Exosome-mediated secretion of miR-127-3p regulated by RAB27A accelerates metastasis in renal cell carcinoma.

BACKGROUND: The exosome-mediated extracellular secretion of miRNAs occurs in many cancers, and RAB27A is a potent regulator of exosome secretion. For metastatic renal cell carcinoma (RCC), this study examines the mechanisms of cancer metastasis via the RAB27A-regulated secretion of specific miRNAs. METHODS: RAB27A knockdown (KD) and overexpressing (OE) RCC cells were used to examine cell migration and adhesion. The particle counts and sizes of exosomes in RAB27A OE cells were analyzed using Exoview, and those of intraluminal vesicles (ILV) and multivesicular bodies (MVB) were measured using an electron microscope. Analysis of RNA sequences, protein-protein interaction networks, and the competing endogenous RNA (ceRNA) network were used to identify representative downregulated miRNAs that are likely to undergo cargo-sorting into exosomes and subsequent secretion. A molecular beacon of miR-137-3p, one of the most representatively downregulated genes with a fold change of 339, was produced, and its secretion was analyzed using Exoview. RAB27A OE and control cells were incubated in an exosome-containing media to determine the uptake of tumor suppressor miRNAs that affect cancer cell metastasis. RESULTS: Migration and cell adhesion were higher in RAB27A OE cells than in RAB27A KD cells. Electron microscopy revealed that the numbers of multivesicular bodies and intraluminal vesicles per cell were higher in RAB27A OE cells than in control cells, suggesting their secretion. The finding revealed that miR-127-3p was sorted into exosomes and disposed of extracellularly. Protein-protein interaction analysis revealed MYCN to be the most significant hub for RAB27A-OE RCC cells. ceRNA network analysis revealed that MAPK4 interacted strongly with miR-127-3p. CONCLUSION: The disposal of miR-127-3p through exosome secretion in RAB27A overexpressing cells may not inhibit the MAPK pathway to gain metastatic potential by activating MYCN. The exosomes containing miRNAs are valuable therapeutic targets for cancer treatment.

Airspace Enlargement with Fibrosis in a Young Heavy Smoker Mimicking Diffuse Cystic Lung Disease.

The widespread use of computed tomography (CT) has led to the increased recognition of cystic lung lesions. Multiple pulmonary cysts can be observed in heterogeneous disorders called diffuse cystic lung diseases (DCLDs), which include pulmonary Langerhans cell histiocytosis, lymphangioleiomyomatosis, lymphocytic interstitial pneumonia, and Birt-Hogg-Dubé syndrome. Recently, airspace enlargement with fibrosis (AEF) has been recognized as an entity on the spectrum of smoking-related lung diseases. We report a young male heavy smoker presenting diffuse pulmonary cysts on chest CT with suspected DCLD. However, histopathological examination of the surgical biopsy specimen revealed dilated emphysematous cysts with prominent mural fibrosis, consistent with AEF.

Validation of Diagnostic Performance and Interobserver Agreement of DTD-TIRADS for Diffuse Thyroid Disease on Ultrasound: A Single-Center Study.

OBJECTIVE. This retrospective study aimed to investigate the capability of the already-proposed thyroid imaging reporting and data system for detecting diffuse thyroid disease (DTD-TIRADS) on ultrasound (US) by assessing interobserver agreement and diagnostic performance. MATERIALS AND METHODS. A total of 180 patients who underwent thyroid US before thyroid surgery were included. Three radiologists blinded to the pathologic and serologic data independently categorized the US features according to a four-category DTD-TIRADS classification system. On the basis of the pathologic results of thyroid parenchyma, diagnostic performance values were calculated using ROC curve analyses. Interobserver agreements of each US feature and DTD-TIRADS category among the three radiologists were also assessed. RESULTS. Of the 180 patients, 143 (79.4%) had normal thyroid parenchyma and 37 (20.6%) had diffuse thyroid disease (DTD). The areas under the ROC curve for DTD were not significantly different among the three radiologists: 0.876 (95% CI, 0.819-0.920) for radiologist 1, 0.883 (95% CI, 0.827-0.926) for radiologist 2, and 0.861 (95% CI, 0.801-0.908) for radiologist 3 (p > .05). The cutoff for the diagnosis of DTD was category III DTD-TIRADS. The sensitivity, specificity, and accuracy of DTD-TIRADS for detecting DTD were 86.5%, 81.1%, and 82.2% for radiologist 1; 86.5%, 83.2%, and 83.9% for radiologist 2; and 83.8%, 82.5%, and 82.8% for radiologist 3, respectively. Interobserver agreement of DTD-TIRADS categorization was almost perfect (κ = 0.81). CONCLUSION. DTD-TIRADS has high diagnostic performance and almost-perfect interobserver agreement. Thus, DTD-TIRADS can be considered to be an effective classification system for diagnosing DTD.

Prevalence and Clinical Implications of Incidentally Detected Parotid Lesions as Blind Spot on Brain MRI: A Single-Center Experience.

Background and objective: This study was conducted to assess the prevalence and clinical implications of parotid lesions detected incidentally during brain magnetic resonance imaging (MRI) examination. Materials and Methods: Between February 2016 and February 2021, we identified 86 lesions in the brain MRI reports of 84 patients that contained the words "parotid gland" or "PG". Of these, we finally included 49 lesions involving 45 patients following histopathological confirmation. Results: Based on the laboratory, radiological or histopathological findings, the prevalence of incidental parotid lesions was low (1.2%). Among the 45 study patients, 41 (91.1%) had unilateral lesions, and the majority of the lesions were located in the superficial lobe (40/49, 81.6%). The mean size of the parotid lesions was 1.3 cm ± 0.4 cm (range, 0.5 cm-2.8 cm). Of these, 46 parotid lesions (93.9%) were benign, whereas the remaining three lesions were malignant (6.1%). Conclusions: Despite the low prevalence and incidence of malignancy associated with incidental parotid lesions detected on brain MRI, the clinical implications are potentially significant. Therefore, clinical awareness and appropriate imaging work-up of these lesions are important for accurate diagnosis and timely management.

Comprehensive analyses with radiological and biological markers of breast cancer on contrast-enhanced chest CT: a single center experience using dual-layer spectral detector CT.

OBJECTIVES: To evaluate the predictive value of virtual monoenergetic images (VMIs) by assessing tumor conspicuity on dual-layer spectral detector CT (SDCT) and correlate tumor conspicuity on VMI with prognostic biomarkers in patients with breast cancer. METHODS: Sixty-four patients underwent arterial phase and 90-s delayed phase dual-layer SDCT. A retrospective tumor conspicuity analysis of 14 benign tumors and 65 breast cancers was performed using conventional images (CIs) and VMI at 40 keV (VMI40) on arterial and delayed phase scans (CIART, VMI40ART, CIDE, VMI40DE). Mean Hounsfield units (HU) of tumors were measured on VMI40ART and VMI40DE. A receiver operating characteristic (ROC) curve analysis was performed to compare diagnostic accuracy between image sets. Estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and Ki67 levels were evaluated using histopathology. Correlations between VMI analyses and histological characteristics of cancers were analyzed. RESULTS: Cancers on VMI40 had a significantly higher conspicuity score and mean HU than benign tumors (p < 0.001). VMI40DE showed the highest conspicuity for cancers (mean, 3.79) and the greatest area under the ROC curve (0.817; 95% confidence interval 0.745-0.889). VMI40DE yielded significantly higher mean HU for cancers than VMI40ART (p < 0.001). The conspicuity score and mean HU on VMI40ART were significantly higher in cancers with ER negativity, PR negativity, and Ki67 positivity (p < 0.05). CONCLUSIONS: VMI40DE may be useful in the diagnosis of breast cancers due to higher tumor conspicuity and better enhancement than VMI40ART. VMI40ART may be beneficial for the prediction of poor breast cancer prognoses. KEY POINTS: • VMI40 improved conspicuity of breast cancer than CI. • VMI40DEyielded higher diagnostic performance of breast cancer than VMI40ART. • VMI40ARThas an additional benefit in terms of prognosis prediction in patients with breast cancers.

Chronic Intradiploic Organizing Hematoma of the Skull Mimicking Calvarial Tumor Diagnosed Using Zero TE MRI: A Case Report and Review of Literature.

Chronic intradiploic organizing hematoma of the skull is a rare lesion that usually presents as a progressively growing mass after head trauma, thus making it difficult to diagnose. To date, only nine cases that have been histopathologically confirmed as organizing hematoma of the skull have been reported in the literature. Herein, we describe a case of a chronic organizing hematoma involving the right parietal bone, presenting as a slowly growing mass in a 54-year-old man. The lesion was also visualized on magnetic resonance imaging (MRI) with a zero echo time sequence. In this case report, we emphasize that chronic intradiploic organizing hematoma should be considered in the differential diagnosis of a palpable scalp mass. We also highlight the importance of meticulous radiological review in the context of appropriate clinical suspicion and the usefulness of the zero TE sequence in evaluating calvarial lesions.

Cervical Lymph Nodes Detected by F-18 FDG PET/CT in Oncology Patients: Added Value of Subsequent Ultrasonography for Determining Nodal Metastasis.

Background and Objectives: To investigate the diagnostic performance of F-18 fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) and subsequent ultrasonography (US) for determining cervical nodal metastasis in oncology patients. Materials and Methods: Fifty-nine cervical lymph nodes (LNs) initially detected by PET/CT with subsequent neck US were included in this retrospective study. All LNs were subjected to US-guided fine-needle aspiration or core needle biopsy. The maximum standardized uptake value (SUVmax) and sonographic features were assessed. Results: Forty-three of 59 cervical LNs detected by PET/CT were malignant. PET/CT alone showed a highest diagnostic value for metastatic LNs with 81.4% sensitivity, 68.8% specificity, and 78% accuracy when SUVmax ≥5.8 was applied as an optimal cut-off value. Combined PET/CT and subsequent US diagnoses for determining nodal metastasis showed the following diagnostic performance: 81.4% sensitivity, 87.5% specificity, and 83.1% accuracy. There was a significant difference in the diagnostic performance between the two diagnostic imaging approaches (p = 0.006). Conclusions: Combined diagnosis using subsequent US showed a significantly higher diagnostic performance for determining nodal metastasis in the neck. Therefore, we believe that our proposed diagnostic strategy using subsequent US can be helpful in evaluating cervical LNs on PET/CT. Moreover, our results clarify the need for US-guided tissue sampling in oncology patients.

Multifocal Kaposiform Hemangioendothelioma Causing Massive Fetal Chylous Ascites.

Kaposiform hemangioendothelioma (KHE) is a locally aggressive vascular tumor that usually occurs in soft tissues of the extremity and rarely in the retroperitoneum. We report a unique case of isolated massive fetal ascites attributed to KHE, involving the retroperitoneum and multiple visceral organs, along with the Kasabach-Merritt phenomenon. We suspect that retroperitoneal KHE might have caused massive fetal ascites because of its high potential to invade the lymphatic vessels aggressively in the retroperitoneal space, which possibly permits intestinal lymph leakage into the peritoneal cavities.

PD-L1 and PD-1 Expression in Early Stage Uterine Endometrioid Carcinoma.

BACKGROUND/AIM: Immune checkpoint inhibitors (ICI) and tumor-infiltrating lymphocytes (TILs) for cancer treatment in clinical oncology have revolutionized patient care. However, no gold standard exists for the criteria of analytical validity of TILs of different types of cancer. MATERIALS AND METHODS: Clinicopathological data from 60 patients with endometrioid carcinoma (EC) who had undergone surgical treatment at the Gyeongsang National University Hospital between January 2002 and December 2009, were investigated. The programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PDL1) expression levels were characterized by immunohistochemical staining patterns, and the interpretations derived from machine learning morphometric analysis (Genie) and the pathologists' assessments were compared. In solid tumors, pathologists assessed the proportion of positive cells in each core of the tissue microarray. For Genie, the proportion of positive cells in the entire core and the number of positive cells per 1 mm2 were used. RESULTS: Both the pathologists and Genie identified the same trend in association with tumor size, with significant differences (p=0.026, p=0.033). Genie expression showed a significant association with PD1 expression, and pathologists identified a significant association with PDL1 expression in immune cells. CONCLUSION: The PD1 expression levels identified in immune cells of EC specimens were similar between the pathologists and Genie, suggesting that there is little resistance to the introduction of morphometric analysis. To our knowledge, this is the first study to introduce and validate machine learning as an integrated method for predicting prognosis and treatment based on PD1 expression in EC tumor microenvironments.

High-Grade Surface Osteosarcoma of the Rib Mimicking a Neurogenic Tumor: Radiologic and Pathologic Findings.

Osteosarcoma commonly occurs in the intramedullary cavity of long bones such as the femur, tibia, and humerus in children and adolescents. Osteosarcoma occurring as a primary tumor in the chest wall is rare. Only a limited number of such cases have been documented in the existing literature. Herein, we present radiologic and pathologic findings of a high-grade surface osteosarcoma of the rib mimicking a neurogenic tumor in a 44-year-old woman.

Kikuchi-Fujimoto Disease in the Axilla after COVID-19 Vaccination: A Case Report.

BACKGROUND: Kikuchi-Fujimoto disease (KFD) is a rare, self-limiting inflammatory condition of unknown etiology that is characterized by fever and painful lymphadenopathy. KFD commonly involves the posterior cervical region and very rarely occurs in the axilla. CASE PRESENTATION: We report on a case of KFD that presented 3 weeks after receiving the messenger ribonucleic acid-based coronavirus disease 2019 (COVID-19) vaccine. In this case, we suspected the lesions as COVID-19 vaccination-related lymphadenopathy on the initial ultrasonographic examination. CONCLUSION: Through this case report, we highlight that KFD should be considered in the differential diagnosis of patients with axillary lymphadenopathy who have undergone COVID-19 vaccination, as unusual side effects of COVID-19 vaccination have been increasingly reported in the literature owing to the rapid development of various COVID-19 vaccines during the pandemic period. In addition, we emphasize the importance of clinical suspicion in diagnosing KFD due to the fact that axillary involvement of KFD is extremely rare.

IgA nephropathy with minimal change disease associated with primary Sjögren's syndrome: A case report.

RATIONALE: Only 1 case of IgA nephropathy (IgAN) with minimal change disease (MCD) associated with primary Sjögren's syndrome (SS) has been reported. We additionally describe IgAN with MCD associated with primary SS. PATIENT CONCERNS: A 80-year-old woman visited our hospital complaining of generalized edema that had started 4 weeks prior. She reported a sense of thirst and dry eye for the last 5 years. DIAGNOSES: Her initial laboratory findings were compatible with nephrotic syndrome; both the antinuclear antibody (1:80) and anti-SS-A (Ro) antibody (200 U/mL) tests were positive. A salivary gland scan revealed markedly decreased uptake for both the parotid and submandibular glands. The Schirmer test was positive. The random urine protein/creatinine ratio was 10 mg/mg. Renal biopsy was compatible with IgAN with superimposed MCD. INTERVENTIONS: Furosemide was intravenously administered with intermittent albumin infusion for her edema control. She was started on prednisone 40mg daily for 6 weeks, which was tapered to 5 mg for another 6 months after starting prednisolone. OUTCOMES: Over the next 6 months, her edema improved and the proteinuria decreased significantly. LESSONS: Physician should suspect IgA with MCD when patient with SS clinically showed nephrotic syndrome, and perform renal biopsy for pathologically diagnosis and appropriate treatment.

Impact of ACE2 and TMPRSS2 Expression in Patients With Preeclampsia.

BACKGROUND/AIM: As maternal morbidity and mortality during pregnancy have increased during the COVID-19 pandemic, studies on pregnancy-related complications from SARS-CoV-2 infection are being actively conducted. Considering that pregnant women with COVID-19 may develop a preeclampsia (PE)-like syndrome, it is necessary to differentiate it from PE because true PE can result in an unfavorable perinatal outcome during a hasty delivery. MATERIALS AND METHODS: We investigated the protein expression of transmembrane serine protease 2 (TMPRSS2) and angiotensin-converting enzyme 2 (ACE2) in placental samples from 42 normotensive (n=9) and PE (n=33) patients without SARS-CoV-2 infection. We isolated placental trophoblast cells from normotensive and PE patients without evidence of SARS-CoV-2 infection to determine the mRNA and protein expression levels of TMPRSS2 and ACE2. RESULTS: High ACE2 cytoplasmic expression in extravillous trophoblasts (EVTs) was correlated with lower fibrin deposition (p=0.017). In comparison with high nuclear TMPRSS2 expression, low nuclearTMPRSS2 expression in endothelial cells (ECs) was positively correlated with PE (p=0.005), significantly higher systolic blood pressure (p=0.006), and higher urine protein-to-creatinine ratio (p=0.022). In contrast, high cytoplasmic TMPRSS2 expression in fibroblasts (FBs) was correlated with higher urine protein-to-creatinine ratio (p=0.018). Trophoblast cells extracted from PE placental tissue showed lower mRNA levels for both ACE2 and TMPRSS2. CONCLUSION: TMPRSS2 nuclear expression in ECs and cytoplasmic expression in FBs of the placenta may be related to a trophoblast-independent PE mechanism, and TMPRSS2 could be a new biomarker to discriminate actual PE from a PE-like syndrome associated with COVID-19.

Perilipin1 Expression as a Prognostic Factor in Patients with Squamous Cell Carcinoma of the Lung.

Perilipin (PLIN) is a major structural protein located on the surface of lipid droplets. PLIN plays an important role in human metabolism and is associated with metabolic diseases, such as obesity, diabetes, hypertension, and endocrine disorders. The dysregulation of lipid metabolism is one of the most prominent metabolic changes observed in cancers. Therefore, the PLIN protein family has recently attracted attention owing to its role in lipid metabolism and cancer. To date, no studies have addressed the association between the prognosis of lung cancer and PLIN1 expression. For the first time, we found that high PLIN1 expression was significantly correlated with worse disease-free survival (DFS) in lung squamous cell carcinoma (SCC). We examined PLIN1 expression by the immunohistochemical analysis of surgical lung SCC specimens obtained from 94 patients. We analyzed the correlation between PLIN1 expression, clinicopathological data, and patient survival, using a chi-squared test, Kaplan-Meier analysis with log-rank tests, and the multivariate Cox proportional hazards regression test. High PLIN1 expression was significantly correlated with lower DFS in the Kaplan-Meier analysis and the multivariate Cox proportional hazards regression model. High PLIN1 expression was significantly correlated with worse prognosis in lung SCC.

Quantitative analysis of exosomes in the aqueous humor of Korean patients with pseudoexfoliation glaucoma.

We aimed to quantitatively analyze the exosome and its cargo in individual aqueous humor (AH) samples from pseudoexfoliation (PEX) glaucoma patients compared to controls using a novel detection platform. We investigated the size distribution and measured the quantitative exosome particle counts in each AH sample. AH (80-120 µL) was obtained during cataract surgery or glaucoma filtering surgery from 12 Korean subjects (six with PEX glaucoma and six age-matched controls). The mean size of the exosomes was 58.9 ± 18.5 nm measured by a tangential flow filtration system using single-particle interferometric reflectance imaging sensor. Exosome particle count in each CD 63, CD 81, and CD9 spot was significantly greater in PEX glaucoma than in controls in total, CD 63, CD9, syntenin, and scattering(all p < 0.003). The CD63 spot showed a particle count of 8319.1 ± 797.7 in PEX glaucoma patients and 4786.8 ± 1302.1 in controls (p = 1.88E-11). Individual fluorescent capture spot images also revealed denser exosome particles in PEX patients than in controls. Syntenin, indicating exosomal origin, was detected in all AH samples. Exosomes differentially detected in AH suggest the possible role of exosomes in the pathogenesis of PEX glaucoma.

Cavernous Hemangioma of the Maxillary Sinus Masquerading Recurrent Hemorrhagic Mass: Histological-Radiological Correlation and a Literature Review.

BACKGROUND: Sinonasal cavernous hemangioma is rare. To date, fewer than 20 cases have been reported in the literature; however, they may be a source of recurrent epistaxis and masquerade of a hemorrhagic mass on CT and MRI. CASE REPORT: A 68-year-old woman was presented with recurrent epistaxis and progressive right malar fullness. On rhinoscopy, a bulge lesion was observed with multifocal hemorrhagic and friable surfaces in the right nasal cavity. CT and MRI demonstrated a well-defined mass in the right maxillary sinus with inhomogenous T2 hyperintensity, hypointense septa, peripheral rim, and multiple papillary enhancement, suggesting a recurrent hemorrhagic mass. The mass was excised endoscopically, and the histologic diagnosis was cavernous hemangioma. CONCLUSION: Imaging studies, such as CT and MRI, are essential in making an accurate diagnosis of cavernous hemangioma of the maxillary sinus. Endoscopic excision of the lesion can be curative.

Classification of subtypes including LCNEC in lung cancer biopsy slides using convolutional neural network from scratch.

Identifying the lung carcinoma subtype in small biopsy specimens is an important part of determining a suitable treatment plan but is often challenging without the help of special and/or immunohistochemical stains. Pathology image analysis that tackles this issue would be helpful for diagnoses and subtyping of lung carcinoma. In this study, we developed AI models to classify multinomial patterns of lung carcinoma; ADC, LCNEC, SCC, SCLC, and non-neoplastic lung tissue based on convolutional neural networks (CNN or ConvNet). Four CNNs that were pre-trained using transfer learning and one CNN built from scratch were used to classify patch images from pathology whole-slide images (WSIs). We first evaluated the diagnostic performance of each model in the test sets. The Xception model and the CNN built from scratch both achieved the highest performance with a macro average AUC of 0.90. The CNN built from scratch model obtained a macro average AUC of 0.97 on the dataset of four classes excluding LCNEC, and 0.95 on the dataset of three subtypes of lung carcinomas; NSCLC, SCLC, and non-tumor, respectively. Of particular note is that the relatively simple CNN built from scratch may be an approach for pathological image analysis.