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Objective The aim of this study was to determine the added value of high-resolution diffusion-weighted imaging (DWI) to T2-weighted imaging (T2WI) for evaluation of extramural tumor invasion (EMTI) in patients with primary rectal cancer. Methods Seventy-eight patients who had undergone 3.0-T magnetic resonance imaging including DWI (b = 0, 1000 s/mm2, 2 mm iso-voxel) and subsequent surgery were included. Two blinded radiologists independently read the T2WI first and then the combined DWI set. They recorded their confidence level using a 5-point scale. The diagnostic accuracy was calculated by receiver operating characteristic curve analysis based on the histopathological results as the reference. Results The study population consisted of EMTI positive (n = 44) and negative (n = 34). The area under the curve was not significantly increased after adding DWI to T2WI (reader 1, 0.868-0.856, P = 0.5618; reader 2, 0.848-0.865, P = 0.4539). Conclusion Adding DWI to T2WI showed no additional diagnostic value for the evaluation of EMTI in patients with primary rectal cancer.

Thyroid lymphoproliferative disorder is known to be associated with Hashimoto thyroiditis. The major histological types of thyroid lymphoproliferative disorders are malignant lymphoma, such as diffuse large B cell lymphoma, extranodal marginal zone B cell lymphoma of mucosa-associated lymphoid tissue (MALT), and follicular lymphoma. All of these are B cell lymphomas; however, T cell lymphoproliferative disorders represent only a minority of cases. Since T cell lymphoproliferative disorder rarely develops and T cell lymphoma is a heterogeneous entity, it is difficult to concisely summarize this complex topic. Here, we present a case of primary thyroid T cell lymphoproliferative disorder reminiscent of indolent T cell lymphoproliferative disorder of the gastrointestinal tract: the pathological findings from this case also were similar to those of MALT lymphoma such as small lymphoid cells, lymphoepithelial lesions, and a low Ki-67 labeling index. T cell lymphoproliferative disorders with these pathological features have been reported in the thyroid gland, lymph nodes, palate, spleen, and gastrointestinal tract. Furthermore, we reviewed and summarized the studies on thyroid T cell lymphoproliferative disorders and compared the cases and their clinicopathological characteristics.

Highlights • PVNS could progress rapidly causing devastating arthritic changes in the joint. • Clinicians should also consider PVNS as a reason for shoulder destruction. • Hemiarthroplasty could be treatment option for PVNS of shoulder joint., Introduction Pigmented villous nodular synovitis is an uncommon proliferative disease of the joints, and rarely reported in the shoulder. It can become symptomatic when proliferating soft tissue infiltrates a joint, causing arthritic changes including bone erosion. The literature has described the disease progression as indolent. Here we report on a case of PVNS of the shoulder joint which rapidly lead to significant bone damage and was subsequently treated by shoulder arthroplasty. Presentation of case We report here on a 71-year old female patient who presented with a 6 month history of aggravating shoulder pain. Radiography imaging over a one month period indicated rapid joint destruction. Magnetic resonance imaging suggested the presence of PVNS of the shoulder joint and significant bone erosion. The patient was subsequently treated by shoulder arthroplasty performed by authors. Histological examination confirmed the PVNS diagnosis. Shoulder pain significantly decreased during the follow up period, and the patient was able to resume daily activities. Discussion Comparing to Milwaukee shoulder syndrome or a joint infection, PVNS is known to progress indolently. However, our case clearly showed that PVNS could also cause radical destruction of the joint. Previous reports showed the high recurrence rate of PVNS after joint preserving surgery. In our experience hemiarthroplasty could be the choice of treatment with the low recurrence rate and high functional outcome. Conclusions Physicians should include PVNS in the differential diagnosis when they are presented with evidence of rapid destruction of the shoulder joint. Hemiarthroplasty could be treatment option for PVNS of shoulder joint.

Gastric heterotopic pancreas is a relatively uncommon incidental finding. On the other hand, the presentation of gastric adenocarcinoma arising from a heterotopic pancreas is rare. This paper reports a case of gastric adenocarcinoma arising from a heterotopic pancreas that presented as a gastric outlet obstruction 10 years after the initial diagnosis of a suspicious submucosal tumor. Endoscopy revealed a pyloric stricture with prepyloric wall thickening and a complete gastric outlet obstruction. Abdominal and pelvic computed tomography exposed a severely distended gastric lumen at the antrum with heterogeneously enhancing circumferential wall thickening in the prepyloric antrum and pylorus. Because conservative treatment was ineffective and a malignancy could not be excluded, laparoscopic subtotal gastrectomy with a gastrojejunostomy was performed for histological confirmation and treatment. The histopathology diagnosis was advanced gastric carcinoma arising from heterotopic pancreatic tissue.

Background: Modified endoscopic mucosal resection (EMR) is considered a treatment option for rectal neuroendocrine tumors (NETs)

Primary pleomorphic liposarcoma of the breast is rare, and only a few cases in the literature have reported imaging findings. Herein, we report a rare case of primary pleomorphic liposarcoma of the breast in a 38-year-old woman and describe the imaging findings including mammography, ultrasonography, computed tomography, magnetic resonance imaging, and 18F-Fluorodeoxyglucose-positron emission tomography. Although most fat-containing breast masses are benign, malignancy can occur. Magnetic resonance imaging can be helpful for further evaluation of breast masses.

Patient: Male, 53-year-old Final Diagnosis: Osteoma Symptoms: Rib mass Medication:— Clinical Procedure: Excision biopsy Specialty: Pathology • Surgery Objective: Rare disease Background: Osteoma is a benign bone tumor that typically arises in facial bones and less frequently in the long bones. It rarely occurs in the appendiceal skeleton. Pathologic findings are similar to those for parosteal osteosarcoma, periostitis ossificans, and osteoid osteoma. Diagnosing osteoma at an unusual site is always problematic. Here, we present a case of costal osteoma that was found incidentally on screening and produced mild symptoms in the patient. Case Report: A 53-year-old man was examined because of a rib mass in the eighth rib on his left side, which had been present for 2 years. A computed tomography scan revealed that the intensely dense mass arose from the external surface of the eighth rib. Microscopic examination showed that the lesion consisted of mature lamellar bone with several Haversian systems, typical of an osteoma. No atypical spindle cells or necrosis were identified. The diagnosis was osteoma. Conclusions: Because the anatomy of the ribs poses a challenge when performing needle biopsy, diagnosing bony lesions solely based on that technique is difficult. The diagnosis of costal osteoma should be made carefully, based on clinical, radiological, and pathological findings. To the best of our knowledge, ours is the first case report about a costal osteoma. It is useful for chest surgeons, pathologists, and radiologists as an example of a rare presentation of this tumor.

Patient: Female, 68-year-old Final Diagnosis: Primary mature teratoma of the rectum Symptoms: Hematochezia Medication:— Clinical Procedure: Colonoscopy with polypectomy Specialty: Gastroenterology and Hepatology Objective: Rare disease Background: Teratomas are embryonal neoplasms that contain tissues derived from 1 or more of the 3 germ layers. They commonly are found in the sacrococcygeal-gonadal location, sometimes in midline locations such as the mediastinum, retroperitoneum, and head and neck region. Primary rectal teratomas are extremely rare. Extragonadal teratomas can originate from pluripotent germ cells present in abnormal embryonic rests. Case Report: Here, we report a rare case of a primary mature, solid teratoma of the rectum. A 68-year-old woman presented with hematochezia and denied any history of abdominal pain or a change in bowel habits. Colonoscopy revealed a 4-cm pedunculated polyp in the rectum. No hair was present on its surface. The polyp was completely removed by polypectomy. Histologically, the tumor consisted of mature components from all 3 germ layers. Its surface was covered by squamous epithelium with hair follicles and sweat glands. Adipose tissue, blood vessels, bone, and glandular epithelium were present inside the mass. No evidence was found of immature elements or malignant features. Conclusions: When polypoid lesions are found in the rectum, teratoma should be considered in the differential diagnosis. Histopathological confirmation is necessary to diagnose teratoma. Primary rectal teratomas should be distinguished from other neoplastic polyps as well as from local spread of teratomas arising in adjacent organs. These neoplasms are usually mature (benign) but may undergo malignant transformation. Therefore, complete resection is recommended to alleviate symptoms and avoid the risk of malignancy.

Minimally invasive therapies, including endoscopic mucosal resection or sentinel node navigation surgery, have been widely applied in early gastric cancer because of their benefits in promoting patient quality of life. However, lymph node dissection is beyond the capability of endoscopic therapy, and in sentinel node navigation surgery, the potential for skip metastasis is not negligible. Therefore, the possibility of lymph node metastasis is the most important factor to consider when deciding whether to apply the minimally invasive therapies. In the present study, the significance of epithelial mesenchymal transition and stem cell marker expression in lymph node metastasis in early gastric cancer was investigated.We evaluated the significance of the expression of 5 epithelial mesenchymal transition-related markers (E-cadherin, MMP7, S100A, Snail-1, and HGF) and 6 stem cell markers (ALDH1, SOX2, CD24, CD44, CD54, and CD133) in 119 early gastric cancer specimens using immunohistochemistry. Because protein expression is heterogeneous in gastric cancer, we analyzed the expression of these markers in two selected regions (one each at the superficial zone and the deep invasive front).Expression of E-cadherin, MMP7, HGF, and CD133 at the deep invasive front was associated with the absence of lymph node metastasis (P=0.013, 0.018, 0.001, and 0.026, respectively). Presence of diffuse-type component, lymphatic invasion, and lack of expression of HGF and CD133 at the deep invasive front were independent predictive markers of lymph node metastasis (P=0.019,0.001, 0.015, and 0.047, respectively).Lymph node metastasis is strongly associated with expression status of HGF and CD133 at the deep invasive front, suggesting the usefulness of these proteins as independent predictive markers of lymph node metastasis in early gastric cancer.

PIK3CA mutations are frequent in gastric cancer. However, their pathological and clinical implications are still unclear. We analyzed the clinicopathological characteristics according to the PIK3CA mutation status of patients with stage IB–IV disease who underwent gastrectomy between May 2003 and Dec. 2005 (cohort 1; n = 302) and of those with stage IV disease who received gastrectomy between Jul. 2006 and Dec. 2012 (cohort 2; n = 120). PIK3CA mutations were detected in 40 patients (13.2%) in cohort 1. In these patients, PIK3CA-mutant tumors were more frequently located in the upper third of the stomach (p = 0.021) and significantly showed poorly differentiated histology (p = 0.018) and increased lymphatic (p = 0.015), vascular (p = 0.005), and perineural invasion (p = 0.026). In addition, these tumors showed significantly increased lymphocyte and neutrophil infiltration in cancer stroma (p < 0.001), Epstein–Barr virus positivity (p < 0.001), and microsatellite instability (p = 0.015). Cytoplasmic Akt expression was significantly increased in these tumors (p = 0.001). In cohort 2, PIK3CA mutations were identified in 15 patients (12.5%). PIK3CA-mutant tumors showed significantly increased vascular invasion (p = 0.019) and microsatellite instability (p = 0.041). In addition, cytoplasmic Akt expression was also significantly increased (p = 0.018). However, in both cohorts, PIK3CA mutations were not associated with the prognosis of patients. In conclusion, PIK3CA mutations were associated with increased tumor aggressiveness, especially in locoregional disease, and Akt activation in gastric cancer. Our data suggest that PIK3CA-mutated gastric cancer is a distinct disease entity, which might need a different therapeutic approach.

Kimura disease (KD) is an immune-mediated chronic inflammatory disease of unknown etiology. KD has many complications associated with hypereosinophilia, including various forms of allergic reactions and eosinophilic lung disease. Additionally, hypereosinophilia is associated with hypercoagulability, which may lead to thromboembolic events. A 36-year-old man with KD presented with acute limb ischemia and coronary artery occlusion. He underwent thrombectomy, partial endarterectomy of both popliteal arteries, and coronary artery stent insertion. KD is a systemic disease that affects many organs and presents with thromboembolism and vasculitis. In a patient with KD, physicians should evaluate the vascular system, including the coronary arteries.

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.

Primary adenosquamous cell carcinoma of the liver, a variant of cholangiocarcinoma is very rare disease and its prognosis is known to be very poor. We describe here a case of primary adenosquamous carcinoma of the liver. The patient was a 60-year-old woman who complained of an eight-month history of intermittent upper abdominal pain. Abdominal computed tomography scan revealed a low density mass and intrahepatic duct stones within the dilated left intrahepatic duct in the left lateral segment. Needle biopsy of the mass was done and the histologic diagnosis was cholangiocarcinoma. Left lobectomy was then performed. Upon gross examination, there was a well defined solid mass and intrahepatic duct stone in the dilated bile duct. Microscopically, the tumor was composed of both adenocarcinoma and squamous cell carcinoma.

The neutrophil–lymphocyte ratio (NLR) and the prognostic nutritional index (PNI) are markers of systemic inflammation known to be useful prognostic indicators of malignancy. However, little evidence has defined the influence of inflammation on the tumor microenvironment. Two hundred eighty-eight patients who underwent curative surgery for gastric cancer were included. Preoperative peripheral blood samples were used to analyze the NLR and PNI. The optimal cutoff levels for the NLR and PNI were defined by receiver operating characteristic curve analysis for survival (NLR = 2.7, PNI = 47.7). The densities of specific immune cells (CD3+, CD4+, CD8+) within the tumor microenvironment were measured in tumor microarrays by immunohistochemical analysis. Two hundred thirty-five patients (81.6 %) had a low NLR and 53 patients (18.4 %) had a high NLR. One hundred seventeen patients (40.6 %) had a low PNI and 171 patients (59.4 %) had a high PNI. CD3+ and CD8+ immune cell density were not associated with the NLR and PNI. However, in the high-NLR group compared with the low-NLR group, CD4+ immune cell density was significantly decreased (P

There are few data on the clinical implications of immunosuppressive protein expression in tumors and immune cell infiltration within the tumor microenvironment in patients with gastric cancer (GC). In this study, 243 patients with curatively resected GC were included. The levels of immunosuppressive protein expression [programmed cell death 1 ligand 1 (PD-L1), cytotoxic T-lymphocyte antigen 4 (CTLA-4), and indoleamine 2,3-dioxygenase (IDO)] in tumors and the densities of immune cells [CD3(+), CD4(+), CD8(+), or PD-1(+) cells] within the tumor microenvironment were measured using immunohistochemical analysis. Positive PD-L1, CTLA-4, and IDO expression was observed in 43.6, 65.8, and 47.7 % of the patients, respectively. Expression of PD-L1, CTLA-4, and IDO was related to less advanced stage, intestinal type, and well/moderately differentiated adenocarcinoma (P

Purpose Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) represent a heterogeneous disease group originating from the neuroendocrine cells. Identification of prognostic markers, related to neuroendocrine tissue-selective tumorigenesis, is necessary to find therapeutic targets. Materials and methods A total of 327 patients with GEP-NETs were included in this study; there were 49 gastric, 29 duodenal, 49 pancreatic, 12 hepatobiliary, 33 appendiceal, 5 proximal colon, and 150 distal colon cases. We performed immunostaining with the tissue microarray method for menin, p27, and p18. Results We observed negative staining for menin, p27, and p18 in 34%, 21%, and 56% of GEP-NETs, respectively. The loss of p27, but not menin, was positively correlated with the grade of Ki-67. Menin-/p27-, menin-/p27+, menin+/p27-, and menin+/p27+ phenotype groups included 13%, 22%, 8%, and 57% of patients, respectively. A dichotomized comparison showed that menin- or p27- tumors were significantly associated with foregut and midgut localizations, high World Health Organization (WHO) grade, lymph node metastasis, and more advanced stage as compared to menin+/p27+ patients. Kaplan-Meier analysis for the overall survival showed that p27 loss was significantly associated with decreased survival. Multivariate analysis showed that p27 loss is an independent factor for poor overall survival. Conclusion Our results revealed that the loss of p27 is associated with poor prognosis and the menin-p27 pathway is important in the tumorigenesis of GEP-NETs.

Background The purpose of our research was to determine the prognostic impact and clinicopathological feature of c-MYC and β-catenin overexpression in colorectal cancer (CRC) patients. Methods Using immunohistochemistry (IHC), we measured the c-MYC and β-catenin expression in 367 consecutive CRC patients retrospectively (cohort 1). Also, c-MYC expression was measured by mRNA in situ hybridization. Moreover, to analyze regional heterogeneity, three sites of CRC including the primary, distant and lymph node metastasis were evaluated in 176 advanced CRC patients (cohort 2). Results In cohort 1, c-MYC protein and mRNA overexpression and ß-catenin nuclear expression were found in 201 (54.8 %), 241 (65.7 %) and 221 (60.2 %) of 367 patients, respectively, each of which was associated with improved prognosis (P = 0.011, P = 0.012 and P = 0.033, respectively). Moreover, co-expression of c-MYC and ß-catenin was significantly correlated with longer survival by univariate (P = 0.012) and multivariate (P = 0.048) studies. Overexpression of c-MYC protein was associated with mRNA overexpression (ρ, 0.479; P 0.05). Conclusions Co-expression of c-MYC and ß-catenin was independently correlated with favorable prognosis in CRC patient. We concluded that the expression of c-MYC and ß-catenin might be useful predicting indicator of CRC patient’s prognosis. Electronic supplementary material The online version of this article (doi:10.1186/s12885-016-2770-7) contains supplementary material, which is available to authorized users.

Objective:Caveolin 1 gene is known as a tumor promoter or suppressor, depending on the tumor type and/or tumor stage. We aimed to investigate the clinical significance of caveolin 1 protein (Cav1) expression in gastric cancer (GC). Methods: Immunohistochemistry was performed on tissue array slides containing 405 GC specimens. The relationships between Cav1 expression and clinicopathological factors, prognosis, focal adhesion kinase expression, mucin phenotypes and p53 expression were analyzed. Results: In non-neoplastic gastric mucosa, Cav1 was not expressed in the epithelial compartment. In GC, positive staining of Cav1 was shown in 22 (5.4%) of 405 cases and was significantly higher in the advanced GC group than in the early GC group (p = 0.037). Also, it was significantly associated with advanced pTNM stage (p = 0.027) and lymph node metastasis (p = 0.018). Moreover, survival analysis showed that Cav1 expression was an independent prognostic factor of poor survival (p = 0.028). In addition, the expression of Cav1 was positively correlated with that of focal adhesion kinase (p = 0.034). Conclusions: These results indicate that the expression of Cav1 is significantly correlated with cancer progression and poor prognosis in GC. Thus, Cav1 could supplement its protein expression for the diagnosis and treatment of GC.

The aim of the present study was to identify the prognostic factors for the propensity for recurrence in sporadic desmoid tumors. The catenin (cadherin-associated protein) β1 (CTNNB1) genotypes and expression of Wnt pathway proteins and midkine (also termed neurite growth-promoting factor 2) were investigated in 159 patients with sporadic desmoid tumors. Formalin-fixed paraffin-embedded tissues of the surgically resected desmoid tumors were examined by direct sequencing of CTNNB1 exon 3, and immunostained for the expression of β-catenin, T-cell factor 4 (TCF-4), phosphorylated protein kinase B (pAkt), midkine and menin using a tissue microarray method. Among the samples, 70% (111/159) exhibited point mutations of the CTNNB1 gene, including T41A (56%), S45F (8%), S45P (2%), S45N (2%) and T42A (1%). In addition, 100, 57, 24, 15 and 92% of the tumors expressed β-catenin, TCF-4, midkine, pAkt and menin, respectively. Positive midkine expression was significantly associated with the recurrence of tumors (P=0.001). The multivariate analysis of recurrence demonstrated that an extra-abdominal tumor site [hazard ratio (HR), 2.625; P=0.001] and midkine expression (HR, 2.077; P

The hematogenous spreading of an infectious pathogen via the portal vein from a mucosal injury in the gastrointestinal tract has been considered as one of the pathologic mechanisms of pyogenic liver abscess. Several studies have presented the association between colorectal cancer and pyogenic liver abscess. However, the cases of stomach cancer concomitant with pyogenic liver abscess have rarely been reported in the world. Herein, we present a case of advanced gastric cancer concomitant with pyogenic liver abscess in a patient who previously underwent subtotal gastrectomy due to peptic ulcer perforation.

Objectives: Nucleic acid amplification tests on formalin-fixed, paraffin-embedded (FFPE) tissue specimens enable Mycobacterium tuberculosis complex (MTB) detection and rapid tuberculosis diagnosis in the absence of microbiologic culture tests. We aimed to evaluate the efficacy of different polymerase chain reaction (PCR) methods for detecting Mycobacterium species in FFPE tissues. Methods: We examined 110 FFPE specimens (56 nonmycobacterial cases, 32 MTB, and 22 nontuberculous mycobacteria [NTM] determined by acid-fast bacilli [AFB] culture) to assess five PCR methods: nested PCR (N-PCR) (Seeplex MTB Nested ACE Detection; Seegene, Seoul, South Korea), an in-house real-time PCR (RT-PCR) method, and three commercial RT-PCR methods (AccuPower MTB RT-PCR [Bioneer, Seoul, Korea], artus M tuberculosis TM PCR [Qiagen, Hilden, Germany], and AdvanSure tuberculosis/NTM RT-PCR [LG Life Sciences, Seoul, Korea]). Results: The results of N-PCR, in-house RT-PCR, and AdvanSure RT-PCR correlated well with AFB culture results (concordance rates, 94.3%, 87.5%, and 89.5%, respectively). The sensitivity of N-PCR (87.5%) was higher than that of the RT-PCR methods, although these differences were not statistically significant between N-PCR and the in-house and AdvanSure RT-PCR methods (68.8% and 80.0%, respectively). All the PCR methods had high specificities, ranging from 98.2% to 100%. Only two NTM cases were detected by AdvanSure RT-PCR, implying a very low sensitivity. Conclusions: Well-designed RT-PCR and N-PCR can effectively identify MTB in FFPE specimens.

Background This study aimed to investigate the significance of circulating HER2 and MYC gene fragments quantification in the diagnosis of gastric cancer. Methods Levels of HER2 and MYC genes were evaluated by fluorescence in situ hybridization and real-time PCR in 81 gastric cancer tissues, and by real-time PCR in 36 gastritis tissues. Real-time PCR for HER2 and MYC products was also performed on 184 plasma samples from 81 gastric cancers, eight gastric adenomas, 63 gastritis patients, and 32 healthy individuals. Results HER2/HBB and MYC/HBB ratios in tissue and cell-free plasma from gastric cancer patients were significantly higher than those of gastritis tissue and cancer-free individuals. An optimized cut-off value of plasma target gene to HBB ratio, used to differentiate cancer patients from cancer-free individuals, was evaluated using receiver operating characteristic (ROC) curves. Values of 2.0 were calculated for HER2 [area under the ROC curve (AUC), 0.760] and 2.725 for MYC (AUC, 0.767). A combination model of HER2 and MYC provided a better differentiation condition than that for HER2 or MYC only (AUC, 0.850). HER2/HBB ratios in plasma from gastric cancer patients correlated with MYC/HBB ratios. Conclusions Our findings suggest that the measurement of plasma HER2 and MYC gene levels could improve the screening of gastric cancer.

Background Glioblastomas may develop de novo (primary glioblastomas, P-GBLs) or through progression from lower-grade astrocytomas (secondary glioblastomas, S-GBLs). The aim of this study was to compare the immunohistochemical classification of glioblastomas with clinically determined P-GBLs and S-GBLs to identify the best combination of antibodies for immunohistochemical classification. Methods We evaluated the immunohistochemical expression of epidermal growth factor receptor (EGFR), p53, and isocitrate dehydrogenase 1 (IDH-1) in 150 glioblastoma cases. Results According to clinical history, the glioblastomas analyzed in this study consisted of 146 P-GBLs and 4 S-GBLs. Immunohistochemical expression of EGFR, p53, and IDH-1 was observed in 62.6%, 49.3%, and 11.1%, respectively. Immunohistochemical profiles of EGFR(+)/p53(-), IDH-1(-)/EGFR(+)/p53(-), and EGFR(-)/p53(+) were noted in 41.3%, 40.2%, and 28.7%, respectively. Expression of IDH-1 and EGFR(-)/p53(+) was positively correlated with young age. The typical immunohistochemical features of S-GBLs comprised IDH-1(+)/EGFR(-)/p53(+), and were noted in 3.6% of clinically P-GBLs. The combination of IDH-1(-) or EGFR(+) was the best set of immunohistochemical stains for identifying P-GBLs, whereas the combination of IDH-1(+) and EGFR(-) was best for identifying S-GBLs. Conclusions We recommend a combination of IDH-1 and EGFR for immunohistochemical classification of glioblastomas. We expect our results to be useful for determining treatment strategies for glioblastoma patients.

We investigated the roles of Lethal giant larvae 2 (Lgl2), an epithelial cell polarity protein, during gastric carcinogenesis and gastric cancer (GC) progression and evaluated the correlation of Lgl2 with epithelial-mesenchymal transition (EMT) markers.Lgl2 protein and mRNA expression were determined by immunohistochemistry and mRNA in situ hybridization in a large series of GC and preneoplastic lesions. Additionally, expression of 7 EMT markers was examined by immunohistochemistry.Loss of membrane Lgl2 staining in GC was observed in 347 of 409 GCs. Lgl2 loss was associated with diffuse histological type (P0.001), advanced stage (P = 0.021), and worse prognosis (P = 0.047). Furthermore, Lgl2 loss correlated with reduced E-cadherin expression (P0.01) and increased expression of vimentin (P0.01). Combined analysis of Lgl2 and the EMT markers, S100A4 and MMP2, improved predictions of patient outcomes. During gastric carcinogenesis, membrane expression of Lgl2 was progressively lost in 4 % of normal mucosa, 75 % of intestinal metaplasia, 58 % of gastric dysplasia, 69 % of intestinal type GC, and 96 % of diffuse type GC.Our results suggest that Lgl2 loss occurs at an early stage of gastric carcinogenesis and contributes to GC progression.

Renal cell carcinoma (RCC) patients occasionally have metastatic disease at the time of presentation (25-30%)1 and local or distant recurrences after nephrectomy in the case of localized RCC (20-40%).2 Although a large study showed that the 5-year survival rate of metastatic RCC patients is less than 10%,3 new therapeutic methods have been developed for the treatment of advanced RCC,4,5 and some can play a prominent role in the treatment of certain subtypes of RCC.6 Therefore, it has become more important to diagnose metastatic RCC and to determine the subtype of the corresponding primary lesion. Each RCC subtype can show typical histologic features but may frequently have areas of diverse histologic variation. For example, in clear cell renal cell carcinoma (CCRCC), tumor cells typically have abundant clear cytoplasm; however, many CCRCCs contain minor populations of cells with non-clear eosinophilic cytoplasm, which is particularly common in high-grade tumors.7 Sarcomatoid differentiation occurs in 5% of tumors and is associated with a poor prognosis.7 In cases with sarcomatoid differentiation, it has been reported that the rate of metastasis at presentation or the time of nephrectomy ranges from 45% to 77%.8-12 A few reports have reported that cases of RCC could have rhabdoid tumor cells at a rate of 3.2% to 7.4%.12-16 The rhabdoid feature is characterized as sheets and clusters of variably large epithelioid cells that often have eccentric nuclei and large, paranuclear intracytoplasmic hyaline globules.17 These features were most often admixed with CCRCC and associated with poor outcome.12 When the diagnosis of RCC or determination of RCC subtypes is difficult by routine histologic examination, immunohistochemical staining may be helpful.18,19 Usually, it is easy to diagnose metastatic RCC and to determine RCC subtype by routine histologic examination of a metastatic specimen. However, diagnosis can be complicated by diverse histologic variations of RCC, as mentioned earlier. In addition, it is not uncommon to diagnose metastatic RCC lesions based only on a small biopsy specimen of a metastatic lesion without having access to the histology of the primary lesion. It can be very difficult to diagnose these samples if the small biop sy specimen consists of tumor cells showing only non-typical histologic features. Therefore, it is important to understand the histologic variations of metastatic CCRCC. Recently, Abel et al.20,21 reported two large consecutive studies regarding histologic features of metastatic RCC and pointed out that a small preoperative needle biopsy specimen from the primary or metastatic lesion may not represent characteristics of the whole tumor. However, further research on the histomorphology of metastatic RCC is still necessary. In this study, we investigated the diverse histologic features of metastatic CCRCCs in comparison with primary lesions.

Molecular classification of lung cancer correlates well with histomorphological features. However, specific histomorphological features that differentiate anaplastic lymphoma kinase (ALK)-rearranged tumors from ALK-negative tumors have not been fully evaluated. Eighty ALK-rearranged and 213 ALK-negative (91 epidermal growth factor receptor-mutated; 29 K-ras-mutated; 93 triple-negative) resected lung adenocarcinomas were analyzed for several histomorphological parameters and histological subtype. ALK-rearranged tumors were associated with younger age at presentation, frequent nodal metastasis, and higher stage of disease at diagnosis. ALK-rearranged tumors were more likely to show a solid predominant pattern than ALK-negative tumors (43.8%; 35/80; p

Anti-tuberculosis drugs can produce levels of hepatotoxicity ranging from mild elevation of aminotransferase to severe acute hepatitis. A few cases of drug-induced autoimmune hepatitis or the drug reaction with eosinophilia and systemic symptom (DRESS) syndrome by anti-tuberculosis medications have been reported. However, concomitant occurrence of these two disorders has not been reported. Here, we present a case of severe acute hepatitis with DRESS syndrome and autoimmune hepatitis resulting from primary standard anti-tuberculosis drugs. Both conditions were successfully treated with a systemic steroid regimen. (Korean J Gastroenterol 2016;67:267-271)

Background The prognostic value of cyclooxygenase-2 (COX-2) in human renal cell carcinoma (RCC) remains unclear. The purposes of this study are to elucidate the clinical significance of COX-2 in clear cell RCC (CCRCC) and to assess the treatment effect of COX-2 inhibition on CCRCC cell lines. Methods Using tumor samples obtained from 137 patients who had undergone nephrectomy at Seoul National University Hospital, we evaluated COX-2 expression on immunohistochemistry. Moreover, we performed the cell proliferation assay using 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl-2H tetrazolium bromide (MTT) and cell invasion assay. Thus, we evaluated the effect of meloxicam, an inhibitor of COX-2, in two human CCRCC cell lines. Results Cancer-specific survival (p=0.038) and progression-free survival (p=0.031) were shorter in the COX-2 high expression group. A multivariate logistic regression model showed that COX-2 expression was an independent risk factor for pTNM stage and Fuhrman nuclear grade. The MTT assay revealed that COX-2 inhibition led to the suppression of the proliferation of CCRCC cell lines. Moreover, it also reduced their invasion capacity. Conclusions This study postulates that COX-2 is a poor prognostic indicator in human CCRCC, suggesting that COX-2 inhibition can be a potential therapy in CCRCC.

Background The aim of this study was to determine the incidence and clinicopathological significance of c-MYC gene copy-number (GCN) gain in patients with primary colorectal cancer (CRC). Methods The c-MYC GCN was investigated in 367 consecutive CRC patients (cohort 1) by using dual-color silver in situ hybridization. Additionally, to evaluate regional heterogeneity, we examined CRC tissue from 3 sites including the primary cancer, distant metastasis, and lymph-node metastasis in 152 advanced CRC patients (cohort 2). KRAS exons 2 and 3 were investigated for mutations. Results In cohort 1, c-MYC gene amplification, defined by a c-MYC:centromere of chromosome 8 ratio ≥ 2.0, was detected in 31 (8.4%) of 367 patients. A c-MYC GCN gain, defined by ≥ 4.0 c-MYC copies/nucleus, was found in 63 (17.2%) patients and was associated with poor prognosis (P = 0.015). Multivariate Cox regression analysis showed that the hazard ratio for c-MYC GCN gain was 2.35 (95% confidence interval, 1.453–3.802; P < 0.001). In a subgroup of stage II-III CRC patients, c-MYC GCN gain was significantly associated with poor prognosis by univariate (P = 0.034) and multivariate (P = 0.040) analyses. c-MYC protein overexpression was observed in 201 (54.8%) out of 367 patients and weakly correlated with c-MYC GCN gain (ρ, 0.211). In cohort 2, the c-MYC genetic status was heterogenous in advanced CRC patients. Discordance between GCN gain in the primary tumor and either distant or lymph-node metastasis was 25.7% and 30.4%, respectively. A similar frequency for c-MYC GCN gain and amplification was observed in CRC patients with both wild-type and mutated KRAS. Conclusions c-MYC GCN gain was an independent factor for poor prognosis in consecutive CRC patients and in the stage II-III subgroup. Our findings indicate that the status of c-MYC may be helpful in predicting the patients’ outcome and for managing CRC patients.

†† Study Design: A case report. Objectives: Nodular fasciitis is a non-neoplastic soft-tissue lesion located in the deep subcutaneous region; it may be misdiagnosed as a malignant tumor due to its rapid growth and microscopic characteristics. We introduce an unusual case of nodular fasciitis which presented as a posterior neck mass. Summary of Literature Review: Nodular fasciitis is an unusual benign lesion.Becaue it sometimes shows aggressive microscopic characteristics, (being hypercellular and polymorphic), the condition has the potential to be misdiagnosed as sarcoma. Materials and Methods: A 20-year-old woman presented with a 1-month history of a progressively enlarging mass on her posterior neck. Computed tomography (CT) scans of the neck showed a markedly enhanced, well-defined, ovoid soft tissue mass at the posterior of the spinous process of C2. The patient underwent marginal excision. There was a 2 cm, well–capsulated, pinkish-gray mass. Results: She recovered without any complications. Histopathologic examination showed a spindle cell proliferation, increased cellularity, and nuclear atypia with mitosis. The immunohistochemistry stain showed negative findings. The mass was diagnosed as nodular fasciitis. Conclusions: A diagnosis of nodular fasciitis, not just malignant tumor, should be considered for a rapidly growing posterior neck mass showing aggressive microscopic appearance, Nodular fasciitis is a self-limiting lesion readily treated by marginal excision. However, follow-ups should be increased to watch for recurrence.

Background: Because of recent advances in the molecular diagnosis of cancer patients, tissue quality has become more important in daily practice. Methods: To evaluate the effects of fixative, duration of fixation, decalcification, and storage periods on nucleic acid integrity, DNA and RNA were extracted from gastrointestinal cancer tissue. The yield and purity were analyzed, and polymerase chain reaction (PCR) for glyceraldehyde 3-phosphate dehydrogenase (GAPDH; 60 bp), β-actin (148 bp), and human growth hormone (hGH; 434 bp) and real-time reverse transcriptionPCR for β-actin (97 bp) were performed. Results: All formalin-fixed paraffin-embedded (FFPE) and methacarn-fixed paraffin-embedded (MFPE) samples tested positive for GAPDH and β-actin by PCR. hGH was successfully detected in all MFPE samples, but in only 46.7% of the FFPE samples. Prolonged formalin fixation resulted in fewer GAPDH and β-actin PCR products, and amplification of hGH was not successful. The PCR and reverse transcription-PCR results were significantly affected by the duration of decalcification. The yield, purity, and integrity of mRNA progressively decreased with increased storage periods of paraffin blocks. Conclusions: Fixation and storage should therefore be standardized in order to improve the quality of molecular pathologic diagnosis.

We report a rare case of an idiopathic pseudoaneurysm causing intraventricular hemorrhage (IVH). A 28-year-old man presented with sudden onset of severe headache. He underwent external ventricular drainage for an isolated IVH in the right lateral ventricle. Digital subtraction angiography (DSA) revealed that the aneurysm (7.5×4.5 mm) arose from the distal part of the medial lenticulostriate artery. Following removal of the external ventricular drainage catheter, the aneurysm decreased in size (4.0×2.3 mm). However, follow-up DSA revealed a slightly enlarged aneurysm (4.2×3.2 mm) with morphologic change. The aneurysm was clipped via the interhemispheric transcallosal approach, but postoperative DSA revealed a residual aneurysm sac beside the clips. Given the risk of rebleeding, a second operation was planned for complete resection of the aneurysm. After revised craniotomy and careful dissection of the caudate nucleus, the aneurysm sac was completely resected. Histopathological examination revealed that the aneurysm was a pseudoaneurysm. The patient recovered without any neurological sequel and was discharged. To the best of our knowledge, this is the first reported case of an idiopathic lenticulostriate artery pseudoaneurysm protruding into the right lateral ventricle and causing an IVH that was successfully treated with microsurgical resection.

Renal cancer is a common cancer, with an incidence of about 10.1% in Korean males in 2010.1 Renal cell carcinoma (RCC) of adults represents 90% of all renal cancers.2 The 5-year survival rate of patients with localized RCC is more than 70%, which is relatively excellent, although there are some differences according to the subtype. However, the 5-year survival rate of patients with advanced RCC is poor.3 Recently, many targeted therapies have been tried on advanced RCC patients.4 After the anaplastic lymphoma kinase (ALK) gene rearrangement was first reported in anaplastic large-cell lymphoma in 1994, it was reported in several human cancers including diffuse large B-cell lymphoma, plasmacytoma, non-small cell lung cancer, and neuroblastoma and its oncogenic role is still under research.5-9 Even though the physiologic role of the ALK gene is still being uncovered, the clinical therapeutic trial for a kinase inhibitor against ALK in non-small lung cancer patients is ongoing, and early reports indicate excellent interim result.10 The recent case report showed an excellent treatment outcome with the ALK inhibitor on an ALK-rearranged inflammatory myofibroblastic tumor patient,11 and some in vitro studies showed the effectiveness of the ALK inhibitor on ALK-positive anaplastic large cell lymphoma, diffuse large B-cell lymphoma, and neuroblastoma.12-14 Therefore, we anticipate increased use of ALK inhibitors in the treatment of human cancers in the future. The detection methods of ALK gene rearrangement are divided into two major categories. One is the method detecting gene rearrangement indirectly via ALK immunohistochemistry, which detects protein overexpression, and the other is the direct method of in situ hybridization.15-17 Several studies have reported RCC cases with ALK gene fusion and the fusion partners of these genes have been diverse. The subtypes of these RCCs were non-clear cell type such as papillary type, medullary type, and unclassified type.18-21 But there has been no study on ALK gene rearrangement in Korean RCC patients. In this study, we screened consecutively resected RCCs from a single institution for ALK protein expression by immunohistochemistry, and then we performed fluorescence in situ hybridization (FISH) analysis to confirm the ALK gene alteration in ALK immunohistochemistry-positive cases. Here, we report a RCC case with ALK gene rearrangement among 829 RCCs.

Background During specimen processing in surgical pathology laboratories, specimen-related adverse events (SRAEs), such as mislabeling and specimen mixed-up might occur. In these situations, molecular techniques using short tandem repeat (STR) loci are required to identify the personal identity. Microsatellite instability (MSI) test is widely used for screening the hereditary non-polyposis colon cancer (Lynch syndrome) in surgical pathologies using polymorphic STR markers. We tried to evaluate the applicability of the MSI test for SRAEs. Methods We obtained 253 MSI test results to analyze the allele frequencies. After calibrating the estimated nucleotide lengths, we calculated the allele frequencies, a random match probability, and a likelihood ratio (LR) of three dinucleotide STR markers (D5S349, D17S250, and D2S123). Results The distribution of LR was 136.38 to 5,606,213.10. There was no case of LR10,000. Furthermore, the combined probability of identity was 9.23×10-4 and the combined power of exclusion was 0.99908. Conclusions Using the three STR markers that are recommended for MSI test, all the cases were positively identified in 1% range and about one-third cases showed high LR (>10,000). These results showed that MSI tests are useful to screen the personal identity in case of SRAE in pathology laboratories.