Subcutaneous Myoepithelioma in the Extremity: A Potential Pitfall in the Differential Diagnosis of Subcutaneous Tumors.

We present a rare case of myoepithelioma in the subcutaneous layer of the shoulder with ultrasonography (US) and magnetic resonance imaging (MRI). US showed a lobulated hyperechoic mass, leading to an impression of lipoma. MRI showed the mass with low signal intensity on T1-weighted images (T1WI), high signal intensity on fat-suppressed T2-weighted images (T2WI), intermediate signal intensity on T2WI, and intense enhancement with adjacent fascial thickening. Imaging findings of soft tissue myoepithelioma have not been established. We report its US and MRI features mimicking features from a lipomatous tumor to infiltrative malignancy. Although soft tissue myoepithelioma has nonspecific image findings to confirm its diagnosis, some findings may help to make the differential diagnosis. Preoperative pathologic confirmation is recommended in a soft tissue neoplasm.

Loss of DUSP4 Expression as a Prognostic Biomarker in Clear Cell Renal Cell Carcinoma.

Dual-specificity protein phosphatase 4 (DUSP4) is a negative regulator of mitogen-activated protein kinases. The prognostic impact of DUSP4 expression in renal cell carcinoma is not well studied. Therefore, we evaluated the clinicopathological implications of DUSP4 expression in clear cell renal cell carcinoma by performing immunohistochemistry (IHC). The clinical outcome according to DUSP4 expression was evaluated through survival analyses, and the association between mRNA expression and prognosis was confirmed by online analysis (Kaplan-Meier plotter). Loss of DUSP4 expression was noted in most histological subtypes of renal cell carcinoma. Loss of DUSP4 expression in clear cell renal cell carcinoma was significantly correlated with old age (p = 0.033), high histologic grade (p < 0.001), tumor necrosis (p < 0.001), and high pT category (p < 0.001). In survival analysis, loss of DUSP4 expression was associated with poor clinical outcomes in cancer-specific survival and recurrence-free survival (p = 0.010 and p = 0.007, respectively). Upon TCGA data analysis, patients with low DUSP4 mRNA expression showed a shorter overall survival (p = 0.023). These results suggest that loss of DUSP4 expression can be used as a potential biomarker for predicting clinical outcomes in clear cell renal cell carcinoma patients.

Clinicopathological Significance of MTUS1 Expression in Patients With Renal Cell Carcinoma.

BACKGROUND/AIM: Microtubule-associated tumor suppressor 1 (MTUS1) is a novel tumor suppressor involved in proliferation and migration, and down-regulation of MTUS1 is associated with the poor prognosis of several cancers. We evaluated the clinicopathological significance of MTUS1 expression in renal cell carcinoma (RCC). PATIENTS AND METHODS: We assessed MTUS1 expression by immunohistochemical staining of tissue microarrays from 249 cases of RCC. We analyzed the correlation of MTUS1 expression and clinicopathological characteristics. Additionally, we used public databases and performed bioinformatics analysis. RESULTS: We investigated The Cancer Genome Atlas databases and identified that MTUS1 mRNA expression was significantly lower in RCC tissues than in normal tissues. Loss of MTUS1 expression was correlated with high WHO/ISUP nuclear grade, lymphovascular invasion, renal vein thrombus, and high pT stage in patients with RCC. Although there was no statistically significant correlation between MTUS1 expression and patients' prognosis in our cohort, MTUS1 overexpression was significantly correlated with a favorable prognosis in public data. CONCLUSION: Loss of MTUS1 expression in RCC might be a potential biomarker for predicting clinical outcome.

Diverse phenotypes and endotypes of fungus balls caused by mixed bacterial colonization in chronic rhinosinusitis.

BACKGROUND: The pathogenic roles of fungus and bacteria in chronic rhinosinusitis (CRS) remain unclear. Recently, we described the bacterial ball, which is distinct from the fungus ball, as an unusual phenotype of bacterial infection. In this study, we investigated the clinical, histopathologic, and immunologic characteristics of sinonasal microorganic materials, including fungus ball and bacterial ball. METHODS: In this study, we enrolled 80 CRS patients with sinonasal microorganic materials and 10 control subjects who underwent skull base surgery or endoscopic dacryocystorhinostomy and had no signs or symptoms of nasal inflammation. All specimens were stained with hematoxylin-eosin, Gomori-methenamine-silver, and Gram stain to identify fungal organisms and Gram-positive/negative bacterial colonies. The expression of tumor necrosis factor (TNF)-α; interleukin (IL)-1ß; S100A7; S100A8/A9; and short, palate, lung, and nasal epithelial clone 1 (SPLUNC1) were evaluated by enzyme-linked immunosorbent assay using sinus lavage fluid. RESULTS: We histologically classified sinonasal microorganic materials into the following 4 groups: fungus ball (n = 45); bacterial ball (n = 6); mixed ball (formed by a mixture of fungus and bacteria, n = 27); and double ball (formed by separate fungal and bacterial balls, n = 2). Compared with the fungus ball, the mixed ball was more frequently detected in immunocompromised patients (p < 0.0001). In addition, TNF-α expression was significantly higher in fungus and mixed balls than in control, whereas the mixed ball showed higher expression of IL-1ß compared with the fungus ball. Moreover, the expression of S100A7 and S100A8/A9 protein in the mixed ball was significantly decreased when compared with the fungus ball, whereas there was no significant difference in SPLUNC1 expression between fungus and mixed balls. CONCLUSION: Our findings suggest that fungal and bacterial interactions are diverse in CRS. Specifically, the mixed ball is prevalent in CRS with an immunocompromised state and it may decrease epithelial barrier function.

Loss of Nuclear BAP1 Expression Is Associated with High WHO/ISUP Grade in Clear Cell Renal Cell Carcinoma.

BACKGROUND: BRCA1-associated protein 1 (BAP1) mutations are frequently reported in clear cell renal cell carcinoma (ccRCC); however, very few studies have evaluated the role of these mutations in other renal cell carcinoma (RCC) subtypes. Therefore, we analyzed BAP1 protein expression using immunohistochemistry in several RCC subtypes and assessed its relationship with clinicopathological characteristics of patients. METHODS: BAP1 expression was immunohistochemically evaluated in tissue microarray blocks constructed from 371 samples of RCC collected from two medical institutions. BAP1 expression was evaluated based on the extent of nuclear staining in tumor cells, and no expression or expression in < 10% of tumor cells was defined as negative. RESULTS: Loss of BAP1 expression was observed in ccRCC (56/300, 18.7%), chromophobe RCC (6/26, 23.1%), and clear cell papillary RCC (1/4, 25%), while we failed to detect BAP1 expression loss in papillary RCC, acquired cystic disease-associated RCC, or collecting duct carcinoma. In ccRCC, loss of BAP1 expression was significantly associated with high World Health Organization (WHO)/International Society of Urological Pathology (ISUP) grade (p = .002); however, no significant correlation was observed between loss of BAP1 expression and survival in ccRCC. Loss of BAP1 expression showed no association with prognostic factors in chromophobe RCC. CONCLUSIONS: Loss of BAP1 nuclear expression was observed in both ccRCC and chromophobe RCC. In addition, BAP1 expression loss was associated with poor prognostic factors such as high WHO/ISUP grade in ccRCC.

High TNFRSF12A level associated with MMP-9 overexpression is linked to poor prognosis in breast cancer: Gene set enrichment analysis and validation in large-scale cohorts.

BACKGROUND: Matrix metalloproteinase-9 (MMP-9) is associated with remodelling of the extracellular matrix and invasion in various cancers. Identifying proteins connected to high MMP-9 expression is important in explaining its mechanisms. Our study aims to shed light on genes associated with high MMP-9 expression and to discuss their clinical impact in breast cancer. METHODS: We evaluated 173 breast cancer cases from the Kangbuk Samsung Hospital, with 1964 cases from the Molecular Taxonomy of Breast Cancer International Consortium database serving as a validation cohort. We investigated relationships between MMP-9 expression and clinicopathological characteristics. We then used gene set enrichment analyses to detect the association of genes with MMP-9 overexpression, and performed survival analyses to determine the significance of the gene in three independent cohorts. RESULTS: High MMP-9 expression correlated with poor prognosis in univariate and multivariate analyses. Using gene set enrichment analysis, we found that tumour necrosis factor receptor superfamily member 12A (TNFRSF12A) was linked to high MMP-9 expression. In the survival analysis of three published data sets (METABRIC, GSE1456, GSE20685), high TNFRSF12A was relevant to a poor survival rate. CONCLUSIONS: High levels of TNFRSF12A associated with MMP-9 overexpression may be important to explain the progression of breast cancer, and survival could be improved using therapy targeting TNFRSF12A.

Loss of Wnt7a expression correlates with tumor progression and poor prognosis in colorectal carcinoma.

Wnt7a is a known tumor suppressor gene in non-small cell lung cancer that regulates normal cellular proliferation and differentiation. The purpose of this study was to investigate the clinicopathologic significance of Wnt7a expression in colorectal adenocarcinoma. Wnt7a expression was immunohistochemically examined in 46 normal colorectal tissues, 47 tubular adenomas, 393 adenocarcinomas, and 93 lymph node metastases. Wnt7a was expressed in the cytoplasm. Loss of Wnt7a expression was more frequent in adenocarcinoma and lymph node metastasis compared to that in normal and tubular adenoma (P < 0.001). Wnt7a expression was inversely correlated with tumor size (P = 0.026), gross type (P = 0.008), differentiation (P = 0.009), vascular invasion (P = 0.038), tumor deposit (P = 0.007), tumor invasion (T category) (P = 0.003), lymph node metastasis (N category) (P < 0.001), and AJCC stage (P < 0.001). There was a significant correlation between loss of Wnt7a expression and overall survival and disease-free survival (P < 0.001 and P = 0.001, respectively) on univariable analysis. On multivariable analysis, loss of Wnt7a expression was an independent prognostic factor for both overall and disease-free survival (P = 0.002 and P = 0.047, respectively). Loss of Wnt7a expression may contribute to the carcinogenesis and tumor progression of colorectal adenocarcinoma and may be a new prognostic marker of colorectal adenocarcinoma.

Bacterial Ball as an Unusual Finding in Patients With Chronic Rhinosinusitis.

OBJECTIVES: Pathophysiology of chronic rhinosinusitis (CRS) is very complex and has not yet been clearly understood. To date, various factors have been researched to have relations with the pathogenesis of CRS, such as superantigens and biofilms. Recently, we found an unusual pathological finding in patients with CRS, and we called this new entity as bacteria ball (or bioball). In this study, we analyze the clinical characteristics of bacteria ball occurred in CRS. METHODS: This study enrolled consecutive 247 patients with CRS who underwent functional endoscopic sinus surgery from January 2015 to August 2016. The diagnosis of bacterial ball was made when negative in Gomori-methenamine-silver stain and positive in Gram stain. Histologically, bacterial ball was defined as acellular mucous materials with bacterial colonies and inflammatory cell infiltrates. We compared clinical data and computed tomography (CT) findings between fungal and bacterial balls. RESULTS: Six cases (2.4%) of CRS were confirmed histologically as bacterial ball. Most of them were found in the maxillary sinus of CRS without nasal polyposis (66.7%). Bacterial ball was green or brown colored materials similar to fungal ball which was harder and tightly adherent to the antral mucosa. Compared to fungal ball, patients with bacterial ball showed significantly less peripheral eosinophils (P=0.011) and calcification in CT scans (P=0.003). CONCLUSION: Bacterial ball is unusual findings occurred in patient with CRS which is different from fungal ball and biofilm. For diagnosis of bacterial ball, Gram stain is essentially required to identify bacterial colonies. Bacterial ball might appear to be evidence of a new strategy for living in the paranasal sinuses.

The Smad4/PTEN Expression Pattern Predicts Clinical Outcomes in Colorectal Adenocarcinoma.

BACKGROUND: Smad4 and PTEN are prognostic indicators for various tumor types. Smad4 regulates tumor suppression, whereas PTEN inhibits cell proliferation. We analyzed and compared the performance of Smad4 and PTEN for predicting the prognosis of patients with colorectal adenocarcinoma. METHODS: Combined expression patterns based on Smad4+/- and PTEN+/- status were evaluated by immunostaining using a tissue microarray of colorectal adenocarcinoma. The relationships between the protein expression and clinicopathological variables were analyzed. RESULTS: Smad4-/PTEN- status was most frequently observed in metastatic adenocarcinoma, followed by primary adenocarcinoma and tubular adenoma (p<.001). When Smad4-/PTEN- and Smad4+/PTEN+ groups were compared, Smad4-/PTEN- status was associated with high N stage (p=.018) and defective mismatch repair proteins (p=.006). Significant differences in diseasefree survival and overall survival were observed among the three groups (Smad4+/PTEN+, Smad4-/PTEN+ or Smad4+/PTEN-, and Smad4-/PTEN-) (all p<.05). CONCLUSIONS: Concurrent loss of Smad4 and PTEN may lead to more aggressive disease and poor prognosis in patients with colorectal adenocarcinoma compared to the loss of Smad4 or PTEN alone.

Wnt7a Deficiency Could Predict Worse Disease-Free and Overall Survival in Estrogen Receptor-Positive Breast Cancer.

PURPOSE: Wnt7a is a glycoprotein involved in embryonic development and the progression of different types of malignant tumors. This study aimed to detect the level of Wnt7a expression in breast cancer and explore its role in the disease progression and prognosis. METHODS: A total of 258 patients diagnosed with invasive ductal carcinoma of the breast were included in this study. Using tissue microarray and immunohistochemical staining, we evaluated the association between Wnt7a expression and clinicopathological parameters, and the prognostic value of Wnt7a. RESULTS: Wnt7a expression was significantly correlated with estrogen receptor (ER) expression (odds ratio, 3.95; 95% confidence interval [CI], 1.99-7.80; p<0.001). On univariate and multivariate analyses, loss of Wnt7a expression was associated with poor disease-free survival (DFS) (multivariate hazard ratio [HR], 9.12; 95% CI, 1.80-46.09; p=0.008), but not with poor overall survival (OS). In the ER-positive group (n=114), loss of Wnt7a expression was an independent prognostic factor for shorter DFS (multivariate HR, 13.54; 95% CI, 1.11-165.73; p=0.042) and OS (multivariate HR, 4.76; 95% CI, 1.29-17.61; p=0.019) on univariate and multivariate analyses. However, in the ER-negative group, there was no significant difference in DFS and OS according to Wnt7a expression. CONCLUSION: The loss of Wnt7a expression might be a meaningful factor in assessing DFS and OS, especially in ER-positive breast cancer.

Persistent elevation of postoperative neutrophil-to-lymphocyte ratio: A better predictor of survival in gastric cancer than elevated preoperative neutrophil-to-lymphocyte ratio.

Postoperative neutrophil-to-lymphocyte ratio change (NLRc) reflects the dynamic change of balance between host inflammatory response and immune response after treatment. In gastric cancer, an elevated initial NLR (iNLR) is reported to be a prognostic predictor, but the clinical application of the NLRc remains unclear. The NLRc was assessed in 734 patients undergoing total/subtotal gastrectomy and endoscopic submucosal dissection for gastric adenocarcinoma. The iNLR and NLRc were recorded within 10 days of the first diagnosis and 3-6 months after surgery, respectively. Using receiver operating characteristic (ROC) curves, we investigated the relationship between NLRc or iNLR and patient survival. The analysis revealed a higher predictive power for correlating patient survival with the NLRc compared with iNLR. NLRc was defined as negative (lower than iNLR) and positive (higher than iNLR). A positive NLRc was frequently observed in patients with advanced AJCC stage, local recurrence, distant metastasis, perineural invasion, and adjuvant chemotherapy (all p < 0.05). Univariate and multivariate analyses revealed a significant relationship between patient survival and NLRc (all p < 0.05) but no association between survival and iNLR. The NLRc could be a better indicator than iNLR for predicting survival in patients with gastric cancer.

Clinicopathologic Correlations of E-cadherin and Prrx-1 Expression Loss in Hepatocellular Carcinoma.

BACKGROUND: Developing predictive markers for hepatocellular carcinoma (HCC) is important, because many patients experience recurrence and metastasis. Epithelial to mesenchymal transition (EMT) is a developmental process that plays an important role during embryogenesis and also during cancer metastasis. Paired-related homeobox protein 1 (Prrx-1) is an EMT inducer that has recently been introduced, and its prognostic significance in HCC is largely unknown. METHODS: Tissue microarray was constructed using surgically resected primary HCCs from 244 cases. Immunohistochemical staining of E-cadherin and Prrx-1 was performed. The correlation between E-cadherin loss and Prrx-1 expression, as well as other clinicopathologic factors, was evaluated. RESULTS: E-cadherin expression was decreased in 96 cases (39.4%). Loss of E-cadherin correlated with a higher recurrence rate (p < .001) but was not correlated with patient's survival. Thirty-two cases (13.3%) showed at least focal nuclear Prrx-1 immunoreactivity while all non-neoplastic livers (n = 22) were negative. Prrx-1 expression was not associated with E-cadherin loss, survival or recurrence rates, pathologic factors, or the Ki-67 labeling index. Twenty tumors that were positive for E-cadherin and Prrx-1 had significantly higher nuclear grades than the rest of the cohort (p = .037). In Cox proportional hazard models, E-cadherin loss and large vessel invasion were independent prognostic factors for shorter disease-free survival. Cirrhosis and high Ki-67 index (> 40%) were independent prognostic factors for shorter overall survival. CONCLUSIONS: Prrx-1 was expressed in small portions of HCCs but not in normal livers. Additional studies with a large number of Prrx-1-positive cases are required to confirm the results of this study.

Clinicopathologic Significance of Extranodal Tumor Extension in Colorectal Adenocarcinoma with Regional Lymph Node Metastasis.

Background. This study investigated the clinicopathologic significance of extranodal tumor extension in colorectal adenocarcinoma with lymph node metastasis. Method. Included were 419 patients who underwent curative resection for primary colorectal adenocarcinoma. Results. Extranodal tumor extension was observed more frequently in tumors with ulceroinfiltrative gross type (p = 0.026), higher histologic grade (p = 0.012), high grade tumor budding (p = 0.003), vascular invasion (p < 0.001), perineural invasion (p = 0.015), tumor deposit (p < 0.001), high ratio of metastatic/total lymph nodes (p < 0.001), and high pN stage (p < 0.001). Overall survival was significantly different between an extranodal tumor extension (-) group and an extranodal tumor extension (+) group for both N1 (p = 0.022) and N2 homogeneous staging (p = 0.007). Both overall (p = 0.002) and disease-free survival (p = 0.001) were significantly different between the two groups in an N1a homogeneous group and overall survival was significantly different (p = 0.016) in an N2b homogeneous group. Conclusion. Our study demonstrated that extranodal tumor extension was a useful prognostic factor for colorectal adenocarcinoma with lymph node metastasis, especially in homogeneous pN staging groups.