules on the buccal mucosa or upper hard palate of the oral cavity are also observed. Some of the lesions assume a 'snail track' appearance. Although there are several similarities between pyodermatitis pyostomatitis vegetans and other diseases, that is pyoderma gangrenosum, pemphigus vegetans and pemphigoid vegetans, the histopathological features of pyodermatitis pyostomatitis vegetans are unique in that epidermal hyperplasia, focal acantholysis and dense inflammatory infiltrates with intraepidermal and subepidermal eosinophilic microabscesses are observed. Direct immunofluorescence findings are principally negative. Activated neutrophils are supposed to play an important role in the pathogenesis of pyodermatitis pyostomatitis vegetans. The expression of IL-36 and neutrophil extracellular traps (NETs) was observed in the lesional skin, and additionally, eosinophil extracellular traps (EETs) was detected in pyodermatitis pyostomatitis vegetans. A possible pathogenic role of NETs and EETs in the innate immunity and autoinflammatory aspects of pyodermatitis pyostomatitis vegetans was discussed.
Topics: Humans; Pemphigus; Pyoderma; Stomatitis; Extracellular Traps; Neutrophils; Erythema; Organic Chemicals
PubMed: 37694984
DOI: 10.1111/exd.14931 -
Rozhledy V Chirurgii : Mesicnik... 2021Granulomatous mastitis (GM) is a rare benign inflammatory disease of the breast, first described by Kessler and Wolloch in 1972. Clinically, it can present as...
Granulomatous mastitis (GM) is a rare benign inflammatory disease of the breast, first described by Kessler and Wolloch in 1972. Clinically, it can present as unilateral, sometimes painful, increasing breast resistance, or as a hard, irregular mass. Sonography is the most useful diagnostic method for GM evaluation. The only method for definitive diagnosis is the use of biopsy. In histological findings, GM is characterized by non-caseifying granulomas, often associated with microabscess and fistula formation. There is considerable heterogeneity in treatment options; this may explain the high recurrence rate which is close to 50%. Such a high recurrence rate is alarming and proves that current treatments are suboptimal. Two treatment options are discussed worldwide: conservative strategies involving drug therapy with corticosteroids versus a surgical approach involving partial or total mastectomy. All conservative treatment options are associated with a high risk of recurrence, and most patients require surgery in the end. Thorough excision of inflammatory tissue is crucial for successful treatment while negative surgical margins are associated with a low recurrence rate. The surgical approach to GM requires sufficient radicality and presumes knowledge in the field of reconstructive breast surgery, similarly to oncosurgical breast conservation operations. However, alternatives to GM treatment with oral steroids may be acceptable for patients concerned about surgery. This article presents six case reports of patients treated at our department.
Topics: Breast; Breast Neoplasms; Female; Granulomatous Mastitis; Humans; Mastectomy; Mastitis; Neoplasm Recurrence, Local
PubMed: 34182762
DOI: 10.33699/PIS.2021.100.4. -
International Braz J Urol : Official... 2018Tuberculous prostatitis is a rare and often overlooked entity that may mimic prostatic adenocarcinoma on imaging exams, especially multiparametric magnetic resonance...
Tuberculous prostatitis is a rare and often overlooked entity that may mimic prostatic adenocarcinoma on imaging exams, especially multiparametric magnetic resonance imaging (MRI) of the prostate. Detection of a prostatic abscess is a clue to the correct diagnosis.
Topics: Abscess; Adenocarcinoma; Aged; Diagnosis, Differential; Humans; Incidental Findings; Magnetic Resonance Imaging; Male; Prostatic Neoplasms; Prostatitis; Tuberculosis, Male Genital
PubMed: 28853817
DOI: 10.1590/S1677-5538.IBJU.2017.0190 -
Biotechnic & Histochemistry : Official... May 2022Mast cells in the brain are associated with increased inflammation during the acute period following exposure to infection; these cells are important for destroying the...
Mast cells in the brain are associated with increased inflammation during the acute period following exposure to infection; these cells are important for destroying the infectious agents. We investigated the relation between histopathological lesions and mast cells in sheep brains infected with . Pons and medulla regions from 17 infected and eight normal sheep brains were examined. Microabscesses and perivascular infiltration were assessed for histopathology. Mast cells were identified using toluidine blue and were investigated immunohistochemically. We found a significant increase in mast cells in infected sheep brains that was related directly to the extent of brain lesions. A strong correlation was found between mast cells and microabscess formation. A correlation between bacteria level and brain lesions also was observed, but not between bacteria level and mast cells. Our findings indicate that mast cells are increased following infection in sheep in proportion to the severity of brain lesions; the increase may contribute to acute inflammatory reactions and also may destroy bacteria directly.
Topics: Animals; Brain; Listeria monocytogenes; Listeriosis; Mast Cells; Sheep; Sheep Diseases
PubMed: 34157924
DOI: 10.1080/10520295.2021.1941256 -
The American Journal of Dermatopathology Nov 2021
Topics: Dermatology; Humans; Mycosis Fungoides; Neoplasm Staging; Skin; Skin Neoplasms
PubMed: 34387195
DOI: 10.1097/DAD.0000000000002054 -
Computers in Biology and Medicine Jan 2022Munro's Microabscess (MM) is the diagnostic hallmark of psoriasis. Neutrophil detection in the Stratum Corneum (SC) of the skin epidermis is an integral part of MM...
Munro's Microabscess (MM) is the diagnostic hallmark of psoriasis. Neutrophil detection in the Stratum Corneum (SC) of the skin epidermis is an integral part of MM detection in skin biopsy. The microscopic inspection of skin biopsy is a tedious task and staining variations in skin histopathology often hinder human performance to differentiate neutrophils from skin keratinocytes. Motivated from this, we propose a computational framework that can assist human experts and reduce potential errors in diagnosis. The framework first segments the SC layer, and multiple patches are sampled from the segmented regions which are classified to detect neutrophils. Both UNet and CapsNet are used for segmentation and classification. Experiments show that of the two choices, CapsNet, owing to its robustness towards better hierarchical object representation and localisation ability, appears as a better candidate for both segmentation and classification tasks and hence, we termed our framework as MICaps. The training algorithm explores both minimisation of Dice Loss and Focal Loss and makes a comparative study between the two. The proposed framework is validated with our in-house dataset consisting of 290 skin biopsy images. Two different experiments are considered. Under the first protocol, only 3-fold cross-validation is done to directly compare the current results with the state-of-the-art ones. Next, the performance of the system on a held-out data set is reported. The experimental results show that MICaps improves the state-of-the-art diagnosis performance by 3.27% (maximum) and reduces the number of model parameters by 50%.
PubMed: 34864301
DOI: 10.1016/j.compbiomed.2021.105071 -
The Journal of Dermatology May 2019Palmoplantar pustulosis (PPP) and pompholyx are both chronic and relapsing diseases occurring on the palms and soles. Although these two diseases have been considered...
Palmoplantar pustulosis (PPP) and pompholyx are both chronic and relapsing diseases occurring on the palms and soles. Although these two diseases have been considered completely different from each other, it is sometimes very difficult even for dermatologists to differentiate them from each other because of their similarities in clinical presentation. In this study, we aimed to analyze the histopathological features of PPP and pompholyx and find out "clues" to differentiate between PPP and pompholyx by their histopathological features. The histopathology of 11 PPP and six pompholyx patients, who were diagnosed with typical clinical history and histopathology, were carefully observed. PPP cases were divided into three phases (vesicle, pustulovesicule and pustule) and pompholyx cases were divided into two phases (vesicle and pustule), and histopathological findings and a 4-point checklist to distinguish between PPP and pompholyx were preliminarily established. To confirm whether the checklist establishes the clues for diagnosis, biopsy samples from 43 patients (32 PPP and 11 pompholyx) who had been already diagnosed at five hospitals were examined according to our checklist without any additional clinical information. According to our 4-point checklist, 31 of 32 PPP patients and all 11 pompholyx patients were diagnosed histopathologically consistent with their clinical diagnosis. In conclusion, histopathological findings of "vesicles without spongiosis" and "microabscess on the edges of vesicles" would be impact points for the differential diagnosis between PPP and pompholyx. The 4-point checklist was trustworthy to distinguish between PPP and pompholyx.
Topics: Adult; Aged; Biopsy; Checklist; Diagnosis, Differential; Eczema, Dyshidrotic; Feasibility Studies; Female; Humans; Male; Middle Aged; Psoriasis; Skin
PubMed: 30919463
DOI: 10.1111/1346-8138.14850