Sarcoidosis Resembling Angiokeratomas: A Case Report.

Sarcoidosis, a multifaceted systemic disorder characterized histologically by the presence of non-caseating granulomas, has a wide array of cutaneous manifestations. We describe a case of a 74-year-old woman with a complex medical history, who presented with asymptomatic hyperpigmented papules on her lower extremities. Histological examination of a punch biopsy specimen showed nodular and angiocentric patterns of granulomatous inflammation consistent with sarcoidosis, and chest radiography demonstrated bilateral hilar opacities, supporting the diagnosis. To our knowledge, this specific cutaneous presentation of sarcoidosis has not been described before, and it can easily be mistaken for other conditions. Therefore, this case underscores the importance of recognizing atypical cutaneous morphologies of sarcoidosis, particularly in patients with complex medical histories, to facilitate accurate diagnosis and timely intervention. We aim to increase awareness among clinicians regarding the diverse manifestations of sarcoidosis, thereby enhancing diagnostic acumen and patient care.

Pyogenic Granuloma in a One-Year-Old Child: A Rare Entity.

Pyogenic granuloma (PG) is a benign vascular neoplasm seen in the first and second decades of life, and it has a female predilection. It presents as a small reddish exophytic lesion, gingiva being the most common site. This article describes an unusual presentation of PG in a one-year-old female child and highlights the importance of its early diagnosis and management to avoid discomfort and distress in these patients. The diagnosis was verified by histological examination, which revealed significant markers such as endothelial growth, vascular abundance, and chronic inflammatory cell infiltration. The chosen treatment protocol was surgical excision, which led to a successful outcome with no symptoms of recurrence, as confirmed by thorough follow-up examinations.

An Unusual Presentation of Midline Lethal Granuloma.

Extranodal natural killer T-cell lymphoma, nasal type (ENKTCL), is a rare form of non-Hodgkin lymphoma that is strongly related to Epstein-Barr Virus (EBV) infection and commonly presents as "midline lethal granuloma." Herein, we report a middle-aged lady who presented with a two-week history of fever, sore throat and constitutional symptoms. Intraoral examination revealed a lacerated soft palate with an ulcerated uvula. A diagnosis of ENKTCL was confirmed through deep biopsies under general anaesthesia supplemented with a positive serum EBV genome. Unfortunately, she succumbed due to disease progression with left frontal brain metastasis with concurrent pulmonary tuberculosis before treatment was completed. The recommended treatment is multimodality with L-asparaginase-containing regimes chemotherapy in an advanced stage, relapsed, or refractory ENKTCL for better outcomes. The quantification of circulating plasma EBV deoxyribonucleic acid (DNA) is helpful as the baseline of tumour load and a biomarker for monitoring treatment response and prognostication. We advocate repeated and deeper core tissue biopsies.

Differentiation of radicular cysts and radicular granulomas via texture analysis of multi-slice computed tomography images.

OBJECTIVES: This study aimed to establish a method for differentiating radicular cysts from granulomas via texture analysis (TA) of multi-slice computed tomography (CT) images. METHODS: A total of 222 lesions with multi-slice computed tomography images acquired at our hospital between 2013 and 2022 that were pathologically diagnosed were included in this study. Cases of contrast-enhanced images, severe metallic artifacts, and lesions that were not sufficiently large to be analyzed were excluded. The images were chronologically divided into a training group and a validation group. The radiological characteristics were determined. Subsequently, a TA was performed. Pyradiomics software was used for the TA of three-dimensionally segmented volumes extracted from 2-mm slice thickness images with a soft-tissue algorithm. Features that differed significantly between the two lesions in the training group were extracted and used to create machine-learning models. The discriminative ability of these models was evaluated in the validation group using receiver operating characteristic curve analysis. RESULTS: A total of 131 lesions, comprising 28 radicular cysts and 103 granulomas, were analyzed. Forty-three texture features that exhibited significant variations were extracted. A support vector machine and decision tree model, with areas under the curves of 0.829 and 0.803, respectively, were created. These models showed high discriminative abilities, even for the validation group, with areas under the curve of 0.727 and 0.701, respectively. Both models showed superior performance compared with that of the models based on radiographic findings. CONCLUSION: Discriminatory models were established for the TA of radicular cysts and granulomas using CT images.

Oral Pyogenic Granuloma at Different Spots: A Series of Case Reports.

Pyogenic granuloma is an inflammatory non-neoplastic lesion of the oral cavity. Chronic, mild, local irritation, trauma, hormonal variables, and certain medications are typical causes of pyogenic granulomas. Women have a higher prevalence than men. The risk is greatest in the second to fifth decades of life. Clinically, the lesion appears smooth, with soft to firm consistency and nontender with a pedunculated or sessile base. Various modalities have been proposed for the treatment of lesion, which include the conventional approach, the use of laser, cryotherapy, and electrocauterization. This case series discusses three cases of pyogenic granuloma in female patients at different locations in the oral cavity. The lesion was subsequently treated with electrosurgery and surgical convention methods. No recurrence of the lesion has been seen in either of the cases.

Incidence, treatment method and recurrence rate in giant cell granulomas: Retrospective study.

Central and peripheral giant cell granulomas are benign entities mostly seen in mandibular anterior region at female individuals, usually with observed recurrence. Their etiology is still unclear, as is the optimal method for treating them. The aim of this study was to evaluate the incidence, treatment methods, recurrence rates, and initial and definitive correlation of central and peripheral giant cell granulomas. Patients who were referred to our clinic between 2013 and 2023 and who had the lesions' definitive diagnosis as "central giant cell granuloma" (CGCG) or "peripheral giant cell granuloma" (PGCG) were included in the study. Demographic data, recurrence rates, treatment methods, lesion location, clinical behaviors, and sizes were noted on the reports. A total of 30 lesions in 23 patients (14 PGCG and 9 CGCG) were evaluated in this study. The mean follow-up time was 62.6 months; 8 of 23 patients had systemic disease. While only 1 patient was observed to have cortical bone destruction in PCGC, all patients were found to have cortical bone destruction in CGCG (p < 0.05). In both lesions, the correlation of preliminary and definitive diagnosis was evaluated, and it was found to be 50% in PGCG while it was 77.7% in CGCG. The recurrence rates were 21.4% in PGCG and 33.3% in CGCG. Curettage was applied in all patients. Additional treatments (intralesional steroid injections, denasumab applications, resection, and graft application) were performed in 5 patients who were found to have CGCG (p = 0.004). However, there was no significant relation between treatment method and recurrence in CGCG (p > 0.05). Various peripheral lesions could mimic PGCG; thus, curettage therapy could be appropriate in the treatment of PGCG. Nevertheless, in some cases of CGCG, additional treatment methods could be more effective for preventing recurrence and any other complications.

Tofacitinib for managing granuloma formation after dermal filler injection: three case reports and literature review.

BACKGROUND: Granuloma formation is an uncommon and persistent skin inflammatory condition caused by the injection of dermal fillers. The exact cause of this reaction is not well understood, but it may be associated with irritating components or abnormal immune function. Treating granulomas can be difficult. However, recent research has shown that Janus kinase (JAK) inhibitors hold promise as a potential therapy for refractory granulomatous diseases. OBJECTIVES: The aim was to evaluate the efficacy and safety of tofacitinib as a treatment for granulomas secondary to filler injection and the possible mechanisms were discussed and summarized. METHODS: This study focuses on three cases of patients who experienced granuloma formation after receiving filler injections and were subsequently treated with tofacitinib. The efficacy and safety of the treatment were evaluated using parameters such as photographs and monitoring for any adverse reactions. In addition, a literature review was conducted to explore the underlying mechanisms and potential effects of tofacitinib. RESULTS: All three cases recovered from swelling and nodules without side effects through the off-label use of oral tofacitinib. Existing data review reveals some approaches for cutaneous granulomatous disorders like inhibiting macrophage activation and downregulation of the JAK-STAT pathway. CONCLUSION: This report emphasizes the effectiveness of JAK inhibitors in treating granulomas caused by filler injections. Recent advancements in understanding the underlying mechanisms of granulomatous reactions have paved the way for JAK inhibitors to be regarded as a promising treatment choice. However, further research is necessary to fully assess the safety and long-term effectiveness of using tofacitinib for granuloma treatment.

Central Giant Cell Granuloma: Negotiating the Diagnostic and Management Dilemmas.

Introduction: Giant cell lesions of orofacial region although rare in presentation, have diagnostic and treatment challenges due to overlapping clinical, radiological, and histopathological signs. Background: We happened to come across a case, which presented to us with an aggressive jaw lesion of nonodontogenic origin, mimicking a malignancy and putting us in a conundrum with regard to work up and treatment. The sequential work up not only helped us reach a definitive diagnosis but also led us the draw algorithms for diagnosis of Giant cell lesions and management of Central giant cell granuloma. Conclusion: Meticulous planning along with molecular studies helps in better delineating one giant cell lesion from other.

Polymer clip granuloma mimicking lymph node recurrence: a case report.

BACKGROUND: Foreign body granulomas are postoperative inflammatory reactions to surgical materials within the body. Traditionally, sutures have been the leading cause of foreign body granulomas in the abdomen, commonly referred to as "suture granuloma". However, the use of polymer clips in modern surgeries has introduced new challenges, and reports of intra-abdominal foreign body granulomas caused by surgical clips are limited. Herein, we present a case of an intra-abdominal foreign body granuloma formed due to polymer clips. CASE PRESENTATION: A 45-year-old woman who underwent laparoscopic resection for sigmoid colon adenocarcinoma subsequently developed a suspected lymph node recurrence during follow-up. Imaging showed an enlarging mass adjacent to the inferior mesenteric artery with increased fluorodeoxyglucose uptake. Laparoscopic surgical resection revealed the formation of a foreign body granuloma in response to the polymer clips. CONCLUSIONS: This case suggests that nonabsorbable polymer clips can induce granulomatous reactions postoperatively, and the appearance of lymph node recurrence may be foreign body granulomas.

Metastatic mucinous adenocarcinoma from breast mimicking a pyogenic granuloma in the gingiva: a case report.

Mucin-producing adenocarcinomas (MAC) are an extremely rare, indistinct group of neoplasm having either a salivary gland origin or with prominent glandular component. The diagnosis is chiefly based on the histological aspect conjoined with immunohistochemical evaluation as clinico-radiographical features are non-specific. It can arise as a primary metastasis to soft tissues, most commonly from either lung, breast, kidney, or colon. This paper reports a 51-year-old woman with buccolingual gingival swelling having a final diagnosis of metastatic mucinous adenocarcinoma from the breast. A tissue biopsy was performed followed by immunohistochemistry that confirmed the diagnosis. They are extremely rare, making the diagnosis challenging as it may mimic a benign neoplasm. It accounts for approximately 1% of all oral malignant neoplasms having gingival propensity. The clinician should therefore take into account every diagnostic aspect while encountering such oral lesions to achieve proper patient welfare.

Necrotizing granulomatous epididymo-orchitis post intravesical BCG administration after brachytherapy for prostate cancer.

Urothelial carcinoma of the bladder remains a challenging disease to treat. Intravesical instillation of BCG has demonstrated tremendous efficacy in preventing recurrence. BCG related necrotizing granulomatous epididymo-orchitis is rare and has not been previously linked to brachytherapy for adenocarcinoma of the prostate. We hypothesize that prior brachytherapy has a deleterious effect on the verumontanum that can result in retrograde transmission of BCG particles leading to granulomatous epididymo-orchitis. This is the first case report of necrotizing granulomatous epididymo-orchitis related to BCG in a patient status post brachytherapy for adenocarcinoma of the prostate.

Cholesterol Granuloma From a Developmental Odontogenic Cyst: A Report of a Rare Case and a Literature Review.

Dentigerous cysts are the second most common developmental odontogenic cysts that develop around the crown of unerrupted teeth with the maxillary canine region being one of the common sites of occurrence. The cystic lining of this lesion has been shown to develop into ameloblastoma, Muco epidermoid carcinoma, and squamous cell carcinomas. However, the development of cholesterol granuloma (CG) in the cystic lining of a dentigerous cyst is extremely rare. CG is a histological observation distinguished by the presence of a conglomeration of connective tissue and granulation tissue. The condition is predominantly seen in the field of otolaryngology, with very few cases reported in the maxillofacial region, most of which are associated with the maxillary sinus. This article presents the findings of a CG in a 39-year-old male patient that developed within the dentigerous cyst and discusses the possible etiopathogenesis, surgical management, and histological presentation.

Prediction of Tuberculosis From Lung Tissue Images of Diversity Outbred Mice Using Jump Knowledge Based Cell Graph Neural Network.

Tuberculosis (TB), primarily affecting the lungs, is caused by the bacterium Mycobacterium tuberculosis and poses a significant health risk. Detecting acid-fast bacilli (AFB) in stained samples is critical for TB diagnosis. Whole Slide (WS) Imaging allows for digitally examining these stained samples. However, current deep-learning approaches to analyzing large-sized whole slide images (WSIs) often employ patch-wise analysis, potentially missing the complex spatial patterns observed in the granuloma essential for accurate TB classification. To address this limitation, we propose an approach that models cell characteristics and interactions as a graph, capturing both cell-level information and the overall tissue micro-architecture. This method differs from the strategies in related cell graph-based works that rely on edge thresholds based on sparsity/density in cell graph construction, emphasizing a biologically informed threshold determination instead. We introduce a cell graph-based jumping knowledge neural network (CG-JKNN) that operates on the cell graphs where the edge thresholds are selected based on the length of the mycobacteria's cords and the activated macrophage nucleus's size to reflect the actual biological interactions observed in the tissue. The primary process involves training a Convolutional Neural Network (CNN) to segment AFBs and macrophage nuclei, followed by converting large (42831*41159 pixels) lung histology images into cell graphs where an activated macrophage nucleus/AFB represents each node within the graph and their interactions are denoted as edges. To enhance the interpretability of our model, we employ Integrated Gradients and Shapely Additive Explanations (SHAP). Our analysis incorporated a combination of 33 graph metrics and 20 cell morphology features. In terms of traditional machine learning models, Extreme Gradient Boosting (XGBoost) was the best performer, achieving an F1 score of 0.9813 and an Area under the Precision-Recall Curve (AUPRC) of 0.9848 on the test set. Among graph-based models, our CG-JKNN was the top performer, attaining an F1 score of 0.9549 and an AUPRC of 0.9846 on the held-out test set. The integration of graph-based and morphological features proved highly effective, with CG-JKNN and XGBoost showing promising results in classifying instances into AFB and activated macrophage nucleus. The features identified as significant by our models closely align with the criteria used by pathologists in practice, highlighting the clinical applicability of our approach. Future work will explore knowledge distillation techniques and graph-level classification into distinct TB progression categories.

Marked IDO2 expression and activity related to autophagy and apoptosis in brain tissue of fatal tuberculous meningitis.

In about 1% of tuberculosis (TB) patients, Mycobacterium tuberculosis (M. tuberculosis) can disseminate to the meninges, causing tuberculous meningitis (TBM) with mortality rate up to 60%. Chronic granulomatous inflammation (non-necrotizing and necrotizing) in the brain is the histological hallmark of TBM. The tryptophan-catabolizing enzyme indoleamine 2,3-dioxygenase 1 (IDO1) and the generated kynurenine metabolites exert major effector functions relevant to TB granuloma functioning. Here we have assessed immunohistochemically IDO1 expression and activity and its effector function and that of its isoform, IDO2, in post-mortem brain tissue of patients that demised with neurotuberculosis. We also related these findings to brain tissue of fatal/severe COVID-19. In this study, IDO1 and IDO2 were abundantly expressed and active in tuberculoid granulomas and were associated with the presence of M. tuberculosis as well as markers of autophagy and apoptosis. Like in fatal/severe COVID-19, IDO2 was also prominent in specific brain regions, such as the inferior olivary nucleus of medulla oblongata and cerebellum, but not associated with granulomas or with M. tuberculosis. Spatially associated apoptosis was observed in TBM, whereas in fatal COVID-19 autophagy dominated. Together, our findings highlight IDO2 as a potentially relevant effector enzyme in TBM, which may relate to the symptomology of TBM.

Evaluation of the relationship between the expression of AgNOR and Ki67 with the recurrence rate in central granulomatous giant cell lesions: A case-control.

OBJECTIVES: Giant cell granuloma is a local nonneoplastic lesion that is divided into two categories, based on its site of occurrence: Central and peripheral giant cell granuloma. Central giant cell granuloma is an intraosseous lesion that has a tendency to recure even in surgically treated cases. Several studies have proven that there is an association between different lesions clinical behavior and their histological features. The aim of this study was to evaluate the expression of AgNOR and Ki67 in lesions with and without recurrency. MATERIAL AND METHODS: Files and records of 35 patients who had been histologically diagnosed with central giant cell granuloma were investigated. Histological features were studied after performing AgNOR staining and Ki67 marker. The data were analyzed by chi-square, Fisher, and T-test. RESULTS: Acquired data indicated that the count of AgNOR staining and Ki67 marker was significantly higher in lesions with recurrency than the lesions with no recurrency. The same results were attained from Ki67 intensity. CONCLUSION: The current study indicated that AgNOR staining and Ki67 marker have prognostic value in predicting recurrency of central giant cell granuloma lesions.

Cutting-Edge Strategies for Renal Tumour-like Lesions in Granulomatosis with Polyangiitis: A Systematic Review.

BACKGROUND: Granulomatosis with polyangiitis (GPA) is characterised by granulomatous inflammation and small-to-medium vessel necrotising vasculitis, mainly affecting respiratory tract and kidneys. Renal involvement presenting as tumour-like lesions poses diagnostic and treatment challenges. METHODS: Following the observation of a GPA patient presenting with multiple renal tumour-like lesions, we conducted a systematic literature review on MEDLINE/PubMed, EMBASE, and Cochrane databases. Data gathered from the literature were analysed to summarise the diagnostic approach, management, and outcome of renal GPA-related tumour-like lesions. RESULTS: a 49-year-old female presented with persistent constitutional symptoms and multiple bilateral renal lesions. Renal biopsy showed chronic interstitial inflammation with necrotising granulomas. Laboratory tests disclosed positive anti-proteinase 3 (PR3) anti-neutrophil cytoplasmic antibody (ANCA) leading to a final diagnosis of GPA. She was effectively treated with high-dose glucocorticoids and rituximab. Literature search yielded 41 articles, concerning 42 GPA patients with renal masses, presenting bilaterally in 23.8% of the cases. Positive PR3-ANCA was observed in 86.5% of the cases. Half of 42 patients showed kidney abnormalities. Treatment with glucocorticoids (83.3%) and immunosuppressive agents (80.9%) resulted in an overall good remission rate and favourable prognosis. CONCLUSIONS: GPA should be considered in the differential diagnoses of kidney tumour-like lesions. The diagnosis is challenging, and histological examination greatly contributes to the diagnostic work-up.

Role of collagen and immunostaining for TGF-β in the clinical andmicroscopic findings of pyogenic granuloma and peripheral ossifying fibroma

Background: Collagen is a component of Pyogenic Granuloma (PG) and Peripheral Ossifying Fibroma (POF) and performs different functions in these lesions. The objective of this study is to evaluate the role of collagen and immunostaining for Transforming Growth Factor beta (TGF-β) in the clinical and microscopic findings of PG and POF. Material and Methods: PG (n=20) and POF (n=20) were selected for clinical evaluation (sex, age, localization, size and evolution time) and microscopic analysis (picrosirius red staining for collagen analysis and immunohistochemistry for TGF-β) performed in the superficial and deep areas of the two lesions. ANOVA/Bonferroni and t-test, Pearson correlation and χ2 were used to compare the sites and parameters analyzed (p<0.05, GraphPad Prism 5.0). Results: The depth of PG presented the highest amount of collagen (p<0.001), and its surface showed the lowest amount of type 1 collagen (yellow-red strong birefringence). Type 1 collagen gradually increased in depth of PG, surface and depth of POF (p<0.001). The number of TGF-β+ cells was lower on the surface of PG compared with the depth of PG and the two areas of POF (p<0.001). Sex and localization did not affect these parameters, but the profile of collagen and immunostaining for TGF-β suffered from modifications by the time of evolution and the size of the lesion. Conclusions: Although PG and POF are reactive gingival lesions, the expression of TGF-β and its role in collagen showed different biological behaviors in these lesions, suggesting different biological origins for its components. (AU)

Prediction of the efficacy of proton-pump inhibitors in patients with contact granuloma using 24-hour combined dual channel pH/impedance monitoring.

OBJECTIVES: We aimed to evaluate the treatment outcomes of proton-pump inhibitors (PPIs) in patients with contact granuloma (CG) and to investigate the parameters of 24 h combined dual channel pH/impedance (24 h pH/MII) monitoring, which are reliable for predicting the response to PPI of CG patients. METHODS: We reviewed the medical records of patients with CG who had been treated with PPIs and had completed more than 6 months of follow-up. We classified the patients into two groups (cured vs. persistent), according to their PPI treatment outcomes. Reflux events were categorized into three groups based on pharyngeal pH during reflux: 1) acid reflux (pH < 4), 2) weak acid reflux (4 < pH < 7), and 3) weak alkaline reflux (pH >7), as detected by a proximal probe. We compared the results of 24h-pH/MII between the two groups and used receiver operating characteristic curve (ROC) analysis to determine the cutoff values of significant parameters for predicting responses to PPIs. RESULTS: Among 22 patients who completed at least 6 months of PPI treatment and follow-up, weak acid reflux events were more frequently observed in persistent group than in the cured group (p = 0.046), and the proportion of weak acid reflux was also higher in the persistent group (p = 0.031) than in the cured group. Reliable parameters predictive of a poor response to PPIs were a number of weak acid reflux events ≥ 11 (area under the curve [AUC], 0.775; p = 0.03) and a proportion of weak acid reflux events ≥ 56.7 % (AUC, 0.763; p = 0.038) in ROC analyses. CONCLUSION: Weak acid reflux was identified as a significant factor associated with the treatment outcomes of PPIs in patients with CG. A number of weak acid reflux events ≥ 11 is considered to be the most reliable predictor of a poor response to PPIs in patients with CG.