Gland Attenuation, a Novel Morphological Feature of Colorectal Cancer: Evidence for an Epithelial-Mesenchymal Transition

PURPOSE: Along the invasive margin, colorectal cancer may show distinctive morphologic changes characterized by an asymmetrically attenuating tumor gland with loss of polarity. The author coined the term ‘gland attenuation (GA)’ for these peculiar changes. The aims of this study were to compare the immunoreactivity of the epithelial-mesenchymal transition (EMT) markers E-cadherin and β-catenin and thus determine whether EMTs occurs at tumor budding (TB) or GA sites and to assess the association of TB and/or GA levels with clinicopathological parameters and prognosis. METHODS: Expression patterns of E-cadherin and β-catenin in the tumor centers at GA and TB sites were examined in 101 patients with well or moderately differentiated CRCs, and the prognostic significance of TB and/or GA was statistically evaluated. RESULTS: GA foci, as well as TB foci, revealed loss of membranous and cytoplasmic E-cadherin expressions and aberrant β-catenin expression with reduced membranous expression and increased localization to the nucleus, suggesting that EMTs occur in GA as well as in TB. The high-TB and the TB-dominant groups were significantly correlated with advanced invasion depth, presence of lymph node metastasis, advanced pathologic staging and presence of lymphovascular invasion. The high-TB and the TB-dominant groups showed poor overall survival (OS) and recurrence-free survival (RFS), and high TB was an independent prognostic factor in the multivariate analyses for OS and RFS. CONCLUSION: This study showed evidence that EMTs occurs at GA sites as well as TB foci. TB is a strong and independent prognostic factor, and TB-dominance may be an indicator of adverse clinical outcome.

Difference of the Nuclear Green Light Intensity between Papillary Carcinoma Cells Showing Clear Nuclei and Non-neoplastic Follicular Epithelia in Papillary Thyroid Carcinoma

BACKGROUND: There is subjective disagreement regarding nuclear clearing in papillary thyroid carcinoma. In this study, using digital instruments, we were able to quantify many ambiguous pathologic features and use numeric data to express our findings. METHODS: We examined 30 papillary thyroid carcinomas. For each case, we selected representative cancer cells showing clear nuclei and surrounding non-neoplastic follicular epithelial cells and evaluated objective values of green light intensity (GLI) for quantitative analysis of nuclear clearing in papillary thyroid carcinoma. RESULTS: From 16,274 GLI values from 600 cancer cell nuclei and 13,752 GLI values from 596 non-neoplastic follicular epithelial nuclei, we found a high correlation of 94.9% between GLI and clear nuclei. GLI between the cancer group showing clear nuclei and non-neoplastic follicular epithelia was statistically significant. The overall average level of GLI in the cancer group was over two times higher than the non-neoplastic group despite a wide range of GLI. On a polygonal line graph, there was a fluctuating unique difference between both the cancer and non-neoplastic groups in each patient, which was comparable to the microscopic findings. CONCLUSIONS: Nuclear GLI could be a useful factor for discriminating between carcinoma cells showing clear nuclei and non-neoplastic follicular epithelia in papillary thyroid carcinoma.

Expression of HuR and Cyclooxygenase-2 in Nodular Fasciitis and Low-Grade Sarcoma: An Immunohistochemical Study

BACKGROUND: Nodular fasciitis is the most common reactive mesenchymal lesion to be misidentified as a type of sarcoma. HuR is an mRNA-binding protein that can stabilize cyclooxygenase-2 (COX-2) mRNA leading to COX-2 overexpression. The aim of this study is a comparison of the expressions of COX-2 and HuR and the relationships between their expressions and the clinicopathological parameters in nodular fasciitis and low-grade sarcoma. METHODS: We measured the expression of HuR and COX-2 in 21 cases of nodular fasciitis and 37 cases of low-grade sarcoma using immunohistochemistry. RESULTS: The frequency of cytoplasmic immunoreactivity for HuR was 5 of 21 cases of nodular fasciitis (23.8%) and 23 of 37 cases of low-grade sarcoma (62.1%) (p=.013). COX-2 expression was moderate or strong in nodular fasciitis (12/21, 57.1%) and in low-grade sarcoma (29/37, 78.4%) (p=.034). In addition, a significant difference existed between these two entities in terms of the relationship between moderate or strong COX-2 expression and HuR cytoplasmic immunoreactivity (p=.009). Moderate or strong COX-2 immunoreactivity correlated with nuclear (p=.016) or cytoplasmic HuR (p=.024) expression in low-grade sarcoma but not in nodular fasciitis. CONCLUSIONS: This study suggests that HuR and COX-2 expression may be useful to differentiate nodular fasciitis from low-grade sarcoma.

Langerhans Cell Sarcoma Arising in a Lymph Node: A Case Report and Review of the Literature

We report a case of Langerhans cell sarcoma presented as a solitary mass in the left supraclavicular area in a 31-year-old woman. Computed tomography revealed a relatively well-defined and lightly enhancing mass in the left supraclavicular area, measuring 5.5x4.5x3.2 cm. Excision was subsequently performed. Microscopically, the specimen consisted of an enlarged and partially effaced lymph node. Nests of different size composed of atypical tumor cells were located in the paracortex and the medulla of the lymph node. The tumor cells exhibited abundant eosinophilic or clear cytoplasm and displayed marked nuclear atypia and increased mitotic figures. Infiltration of many eosinophils was identified in the periphery and between the tumor cells. The tumor cells were reactive for CD1a and S100 protein. Ultrastructually, they were found to have Birbeck granules in the cytoplasm.

The Stromal Overexpression of Decay Accelerating Factor (DAF/CD55) Correlates with Poor Clinical Outcome in Colorectal Cancer Patients

BACKGROUND: Decay accelerating factor (DAF/CD55), regulates the complement system by accelerating decay of the C3 convertase, has been described in several malignancies, however, the clinicopathologic significance of CD55 and its receptor CD97 has not been fully investigated. We examined the expression patterns of both CD55 and CD97 and their association with clinicopathologic parameters in colorectal cancers (CRCs). METHODS: Expression patterns of CD55 and CD97 in the stroma and tumor cells at tumor center and invasive front were examined in 130 CRCs, and their significance was statistically evaluated. RESULTS: CD55-high stroma was correlated with tumor border (p=0.006) and invasion depth (p=0.013). CD55-high tumor cells at tumor center and invasive front were correlated with histologic grade, and CD55-high tumor cells at invasive front with tumor, node and metastasis (TNM) stage (p<0.05). CD97-high stroma was correlated with lymph node metastasis (p=0.016) and TNM stage (p=0.030). CD97-high tumor cells at tumor center and invasive front were correlated with tumor size and CD97-high tumor cells at tumor center with tumor border (p<0.05). Patients with CD55-high stroma showed poor overall and recurrence-free survival (p<0.05) in univariate analysis, and were independently associated with short recurrence-free survival (p=0.025) in multivariate analysis. CONCLUSIONS: Stromal CD55 overexpression would be an indicator of adverse clinical outcome and a useful prognostic factor.

Primary Synovial Sarcoma of the Kidney: A Case Report and Literature Review

Synovial sarcoma is a rare renal neoplasm that is not easy to diagnose unless SYT-SSX fusion transcripts are identified. We report here on a case of primary renal synovial sarcoma in a 35-year-old woman. A mass was discovered by accident in the lower part of the right kidney when ultrasonography was performed, and it was removed via radical nephrectomy. Grossly, the tumor was a homogeneously tan-brown soft mass that measured 4.5x3.2x3.0 cm, and it was encircled by a well-defined cystic space. The lesion exhibited hypercellularity of the oval or short spindle cells that were arranged in various solid sheets or intersecting fascicles. Immunohistochemically, the tumor showed diffuse positivity for vimentin, bcl-2 and CD99, and it showed focal positivity for epithelial membrane antigen. The SYT-SSX fusion transcripts were detected by reverse transcription-polymerase chain reaction (RT-PCR). Synovial sarcoma should be considered in the differential diagnosis when a spindle cell neoplasm is encountered in the kidney.