Mi Jin Gu

Adenocarcinoma of the small intestine: a multi-institutional study of 197 surgically resected cases

Small intestinal adenocarcinoma is a rare malignant neoplasm, and its clinicopathologic characteristics have not been well elucidated. A total of 197 small intestinal adenocarcinoma cases were collected from 22 institutions in South Korea and were evaluated for clinicopathologic factors that affect the prognosis of small intestinal adenocarcinoma patients using univariate and multivariate analyses. The mean patient age was 59 years, and the male-to-female ratio was 1.7:1. Tumors were located in the duodenum of 108 cases (55%), the jejunum in 59 (30%), and the ileum in 30 (15%). Predisposing conditions were observed in 23 cases (12%), including 17 cases with sporadic adenomas, 3 with Peutz-Jeghers syndrome, 2 with Meckel diverticulum, and 1 with Crohn disease. Synchronous or metachronous malignant tumors were identified in 31 cases (16%), including 13 colorectal and 10 stomach cancers. About 90% of tumors were classified as either pT3 (63 cases) or pT4 (112 cases). The median survival time for all small intestinal adenocarcinoma patients was 39.7 months. Compared with small intestinal adenocarcinomas without accompanying sporadic adenomas, small intestinal adenocarcinomas with accompanying adenomas were more well differentiated (P < .0001), with a more polypoid growth pattern (P < .0001), a lower pT classification (P < .0001), less perineural invasion (P = .01), and less lymphatic invasion (P = .03). Small intestinal adenocarcinoma patients with associated sporadic adenomas (77%) had a significantly better 5-year survival rate than those without sporadic adenomas (38%, P = .02). By univariate analysis, small intestinal adenocarcinoma patients had significantly different survival based on pT classification (P = .003), lymph node metastasis (P < .0001), distal location (jejunal and ileal carcinomas) (P = .003), retroperitoneal tumor seeding (P < .0001), vascular invasion (P = .007), lymphatic invasion (P = .001), peritumoral dysplasia (P = .004), and radiation therapy (P = .006). By multivariate analysis, lymph node metastasis (P = .01) and distal location (P = .003) were independent predictors of a worse prognosis. In conclusion, (1) small intestinal adenocarcinomas are diagnosed at an advanced disease stage; therefore, the development of strategies for detection at an earlier stage is needed. (2) Small intestinal adenocarcinoma patients with an adenomatous component had a better survival than those without an adenomatous component. (3) Lymph node metastasis and distal location (jejunum and ileum) of tumor are the most important independent prognostic factors.

Neuroendocrine differentiation correlates with hormone receptor expression and decreased survival in patients with invasive breast carcinoma.

Invasive breast carcinoma (IBC) with neuroendocrine (NE) differentiation has been controversial in terms of its definition and clinical outcome. We investigated the incidence and clinical significance of NE differentiation in patients with IBC.

Primary clear cell sarcoma of bone

Clear cell sarcoma is a rare soft tissue sarcoma of young adults with melanocytic differentiation. It occurs predominantly in the soft tissue of extremities, typically involving tendons and aponeuroses. Primary clear cell sarcoma of bone is extremely rare. We report a case of primary clear cell sarcoma of the right first metatarsal in a 48-year-old woman and provide a literature review of the entity.

Loss of ARID1A expression is associated with poor prognosis in small intestinal carcinoma

To investigate AT‐rich interactive domain‐containing protein 1A (ARID1A) and p53 expression in small intestinal carcinoma (SIC) and to determine its prognostic significance.

Clinicopathologic significance of Sox2, CD44 and CD44v6 expression in intrahepatic cholangiocarcinoma.

Embryonic stem cells (ESC) and cancer stem cells (CSC) have a capacity for self-renewal and differentiation into multiple cell lineages. Sox2 plays a critical role in ESC and has been shown to participate in carcinogenesis and tumor progression in many human cancers. CD44 and CD44v6 are putative CSC markers and their association with tumor progression, metastasis, and tumor relapse after treatment has been demonstrated. We evaluated the immunoexpression of Sox2, CD44, and CD44v6 in 85 cases of Intrahepatic cholangiocarcinomas (IHCC) and assessed their prognostic significance. Sox2 expression showed a significant association with lymph node metastasis (p = 0.025), T4 stage (p = 0.046), and worse overall survival (p = 0.047). Greater expression of Sox2 was observed in IHCC with poor differentiation, vascular invasion, and stage IV, without statistical significance (p > 0.05). CD44 expression showed an association with periductal infiltrative type (p = 0.034), poor differentiation (p = 0.012), and vascular invasion (p = 0.009). CD44v6 expression was evident in patients with stage IV (p = 0.019). These results demonstrated that Sox2 expression is associated with aggressive behavior and poor overall survival in IHCC.

Clinicopathological significance of E-cadherin, β-catenin and epidermal growth factor receptor expression in intrahepatic cholangiocarcinoma.

BACKGROUND/AIMS The study investigated the pathogenetic role of e-cadherin, β-catenin, and epidermal growth factor receptor (EGFR) in cholangiocarcinoma (CC) and analyzed the correlation with clinicopathological factors. METHODOLOGY Eighty three patients with CC who had undergone resection were studied. The expression of E-cadherin, β-catenin and EGFR was examined by immunohistochemistry. RESULTS The down-regulation of E-cadherin and β-catenin was identified in 43/83 patients (51.8%) and 32/83 patients (38.6%), respectively. EGFR expression occurred in 46 of 83 patients (55.4%). The reduced membranous expression of E-cadherin was correlated with poor histological differentiation. The reduced membranous expression of β-catenin was correlated with higher tendency of vascular invasion and was more frequent in males. EGFR was more expressed in poorly differentiated CC. The reduced membranous expression of E-cadherin was significantly correlated with reduced expression of β-catenin. CONCLUSIONS The reduced expression of E-cadherin and β-catenin and EGFR over expression seems to be correlated with tumor differentiation and tumor progression than tumor invasion and tumor proliferation.

Epithelial-mesenchymal transition phenotype is associated with patient survival in small intestinal adenocarcinoma

Aims: We investigated the clinical significance of epithelial-mesenchymal transition (EMT) phenotype in 184 small intestinal adenocarcinomas (SIACs) based on the expression pattern of EMT-related proteins in cancer cells. Methods: Immunohistochemistry for epithelial (E-cadherin) and mesenchymal (vimentin and fibronectin) markers were performed and cases of SIAC were classified into four subtypes of EMT: complete type (E-cadherin–, vimentin+ and/or fibronectin+), wild type (E-cadherin+, vimentin–, fibronectin–), incomplete 1 type (hybrid type; E-cadherin+, vimentin+ and/or fibronectin+), and incomplete 2 type (null type; E-cadherin–, vimentin–, fibronectin–). Results: We identified 19 (10.3%) cases of complete EMT type, 86 (46.7%) cases of wild type and 79 (43%) cases of incomplete EMT type [hybrid type, 22 (12%) cases; null type, 57 (31%) cases]. Complete EMT phenotype showed a significant association with undifferentiated histology (p < 0.001). Overall survival of SIAC patients with complete EMT phenotype was significantly shorter than those of patients with incomplete (p = 0.001) and wild (p < 0.001) types. In multivariate analysis, complete EMT phenotype was an independent prognostic factor in SIAC patients (hazard ratio 2.3; 95% confidence interval 1.15–4.6; p = 0.019). Conclusion: Complete EMT phenotype stratifies a specific group representing a poor clinical outcome in patients with SIAC.

Fascin expression predicts lymph node metastasis and worse survival in small intestinal carcinoma

Summary Fascin expression has been associated with clinicopathological parameters and clinical outcome in many carcinomas. The aim of this study was to evaluate the prognostic impact of fascin expression in small intestinal carcinomas (SICs). We constructed tissue microarrays for evaluation of immunohistochemical expression of fascin in a total of 194 SICs. Fascin was expressed in 47 (24.2%) of the 194 SICs, and fascin expression showed an association with poorly and undifferentiated histology (p < 0.001) and lymphatic invasion (p = 0.019). No fascin expression was observed in tumour cells of metastatic lymph nodes in cases of SIC without fascin expression (p < 0.001). Patients with fascin expression showed significantly shorter overall survival compared to patients without expression (p = 0.001). In multivariate analysis, fascin expression was an independent prognostic factor in SIC patients (p = 0.043). Fascin expression showed significant correlation with lack of differentiation and lymphatic invasion, and may be a useful predictive marker for lymph node metastasis. Fascin expression in SICs showed an association with poor overall survival and was an independent poor prognostic factor.

Imprint Cytology of Soft Tissue Myoepithelioma: A Case Study

Soft tissue myoepithelioma is a rare neoplasm composed of myoepithelial cells. Here, we describe the cytologic features of soft tissue myoepithelioma arising on the right forearm in an 18-year-old man. The excised tumor (3.0×1.8×1.5 cm) was well-demarcated, yellow-gray, soft, and myxoid. The cytologic smears showed round to spindle, epithelioid, and plasmacytoid cells in the myxoid background. The nuclei were uniform, round to ovoid, with finely distributed chromatin and eosinophilic or pale cytoplasm. The tumor cells demonstrated immunoreactivity for cytokeratin (AE1/AE3), epithelial membrane antigen, S100 protein, and glial fibrillary acidic protein. Electron microscopy showed intermediate filaments, desmosomes, and basal lamina.

Molecular Testing for Gastrointestinal Cancer

With recent advances in molecular diagnostic methods and targeted cancer therapies, several molecular tests have been recommended for gastric cancer (GC) and colorectal cancer (CRC). Microsatellite instability analysis of gastrointestinal cancers is performed to screen for Lynch syndrome, predict favorable prognosis, and screen patients for immunotherapy. The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor has been approved in metastatic CRCs with wildtype RAS (KRAS and NRAS exon 2–4). A BRAF mutation is required for predicting poor prognosis. Additionally, amplification of human epidermal growth factor receptor 2 (HER2) and MET is also associated with resistance to EGFR inhibitor in metastatic CRC patients. The BRAF V600E mutation is found in sporadic microsatellite unstable CRCs, and thus is helpful for ruling out Lynch syndrome. In addition, the KRAS mutation is a prognostic biomarker and the PIK3CA mutation is a molecular biomarker predicting response to phosphoinositide 3-kinase/AKT/mammalian target of rapamycin inhibitors and response to aspirin therapy in CRC patients. Additionally, HER2 testing should be performed in all recurrent or metastatic GCs. If the results of HER2 immunohistochemistry are equivocal, HER2 silver or fluorescence in situ hybridization testing are essential for confirmative determination of HER2 status. Epstein-Barr virus–positive GCs have distinct characteristics, including heavy lymphoid stroma, hypermethylation phenotype, and high expression of immune modulators. Recent advances in next-generation sequencing technologies enable us to examine various genetic alterations using a single test. Pathologists play a crucial role in ensuring reliable molecular testing and they should also take an integral role between molecular laboratories and clinicians.