Hepatic Involvement of Diffuse Large B-Cell Lymphoma Mimicking Antinuclear Antibody-Negative Autoimmune Hepatitis Diagnosed by Liver Biopsy.

Non-Hodgkin's lymphoma (NHL) is the fifth most common hematologic disorder in the United States, and its prevalence has been rising in Western countries. Among the subtypes of NHL, diffuse large B-cell lymphoma (DLBCL) mostly involves the lymph nodes, stomach, and gastrointestinal tract, whereas hepatic involvement of DLBCL is rare. On serologic testing, elevated immunoglobulin G (IgG) levels can be observed in DLBCL; however, elevated IgG levels are mainly observed in autoimmune hepatitis. A targeted-lesion biopsy is required for the diagnosis of DLBCL. Based on a final diagnosis, the patient was treated with rituximab-based chemotherapy, including cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy (R-CHOP). Herein, we report a case of DLBCL mimicking antinuclear antibody-negative autoimmune hepatitis, which was finally diagnosed as DLBCL involving the liver, and was confirmed by liver biopsy.

Clinical significance of insulin-growth factor 1 and insulin-growth factor 1 receptor expression in gastrointestinal stromal tumors.

BACKGROUND/AIMS: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors in the gastrointestinal tract and are mostly driven by KIT and PDGFRA-activation mutations. However, other signaling pathways are involved in pathogenesis and proliferation of GISTs. This study investigates the prognostic significance of insulin-like growth factor 1 (IGF1) and IGF1 receptor (IGF1R) and the role of succinate dehydrogenase subunit B (SDHB) in GISTs. METHODOLOGY: Immunohistochemistry (IHC) for IGF1, IGF1R and SDHB was performed in total of 165 GISTs. RESULTS: The overexpression of IGF1 was evident in tumors with high mitotic count, large tumor size and was correlated with high risk of malignant behavior. IGF1R overexpression was correlated with IGF overexpression, high mitotic count and high risk of malignant behavior. Loss of expression for SDHB was found in only 2 gastric GISTs. CONCLUSIONS: The overexpression of IGF1 and IGF1R can be useful marker to predict relapse and aggressive behavior in GISTs and has prognostic implications.

High TEAD4 Expression is Associated With Aggressive Clear Cell Renal Cell Carcinoma, Regardless of YAP1 Expression.

Yes-associated protein 1 (YAP1) and transcriptional coactivator TEA domain transcription factor 4 (TEAD4) are the main effectors of the Hippo signaling pathway. Deregulation of the Hippo signaling pathway significantly impacts tumorigenesis and tumor progression. We evaluated the mRNA expression level of YAP1 and TEAD4 using the Gene Expression Profiling Interactive Analysis database and investigated the roles of YAP1 and TEAD4 in 349 surgically resected clear cell renal cell carcinoma (CCRCC) samples through immunohistochemical analysis. High YAP1 and TEAD4 expression were observed in 57 (16.3%) and 131 (37.5%) cases, respectively. High YAP1 expression was associated with a low nuclear grade only. High TEAD4 expression was significantly associated with large tumor size, high nuclear grade, lymphovascular invasion, advanced pT classification, advanced clinical stage, sarcomatous differentiation, and metastasis. CCRCC with YAP1-low/TEAD4-high expression was significantly associated with aggressive clinicopathological variables and poor outcomes. For CCRCC, higher tumor stage, sarcomatous differentiation, and metastasis were the independent prognostic factors for overall survival (OS) and disease-free survival (DFS). High TEAD4 expression was significantly associated with short OS and DFS but was not an independent prognostic factor. High TEAD4 and YAP1-low/TEAD4-high expression significantly correlated with adverse clinicopathological factors and worse OS and DFS in patients with CCRCC. YAP1 expression was not significantly associated with clinicopathological factors or patient survival. Therefore, TEAD4 plays a critical role in CCRCC tumor progression independent of YAP1 and may be a potential biomarker and therapeutic target for CCRCC.

A Standardized Pathology Report for Gastric Cancer: 2nd Edition.

The first edition of 'A Standardized Pathology Report for Gastric Cancer' was initiated by the Gastrointestinal Pathology Study Group of the Korean Society of Pathologists and published 17 years ago. Since then, significant advances have been made in the pathologic diagnosis, molecular genetics, and management of gastric cancer (GC). To reflect those changes, a committee for publishing a second edition of the report was formed within the Gastrointestinal Pathology Study Group of the Korean Society of Pathologists. This second edition consists of two parts: standard data elements and conditional data elements. The standard data elements contain the basic pathologic findings and items necessary to predict the prognosis of GC patients, and they are adequate for routine surgical pathology service. Other diagnostic and prognostic factors relevant to adjuvant therapy, including molecular biomarkers, are classified as conditional data elements to allow each pathologist to selectively choose items appropriate to the environment in their institution. We trust that the standardized pathology report will be helpful for GC diagnosis and facilitate large-scale multidisciplinary collaborative studies.

A standardized pathology report for gastric cancer: 2nd edition.

The first edition of 'A Standardized Pathology Report for Gastric Cancer' was initiated by the Gastrointestinal Pathology Study Group of the Korean Society of Pathologists and published 17 years ago. Since then, significant advances have been made in the pathologic diagnosis, molecular genetics, and management of gastric cancer (GC). To reflect those changes, a committee for publishing a second edition of the report was formed within the Gastrointestinal Pathology Study Group of the Korean Society of Pathologists. This second edition consists of two parts: standard data elements and conditional data elements. The standard data elements contain the basic pathologic findings and items necessary to predict the prognosis of GC patients, and they are adequate for routine surgical pathology service. Other diagnostic and prognostic factors relevant to adjuvant therapy, including molecular biomarkers, are classified as conditional data elements to allow each pathologist to selectively choose items appropriate to the environment in their institution. We trust that the standardized pathology report will be helpful for GC diagnosis and facilitate large-scale multidisciplinary collaborative studies.

ATRX protein is a potential prognostic marker in clear cell renal cell carcinoma.

Objective: Cancer cells activate either telomerase or alternative lengthening of telomeres (ALT) to maintain telomere length and achieve immortalization. Alpha thalassemia/mental retardation X-linked (ATRX) is involved in chromatin remodeling. Mutations in ATRX genes are associated with the loss of nuclear expression and correlated with the ALT phenotype. ATRX expression has been evaluated in various cancers, especially sarcoma and neuroendocrine tumors, and its clinical significance has been shown to be diverse, depending on the tumor types. The role and prognostic value of ATRX expression in clear cell renal cell carcinoma (CCRCC) have not been elucidated. Methods: We investigated the messenger RNA (mRNA) expression levels of ATRX using the gene expression profiling interactive analysis (GEPIA) database and evaluated the expression of ATRX using immunohistochemical (IHC) staining in 302 CCRCC cases. Results: Loss of ATRX expression was significantly associated with larger tumor size, higher nuclear grade (NG), lymphovascular invasion (LVI), pathologic T (pT) stage, recurrence/metastasis, and stage. Although ATRX was not an independent prognostic factor, patients with loss of ATRX expression showed poor survival. Conclusion: Our findings suggest that loss of ATRX expression could be a potential biomarker for predicting aggressive tumor behavior and poor clinical outcomes in CCRCC.

Prognostic significance of MCM6 expression in gastrointestinal stromal tumor.

Minichromosome maintenance (MCM) proteins are essential for the initiation of DNA replication and they are prognostic markers in various human cancers. The aim of this study was to investigate the role of the MCM6 protein in gastrointestinal stromal tumor (GIST) and its clinical and prognostic significance. We evaluated MCM6 expression in 211 GIST samples using immunohistochemistry. We used the receiver operating characteristic curve (ROC) to identify optimal cut-off values. High MCM6 expression was associated with tumor size, mitosis, tumor necrosis, presence of recurrence/metastasis, and the National Institute of Health (NIH) and Armed Forces Institute of Pathology (AFIP) malignant risk criteria. Patients with high MCM6 expression had significantly shorter overall survival (OS) and disease-free survival (DFS) than those with low MCM6 expression. Univariate analysis indicated that tumor size, mitosis, AFIP and NIH malignant risk criteria, and high MCM6 expression were significantly associated with poor OS and DFS. High MCM6 expression and high-risk group categorization based on the NIH criteria were independent prognostic factors for OS and DFS. High MCM6 expression is significantly associated with tumor progression and aggressiveness and is an independent factor for shorter survival in GIST patients. MCM6 expression could be a predictive biomarker for tumor aggressiveness as well as a treatment target.

High MCM6 Expression as a Potential Prognostic Marker in Clear-cell Renal Cell Carcinoma.

AIM: Minichromosome maintenance (MCM) proteins are involved in initiation of DNA replication and cell-cycle progression. Loss of MCM function results in genomic instability and causes carcinogenesis. Among MCM genes, the role and prognostic value of MCM6 expression in clear-cell renal cell carcinoma (ccRCC) has not been elucidated. MATERIALS AND METHODS: We assessed the mRNA expression level of MCM6 using the Gene Expression Profiling Interactive Analysis database and investigated MCM6 protein expression by immunohistochemistry in 238 ccRCC cases. RESULTS: High MCM6 expression was significantly associated with increasing tumor size, pT, stage, tumor necrosis, and metastasis. Furthermore, high MCM6 expression was significantly associated with shorter overall and disease-free survival, and was an independent unfavorable prognostic marker. Regarding patients with metastasis, high MCM6-expressing ccRCC conferred significantly shorter survival than for those with low expression. CONCLUSION: A high MCM6 expression level may be a promising biomarker to predict tumor progression, metastasis, and survival in patients with ccRCC.

Current trends in the epidemiological and pathological characteristics of gastrointestinal stromal tumors in Korea, 2003-2004.

Despite remarkable progress in understanding and treating gastrointestinal stromal tumors (GISTs) during the past two decades, the pathological characteristics of GISTs have not been made clear yet. Furthermore, concrete diagnostic criteria of malignant GISTs are still uncertain. We collected pathology reports of 1,227 GISTs from 38 hospitals in Korea between 2003 and 2004 and evaluated the efficacy of the NIH and AFIP classification schemes as well as the prognostic factors among pathologic findings. The incidence of GISTs in Korea is about 1.6 to 2.2 patients per 100,000. Extra-gastrointestinal GISTs (10.1%) are more common in Korea than in Western countries. In univariate analysis, gender, age, tumor location, size, mitosis, tumor necrosis, vascular and mucosal invasions, histologic type, CD34 and s-100 protein expression, and classifications by the NIH and AFIP criteria were found to be significantly correlated with patient's survival. However, the primary tumor location, stage and classification of the AFIP criteria were prognostically significant in predicting patient's survival in multivariate analysis. The GIST classification based on original tumor location, size, and mitosis is more efficient than the NIH criteria in predicting patient's survival, but the mechanism still needs to be clarified through future studies.

Analysis of microsatellite instability, protein expression and methylation status of hMLH1 and hMSH2 genes in gastric carcinomas.

BACKGROUND/AIMS: Microsatellite instability (MSI) is a manifestation of a defective DNA mismatch repair system. It is caused by germline mutations of mismatch repair genes or CpG islands hypermethylation. The majority of cancers of hereditary nonpolyposis colorectal cancer (HNPCC) syndrome have MSI+ phenotype. The colorectal cancers show distinctive clinicopathological characteristics and prognoses according to the MSI status. However, there is a wide variety of results between MSI and clinicopathological parameters in gastric carcinomas. METHODOLOGY: Five hundred and twenty-one surgically resected gastric carcinomas were studied and the correlation with clinicopathological parameters, MSI status by using five microsatellite markers, expression of hMLH1 and hMSH2 protein by immunohistochemical stain, and methylation of hMLH1 and hMSH2 by methylation-specific polymerase chain reaction was analyzed. RESULTS: There were 50 (9.6%) high-frequency MSI (MSI-H) cases. The MSI-H gastric carcinomas were associated with older age, expanding type by Ming's classification, lymphatic invasion, tumor multiplicity, losses of hMLH1 and hMSH2 protein expressions. The methylation frequency of hMLH1 was 75.5% in MSI-H gastric carcinomas. CONCLUSIONS: Our results suggest that epigenetic inactivation of hMLH1 might play a role in the carcinogenesis of MSI-H gastric carcinomas. The immunohistochemical stain for hMLH1 protein expression could be used in routine diagnostic methods for predicting MSI status.

CA9 overexpression is an independent favorable prognostic marker in intrahepatic cholangiocarcinoma.

The aim of this study is to evaluate the expression of carbonic anhydrase IX (CA9) and to identify its prognostic significance in intrahepatic cholangiocarcinoma (IHCC). We performed immunohistochemistry (IHC) for CA9 in a total of 85 IHCCs. CA9 overexpression was observed in 38 of 85 (44.7%) IHCCs. CA9 overexpression was related to tumors with intraductal growth than mass forming or periductal infiltrative type. CA9 overexpression was more observed in tumors with well/moderate differentiation than poor differentiation and without lymph node metastasis. No significant correlation was observed in CA9 overexpression with tumor size, pT, stage and lymphovascular invasion. Intrahepatic cholangiocarcinomas with CA9 overexpression showed better overall survival than that without expression (P = 0.001). In multivariate analysis, lymph node metastasis (95% CI: 2.103 (1.167-3.791), P = 0.013) was an independent poor prognostic factor. IHCC with CA9 overexpression showed a 0.5-fold (95% confidence interval, 0.328-0.944) lower risk of death compared with those of no or weak expression. CA9 overexpression was related to histologic differentiation and an independent good prognostic factor.

Sclerosing extramedullary hematopoietic tumor presenting as an inguinal mass in a patient with primary myelofibrosis: a diagnostic pitfall.

Sclerosing extramedullary hematopoietic tumor (SEMHT) is a rare lesion and presented as retroperitoneal or serosal-based mass. A 53-year-old man with a long history of primary myelofibrosis, presented with abdominal distension and inguinal mass. Pathologic examination of inguinal mass revealed a prominent sclerotic background with thick collagen deposits and mono, bi, or tri-lineage hematopoietic tissue containing atypical megakaryocytes and variable proportions of myeloid and erythroid series. The atypical megakaryocytes were positive for Factor VIII and CD61. SEMHT may be misdiagnosed as lymphocyte depleted Hodgkin's disease, as a mesenchymal neoplasm, or as carcinoma, because of the presence of large atypical cells and marked fibrosis when clinical information regarding PMF is unknown. Awareness of the bizarre atypical megakaryocyte morphology with immature hematopoietic cells and of clinical history is essential to prevent misdiagnosis.

Metastasizing dermatofibroma in lung.

Benign dermatofibroma is very common skin tumor and can very rarely metastasize. We report a case of metastasizing dermatofibroma on a 36-year-old woman who presented multiple bilateral lung nodules. She underwent incisional biopsy for cellular dermatofibroma of the right shoulder 7 years ago. Chest computed tomographic scanning shows multiple nodules in both lung fields. Segmental and wedge resections were done. Grossly, the masses were hemorrhagic cysts. Microscopically, there were dilated cystic airspaces. The airspaces were lined by respiratory and metaplastic squamous epithelium with underlying layers of fibrohistiocytic spindle cells with storiform and fascicular pattern. The tumor cells stained for CD68 and CD10. The lung mass shows same histologic features with skin lesion.