Diesel exhaust exposure induced squamous metaplasia of corneal epithelium via yes-associated protein activation.

Atmospheric pollution has been demonstrated to be associated with ocular surface diseases characterized by corneal epithelial damage, including impaired barrier function and squamous metaplasia. However, the specific mechanisms underlying the impact of atmospheric pollution on corneal damage are still unknow. To address this gap in knowledge, we conducted a study using a whole-body exposure system to investigate the detrimental effects of traffic-related air pollution, specifically diesel exhaust (DE), on corneal epithelium in C57BL/6 mice over a 28-day period. Following DE exposure, the pathological alterations in corneal epithelium, including significant increase in corneal thickness and epithelial stratification, were observed in mice. Additionally, exposure to DE was also shown to disrupt the barrier functions of corneal epithelium, leading to excessive proliferation of basal cells and even causing squamous metaplasia in corneal epithelium. Further studies have found that the activation of yes-associated protein (YAP), characterized by nuclear translocation, may play a significant role in DE-induced corneal squamous metaplasia. In vitro assays confirmed that DE exposure triggered the YAP/ß-catenin pathway, resulting in squamous metaplasia and destruction of barrier functions. These findings provide the preliminary evidence that YAP activation is one of the mechanisms of the damage to corneal epithelium caused by traffic-related air pollution. These findings contribute to the knowledge base for promoting eye health in the context of atmospheric pollution.

Biological effects of intraoperative radiation therapy: histopathological changes and immunomodulation in breast cancer patients.

Introduction: Intraoperative radiation therapy (IORT) delivers a single accelerated radiation dose to the breast tumor bed during breast-conserving surgery (BCS). The synergistic biologic effects of simultaneous surgery and radiation remain unclear. This study explores the cellular and molecular changes induced by IORT in the tumor microenvironment and its impact on the immune response modulation. Methods: Patients with hormone receptor (HR)-positive/HER2-negative, ductal carcinoma in situ (DCIS), or early-stage invasive breast carcinoma undergoing BCS with margin re-excision were included. Histopathological evaluation and RNA-sequencing in the re-excision tissue were compared between patients with IORT (n=11) vs. non-IORT (n=11). Results: Squamous metaplasia with atypia was exclusively identified in IORT specimens (63.6%, p=0.004), mimicking DCIS. We then identified 1,662 differentially expressed genes (875 upregulated and 787 downregulated) between IORT and non-IORT samples. Gene ontology analyses showed that IORT was associated with the enrichment of several immune response pathways, such as inflammatory response, granulocyte activation, and T-cell activation (p<0.001). When only considering normal tissue from both cohorts, IORT was associated with intrinsic apoptotic signaling, response to gamma radiation, and positive regulation of programmed cell death (p<0.001). Using the xCell algorithm, we inferred a higher abundance of γδ T-cells, dendritic cells, and monocytes in the IORT samples. Conclusion: IORT induces histological changes, including squamous metaplasia with atypia, and elicits molecular alterations associated with immune response and intrinsic apoptotic pathways. The increased abundance of immune-related components in breast tissue exposed to IORT suggests a potential shift towards active immunogenicity, particularly immune-desert tumors like HR-positive/HER2-negative breast cancer.

High frequency of concomitant squamous metaplasia in bulbar urethral stricture and its association with reconstructive delay and urethral rest.

PURPOSE: To determine the prevalence of concomitant squamous metaplasia (SM), the initial histological change from normal urethra to urethral stricture, in bulbar urethral strictures and to investigate the associated clinical factors. METHODS: A retrospective review was conducted on 165 male patients with bulbar urethral strictures who underwent excision and primary anastomosis (EPA) between 2010 and 2020, for whom complete clinical data and excised urethral specimens were available. An experienced pathologist histologically evaluated concomitant SM in paraffin sections of the proximal end of the excised urethra blinded to the clinical data. Disease duration was calculated as the period from the initial diagnosis of urethral stricture to the date of EPA. The association between concomitant SM and clinical background was investigated. RESULTS: SM was identified in 86 (52.1%) patients. The median disease duration in patients with SM (38 months) was significantly longer than that in patients without SM (9 months, p < 0.0001). In multivariate analysis, the longer disease duration, non-traumatic stricture etiology, and failure to maintain urethral rest with urinary diversion via a suprapubic tube for more than 90 days were independent factors predicting concomitant SM. No significant difference was observed in success rates of EPA between patients with SM (93.2%) and those without SM (97.5%, p = 0.18). CONCLUSIONS: Reconstructive urologists need to be aware that concomitant SM is frequent in patients with bulbar urethral stricture, especially in those with long disease duration and those who were voiding volitionally during the period of urethral rest.

A case report of uncommon giant epidermal inclusion cyst found in the thyroid gland.

Introduction and importance: This case report describes a rare occurrence of an epidermal inclusion cyst (EIC) being found in the thyroid gland and highlights the importance of considering uncommon entities like EIC in the differential diagnosis of thyroid lesions. Case presentation: A 68-year-old male presented with a large, painless swelling in the anterior neck, causing dysphagia and dysphonia. Imaging and cytology confirmed a benign EIC involving the left lobe of the thyroid, which was successfully removed via hemithyroidectomy, resulting in resolution of symptoms. Clinical discussion: Epidermoid inclusion cysts are rare in the thyroid gland, with only 16 reported cases worldwide. The cyst was diagnosed through ultrasound-guided fine needle aspiration and confirmed by surgical pathology. Treatment involves complete removal of the cyst and its capsule, which was successfully performed in this case under local anaesthesia with sedation due to the patient's medical history of COPD. Conclusion: it is important to consider the possibility of EIC when benign squamous cells are detected in a thyroid aspirate without any follicular cells. In such cases, hemithyroidectomy can be a successful management strategy.

Idiopathic Subglottic Stenosis Is Associated With More Frequent and Abnormal Squamous Metaplasia.

OBJECTIVES: Gain insights into the pathophysiology of idiopathic subglottic stenosis (iSGS) by investigating differences in transcriptome of subglottic mucosal tissue between patients with iSGS and controls, and between tracheal and subglottic tissue within patients. METHODS: RNA sequencing was conducted on biopsied mucosal samples collected from subglottic and tracheal (in-patient control) regions in iSGS patients, and from subglottis in controls. The gene expression differences were validated on a protein level by (1) staining the tissue samples obtained from a second cohort of patients and controls; and (2) in vitro functional assays using primary subglottic epithelial cells from both iSGS patients and healthy donors. RESULTS: We found 7 upregulated genes in the subglottic region of iSGS patients relative to both the tracheal mucosa and subglottic region of controls. A gene ontology enrichment analysis found that the epithelial cell differentiation and cornification pathways are significant, involving specifically 3 of the genes: involucrin (IVL), small proline rich protein 1B (SPRR1B), and keratin 16 (KRT16). Involvement of these pathways suggests squamous metaplasia of the epithelium. Histological analyses of epithelium in subglottic mucosal biopsies revealed squamous metaplasia in 41% of the samples from iSGS patients and in 25% from controls. Immunohistochemical evaluation of the samples presented with squamous epithelium revealed increased expression of the protein encoded by SPRR1B, hyperproliferative basal cells, shedding of apical layers, and accompanying lesions in iSGS compared to CTRL. Cultured primary subglottic epithelial cells from iSGS patients had higher proliferation rates compared to healthy donors and squamous metaplastic differentiation formed thinner epithelia with increased expression proteins encoded by INV, SPRR1B, and KRT16, suggesting intrinsic dysfunction of basal cells in iSGS. CONCLUSIONS: Abnormal squamous differentiation of epithelial cells may contribute to the pathogenesis of iSGS. Patients having metaplastic epithelial phenotype may be sensitive to drugs that reverse it to a normal phenotype.

Ozone exposure affects corneal epithelial fate by promoting mtDNA leakage and cGAS/STING activation.

Ozone is a common air pollutant associated with various human diseases. The human ocular surface is frequently exposed to ozone in the troposphere, but the mechanisms by which ozone affects the ocular surface health remain unclear. This study aimed to establish a mouse model to investigate the effects of ozone exposure on the ocular surface and the corneal epithelium. The findings revealed that ozone exposure disrupted corneal epithelial homeostasis and differentiation, resulting in corneal squamous metaplasia. Further, ozone exposure induced oxidative damage and cytoplasmic leakage of mitochondrial DNA (mtDNA), thereby activating the cGAS/STING signaling pathway. The activation of the cGAS/STING signaling pathway triggered the activation of downstream NF-κB and TRAF6 signaling pathways, causing corneal inflammation, thereby promoting corneal inflammation and squamous metaplasia. Finally, C-176, a selective STING inhibitor, effectively prevented and treated corneal inflammation and squamous metaplasia caused by ozone exposure. This study revealed the role of mtDNA leakage-mediated cGAS/STING activation in corneal squamous epithelial metaplasia caused by ozone exposure. It also depicted the abnormal expression pattern of corneal epithelial keratin using three-dimensional images, providing new targets and strategies for preventing and treating corneal squamous metaplasia and other ocular surface diseases.

Central airway squamous metaplasia following radiation therapy mimicking local tumour recurrence.

Radiation therapy can result in injury to the lung parenchyma and central airways; the latter is less well documented in the literature. Here, we describe a 65-year-old Caucasian male, who developed focal endobronchial nodules and right main bronchial stenosis suggesting tumour recurrence, 32 months following curative intent concurrent chemoradiation therapy for Stage 3B squamous cell carcinoma of the lung. Computed tomography and positron emission tomography results are detailed. Flexible bronchoscopy with bronchial biopsies revealed squamous metaplasia rather than malignant tumour recurrence, with ongoing observation planned.

Squamous Cell Carcinoma In Situ of the Breast With the Configuration of an Intraductal Papilloma.

A 64-year-old woman presented to our institution with a palpable and painful left breast mass. She denied any other breast symptoms. Subsequent imaging classified it as a US Breast Imaging-Reporting and Data System (BI-RADS) 4A lesion. A core needle biopsy was performed showing atypical proliferating fragments of squamous epithelium suspicious for malignant neoplasm. An excisional biopsy was recommended. Gross examination showed a well-circumscribed pink soft mass measuring 2.0 x 1.4 x 1.3 cm. The entire lesion was submitted for histologic evaluation, demonstrating a neoplasm with branching stroma and exuberant squamous differentiation. The lesion exhibited obvious cytologic features of malignancy like mitotic figures, prominent nucleoli, irregular nuclei, and multinucleation. Collagen IV stain ruled out invasion. The lesion was finally classified as squamous cell carcinoma (SCC) in situ with the configuration of an intraductal papilloma. The possibility of metastatic disease was suggested. A PET scan was negative, and no other foci of disease were found in the remainder of the specimen. The mass was also independent of nipple and skin. Based on the architectural features, we believe that this is a case of an intraductal papilloma that underwent complete squamous metaplasia with no residual adenomyoepithelial components and transformation into an SCC in situ demonstrated by stains. Papillomas can undergo reactive metaplastic changes, usually benign and in small foci. This is the first reported case of exuberant squamous epithelium that transformed into carcinoma in situ with papillary architecture in the breast.

Recurrence of Rathke's Cleft Cyst Following Surgery and Histopathological Considerations for Recurrence: A Case Presentation.

Recurrence of Rathke's cleft cysts (RCC) following surgery is not uncommon. We present a 33-year-old male patient with chronic headache and visual disturbances whose MRI showed mostly cystic, suprasellar mass with peripheral enhancement. Endoscopic extended transsphenoidal approach and tumor resection was performed and RCC was pathologically confirmed postoperatively. Early recurrence was first suspected at 3 months following surgery, and his serial MRIs showed a recurred mass without associated clinical symptoms. Upon further histopathological study, extensive squamous metaplasia and high Ki-67 were seen. Also, in this study, we discuss important factors associated with cyst recurrence following surgery.

Pleomorphic adenoma with extensive oncocytic papillary cystic areas and trichilemmal keratinisation - A unique presentation.

Pleomorphic adenoma (PA) is a commonly occurring benign salivary gland tumour known for its surfeit of histo-morphologic appearances ranging from myxochondroid, plasmacytoid, and squamoid elements to the infrequently seen osseous and adipose tissue metaplasia. Oncocytic metaplastic changes, a rare finding, present in the form of sheets/islands/cords of polygonal cells with rich eosinophilic or occasionally clear cytoplasm and an oval/round nucleus. We report one such rare case which portrayed extensive oncocytic changes in a unique bilayered/multi-layered epithelium, lining the papillary cystic areas similar to that of Warthin's tumour and extensive keratinisation simulating the newly recognised entity "adnexa-like differentiation/trichilemmal keratinisation", along with foci of cholesterol clefts and multi-nucleated giant cells.

Central airway squamous metaplasia following radiation therapy mimicking local tumour recurrence.

Radiation therapy can result in injury to the lung parenchyma and central airways; the latter is less well documented in the literature. Here, we describe a 65-year-old Caucasian male, who developed focal endobronchial nodules and right main bronchial stenosis suggesting tumour recurrence, 32 months following curative intent concurrent chemoradiation therapy for Stage 3B squamous cell carcinoma of the lung. Computed tomography and positron emission tomography results are detailed. Flexible bronchoscopy with bronchial biopsies revealed squamous metaplasia rather than malignant tumour recurrence, with ongoing observation planned.

Squamous and glandular metaplasia related to a renal pelvis stone leading to secondary pyeloureteral junction syndrome.

Keratinizing squamous metaplasia of the renal pelvis is a rare lesion of the upper urinary tract that can occur in the context of chronic aggression to the urothelium, potentially leading to a secondary pyeloureteral junction syndrome. We report the case of a 43-year-old patient discovered intraoperatively in relation to a renal pelvis stone causing a pyeloureteral junction syndrome. The extemporaneous histological examination ruled out a malignant process, and we performed a pyeloplasty according to KUSS-ANDERSON technique. This pathology should be recognized by the urologist for appropriate management. Treatment is conservative, with extended follow-up to detect recurrences or carcinomatous degenerations.

DNA methylome analysis reveals potential alterations contributing to the progression of bronchial hyperplasia.

BACKGROUND: Squamous cell lung cancer (SCLC) arises from bronchial changes: basal cell hyperplasia (BCH), squamous metaplasia (SM), and dysplasia. However, the premalignant process preceding SCLC is not inevitable; it can stop at any of the bronchial lesions. Previously, we hypothesized that combinations of premalignant lesions observed in the small bronchi of SCLC patients can reflect the different "scenarios" of the premalignant process: BCHi-the stoppage at the stage of hyperplasia and BCHSM-the progression of hyperplasia to metaplasia. METHODS AND RESULTS: In this study, using whole-genome bisulfite sequencing we analyzed the DNA methylome of two forms of BCH: isolated BCH (BCHi) and BCH co-occurred with SM (BCHSM) in the small bronchi of SCLC patients. It was shown that BCHi harbored differentially methylated regions (DMRs) affecting genes associated with regulating phosphatase activity. In BCHSM, DMRs were found in genes involved in PI3K-Akt and AMPK signaling pathways. DMRs were also found to affect specific miRNA genes: miR-34a and miR-3648 in BCHi and miR-924 and miR-100 in BCHSM. CONCLUSIONS: Thus, this study demonstrated the significant changes in DNA methylome between the isolated BCH and BCH combined with SM. The identified epigenetic alterations may underlie different "scenarios" of the premalignant process in the bronchial epithelium.

Cystic squamous metaplasia in a giant benign phyllodes tumor of the breast: a case report.

Phyllodes tumor is a rare tumor of the breast, which encompasses both stromal and epithelial components. In these components, metaplastic changes can be observed occasionally. We report the case of a 51-year-old woman nulligest menopaused who presented a huge mass, largely ulcerated in her right breast. The radiological examination revealed a large tumor with microcalcifications classified as Breast Imaging and Reporting Data System Category 5. The patient undergone right mastectomy and the histological analysis revealed benign phyllodes tumor with cystic squamous metaplasia. Therefore, we aim to present this uncommon event occasionally occurring in phyllodes tumor of the breast.

Foreign Body Aspiration Mimicking an Endobronchial Neoplasm: A Case Report and Review of the Literature.

Foreign body aspiration (FBA) is infrequently encountered in the adult population, with major risk factors including advancing age, intoxication, and disorders of the central nervous system. Here, we present a case of FBA in an adult undergoing routine lung cancer screening to review imaging findings and highlight potential pitfalls for the practicing radiologist. A low-dose chest computed tomography (CT) scan was performed for lung cancer screening in a 57-year-old male with a one-month history of worsening dyspnea and cough. An endobronchial lesion was identified in the right bronchus intermedius. A follow-up 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET-CT) revealed hypermetabolic activity in the region of interest, raising concern for malignancy. Bronchoscopy was performed, revealing a nodular mass adjacent to a foreign body in the bronchus intermedius. Histopathologic analysis of the tissue sample revealed the presence of an aspirated foreign body with squamous metaplasia of the respiratory epithelium. Adult FBA is an uncommon clinical entity that may be incidentally observed on a screening chest CT. Relevant multimodality imaging findings are discussed here, along with a review of the accompanying pathologic changes seen with chronic airway impaction.

Basal cell carcinoma of the prostate with squamous metaplasia: A case report and literature review.

Basal cell carcinoma of the prostate (BCCP) is a rare tumor with a total incidence of 140 cases to date. However, BCCP with squamous metaplasia has not been reported as of date. In this paper, we report the first case of BCCP with squamous metaplasia. The patient was hospitalized for progressive dyspareunia and had been treated for recurrent urinary retention four times in 5 years. Rectal examination showed that the prostate was medium in texture with no palpable nodules. The levels of total prostate specific antigen (tPSA), free prostate specific antigen (fPSA), and fPSA/tPSA (f/t) ratio were 1.29 ng/mL, 0.4 ng/mL, and 0.31, respectively. Ultrasound of the urinary tract showed that the prostate gland was 51 mm*40 mm*38 mm in size. We performed transurethral resection of the prostate. Histopathology confirmed the diagnosis of basal cell carcinoma with focal squamous differentiation, and immunohistochemical staining was positive for P63 and 34ßE12. A laparoscopic radical prostatectomy was performed 45 days after the first surgery and the postoperative pathology showed a small amount of residual tumor with negative margins and no involvement of the seminal vesicles and vas deferens. The patient was followed up for 50 months and was doing well by the end of our study. We describe the clinical symptoms, pathological features, treatment, and prognosis of patients with BCCP with squamous metaplasia. The relevant published literature is also briefly reviewed.

Bronchiolar adenoma with squamous metaplasia: a distinct phenotype.

AIMS: Pulmonary bronchiolar adenoma is a benign lung tumour characterised by nodular proliferation of bilayered bronchiolar-type epithelium with a continuous layer of basal cells. The aim of this study was to describe a distinct and rare histological type of pulmonary bronchiolar adenoma: bronchiolar adenoma with squamous metaplasia. METHODS AND RESULTS: We examined the clinicopathological, immunohistochemical, and molecular characteristics of five cases (two cases from the same patient). The samples were histopathologically characterised by bilayered bronchiolar-type cells with sheets like spindle-oval and polygonal cells. Immunohistochemistry analysis revealed that columnar surface cells of the tumour were diffusely positive for TTF-1 and Napsin A, while basal cells were positive for P40 and P63. Moreover, the squamous metaplastic cells in the stroma were positive for P40, and P63, while being negative for TTF-1, Napsin A, S100, and SMA. Genomic analyses uncovered that all five samples had BRAF V600E mutations. Notably, both squamous metaplastic and basal cells were positive for BRAF V600E staining. CONCLUSION: We discovered a distinct subtype of pulmonary bronchiolar adenoma termed bronchiolar adenoma with squamous metaplasia. It is composed of columnar surface cells, basal cells, and sheet-like spindle-oval cells with squamous metaplasia in the stroma. All five samples harboured the BRAF V600E mutation. Importantly, BASM may be misdiagnosed as pulmonary sclerosing pneumocytoma upon frozen sections analysis. It may need further immunohistochemistry staining.

Gastric squamous metaplasia observed by image-enhanced endoscopy.

A 61-year-old Helicobacter pylori-positive female with gastroesophageal reflux disease has undergone surveillance endoscopy every year for 13 years at Tokyo Medical University Hospital. At the first surveillance in 2009, conventional white light endoscopy showed a 10-mm whitish slightly depressed lesion at the lesser curvature of the gastric cardia. This lesion gradually increased in size to 15 mm over the 13-year observational period. Indigo carmine chromoendoscopy, narrow band imaging, and texture and color enhancement imaging in both mode 1 and mode 2 clearly emphasized the presence of a depressed whitish mucosa around the gastric mucosa compared with white light imaging. None of the three image-enhanced endoscopy techniques showed any abnormality in the vascular or structural pattern. Pathological findings showed squamous epithelium without atypia and revealed no evidence of malignancy in the stomach. We thus report a case of gastric squamous metaplasia without gastric neoplastic lesion in the gastric cardia whose lesions were endoscopically observed to change the size for more than 10 years and whose lesions were endoscopically evaluated with a texture and color enhancement imaging mode 1 and mode 2 and narrow band imaging.

Huge sialolith of the submandibular gland: a case report and review of literature.

The formation of stone in the ductal system of the salivary gland is termed sialolithiasis, with the submandibular gland being the most commonly affected. The precise aetiology is unknown but certain factors peculiar to the submandibular gland accounts for its likelihood of developing a calculous disease. Stones are classified based on their dimension, and may be silent or present with symptoms attributable to the size, location and complications. Here, a 50-year-old female who presented with a painless swelling in the left submandibular region that had grown slowly over the previous year, is reported. Following clinical and radiologic evaluation, left submandibular stone disease was preoperatively diagnosed. The patient underwent sialoadenectomy with transient palsy of the marginal mandibular branch of the facial nerve. Histopathology confirmed sialolith (2.7 cm) with severe squamous metaplasia of the duct. This presentation demonstrates some peculiar features attributable to the size, vertical orientation and location of the stone, in addition to the compression of the gland, thick fibrous capsule and significant squamous metaplasia of the duct. These findings require further evaluation for optimal treatment in view of the emerging trends for managing sialolithiasis.

Targeting Type I IFN/STAT1 signaling inhibited and reversed corneal squamous metaplasia in Aire-deficient mouse.

Corneal transparency and integrity are essential for obtaining good vision; nevertheless, squamous metaplasia (SQM) of ocular epithelium is a kind of serious blinding corneal diseases, without therapeutic medication in clinic. Here, we found that deficiency of the autoimmune regulator (AIRE) in corneas spontaneously developed corneal plaques. Using corneal abrasion model, we revealed that deletion of Aire not only resulted in delayed corneal re-epithelialization, but also promoted a cell-fate transition from transparent corneal epithelium to keratinized epithelium, histopathologically characterized with SQM based on the transcriptomic analysis. Mechanistically, Aire-deficient corneas led to the heightened Type I interferon (IFN-I)/STAT1 signaling after abrasion. Pharmacological blockade of IFN-I/JAK/STAT1 signaling in Aire-knockout (KO) corneas not only accelerated epithelial wound healing, but also alleviated corneal plaques and SQM. Collectively, our findings revealed critical roles of AIRE in governing corneal epithelial homeostasis and pathologic keratinization, and further identified IFN-I/STAT1 signaling as a potential target for treating ocular surface diseases with SQM, and even for treating pathological scenarios related to SQM in other tissues.