Search

Mazabraud syndrome (MS) is a rare and sporadic disorder. It is mainly characterized by fibrous dysplasia (FD) of single or multiple bones and intramuscular myxomas (IM). Data on the prevalence since it was first reported, clinical features, and prognosis are extremely scarce. We report a case of a 59-year-old woman with IM and polyostotic FD. She also had multiple cafe’-au-lait spots suggestive of McCune-Albright syndrome (MAS). On magnetic resonance imaging, there are masses with well-defined heterogeneous enhancement, accompanied by an inner cyst in the vastus lateralis muscle and femur. These radiological results are identical to those of FD. After surgical intervention with excision of intramuscular soft-tissue mass, a diagnosis of IM of MS was confirmed. Given that cafe’-au-lait spots also appeared, the patient was diagnosed with a variant of MS with some of the clinical characteristics of MAS.

BACKGROUND Thread rhinoplasty can trigger a reaction to thread material, which is a foreign body. We compared clinical features induced by absorbable and non-absorbable threads following thread rhinoplasty. CASE SUMMARY Two patients who underwent different thread materials showed different clinical courses and different Hounsfield unit (HU) values in computed tomography. Patients with absorbable thread showed high HU values similar to a metallic material, and the HU value of inflammation was similar to vascular tissues with a lot of water (250). In the intraoperative field, absorbable thread materials and micro-abscesses were observed. In contrast, in the case of a non-absorbable thread, an object presumed to be thread was seen on the computed tomography (CT), and the HU value of inflammatory tissues was less than 100. In both patients, post-operative HU decreased to less than 100 and the clinical course improved. In both cases, histopathologic findings revealed foreign body granuloma associated with inflammation. CONCLUSION Absorbable threads were more aggressive and are more easily detected on CT.

The relationship between 2-deoxy-2-[18F]fluoro-D-glucose (FDG) positron emission tomography/computed tomography (PET/CT) textural features and histopathological findings in gastric cancer has not been fully evaluated. We investigated the relationship between the textural features of primary tumors on FDG PET/CT with histopathological findings and recurrence-free survival (RFS) in patients with advanced gastric cancer (AGC). Fifty-six patients with AGC who underwent FDG PET/CT for staging work-ups were retrospectively enrolled. Conventional parameters and the first- and second-order textural features of AGC were extracted using PET textural analysis. Upon histopathological analysis, along with histopathological classification and staging, the degree of CD4, CD8, and CD163 cell infiltrations and expressions of interleukin-6 and matrix-metalloproteinase-11 (MMP-11) in the primary tumor were assessed. The histopathological classification, Lauren classification, lymph node metastasis, CD8 T lymphocyte and CD163 macrophage infiltrations, and MMP-11 expression were significantly associated with the textural features of AGC. The multivariate survival analysis showed that increased FDG uptake and intra-tumoral metabolic heterogeneity were significantly associated with an increased risk of recurrence after curative surgery. Textural features of AGC on FDG PET/CT showed significant correlations with the inflammatory response in the tumor microenvironment and histopathological features of AGC, and they showed significant prognostic values for predicting RFS.

Background/purpose The aim of the present study was to investigate the relationship between hepatobiliary scintigraphy findings and histopathological results in patients with recurrent biliary colic. Methods We retrospectively enrolled 107 patients who underwent hepatobiliary scintigraphy for recurrent biliary colic and subsequent cholecystectomy. According to the hepatobiliary scintigraphy findings, patients were categorized into a nonvisualization of gallbladder activity (nonvisualized GB) group, low gallbladder ejection fraction (GBEF) group, and normal GBEF group. Differences in histopathologic factors between the three groups were evaluated and multivariate logistic regression analyses were performed to identify histopathological predictors for hepatobiliary scintigraphy findings. Results The nonvisualized group had a higher frequency of patients with empyema and severe infiltration by neutrophils, lymphoplasma cells, and eosinophils. The low GBEF group had a higher muscle-to-total wall thickness ratio and muscle-to-fibrosis thickness ratio of the gallbladder wall than those in the normal GBEF group. On multivariate logistic regression analyses, severe degrees of lymphoplasma cell infiltration and eosinophil infiltration were independent predictors for nonvisualization of gallbladder activity, and a higher muscle-to-fibrosis thickness ratio was an independent predictor for low GBEF. Conclusions In patients with recurrent biliary colic, nonvisualization of gallbladder activity on hepatobiliary scintigraphy was related to the degree of inflammation in the gallbladder, while low GBEF was related to muscular hypertrophy of the gallbladder.

Objective Diet-induced obesity is often associated with nonalcoholic fatty liver disease (NAFLD), which instigates severe metabolic disorders, including cirrhosis, hepatocellular carcinoma, and type 2 diabetes. We have shown that hepatic depletion of CREB regulated transcription co-activator (CRTC) 2 protects mice from the progression of diet-induced fatty liver phenotype, although the exact mechanism by which CRTC2 modulates this process is elusive to date. Here, we investigated the role of hepatic CRTC2 in the instigation of NAFLD in mammals. Methods Crtc2 liver-specific knockout (Crtc2 LKO) mice and Crtc2 flox/flox (Crtc2 f/f) mice were fed a high fat diet (HFD) for 7–8 weeks. Body weight, liver weight, hepatic lipid contents, and plasma triacylglycerol (TG) levels were determined. Western blot analysis was performed to determine Sirtuin (SIRT) 1, tuberous sclerosis complex (TSC) 2, and mammalian target of rapamycin complex (mTORC) 1 activity in the liver. Effects of Crtc2 depletion on lipogenesis was determined by measuring lipogenic gene expression (western blot analysis and qRT-PCR) in the liver as well as Oil red O staining in hepatocytes. Effects of miR-34a on mTORC1 activity and hepatic lipid accumulation was assessed by AAV-miR-34a virus in mice and Ad-miR-34a virus and Ad-anti-miR-34a virus in hepatocytes. Autophagic flux was assessed by western blot analysis after leupeptin injection in mice and bafilomycin treatment in hepatocytes. Lipophagy was assessed by transmission electron microscopy and confocal microscopy. Expression of CRTC2 and p-S6K1 in livers of human NAFLD patients was assessed by immunohistochemistry. Results We found that expression of CRTC2 in the liver is highly induced upon HFD-feeding in mice. Hepatic depletion of Crtc2 ameliorated HFD-induced fatty liver disease phenotypes, with a pronounced inhibition of the mTORC1 pathway in the liver. Mechanistically, we found that expression of TSC2, a potent mTORC1 inhibitor, was enhanced in Crtc2 LKO mice due to the decreased expression of miR-34a and the subsequent increase in SIRT1-mediated deacetylation processes. We showed that ectopic expression of miR-34a led to the induction of mTORC1 pathway, leading to the hepatic lipid accumulation in part by limiting lipophagy and enhanced lipogenesis. Finally, we found a strong association of CRTC2, miR-34a and mTORC1 activity in the NAFLD patients in humans, demonstrating a conservation of signaling pathways among species. Conclusions These data collectively suggest that diet-induced activation of CRTC2 instigates the progression of NAFLD by activating miR-34a-mediated lipid accumulation in the liver via the simultaneous induction of lipogenesis and inhibition of lipid catabolism. Therapeutic approach to specifically inhibit CRTC2 activity in the liver could be beneficial in combating NAFLD in the future., Graphical abstract Image 1, Highlights • CRTC2 expression is elevated in livers of HFD-fed mice. • Liver-specific depletion of Crtc2 ameliorated HFD-induced fatty liver phenotype in mice. • Crtc2 knockout dampened miR-34a-mTORC1 pathway, leading to the inhibition of lipogenesis and the activation of lipophagy. • Close association of CRTC2 with mTORC1 activity was also demonstrated in the human NAFLD patients. • Diet-induced activation of CRTC2 instigates the progression of NAFLD by activating the miR-34a-mTORC1 pathway.

Artificial intelligence has enabled the automated diagnosis of several cancer types. We aimed to develop and validate deep learning models that automatically classify cervical intraepithelial neoplasia (CIN) based on histological images. Microscopic images of CIN3, CIN2, CIN1, and non-neoplasm were obtained. The performances of two pre-trained convolutional neural network (CNN) models adopting DenseNet-161 and EfficientNet-B7 architectures were evaluated and compared with those of pathologists. The dataset comprised 1,106 images from 588 patients; images of 10% of patients were included in the test dataset. The mean accuracies for the 4-class classification were 88.5% (95% confidence interval [CI], 86.3–90.6%) by DenseNet-161 and 89.5% (95% CI, 83.3–95.7%) by EfficientNet-B7, which were similar to human performance (93.2% and 89.7%). The mean per-class area under the receiver operating characteristic curve values by EfficientNet-B7 were 0.996, 0.990, and 0.971 in the non-neoplasm, CIN3, CIN1 groups, respectively. The class activation map detected the diagnostic area for CIN lesions. In the 3-class classification of CIN2 and CIN3 as one group, the mean accuracies of DenseNet-161 and EfficientNet-B7 increased to 91.4% (95% CI, 88.8–94.0%) and 92.6% (95% CI, 90.4–94.9%), respectively. CNN-based deep learning is a promising tool for diagnosing CIN lesions on digital histological images.

Intramuscular hemangioma (IH) is rare, accounting for only 0.8% of all hemangioma cases. In particular, IH of the foot has only been reported a few times. In such cases, the symptoms typically include tenderness and swelling, often in relation to physical activity, but tingling or impaired function may also be present. Here, we report a patient who presented with a significant IH in the plantar area treated surgically. A 25-year-old female visited our hospital with pain in the plantar aspect of the right foot. She had noticed a mass about 10 years prior. She had previously experienced pain only when pressing the mass, but the pain subsequently became more regular pain and was exacerbated by exercise. In fact, the pain became so intense that she could not sleep well. Upon physical examination, mild swelling and tenderness of the plantar area were noted in the second to the fourth metatarsal. Sensation and motor reflexes were normal and the results of Tinel’s test were negative. Plain radiographs of the right foot revealed phleboliths scattered throughout the first to third intermetatarsal spaces. Magnetic resonance imaging revealed a space-occupying multilobulated mass (5.6 × 2.8 × 2.5 cm) located in the flexor digitorum brevis (FDB) muscle, which penetrated the plantar fascia and spread to the subcutaneous layer. In T2-weighted images, the lesion displayed a hyperintense signal compared to the surrounding skeletal muscle. Based on radiological findings, we suspected IH. The mass surrounded by the FDB muscle was exposed and completely removed via wide excision. IH consisting of cavernous-like vascular structures was diagnosed on pathology. At 1-year follow-up, the patient was almost asymptomatic and had recovered almost full range of motion in the plantar area. Histological analysis and surgery are recommended to remove intramuscular hemangiomas in the plantar area, but if the patient is not suitable for surgery, sclerotherapy or combination treatment should also be considered.

Adenine-thymine-rich inactive domain-containing protein 1A (ARID1A) is a large subunit of the switch-sucrose nonfermenting (SWI-SNF) complex. ARID1A is considered to be a tumor suppressor in various cancers. We investigated the clinicopathological significance including prognosis of ARID1A expression in non-small cell lung cancer (NSCLC). ARID1A expression was studied by tissue microarray immunohistochemical analysis of 171 surgically resected NSCLC specimens including adenocarcinoma (ADC) and squamous cell carcinoma (SCC) on tissue microarray. Semiquantitative immunohistochemical score was obtained by multiplying the intensity and percentage scores. The overall score was further simplified by dichotomizing into either negative (score < 4) or positive (score ≥ 4) for each patient. The ARID1A-negative group revealed significantly higher correlations with male sex (p = 0.020), larger tumor size (p = 0.007), SCC than with ADC (p = 0.023) and smoking (p = 0.001). Univariate survival analysis showed that the ARID1A-negative group had a significantly shorter cancer specific survival than the ARID1A-positive group (p = 0.018). Multivariate survival analysis showed that ARID1A negativity (p = 0.022) were independent prognostic factors related with shorter cancer specific survival for NSCLC. In conclusion, Loss of ARID1A expression is a potential molecular marker to predictive of poor prognosis of NSCLC.

The immunohistochemical analysis of PD-L1 expression is still important in cancer immunotherapy. PD-L1 expression is affected by various tumor microenvironmental factors including tumor infiltrating lymphocytes (TILs) and DNA methylation biomarkers. Given the complex communication between tumor cells and immune cells, we analyzed the expression of PD-L1 and TET1 with TILs in human NSCLC and the correlation with various clinicopathological characteristics and patient prognosis. A total of 96 cases of NSCLC were enrolled in this study. Using tissue microarray, we performed immunohistochemical staining to analyze PD-L1 and TET1 expression. Image-Pro Plus was used as an automated imaging analysis software program to analyze the density of CD3+, CD4+ and CD8 + TILs. PD-L1 expression was positively correlated with the density of CD3+, CD4+ and CD8 + TILs (p = 0.038, p = 0.020, and p = 0.009, respectively); however, no significant relationship existed between TET1 expression and any TILs. The survival analysis revealed that a high PD-L1 expression was associated with favorable prognosis for OS (p = 0.049) and DFS (p = 0.029) in advanced-stage II-IV patients, but not in early stage I. Density of CD8+ TILs was an independent and favorable prognostic factor for DFS (p = 0.008) and OS (p = 0.002) in early-stage I patients. However, high TET-1 expression was associated with poor prognosis for OS (p = 0.029) in total NSCLC patients. These findings suggest the correlation and favorable prognostic impact of PD-L1 and TILs in NSCLC. In addition, DNA demethylase TET1 has oncogenic effects, showing association with poor prognosis.

The Oxford classification was developed to predict the outcome of IgA nephropathy (IgAN). Based on the upper reference limit (95th percentile) for the number of globally sclerotic glomeruli (GSG) expected on biopsy according to age, we evaluated whether the prognosis of IgAN was affected by the age-calibrated numbers of GSG independent of the Oxford classification. Patients diagnosed with IgAN on renal biopsy in a single center from January 2011 to December 2018 were analyzed retrospectively. Patients with more GSG number than the upper reference limit expected on biopsy according to age were categorized in a group of GSG abnormal for age. We analyzed in two ways, calculating the median rate of decline in estimated glomerular filtration rate (eGFR) and time-to-event defined as a decline of eGFR level to 40% lower than the baseline. There were 111 patients in the group of GSG abnormal for age. In this group, the rate of eGFR decline was faster by 1.85 (3.68–0.03) ml/min/1.73 m2 per year in the fully-adjusted robust regression model. The adjusted hazard ratio for eGFR decline for renal outcome was 29.10 (2.18–388.49). The cumulative incidence of CKD progression was significantly higher, especially for those with T score of 0 in the Oxford classification. We suggest that GSG abnormal for age is an independent risk factor in predicting the renal outcome of IgAN.

Background : : Proteinuria is a significant risk factor for progression of IgA nephropathy (IgAN) and has a positive correlation with severity of foot process effacement (FPE). We evaluated the relationship of FPE with proteinuria and histologic characteristics, including the Oxford classification. Methods : : Patients who underwent renal biopsy and were diagnosed with IgAN at a single center were retrospectively reviewed. Patients aged less than 18 years and those with the possibility of secondary causes were excluded from the study. Subsequently, we evaluated the association between degree of proteinuria, severity of FPE, and histologic characteristics, including the Oxford classification and other immunofluorescence stains. Results : : A total of 805 cases of renal biopsy was performed at our institution, and 327 patients were diagnosed with IgAN. Among them, 82 patients were excluded. Severity of FPE had an impact on the degree of proteinuria. Notably, the group with diffuse FPE had more than about 1.3 g/day of urine protein compared to those with rare FPE. Among the histologic characteristics, M1 score and immune deposition of IgG affected severity of FPE (hazard ratios [95% confidence interval], 1.90 [1.10 to 3.26], and 3.77 [1.66 to 8.54], respectively). Conclusion : : Severity of FPE had an impact on the degree of proteinuria and may be associated with the pathogenesis of IgAN.

Large tumor suppressor kinase 2 (LATS2) is a core component in the Hippo signaling pathway, and it functions as a tumor suppressor associated with tumor cell proliferation and apoptosis. The purpose of this study is to explore LATS2 expression and its clinicopathological significance in non-small cell lung cancer (NSCLC). We examined LATS2 protein expression by immunohistochemistry in 184 resected NSCLC specimens using tissue microarrays. Low LATS2 expression was significantly related to disease recurrence (p = 0.047). In survival analysis, the low LATS2 expression group showed a statistically poorer overall survival (OS) (p = 0.004) and disease-free survival (DFS) (p = 0.014) than the high expression group. In multivariate analysis, downregulated LATS2 expression in NSCLC could be an independent prognostic factor of poor OS and DFS. Furthermore, we evaluated the prognostic significance of LATS2 expression in two major NSCLC subtypes, squamous cell carcinoma and adenocarcinoma. The low LATS2 expression group showed worse prognosis than the high LATS2 expression group (OS [p = 0.144] and DFS [p = 0.022] in squamous cell carcinoma and OS [p = 0.045] and DFS [p = 0.271] in adenocarcinoma). We demonstrated that downregulated LATS2 expression may predict aggressive biologic behavior and a worse prognosis in NSCLC and we also suggested the possibility of LATS2 as a therapeutic target in both squamous cell carcinoma and adenocarcinoma.

EGFR tyrosine kinase inhibitor (EGFR TKI) is approved as first-line treatment for advanced-stage EGFR mutant lung adenocarcinoma (LADC). Yes-associated protein 1 (YAP1), a main effector of the Hippo pathway, is associated with adverse prognosis and disruption of EGFR TKI modulation of non-small cell lung cancer. In this study, we demonstrated a prognostic role of YAP1 in EGFR mutant LADC and efficacy of EGFR TKI therapy. A total of 63 patients, including 41 with paired lung cancer specimens before and after EGFR TKI therapy and 22 with non-paired lung cancer specimens prior to EGFR TKI, were enrolled for examination. Expression of YAP1 protein was evaluated using immunohistochemistry. Fifteen paired cases (36.6%) with high nuclear YAP1 expression were detected in the pre-EGFR TKI LADC group and 21 paired cases (52.5%) after treatment with EGFR TKI. Nuclear YAP1 expression was significantly upregulated after EGFR TKI therapy (P = .002). Fifteen paired cases with high nuclear YAP1 expression before EGFR TKI LADCs showed poorer overall survival (OS) (P = .023) and progression-free survival (PFS) (P = .041). Among the 63 patients under study, those with high nuclear YAP1 expression before EGFR TKI showed shorter OS (P = .038) and PFS (P .001). High nuclear YAP1 expression in cases with acquired EGFR exon 20 T790 M mutant LADCs showed poorer OS (P .001). We demonstrated that YAP1 burden before clinical application of EGFR TKI plays a crucial role in prognosis of EGFR mutant LADC treated using EGFR TKI.

This study investigated the relationship of imaging features of primary tumor and peritumoral VAT on PET/CT with histopathological findings of peritumoral VAT and recurrence-free survival (RFS) in patients with colorectal cancer.We retrospectively reviewed 133 patients diagnosed with colorectal cancer who underwent staging FDG PET/CT and received curative surgery. Histogram-based imaging features of primary tumor and peritumoral VAT were extracted from PET/CT images. Based on histopathological analysis of peritumoral VAT, the degree of CD4, CD8, and CD163 cell infiltration and the expression of matrix metalloproteinase-11 and interleukin 6 (IL-6) were graded. Differences in imaging parameters based on the histopathological results and the relationships between imaging features and RFS were assessed.Mean CT-attenuation and SUV of peritumoral VAT showed significant positive correlation with CD163 cell infiltration and IL-6 expression of peritumoral VAT. Univariable survival analysis revealed significant correlation between RFS and the mean CT-attenuation, mean SUV, and first-order SUV entropy of peritumoral VAT (p 0.05). Multivariable analysis indicated that mean SUV and SUV entropy of peritumoral VAT remained significant predictors of RFS after adjustment for age, sex, and T stage (p 0.05).FDG uptake of peritumoral VAT was significantly associated with inflammatory response in peritumoral VAT and was an independent predictor of RFS in colorectal cancer patients.

Tracheal sarcomatoid carcinoma is an extremely infrequent neoplasm with unclear pathogenesis and clinical outcomes. To date, only two cases have been described in English literature. We report a case of a 37-year-old patient complaining of hemoptysis, dyspnea, and cough. An intraluminal polypoid mass in the trachea was found and ultimately diagnosed as tracheal sarcomatoid carcinoma in the cervical trachea with both carcinomatous and sarcomatoid morphology. The patient is alive without recurrence after segmental resection of the trachea. We also present a comparative analysis of our case with a prior tracheal sarcomatoid carcinoma case.

Rationale: Smooth muscle tumors of the vulva are infrequent neoplasms with diverse histologic features and unclear biologic behavior. Herein, we report a very rare case of vulvar epithelioid leiomyoma and review of previous reported cases of these tumors. In addition, we have discussed the representative diagnostic criteria of vulvar smooth muscle tumors and prognostic significance of epithelioid morphology. Patient concerns: We recently met a 45-year-old woman with complaint of painful vulvar mass. Interventions: Excisional biopsy was performed. Diagnoses: Pathologic examination revealed a vulvar epithelioid leiomyoma with multinodular growth pattern. Mitotic activity was rare and cellular atypia was not identified. Based on histology and immunohistochemical staining results, the case was diagnosed as vulvar epithelioid leiomyoma. Outcomes: After mass excision, the patient was discharged with no complication and there was no evidence recurrence for 6 months. Lessons: After reviewing previous papers and diagnostic criterion, we thought that vulvar smooth muscle tumors with predominant epithelioid morphology may be associated with unfavorable prognosis, Therefore, pathologists should examine the epithelioid component in vulvar smooth muscle tumors carefully.

A malignant phyllodes tumor is a rare disease of the breast that usually differentiates into fibrosarcoma, with liposarcomatous differentiation rarely being reported. In general, malignant phyllodes tumors appear as hypoechoic lesions on ultrasonography examination, and have rarely been reported as hyperechoic tumors. Here, we present an extremely rare case of a 62-year-old woman with a palpable mass that was diagnosed as a malignant phyllodes tumor with liposarcomatous differentiation, seen as an unusual hyperechoic mass on ultrasonography. She underwent resection and biopsy, and there was no evidence of tumor recurrence on follow-up examinations. Radiological explanations of this case are presented in detail, and the possible associations between hyperechoic appearance and liposarcomatous differentiation are described. Through our case report, we can identify several potential rare features of various and unpredictable phyllodes tumors.

Purpose The interaction of programmed death receptor 1 (PD-1) and its ligand, programmed death receptor ligand 1 (PD-L1), negatively regulates immune responses. This study aimed to clarify PD-L1 expression levels in breast cancer through immunohistochemistry (IHC) and to evaluate associations between these findings and clinicopathologic variables, including prognosis. Methods PD-L1 expression was analyzed using IHC on tissue microarrays of 465 invasive breast carcinomas. Results High PD-L1 expression was demonstrated in 63 of 465 tumors (13.5%). High PD-L1 expression was significantly associated with high histologic grade (p

PURPOSE Somatic mutations of the chromatin remodeling AT-rich interactive domain 1A (SWI-like) gene (ARID1A) have been identified in many human cancers, including breast cancer. The purpose of this study was to evaluate the nuclear expression of ARID1A in breast cancers by immunohistochemistry (IHC) and to correlate the findings to clinicopathologic variables including prognostic significance. METHODS IHC was performed on tissue microarrays of 476 cases of breast cancer. Associations between ARID1A expression and clinicopathologic characteristics and molecular subtype were retrospectively analyzed. RESULTS Low expression of ARID1A was found in 339 of 476 (71.2%) cases. Low expression of ARID1A significantly correlated with positive lymph node metastasis (p=0.027), advanced pathologic stage (p=0.001), low Ki-67 labeling index (p=0.003), and negative p53 expression (p=0.017). The ARID1A low expression group had significantly shorter disease-free and overall survival than the ARID1A high expression group (p

Objective In this study, we assessed the effectiveness of a tonsil-derived mesenchymal stem cell (TMSC)-transplanted polycaprolactone/beta-tricalcium phosphate prosthesis (specifically designed for easier fixing and grafting with a single scaffold) on rabbit mandible osteogenesis. Methods The mandibles of 18 rabbits were exposed, and 10 × 8-mm bone defects were made. Two rabbits did not receive implants; four were reconstructed with the scaffold control (SC) (SC group); four were reconstructed with scaffolds soaked in peripheral blood (PB) (PB group); four were reconstructed with TMSC-transplanted scaffolds (TMSC group); and four were reconstructed with differentiated osteocyte-transplanted scaffolds (DOC) (DOC group). Each rabbit was sacrificed 12 weeks after surgery, and the area of new bone formation was investigated by mechanical testing, histology, and micro-computed tomography. Results More extended and denser new bone masses were observed in the TMSC and DOC groups, although fibrosis and vascular formation levels were similar in all groups, suggesting that the dual-structured scaffold alone provides a good environment for bone attachment and regeneration. The bone volumes of representative scaffolds from the SC, PB, TMSC, and DOC groups were 43.12, 48.35, 53.10, and 57.44% of the total volumes, respectively. Conclusion The design of the scaffold resulted in effective osteogenesis, and TMSCs showed osteogenic potency, indicating that their combination could enable effective bone regeneration. Level of evidence NA Laryngoscope, 130:358-366, 2020.

Klotho deficiency is relevant to renal fibrosis and podocyte injury in vivo and in vitro. We examined whether histological findings of renal biopsy specimens were associated with the levels of soluble klotho in humans. We investigated renal biopsy specimens of 67 patients and detailed microscopic findings were reviewed. Soluble serum/urinary klotho and urinary angiotensinogen were assessed by enzyme-linked immunosorbent assays, and tissue klotho expression was assessed by immunohistochemical staining. The median age of the study participants was 35.6 years. High serum klotho levels (≥14 pg/mL) were associated with decreased odds ratios (ORs) of interstitial fibrosis (OR = 0.019, P = 0.003) and segmental sclerosis (OR = 0.190, P = 0.022) in multivariable logistic regression analysis. Patients with a lower urinary klotho-to-creatinine ratio (UKCR) were significantly more likely to have diffuse foot process effacement (OR = 0.450, P = 0.010). The area under the receiver-operating characteristic curve (AUC) of serum klotho for predicting interstitial fibrosis was 0.920 (95% CI, 0.844–0.996), and the best cut-off value of serum klotho was 138.1 pg/mL. The AUC of UKCR for predicting diffuse foot process effacement was 0.754 (95% CI, 0.636–0.872), and the best cut-off value of UKCR was 96.7 pg/mgCr. Urinary angiotensinogen-to-creatinine ratio was not associated with serum klotho, UKCR, or any pathological finding. Our data suggested that soluble serum and urinary klotho levels represent a potential biomarker to predict renal fibrosis and podocyte injury in humans.

A glomus tumor in the mediastinum is very uncommon, and only five cases have been reported in the English literature. We recently encountered a 21-year-old woman with an asymptomatic mediastinal mass that measured 5.3 × 4.0 cm. Surgical excision was performed, and the tumor was finally diagnosed as mediastinal glomus tumor with an uncertain malignant potential. After reviewing this case and previous reports, we analyzed the clinicopathologic features associated with progression of such a tumor.

// Dong-Hui Shin 1, * , Ji-Hye Park 2, * , Jeong-Yeon Lee 2, * , Hee-Young Won 1 , Ki-Seok Jang 1 , Kyueng-Whan Min 1 , Si-Hyong Jang 1 , Jong-Kyu Woo 3 , Seung Hyun Oh 3 , Gu Kong 1, 2 1 Department of Pathology, College of Medicine, Hanyang University, Seoul, Republic of Korea 2 Institute for Bioengineering and Biopharmaceutical Research (IBBR), Hanyang University, Seoul, Republic of Korea 3 College of Pharmacy, Gachon University, Incheon, Republic of Korea * These authors have contributed equally to this work Correspondence to: Gu Kong, e-mail: gkong@hanyang.ac.kr Keywords: basal-like breast cancer, cancer stem cell, Id1, mammary stem cell, c-Myc Received: January 14, 2015 Accepted: April 06, 2015 Published: April 16, 2015 ABSTRACT Inhibitor of differentiation/DNA binding (Id)1 is a crucial regulator of mammary development and breast cancer progression. However, its effect on stemness and tumorigenesis in mammary epithelial cells remains undefined. Herein, we demonstrate that Id1 induces mammary tumorigenesis by increasing normal and malignant mammary stem cell (MaSC) activities in transgenic mice. MaSC-enriched basal cell expansion and increased self-renewal and in vivo regenerative capacity of MaSCs are observed in the mammary glands of MMTV-Id1 transgenic mice. Furthermore, MMTV-Id1 mice develop ductal hyperplasia and mammary tumors with highly expressed basal markers. Id1 also increases breast cancer stem cell (CSC) population and activity in human breast cancer lines. Moreover, the effects of Id1 on normal and malignant stem cell activities are mediated by the Wnt/c-Myc pathway. Collectively, these findings provide in vivo genetic evidence of Id1 functions as an oncogene in breast cancer and indicate that Id1 regulates mammary basal stem cells by activating the Wnt/c-Myc pathway, thereby contributing to breast tumor development.

Struma ovarii is a rare, monodermal and highly specialized teratoma, composed entirely or predominantly ( > 50%) of thyroid tissue. Presenting symptoms are not specific. Despite containing thyroid tissue, only 5% of struma ovarii have features of hyperthyroidism. Therefore, preoperative diagnosis of struma ovarii is difficult. Recently, the authors experienced a case of struma ovarii found in a young woman who presented with known pelvic mass and dysmenorrhea. A transabdominal ultrasonography and computed tomography detected a 16-cm sized multiloculated mass in pelvic cavity. She underwent laparoscopic unilateral ovarian wedge resection. The final histopathologic diagnosis was struma ovarii of the mature cystic teratoma. Therefore, we report this rare case with a brief review of the literature.

Purpose The aims of this study were to evaluate the expression of the large tumor suppressor (LATS) genes LATS1 and LATS2 by immunohistochemical staining of gastric cancer, and to evaluate the clinicopathological significance of LATS expression and its correlation with overall survival (OS). Materials and Methods LATS1 and LATS2 expression in a tissue microarray was detected by immunohistochemistry, using 264 gastric cancer specimens surgically resected between July 2006 and December 2009. Results Low expression of LATS1 was significantly associated with more advanced American Joint Committee on Cancer (AJCC) stage (P=0.001) and T stage (P=0.032), lymph node (LN) metastasis (P=0.040), perineural invasion (P=0.042), poor histologic grade (P=0.007), and diffuse-type histology by the Lauren classification (P=0.033). Low expression of LATS2 was significantly correlated with older age (≥65, P=0.027), more advanced AJCC stage (P=0.001) and T stage (P=0.001), LN metastasis (P=0.004), perineural invasion (P=0.004), poor histologic grade (P

We report the case of a 46-year-old woman with acute febrile symptom who had multiple pulmonary nodules and a renal mass. She underwent (18)F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) to find a hidden malignancy and the cause of her fever. FDG PET/CT images demonstrated a renal mass and multiple lung nodules with intense FDG uptake, which was suspicious of a renal malignancy with multiple pulmonary metastatic lesions. CT-guided biopsies of the pulmonary and renal lesions only showed chronic inflammatory infiltrates without evidence of malignancy. She was diagnosed with septic pulmonary embolism from a renal abscess. One month after antibiotic treatment, the follow-up chest and abdomen CT showed improvement of the lung and renal lesions. This is the first case demonstrating the FDG PET/CT finding of septic pulmonary embolism associated with renal abscess in the published literature.

Background Large tumor suppressor kinase 2 (LATS2) is one of the core components in the Hippo signaling pathway, and it functions as a tumor suppressor associated with regulating tumor cell proliferation and apoptosis. Dysregulated LATS2 expression has been reported in various human cancers. The purpose of this study is to explore LATS2 expression and its clinicopathological significance in non-small cell lung cancer (NSCLC) and its subtypes. Methods We examined LATS2 protein expression by immunohistochemistry in 184 resected NSCLC specimens on tissue microarray. We also reviewed the clinical data and performed a clinicopathological analysis. Results Of 184 lung cancer specimens, 40 (21.7%) showed low LATS2 expression. Low LATS2 expression was significantly correlated with disease recurrence (p = 0.047) and low LATS2 expression had a tendency of poor prognostic clinicopathological features including large tumor size, the presence of vascular and lymphatic invasion and distant metastasis. The low LATS2 expression group showed a statistically poorer overall survival (OS) (p = 0.004) and disease-free survival (DFS) (p = 0.014) than did the high expression group in Kaplan-Meier analysis with log-rank test. In multivariate analysis with the Cox proportional hazards model, downregulated LATS2 expression in NSCLC was an independent prognostic factor of poor OS and DFS. Furthermore, we evaluated the prognostic significance of LATS2 expression in two major subtypes of NSCLC, squamous cell carcinoma and adenocarcinoma, using the Kaplan-Meier curves with log-rank test. In both squamous cell carcinoma and adenocarcinoma, low LATS2 expression group showed worse prognosis than high LATS2 expression group (OS (p = 0.144), DFS (p = 0.022) in squamous cell carcinoma and OS (p = 0.045), DFS (p = 0.271) in adenocarcinoma). Conclusions In conclusion, we demonstrated that downregulated LATS2 expression may predict aggressive biologic behavior and a worse prognosis in NSCLC and we also suggested the possibility of LATS2 as a therapeutic target in both squamous cell carcinoma and adenocarcinoma of the lung. Legal entity responsible for the study The authors. Funding Soonchunhyang University Research Fund. Disclosure All authors have declared no conflicts of interest.

In patients with advanced non-small cell lung cancer harboring epidermal growth factor receptor (EGFR) mutations, the epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are used as first treatment option. Because adenosquamous carcinoma (ASC) is a rare histologic subtype, evidences about EGFR-TKIs as first treatment option for advanced ASC are lacking. We report a case of an advanced ASC patient with the EGFR mutation, who showed good responses during 4-month treatment with gefitinib. And we will review about a necessity of EGFR mutation test and efficacy of EGFR-TKIs in ASC patients from the recent studies.

PURPOSE Transducin-like enhancer of split 1 (TLE1) is a member of the TLE family of transcriptional co-repressors that control the transcription of a wide range of genes. We investigated the prognostic significance of TLE1 protein expression in breast cancers by using immunohistochemistry and explored the relationship of TLE1 with clinicopathological parameters. METHODS Immunohistochemistry was performed on 456 cases of breast cancer tiled on tissue microarrays. The relationship between TLE1 expression in normal breast specimens and ductal carcinoma in situ (DCIS) was also analyzed. RESULTS TLE1 was highly expressed in 57 of 456 (12.5%) carcinoma samples. TLE1 was more frequently expressed in DCIS and invasive breast cancers than in normal breast tissue (p=0.002). High expression of TLE1 significantly correlated with negative lymph node (LN) metastasis (p=0.007), high histologic grade (p

AimsLung cancer is the leading cause of cancer-related deaths worldwide, and it still results in a poor prognosis despite research and development of a treatment modality. Angiomotin (AMOT) was first described as a protein involved in angiogenesis, and although the oncogenic and tumour-suppressive roles of AMOT were recently reported, the biological function of AMOT has not yet been clarified. The aim of this study was thus to evaluate the relationship between reduced AMOT p130 expression and clinicopathological parameters, including patients' survival.MethodsWe enrolled 67 patients with lung adenocarcinoma in this study and measured the immunoreactivity of AMOT p130 in a tissue microarray. The data were analysed using a χ2 test, Cox regression hazards model and log-rank test with Kaplan–Meier curves.ResultsReduced AMOT p130 expression is related to lung adenocarcinoma developed at a young age with statistical significance, but there is no statistical significance for the other clinicopathological parameters. Kaplan–Meier curves with log-rank test showed that reduced AMOT p130 expression had significantly better survival rate compared with the retained group (p=0.002). Univariable and multivariable analyses of the disease free survival revealed that the decreased AMOT expression was an independent prognostic factor (p=0.004, p=0.008, respectively).ConclusionsDecreased AMOT p130 could be an independent indicator of poor survival in patients with lung adenocarcinoma.

Ampullary adenoma is a common indication for endoscopic papillectomy. Ampullary neuroendocrine tumor (NET) is a rare disease for which complete surgical resection is the treatment of choice. However, because of the morbidity and mortality associated with surgical resection, endoscopic papillectomy is increasingly used in selected cases of low grade, with no metastasis and no invasion of the pancreatic or bile duct. Also, confirmed and complete endoscopic resection of ampullary NET accompanied by adenoma has not been reported to date. We report herein a rare case of an ampullary NET accompanied with adenoma, which was successfully and completely resected via endoscopic papillectomy. Prior to papillectomy, this case was diagnosed as an ampullary adenoma.

Cell adhesion molecule 4 (CADM4) is a novel tumour suppressor. The purpose of this study was to investigate the correlation between its expression and the expression of E-cadherin and Ki-67 in colorectal adenocarcinomas, as well as its effect on patient survival.We evaluated CADM4 expression in tissue microarrays of 513 colorectal adenocarcinomas by immunohistochemistry.CADM4 was highly expressed in 210 of the 513 colorectal adenocarcinomas; expression was reduced in 185 cases and absent in the remaining cases. Loss of CADM4 expression was correlated with larger tumour size (6.2±2.1 cm vs 5.3±2.0 cm, p0.001), mucinous tumour type (61.5% vs 20.9%, p0.001), lymph node metastasis (31.4% vs 20.9%, p=0.022), higher Dukes stage (25.5% vs 19.6%, p=0.044), poorer differentiation (38.5% vs 18.8%, p0.001), absence of E-cadherin expression (28.5% vs 16.0%, p=0.007) and presence of Ki-67 expression (27.3% vs 12.3%, p0.001). In univariable Cox regression analysis, absence of CADM4 expression was associated with poorer overall survival (HR 0.712; 95% CI 0.512 to 0.989, p=0.042) and disease-free survival (HR 0.732; 95% CI 0.546 to 0.981, p=0.037). In multivariate analysis with the Cox proportional hazards model, CADM4 expression was not an independent prognostic factor of overall survival (HR 0.726; 95% CI 0.516 to 1.021, p=0.066) and disease-free survival (HR 0.762; 95% CI 0.563 to 1.033, p=0.080).Loss of CADM4 expression is relatively frequent in colorectal adenocarcinomas and may play an important role in cancer progression and patient survival.

PURPOSE Transducer-like enhancer of split 1 (TLE1) is a member of the Groucho/TLE family of transcriptional co-repressors that regulate the transcriptional activity of numerous genes. TLE1 is involved in the tumorigenesis of various tumors. We investigated the prognostic significance of TLE1 expression and its association with clinicopathological parameters in gastric cancer (GC) patients. MATERIALS AND METHODS Immunohistochemical analysis of six tissue microarrays was performed to examine TLE1 expression using 291 surgically resected GC specimens from the Soonchunhyang University Cheonan Hospital between July 2006 and December 2009. RESULTS In the non-neoplastic gastric mucosa, TLE1 expression was negative. In GC, 121 patients (41.6%) were positive for TLE1. The expression of TLE1 was significantly associated with male gender (P=0.021), less frequent lymphatic (P=0.017) or perineural invasion (P=0.029), intestinal type according to the Lauren classification (P=0.024), good histologic grade (P

Background and aim: Cyclooxygenase-2 (COX-2) plays an important role in colorectal cancer development and is frequently up-regulated in colorectal cancer. The purpose of this study was to investigate COX-2 overexpression in colorectal adenocarcinoma and to evaluate the correlation with the clinicopathological parameters and p53 expression, as well as its effect on patient survival. Methods: We evaluated the expression of COX-2 and p53 on the tissue microarray of 414 colorectal adenocarcinomas by immunohistochemistry. Data was analyzed by Fisher's exact test, χ2-test, one-way ANOVA, Cox regression hazards model and log-rank test with Kaplan–Meier curves. Results: The cytoplasmic COX-2 overexpression was detected in 56.3% of colorectal adenocarcinoma samples. COX-2 overexpression was correlated with favorable clinicopathologic factors in lymph node metastasis (P= 0.002), American Joint Committee on Cancer and Dukes’ stage (P= 0.008 and P= 0.017, respectively), and lymphatic invasion (P= 0.001). Other characteristics associated with COX-2 overexpression were colonic site of tumor (P= 0.008) and poor differentiation (P= 0.017). There was no correlation between COX-2 overexpression and p53 expression (P= 0.485). In univariate survival analysis, patients with COX-2 overexpression revealed better overall survival and disease-free survival (P= 0.021 and P= 0.017, respectively, log-rank test). In multivariate survival analysis with the Cox proportional hazards model, COX-2 overexpression was an independent prognostic factor of overall survival and disease-free survival (P= 0.029 and P= 0.039, respectively). Conclusions: COX-2 overexpression was significantly associated with favorable clinicopathologic phenotype and an indicator of better survival in our cohort of colorectal cancer patients.

Apoptotic protease activating factor-1 (Apaf-1) is one of the key regulators in the mitochondrial apoptotic pathway, and the loss of Apaf-1 leads to cellular resistance against the apoptotic signals. We investigated the expression of Apaf-1 in colorectal tissues corresponding to the multistep carcinogenesis model to determine correlations between the clinicopathologic characteristics and the expression of this molecule and to evaluate the role of Apaf-1 in the development and progression of colorectal adenocarcinoma. Immunohistochemistry for Apaf-1 was performed on the tissue microarray of 38 normal mucosal tissues, 46 adenomatous polyps, 529 colorectal adenocarcinomas, and 76 metastatic tumors. Normal colonic mucosa tissues and adenomas were positive for Apaf-1 with no exceptions (100%). However, in colorectal adenocarcinomas, 119 of 529 cases (22.5%) were positive and 410 cases (77.5%) were negative. Moreover, 67 of 76 metastatic cases (88.2 %) were negative and only nine cases (11.8%) were positive for Apaf-1 expression. In the analyses between Apaf-1 expression and clinicopathologic parameters, reduced expression of Apaf-1 correlated with left colon location (p < 0.001), deeper tumor invasion (p < 0.001), frequent lymph node metastasis ( p= 0.021), higher American Joint Committee on Cancer (AJCC) and Dukes’ stage (p = 0.02 and p = 0.001, respectively) and poorer differentiation (p < 0.001). The patient survival was significantly associated with age, histological grade, AJCC stage, and lymphovascular invasion, but not Apaf-1 expression (p = 0.478). The results suggest that the loss of Apaf-1 expression is a relatively frequent late event and the loss of Apaf-1 expression may play an important role in tumorigenesis and tumor progression in colorectal adenocarcinoma.

Synovial sarcoma is a rare but distinct soft tissue neoplasm, most commonly occurring in para-articular regions of the extremities of young adults and also occurring in the head and neck region. To the best of our knowledge, only one case of primary synovial sarcoma of the thyroid has been previously reported. Here, we report a 15-yr-old man who had a chief complaint of a palpable neck mass. The neck computed tomography revealed a relatively well-demarcated solid mass in the left thyroid gland. After fine needle aspiration cytology, total thyroidectomy and lymph node dissection were performed. Grossly, the mass was covered by the same capsule as the thyroid gland, measuring 6×5×5 cm in dimensions and weighing 78 gm. The cut surface showed a well demarcated, lobulated, grayish tan, and rubbery solid tumor. Histologically, this tumor was a biphasic synovial sarcoma. Immunohistochemical, ultrastructural, genetic studies, and cytologic findings were all consistent with synovial sarcoma. When synovial sarcomas arise in this unusual site, recognition and differential diagnosis become more difficult. The differential diagnosis of a spindle epithelial tumor with thymus-like differentiation is very difficult due to their similar clinical, histological, and immunohistochemical features. Ultrastructural and cytogenetic studies for synovial sarcoma are necessary to establish a definitive diagnosis.