Increasing tumor budding in cholangiocarcinoma is associated with decreased disease-specific survival.

Tumor budding (TB) has been shown to be an adverse prognostic factor in several gastrointestinal malignancies, most notably colorectal carcinoma (CRC). TB has undergone some evaluation in Eastern cohorts of cholangiocarcinoma (CC), and we undertook this study to evaluate whether TB in CC was linked to other clinicopathologic factors or to outcome in a Western cohort. We evaluated 112 cases of CC for age, sex, margin status, location, size, grade, lymphovascular invasion (LVI), perineural invasion (PNI), subtype (large or small duct), staging parameters, recurrence-free survival, disease-specific survival (DSS), and TB. Budding was scored using International Tumor Budding Consensus Conference recommendations for CRC: The highest tumor bud count at the invasive tumor front in a 0.785 mm2 area was recorded and stratified into Bd1 (0-4 buds), Bd2 (5-9 buds), and Bd3 (≥10 buds). Our cohort included 54 (48%) extrahepatic CCs and 58 (52%) intrahepatic CCs. TB was more commonly seen in the settings of higher-grade lesions, males, extrahepatic CC, PNI, LVI, and positive resection margin (all P ≤ 0.021). In multivariate analysis, worse DSS was correlated with budding score Bd2/Bd3 (hazard ratio [HR] 2.6687, 95% confidence interval [CI] 1.585-5.217, P = 0.001) and with nodal disease (HR 2.876, 95% CI 1.585-5.217, P = 0.001). TB is associated with higher-grade disease in CC, and increased TB is associated with poor disease-specific survival. Our findings support the notion that TB may serve as useful information for clinicians with respect to patient prognosis in CC, as in CRC.

Incidence and Significance of GATA3 Positivity in Pancreatic Ductal Adenocarcinoma and Cholangiocarcinoma.

GATA3 is a transcription factor involved in the development and differentiation of lymphocytes, breast, and hair follicles. The protein is a useful immunohistochemical (IHC) marker for supporting diagnoses of breast or urothelial carcinoma. This can be especially helpful in metastatic neoplasms to help delineate site of origin. GATA3 is also reportedly positive in a percentage of pancreatic ductal adenocarcinomas (PDACs) and cholangiocarcinomas (CCs), but no study has closely evaluated this relationship with respect to clininopathologic features or patient outcome. Using tissue microarrays, we analyzed 240 PDACs and 60 CCs with GATA3 IHC and compared expression to various clinical and pathologic parameters. Overall, GATA3 positivity was seen in 16% of PDACs and 5% of CCs. GATA3 positivity in PDAC cases was more common in male patients (P=0.013). GATA3-positive PDACs trended toward worse survival on multivariate analysis (P=0.074). The only 3 GATA3-positive CCs were poorly differentiated (P=0.069); low case number precluded multivariate survival analysis for CCs. GATA3 positivity can occur in carcinomas of the pancreatobiliary system, which should be considered during IHC workup of neoplasms of unclear origin. This positivity seems to have minimal relevance to patient outcome.

Primary Esophageal Melanoma with Aberrant CD56 Expression: A Potential Diagnostic Pitfall.

Primary esophageal malignant melanoma (MM) is rare and extremely aggressive. For pathologists, it can be challenging to diagnose and differentiate from other poorly differentiated malignant neoplasms in the esophagus. Complicating this fact, MM can have divergent differentiation and express nonmelanocytic immunohistochemical markers including epithelial markers (cytokeratins) and rarely neuroendocrine markers. Lack of awareness of this fact by a pathologist can lead to an erroneous diagnosis and delay treatment for an already aggressive disease. Herein, we report a case of primary esophageal malignant melanoma with aberrant CD56 expression without accompanying synaptophysin or chromogranin expression.