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Intrahepatic cholangiocarcinoma (iCCA) arises from bile ducts within the liver. Thailand has the highest incidence of CCA worldwide, with a high mortality rate. Early diagnosis and accurate prognostic stratification can improve overall survival. We aim to modify the AJCC/UICC 8th edition staging system for iCCA by creating the Khon Kaen University (KKU) staging system for more precise patient stratification and prognostic prediction.A total of 298 iCCA patients who underwent hepatectomy were included in this retrospective study at the Srinagarind Hospital, Khon Kaen University, Thailand. Univariate and multivariate analysis were performed to examine survival rate, hazard ratio, and prognostic factors.Univariate and multivariate analysis of the cohort showed that growth patterns, histological type, histological grade, lymph node metastasis and distant metastasis were independent prognostic factors when compared to the respective reference groups. The 8th AJCC staging system incorporated growth patterns into the KKU staging system. This model modified AJCC stages I, II, and III for better prediction of patient survival.Growth patterns were incorporated to improve the 8th AJCC staging system for prognostication of iCCA patients in Northeast Thailand. We propose the KKU staging system as an alternative model for iCCA staging to augment the accuracy of survival prognostication.

AIMS Confirmation of a breast origin for triple-negative breast cancer (TNBC) is sometimes problematic. The traditional breast markers GATA-binding protein 3 (GATA3), mammaglobin (MGB) and gross cystic disease fluid protein 15 (GCDFP15) have shown limitations in identifying TNBC. Here, we aimed to examine the diagnostic potential of the newly proposed TNBC marker, Sry-related high-mobility-group/HMG box 10 (SOX10). METHODS AND RESULTS We analysed and compared SOX10 expression with GATA3, MGB and GCDFP15 expression in a test cohort of 1838 invasive breast cancers (IBCs) by using tissue microarrays. The findings from the test cohort were further examined with a validation cohort of 42 TNBCs in whole sections. The overall expression rates of SOX10, GATA3, MGB and GCDFP15 were 6.9%, 83.1%, 47.0%, and 34.8%, respectively. Among the TNBCs within this cohort, the expression rates of SOX10, GATA3, MGB and GCDFP15 were 31.3%, 34.5%, 27.9%, and 25.2%, respectively. SOX10 was strongly associated with TNBC (P

For invasive breast cancer (IBC), high SOX10 expression was reported particularly in TNBC. This raised the possibility that SOX10 may complement other breast markers for determining cancers of breast origin. Here, we compared the expression of SOX10 with other breast markers (GATA3, mammaglobin and GCDFP15) and their combined expression in a large cohort of IBC together with nodal metastases. We have also evaluated the expression of GATA3 and SOX10 in a wide spectrum of non-breast carcinomas to assess their value as breast specific markers. Compared with other markers, SOX10 showed lower overall sensitivity (6.5%), but higher sensitivity in TNBC (31.4%) than other breast markers including GATA3 (29.7% for TNBC). Its expression demonstrated the highest concordance between the paired IBC and nodal metastases (96.4%, κ = 0.663) among all the breast markers. More importantly, SOX10 identified many GATA3-negative TNBC, thus the SOX10/GATA3 combination was the most sensitive marker combination for IBC (86.6%). For non-breast carcinoma, a high SOX10/GATA3 expression rate was found in melanoma (77.9%, predominately expressed SOX10), urothelial carcinoma (82.0%, predominately expressed GATA3) and salivary gland tumors (69.4%). Other carcinomas, including cancers from lungs, showed very low expression for the marker combination. The data suggested that SOX10/GATA3 combination can be used for differentiating metastases of breast and multiple non-breast origins. However, the differentiation with melanoma and urothelial tumors required more careful histologic examination, thorough clinical information and additional site-specific IHC markers. For salivary gland tumors, the overlapping tumor types with IBC renders the differentiation difficult.

Papillary structures are frequently encountered in metastatic carcinomas from various organs and tumours of different histotypes. This study aims to investigate the predictive value of fine needle aspiration cytology (FNAC), immunohistochemistry (IHC) and the clinical parameters which can be examined in the assessment of the primary sites of metastatic carcinomas with papillary architecture.FNAC samples of metastatic carcinomas with papillary architecture were evaluated for overall cellularity, epithelial cohesion, background features, papillary architecture, cytology and IHC. The corresponding clinical information was also reviewed.A total of 130 cases were included. The most common primary sites were thyroid (38.5%), lung (30.8%) and gynecological organs (22.3%); the others were pancreaticobiliary, urothelial, colorectal, and esophageal. Age (P = 0.039), biopsy site (P 0.001) and laterality (P = 0.006) correlated with primary site. Papillary structures were confirmed on biopsy/excision of most cases (n = 85/87, 97.7%). Thyroid primaries exhibited broad papillary stalks, thin lining epithelium, fewer epithelial polymorphs, and the presence of background giant cells and histiocytes (P = 0.021-0.001). Low-grade cytological features, nuclear grooves and inclusions (P 0.001) were seen in thyroid primaries. High-grade features (P 0.001-0.49), multinucleated tumour cells, apoptotic bodies and mitoses (P 0.001-0.49) were more common in lung/gynecological primaries. Multivariate analysis identified nuclear/cytoplasmic ratio, chromatin character, the presence of nuclear grooves and mitosis as independent features (P = 0.001-0.024). TTF1/TGB/PAX8 panel results showed good agreement with the cytological assessment and site of primary.Papillary structures and cytological features are reproducible in FNAC assessment of metastases and their corresponding primary sites. Cytological features, IHC and clinical information are invaluable in determining the primary site.

Mucin type O-glycosylation is a posttranslational modification of membrane and secretory proteins. Transferring of N-acetylgalactosamine, the first sugar of O-glycosylation, is catalyzed by one of the 20 isoforms of polypeptide N-acetylgalactosaminyltransferases (GALNTs). In this study, Vicia villosa lectin (VVL), a lectin that recognizes O-GalNAcylated glycans, was used to detect VVL-binding glycans (VBGs) in cholangiocarcinoma (CCA). The elevation of VBGs in tumor tissues of the liver fluke associated with CCA from hamsters and patients was noted. VBGs were detected in hyperplastic/dysplastic bile ducts and CCA but not in normal biliary epithelia and hepatocytes, indicating the association of VBGs with CCA development and progression. GALNT5 was shown to be the major isoform found in human CCA cell lines with high VBG expression. Suppression of GALNT5 expression using siRNA significantly reduced VBG expression, signifying the connection of GALNT5 and VBGs observed. Knocked-down GALNT5 expression considerably inhibited proliferation, migration and invasion of CCA cells. Increased expression of GALNT5 using pcDNA3.1-GALNT5 expression vector induced invasive phenotypes in CCA cells with low GALNT5 expression. Increasing of claudin-1 and decreasing of slug and vimentin expression together with inactivation of Akt/Erk signaling were noted in GALNT5 knocked-down cells. These observations were reversed in GALNT5 over-expressing cells. GALNT5-modulated progression of CCA cells was shown to be, in part, via GALNT5-mediated autocrine/paracrine factors that stimulated activations of Akt/Erk signaling and the epithelial to mesenchymal transition process. GALNT5 and its O-GalNAcylated products may have important roles in promoting progression of CCA and could possibly be novel targets for treatment of metastatic CCA.

Distal cholangiocarcinoma (dCCA) is a rare type of CCA in Asia, even in

Cholangiocarcinoma (CCA) is the most prevalent malignancy in Thailand, with unfortunate late diagnosis and frequent metastatic disease outcomes. An accurate tissue diagnosis is the first and most important step in the treatment of CCA. Tissue quality and preservation during the pre-analytical phase play major roles in the proper histological evaluation and potential biomarker testing. This study evaluated the impact of using the “Cholangiocarcinoma Screening and Care Program (CASCAP)” container, as an innovative tool to address pre-analytical challenges faced by pathology laboratories in Thailand. This is a comparison study examining the quality of CCA specimens using the CASCAP container vs. the conventional method, using hematoxylin and eosin (H&E) and immunohistochemistry (IHC). CCA tissue quality using the CASCAP container significantly reduced artifact deposition while improving the cellular structure and nuclear and cytoplasmic morphologies. The immunohistochemical expression of cytokeratin 19 (CK19), a prognostic marker in CCA, significantly improved in the CASCAP container group in comparison with the conventional method. This innovation is proven to significantly enhance the CCA tissue quality diagnostics and prognostic biomarker testing, hence improving overall cancer care, diagnosis, and treatment in Thailand.

BACKGROUND The aim of the International Academy of Cytology Yokohama System for Reporting Breast Fine Needle Aspiration Biopsy Cytopathology is to improve cytology practice. This study assessed cytologic diagnoses made with the system and its efficacy when it was applied by pathologists with different levels of experience. METHODS In all, 1080 cases of breast fine-needle aspiration biopsy (FNAB) over a period of 16 years were reviewed and reclassified with the system. The category distribution and the diagnostic performance were compared with the original diagnoses. The concordance rates for diagnoses from pathologists with different levels of experience were also determined. RESULTS The distribution of cytologic diagnoses made with the system was as follows: 11.7% were insufficient, 56.6% were benign, 20.1% were atypical, 6.1% were suspicious for malignancy, and 5.6% were malignant. The rates for the insufficient and atypical categories were lower than the original diagnosis rates (13.1% and 23.8%, respectively). Overall, 120 cases (11.1%) were recategorized. Among those recategorized as benign, suspicious, or malignant with follow-up data, 96.7% were correctly reclassified. A significant improvement in diagnostic performance was found with the system (P

BACKGROUND The cytologic diagnosis of papillary lesions of the breast is challenging because of the diverse morphology, including epithelial hyperplasia, atypia, low-grade malignancy, and neuroendocrine differentiation; also, traditional malignant features such as necrosis and myoepithelial cell loss can be lacking. Thus, the diagnostic criteria for papillary lesions may differ from those for other breast lesions. This study evaluated various cytologic parameters in a large cohort to identify useful diagnostic features. METHODS Cytologic preparations of papillary lesions with histologic follow-up were reviewed for features related to cellularity, epithelial cohesiveness, cellular and stromal architecture, cytomorphology, and background. Corresponding histologic slides were also reviewed. RESULTS In all, 153 cases were included. Epithelial discohesion, solid and cribriform patterns, atypical nuclear features, and mitoses (P ≤ .001 to P = .017) were associated with malignancy. Cell balls, monolayer sheets, and features of cystic change (P < .001 to P = .016) were associated with benign lesions. Complex (P = .031) and slender (P = .026) papillae and neuroendocrine features (P < .001) were associated with malignancy. Hemorrhage, background, and infiltrating neutrophils (P < .001 to P = .025) were associated with malignancy; fibrotic broad papillary stromal fragments (naked papillary fronds [NPFs]; P = .043) were associated with benignity. The presence of any single parameter, including the absence of myoepithelial cells within epithelial structure, the presence of cytoplasmic granules, an increased amount of cytoplasm, and a nuclear to cytoplasmic (N/C) ratio greater than 0.7, which were identified by principal component analysis, yielded a sensitivity of 95.1% and a specificity of 100.0% in predicting malignancy. CONCLUSIONS Methodological assessment of multiple features is recommended. Myoepithelial cells, cytoplasmic granules, the amount of cytoplasm, and the N/C ratio are key features for diagnosis.