Benign Inflammatory Disease Research Articles

A rare case of granulomatous mastitis by Brucella species.

Granulomatous mastitis (GM) is a rare, chronic, benign inflammatory disease of the breast. Here, we present a rare case of GM caused by brucellosis and present the first review to compile the cases in the literature. The diagnosis was confirmed by the patient's serological and histopathological results. The patient was successfully treated with doxycycline+rifampicin combination therapy for six weeks. In conclusion, infectious agents, especially brucellosis, should be considered in the differential diagnosis of GM in endemic regions. Diagnostic methods, such as tissue culture and serological tests, should be used to detect possible infectious agents if necessary.

Chronic sclerosing sialadenitis of the parotid gland mimicking a neoplasm

Chronic sclerosing sialadenitis or Küttner tumor is a benign chronic inflammatory disease of the salivary gland, most commonly involving the submandibular salivary gland in middle aged adults. We describe the magnetic resonance imaging features of a rare case of Küttner tumor with isolated parotid gland involvement in a child, to emphasize on the need for increased awareness among radiologists regarding the possibility and imaging features of this condition, and to enable its timely diagnosis and appropriate management.

Granulomatous mastitis forming a well-defined large mass diagnosed by surgical excision: a case report

BackgroundGranulomatous mastitis is a relatively rare benign inflammatory disease of the breast, but it is sometimes difficult to distinguish from breast cancer by imaging. We experienced a case that was definitively diagnosed as granulomatous mastitis from the surgical specimen. The mass appeared as a large cystic lesion on imaging, which is unusual for granulomatous mastitis, and was initially suspected to be an encapsulated papillary carcinoma.Case presentationA 43-year-old woman presented with a painful mass in her right breast. Ultrasonography revealed a cystic mass lesion with internal solid components, with partially indistinct cyst walls and abundant blood flow. Additionally, lymphadenopathy of one axillary lymph node was observed. Magnetic resonance imaging findings showed irregularly spreading enhanced nodules within the cystic lesion, raising the suspicion of encapsulated papillary carcinoma. Although the histological findings from a needle biopsy were consistent with granulomatous mastitis, the possibility of malignancy could not be ruled out based on imaging, prompting a diagnostic probe lumpectomy. However, the surgical specimens did not reveal any tumorous lesions, and we reached a final diagnosis of granulomatous mastitis. Postoperatively, the patient was followed-up without steroid therapy and has been free from recurrence of mastitis for 22 months after surgery.ConclusionsWe report a case of granulomatous mastitis that was detected as a large cystic lesion with a well-defined border on imaging and a definitive diagnosis was made from a surgical specimen.

Clinical Identification of Two Novel C. kroppenstedtii-like Species Isolated as Pathogens of Granulomatous Lobular Mastitis.

Granulomatous lobular mastitis (GLM) is a rare benign breast inflammatory disease that affects women of childbearing age. Corynebacterium species, especially Corynebacterium kroppenstedtii, was reported as the pathogen of GLM. A recent study showed that the C. kroppenstedtii complex is composed of C. kroppenstedtii and two novel species, C. parakroppenstedtii and C. pseudokroppenstedtii. The study presents seven C. kroppenstedtii-like strains isolated from GLM patients. However, they turned out to be six strains of C. parakroppenstedtii and one strain of C. pseudokroppenstedtii according to 16sRNA sequencing. In order to conduct a phylogenetic study, we further sequenced the fusA and rpoB genes, which were frequently employed in studies of Corynebacterium species. Novel Mass Spectral Peaks (MSPs) for C. parakroppenstedtii were created with Bruker MALDI-TOF MS. Then, the identification power of the MSPs was tested by C. parakroppenstedtii strains and remotely related Corynebacterum spp. The antibiotic sensitivity tests were performed according to the CLSI M45 guidelines. All of the strains were not resistant to β-lactams, vancomycin or linezolid. However, applying erythromycin and clindamycin could be fruitless. Phenotypic identification using a Vitek2 ANC ID card proved all of the C. parakroppenstedtii strains were identified as Actinomycete naeslundii. The test of Ala-Phe-Pro arylamidase and urease could be employed as the characteristics to distinguish C. pseudokroppenstedtii from C. parakroppenstedtii. Here, we present the identification, antibiotic sensitivity tests (ASTs) and epidemiological investigation of two novel C. kroppenstedtii-like species with the purpose of improving the understanding of C. kroppenstedtii-like species and related diseases.

The impact of cotrimoxazole in idiopathic granulomatous mastitis treatment

Introduction and importanceIdiopathic granulomatous mastitis (IGM) is a benign inflammatory breast disease, commonly presented with a sensitive breast lump and developing scars. Currently, there is no definitive treatment for IGM but Antibiotics, steroids, immunosuppressive drugs or a surgical treatments are the usual options. This case series aimed to evaluate the effectiveness of cotrimoxazole in treatment of IGM as there is no clinical consensus on the best and most widely acknowledged therapeutic management for IGM. Case presentationAll IGM patients were treated by Cotrimoxazole (800 mg BD for one week), and they were assessed at a month, 3 months, and 6 months after that. The primary outcome was an improvement in presenting complaints and symptoms such as palpable mass, bulging, pain, erythema and hypersensitivity of breast skin, breast discharge and fluctuation. The secondary outcome was the refractory rate within 6 months. Number of 20 patients were included. At the baseline, participants exhibited various symptoms such as bulging, pain and erythema (100 %), breast discharge (80 %), and fluctuation (30 %). After the intervention, there was a significant decrease in the prevalence of symptoms over the study period. The prevalence of bulging and pain, erythema, discharge, and fluctuation symptoms were decreasedto 5 %, 0 %, and 0 %, respectively. The refractory rate of IGM within six months of cotrimoxazole treatment was estimated 30 %. Clinical discussionIn this study, the treatment approach did not involve corticosteroids and invasive procedures and the recurrence rate of IGM within the six months was lower than in similar studies that employed steroids alone or any more invasive treatments. Additionally, our study showed a high healing rate with resolution of inflammation, pain, discharge, and fluctuation. These results suggest that cotrimoxazole may be a more favorable option than high-dose corticosteroids and a comparable alternative to low-dose corticosteroids regarding recurrence rates. ConclusionCotrimoxazole may be an effective treatment option for idiopathic granulomatous mastitis. However, further research is needed on different treatment options.

Evaluation of significantly changed chemokine factors of idiopathic granulomatous mastitis in non‐puerperal patients

AbstractIdiopathic granulomatous mastitis (IGM), a recurrent inflammation disease of the non‐lactating breast, has had an increasing clinical morbidity rate in recent years, and its complicated symptoms and unclear etiology make it challenging to treat. This rare benign inflammatory breast disease, centered on the lobules, represents the most challenging type of non‐puerperal mastitis (NPM), also known as non‐lactating mastitis. In this study, patients diagnosed with IGM (M, n = 23) were recruited as cases, and patients with benign control breast disease (C, n = 17) were enrolled as controls. Cytokine microarray detection measured and analyzed the differentially expressed cytokine factors between IGM and control patients. Then, we verified the mRNA and protein expression levels of the significantly changed cytokine factors using Q‐RT‐PCR, ELISA, western blot, and IHC experiments. The cytokine factor expression levels significantly changed compared to the control group. We observed a significant increase between IGM and control patients in cytokine factors expression, such as interleukin‐1β (IL‐1β), monokine induced by gamma interferon (MIG), macrophage inflammatory protein (MIP)‐1α, MIP‐1β, tumor necrosis factor receptor 2 (TNF RII). Then, we verified the expression of these top five dysregulated factors in both mRNA and protein levels. Our results demonstrated the cytokine map in IGM and indicated that several cytokines, especially chemokines, were associated with and significantly dysregulated in IGM tissues compared to the control group. The chemokine factors involved might be essential in developing and treating IGM. These findings would be helpful for a better understanding of IGM and offer valuable insights for devising novel diagnostic and therapeutic strategies.

Stage-related increase in PIM2 expression in mycosisfungoides.

The oncogene PIM2 is upregulated in several malignancies but has never been investigated in mycosis fungoides (MF), the most common type of cutaneous T-cell lymphoma (CTCL). PIM2 is a well-known oncogene and is regulated by cell signaling pathways like the JAK/STAT- and NF-kB-pathway, key regulators in the pathogenesis of CTCL. The aim of this study was to examine the role of PIM2 in MF. PIM2 gene expression was measured in 81 formalin-fixed paraffin-embedded skin biopsies from patients with MF and 46 control biopsies from healthy skin (HS) and benign inflammatory skin disease (BID). Validation of PIM2 protein expression was performed on selected biopsies with immunohistochemical staining. We found a significant difference in gene expression levels between both early stage MF and HS (p < 0.0001), and BID (p < 0.0001). In addition, the PIM2 gene expression was higher in advanced-stage MF compared to early stage disease (p = 0.0001). No significant difference in gene expression levels was found between patients with and without disease progression. In conclusion, we found PIM2 expression is significantly increased in MF compared to controls, and in advanced-stage MF compared to early stage MF. These findings could potentially have diagnostic value in discriminating early stage MF from BID.

Role of Molecular Biomarkers in Endometriosis-Related Infertility: A Narrative Review of the Literature.

Endometriosis is a chronic benign inflammatory disease that affects womenof reproductive age. The clinical presentations of endometriosis include dysmenorrhea, dyspareunia, chronic pelvic pain, and infertility. There is awell-established association between endometriosis and infertility. Therefore, there is a need for an early diagnosis of endometriosis-related infertility. In this study, we aim to identify the role of biomarkers as predictive factors of the presence of the disease and its severity and their correlation with the pregnancy outcome. We performed an electronic database search of all published studies in PubMed and EMBASE from January 2018 to May 2023. Numerous innovative biomarkers identified in cases of endometriosis and infertility have been studied over the past years, including micro-RNAs, BCL6 endometrial expression, cytotoxic T-lymphocyte antigen 4, human leukocyte antigen G, programmed cell death protein 1, programmed cell death ligand 1 immune checkpoint molecules, plasma fibronectin-fibrin complexes, homeobox A10 gene, systemic inflammatory response markers, uterine natural killer cells, and the eutopic endometrium proteome. Considerable research has been done to identify diagnostic biomarkers for the early detection and prevention of endometriosis-associated infertility. However, none of these biomarkers displayed enough diagnostic accuracy to be used in daily clinical practice. Future research is valuable to establish them as reliable diagnostic tools.

OA15 A case series of idiopathic granulomatous mastitis patients and their immunosuppressive management

Abstract Background/Aims Rheumatologists are experts in managing immunosuppression and are asked to supervise immunosuppression for non-rheumatic conditions. Thus, it is important to be aware of these conditions and the regimes required. Idiopathic granulomatosis mastitis (IGM) is a rare inflammatory breast condition which can have systemic manifestations including arthritis. Methods Our index case presented with peripheral ankle synovitis/tenosynovitis, struggling to weight bear, whilst being investigated for a breast mass. Breast US, mammogram and biopsy (acute and chronic inflammatory cells including multi-nucleated giant cells) were completed and there was little response to 3 courses of antibiotics. No mycobacteria were seen on microscopy, ZN stain negative, CXR normal, T spot negative and serum ACE normal. There was no rash and no conditions associated with a seronegative spondyloarthropathy. RF, anti-CCP and ANA were negative. A moderate course of prednisolone immediately resolved the peripheral arthritis, but high-dose steroids were required to reduce the breast mass. The mass recurred upon weaning prednisolone requiring the addition of azathioprine as a steroid-sparing agent. Results Our case series includes the immunosuppressive management of 3 other IGM patients: 1) 43-year-old referred after an 8 year history of alternating breast ‘abscesses’ and sinuses treated with courses of antibiotics to little avail. High dose prednisolone and methotrexate resolved the breast mass within a month. 2) 37-year-old referred with a 14 year history of breast masses and fistulae previously treated with surgery and antibiotics. Currently asymptomatic so commenced on methotrexate. 3) 39-year-old referred with a 3 year history of recurrent sterile breast abscesses previously managed with antibiotics, incision and drainage. Recent small masses had settled with NSAIDs. Conclusion IGM is a rare benign inflammatory breast disease of unknown aetiology, commonest in Middle Eastern populations, median age 30s. The most common presentation is a unilateral painful mass, which can ulcerate, fistulate and form abscesses. Management of IGM varies from expectant/topical steroids/NSAIDs to high dose steroids and DMARDs. A literature review shows that the usual starting dose of prednisolone is 40-60mg; the addition of methotrexate and azathioprine increases likelihood of successful treatment and allows for faster steroid tapering. Surgery for specific types of IGM can also be useful; for example, where there is duct granuloma, surgical excision can be curative. IGM can associate with arthritis, erythema nodosum, and episcleritis. One case series found that 14% of patients with IGM had concomitant arthritis. Key points: In our local experience we have had four patients with IGM, all previously treated with antibiotics or surgical methods but subsequently diagnosed with IGM and referred for immunosuppressive therapy. Being a rare condition, we feel it’s important for clinicians to be aware of IGM and its link with inflammatory arthritis. Disclosure S. Islam: None. P. Stonelake: None. H. John: None.

Skin Cancer: Back to Basics, Mycosis Fungoides

ABSTRACT Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma occurring when T-cell lymphocytes become malignant and proliferate as well as manifest in the skin. Most commonly, the disease affects the elderly population but has been seen in all ages. Presentations of MF include erythematous patches and plaques with fine scale anatomically favoring the buttocks, trunk, and extremities with complaints of significant pruritus. MF can mimic other benign inflammatory diseases such as atopic dermatitis or psoriasis. Skin biopsy of the rash for simple histology and immunophenotyping will aid in the differentiation from other diseases and confirm accurate diagnosis. Repeat biopsy is often required. A wide range of treatment options exist based on the extent of the disease and patient compliance. The prognosis is good with early detection and treatment. No cure currently exists for the disease, but a deeper understanding of triggers can guide prevention techniques and help develop targeted treatment modalities.

Treatment of Granulomatous Mastitis With Steroids: Should the Decision to End the Treatment be Made Radiologically?

Idiopathic granulomatous mastitis (IGM) is a benign inflammatory breast disease of unknown etiology that affects women in their reproductive period. The most commonly preferred option as first-line treatment is steroids, but the lack of a standard treatment protocol and high recurrence rate after treatment constitutes a recurring challenge during its management. The aim of this study was to investigate whether the decision to end the treatment should be made radiologically or clinically. This retrospective cohort study included IGM patients who had complete clinical recovery with steroids and were followed for a minimum of 30 months. Patient demographics, disease severity and findings, treatment regimens and duration, and magnetic resonance imaging (MRI) findings at clinical recovery were assessed for their relation to recurrence. Eighty-nine patients who were clinically completely healed after steroid treatment for IGM were included in the study. At the time of clinical healing, 51 (57.3%) patients had a complete radiological response and 38 (42.7%) had a partial radiological response (PRR) on MRI. Overall, recurrence developed in 22 (24.7%) patients after a median 38.6-month follow-up. Patients who experienced recurrence were significantly older and had PRR when their treatment was stopped upon clinical healing. During the process of clinical healing, the imaging findings revealed that the remaining disease seems to be a significant predictor for recurrence in IGM patients. In patients with PRR, extending the treatment with either prolonged steroid therapy or by surgical excision of the occult residual disease may prevent recurrences in IGM patients.

A Case Series of Idiopathic Granulomatous Mastitis: Surgical Intervention is not the Only Option

Idiopathic Granulomatous Mastitis (IGM) is a benign inflammatory disease of the breast that is difficult to treat, as there is no definitive protocol for management and it has a higher recurrence rate. The present case series presents five patients who exhibited clinical symptoms such as breast swelling, pain and nipple discharge, and were diagnosed with IGM. They were treated with a multimodality approach (surgical and/or conservative management) based on their symptoms. All patients were successfully treated for IGM using the multimodality approach. While a recurrence was observed in one out of five patients, it was further successfully treated with additional conservative management. The proposed multimodality treatment is effective in treating IGM. It eliminates the risk associated with surgical intervention among patients clinically diagnosed with IGM. It also eliminates the risk of corticosteroid side-effects among patients whose initial clinical diagnosis and postoperative histopathological examination is negative for IGM.

Metastasis from renal cell carcinoma-unusual presentations

ABSTRACT Renal cell carcinoma is one of the most lethal tumors of the urologic system and has high metastatic potential. The usual sites of metastasis are lung, bone, liver adrenal, lymph node, and brain. Thumb and oral cavity metastasis are unusual sites of metastasis. This case report describes two cases reported with unusual thumb and oral cavity metastasis. Patients with acral and oral metastasis are often misdiagnosed as benign inflammatory disease and treatment initiation is often delayed. This case report helps in drawing the attention that such lesions can be metastatic also.

Identification of potential diagnostic biomarkers for tenosynovial giant cell tumour by integrating microarray and single-cell RNA sequencing data

PurposeTenosynovial giant cell tumour (TGCT) is a benign hyperplastic and inflammatory disease of the joint synovium or tendon sheaths, which may be misdiagnosed due to its atypical symptoms and imaging features. We aimed to identify biomarkers with high sensitivity and specificity to aid in diagnosing TGCT.MethodsTwo scRNA-seq datasets (GSE210750 and GSE152805) and two microarray datasets (GSE3698 and GSE175626) were downloaded from the Gene Expression Omnibus (GEO) database. By integrating the scRNA-seq datasets, we discovered that the osteoclasts are abundant in TGCT in contrast to the control. The single-sample gene set enrichment analysis (ssGSEA) further validated this discovery. Differentially expressed genes (DEGs) of the GSE3698 dataset were screened and the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of DEGs were conducted. Osteoclast-specific up-regulated genes (OCSURGs) were identified by intersecting the osteoclast marker genes in the scRNA-seq and the up-regulated DEGs in the microarray and by the least absolute shrinkage and selection operator (LASSO) regression algorithm. The expression levels of OCSURGs were validated by an external dataset GSE175626. Then, single gene GSEA, protein–protein interaction (PPI) network, and gene-drug network of OCSURGs were performed.Result22 seurat clusters were acquired and annotated into 10 cell types based on the scRNA-seq data. TGCT had a larger population of osteoclasts compared to the control. A total of 159 osteoclast marker genes and 104 DEGs (including 61 up-regulated genes and 43 down-regulated genes) were screened from the scRNA-seq analysis and the microarray analysis. Three OCSURGs (MMP9, SPP1, and TYROBP) were finally identified. The AUC of the ROC curve in the training and testing datasets suggested a favourable diagnostic capability. The PPI network results illustrated the protein–protein interaction of each OCSURG. Drugs that potentially target the OCSURGs were predicted by the DGIdb database.ConclusionMMP9, SPP1, and TYROBP were identified as osteoclast-specific up-regulated genes of the tenosynovial giant cell tumour via bioinformatic analysis, which had a reasonable diagnostic efficiency and served as potential drug targets.

Evaluation of pathologically confirmed benign inflammatory breast diseases using artificial intelligence on ultrasound images

ObjectivesIt was aimed to use AI retrospectively to evaluate US images of pathologically confirmed benign inflammatory lesions, to compare the results of AI with our US reports, and to test the reliability of AI in itself. MethodsUS images of 71 histopathologically confirmed benign inflammatory breast lesions were analysed by the FDA-approved AI programme (Koios Decision Support) using 2 orthogonal projections. The lesions' probability of malignancy based on AI and BI-RADS categories of the lesion based on initial US interpretations were recorded. Categories obtained by both systems were divided into 2 groups as unsuspicious and suspicious in terms of malignancy and compared statistically. Reliability of AI was also evaluated. ResultsNo statistically significant difference was found in the lesions' likelihood of malignancy based on the AI and initial US interpretations (P = .512). Additionally, a positive and substantial association (τ-b = 0.458, P < .001) between the levels of suspicion by AI and the initial US interpretation reports was discovered, as per Kendall-b correlation analysis. With a Cronbach alpha correlation coefficient of 0.727, the reliability was high for AI. ConclusionsBenign inflammatory breast lesions may show suspicious appearances in terms of malignancy with US and AI. Artificial intelligence produces results comparable to radiologists' US reports for benign inflammatory diseases. AI has high reliability within itself.

121 A B cell-rich tumor microenvironment delineates cutaneous T cell lymphoma from benign inflammatory skin diseases

121 A B cell-rich tumor microenvironment delineates cutaneous T cell lymphoma from benign inflammatory skin diseases

REPORTING HIGH RISK HISTOPATHOLOGICAL FEATURES IN OPHTHALMIC PATHOLOGY

Background: There can be a wide variety of space-occupying lesions in and around the orbit. These include congenital lesions, benign vascular lesions, inflammatory and infectious diseases and malignant neoplasms. In surgical pathology, the idea of a critical diagnosis in ophthalmic pathology entails a determination of the gravity of an anatomic finding and whether or not it was clinically predicted.If pertinent clinical information is included with the specimen before it is sent to the lab, pathologists are less likely to wrongly label a diagnosis as unexpected. Objective: The aim of this study was to determine critical diagnosis in different neoplastic and non-neoplastic lesions in ophthalmic pathology. Materials and methods: Eighty-six cases of different lesions in the orbit were collected from Mayo Hospital, Lahore. Results: For 29 benign lesions, the ages of the patients ranged from 1-60 years with a mean of 31.48 years ±14.43 SD. Cystic lesions were most common benign lesions. There were 27 malignant lesions of orbit. Basal cell carcinoma and squamous cell carcinoma were the most frequent malignancies in adults whereas retinoblastoma was the most common tumor of children. Age ranged from 3-82 with a mean of 51.54 years ±24.58 SD. The lesions were more frequent in females. Conclusion: In this study of 86 cases of lesions in orbit, it was concluded that non-neoplastic cystic lesions including epidermal inclusion cyst and dermoid cysts were most common. Among the malignant tumors, basal cell carcinoma is the most common malignant tumor followed by squamous cell carcinoma.

SAT612 Granulomatous Mastitis: An Unusual Presentation Of Prolactinoma

Abstract Disclosure: H.R. Alkaissi: None. E. Kim: None. S. McFarlane: None. Background: Granulomatous mastitis (GM) is a rare, benign inflammatory breast disease of unclear etiology with clinical presentation that is similar to inflammatory breast cancer and periductal lobular mastitis. It occurs mainly in younger females and during the postpartum period. Prolactin (PRL) is an essential hormone of pituitary and extrapituitary origin that promotes lactation and the development of mammary glands within breast tissues. In addition to its lactogenic effect, it has over 300 other effects, several of which are immunomodulatory, including the expression and secretion of proinflammatory cytokines from macrophages. Clinical Case: A 37-year-old African American woman presented with right breast pain and swelling for a few weeks. Her medical history includes amenorrhea for five years. She is gravida 1, para 1 with normal spontaneous vaginal delivery at the age of 20. Physical exam showed non-bloody, non-purulent nipple discharge bilaterally, otherwise unremarkable. A breast ultrasound showed a 1 cm complex cystic mass. Biopsy showed benign breast tissue, with noncaseating granulomas formed by macrophages (CD68 positive on immunohistochemistry). Ziehl-Neelsen staining for acid-fast bacilli was negative. Staining for fungi was also negative. Prolactin level was 237 ng/mL. TSH, IGF-1, and ACTH were within normal. Pituitary MRI showed a focus of abnormal signal and diminished enhancement measuring 2.8x3.2x4.2 mm within the left side of the pituitary gland is compatible with a microadenoma. The patient was started on bromocriptine 2.5mg daily. Discussion: Our patient represents a rare case of granulomatous mastitis in the setting of microprolactinoma, likely long-standing, given the five years history of amenorrhea. The immunomodulatory effect of PRL on several immune system cells, including B-cells, T-cells, and macrophages, might be an underlying mechanism. In a recent study of 25 samples of GM, metagenomics studies identified unusual organisms in 68% of the samples. Of these, Corynebacterium kroppenstedtii was the most common (60%), followed by Pseudomonas oleovorans (16%), Epstein-Barr virus (4%), Acinetobacter baumannii (4%), and Tepidiphilus thermophilus (4%). In addition, 50% of the patients had elevated PRL, and elevated immunological markers, such as C3 and IgA [1]. This suggests that GM results from an interaction between the presence of certain pathogens in a host with elevated PRL that mediates proinflammatory response.

The Distinct Pattern of Granulomatous Lobular Mastitis with Erythema Nodosum: More Severe Conditions and Extensive Lesions

Purpose Granulomatous lobular mastitis (GLM) is a benign inflammatory disease of the mammary gland with unknown etiology. Erythema nodosum (EN) is a rare, extramammary symptom of GLM. The purpose of this article was to investigate the clinical features of EN associated with GLM. Methods We recruited 102 GLM patients diagnosed between December 2018 and December 2021 at Renmin Hospital of Wuhan University. The clinical characteristics and laboratory indices of the EN group (n = 12) and the non-EN group (n = 90) were compared. Results The proportion of GLM patients with lesions involving ≥2 quadrants and high peripheral white blood cell count, absolute neutrophil count and neutrophil-to-lymphocyte ratio (NLR) was larger in the EN group than in the non-EN group (p = 0.002, 0.025, 0.014, 0.002, respectively). The duration of EN was longer in GLM patients with EN than in GLM patients without EN (p = 0.005). GLM patients with EN had more abscesses and sinus tracts than those without EN (p = 0.003, 0.038). Lesions involving ≥2 quadrants and the NLR were positively associated with the occurrence of EN (R = 0.304, 0.0302, p = 0.002, 0.002). Receiver operating characteristic curve analysis revealed that the area under the curve of the NLR was 0.770. When NLR > 5.73, the sensitivity and specificity of predicting EN were 66.67% and 87.78%, respectively. Conclusion Our findings suggest that GLM concomitant with EN suggests the presence of a more severe condition and extensive lesions.

Transcriptomic analyses of ovarian clear-cell carcinoma with concurrent endometriosis.

Endometriosis, a benign inflammatory disease whereby endometrial-like tissue grows outside the uterus, is a risk factor for endometriosis-associated ovarian cancers. In particular, ovarian endometriomas, cystic lesions of deeply invasive endometriosis, are considered the precursor lesion for ovarian clear-cell carcinoma (OCCC). To explore this transcriptomic landscape, OCCC from women with pathology-proven concurrent endometriosis (n = 4) were compared to benign endometriomas (n = 4) by bulk RNA and small-RNA sequencing. Analysis of protein-coding genes identified 2449 upregulated and 3131 downregulated protein-coding genes (DESeq2, P< 0.05, log2 fold-change > |1|) in OCCC with concurrent endometriosis compared to endometriomas. Gene set enrichment analysis showed upregulation of pathways involved in cell cycle regulation and DNA replication and downregulation of pathways involved in cytokine receptor signaling and matrisome. Comparison of pathway activation scores between the clinical samples and publicly-available datasets for OCCC cell lines revealed significant molecular similarities between OCCC with concurrent endometriosis and OVTOKO, OVISE, RMG1, OVMANA, TOV21G, IGROV1, and JHOC5 cell lines. Analysis of miRNAs revealed 64 upregulated and 61 downregulated mature miRNA molecules (DESeq2, P< 0.05, log2 fold-change > |1|). MiR-10a-5p represented over 21% of the miRNA molecules in OCCC with endometriosis and was significantly upregulated (NGS: log2fold change = 4.37, P = 2.43e-18; QPCR: 8.1-fold change, P< 0.05). Correlation between miR-10a expression level in OCCC cell lines and IC50 (50% inhibitory concentration) of carboplatin in vitro revealed a positive correlation (R2=0.93). MiR-10a overexpression in vitro resulted in a significant decrease in proliferation (n = 6; P< 0.05) compared to transfection with a non-targeting control miRNA. Similarly, the cell-cycle analysis revealed a significant shift in cells from S and G2 to G1 (n = 6; P< 0.0001). Bioinformatic analysis predicted that miR-10a-5p target genes that were downregulated in OCCC with endometriosis were involved in receptor signaling pathways, proliferation, and cell cycle progression. MiR-10a overexpression in vitro was correlated with decreased expression of predicted miR-10a target genes critical for proliferation, cell-cycle regulation, and cell survival including [SERPINE1 (3-fold downregulated; P< 0.05), CDK6 (2.4-fold downregulated; P< 0.05), and RAP2A (2-3-fold downregulated; P< 0.05)]. These studies in OCCC suggest that miR-10a-5p is an impactful, potentially oncogenic molecule, which warrants further studies.