There is no uniformly applied grading system for pancreatic ductal adenocarcinoma (DA). The scheme advocated by the WHO is essentially that of Kloppel et al, and is based on the "highest grade" focus. Although it is precise with good prognostic value, it is unfortunately not widely applied, largely because of the lack of recognition and partly because of its complex nature (interpretation of multiple parameters). Furthermore, it is fundamentally different from the one used in Japan, which evaluates the overall pattern. To establish a more widely applicable, practical, and clinically relevant grading system, a scheme similar to Gleason's scoring system was developed and tested on 112 cases of resected pancreatic DA and was compared with the WHO system. In the grading system devised, patterns (P) of infiltration were classified as follows: P1, well-defined glands with easily discernible contours; P2, fused or poorly formed glands with ill-defined contours; P3, nonglandular patterns. A score was then obtained by the summation of the predominant and the secondary patterns. Scores < or =3 (at least some well-formed glands and no nonglandular pattern) was graded as G1, 4 as G2, and > or =5 (at least some nonglandular patterns and no well-formed glandular pattern) as G3. Seventy-three percent of the cases displayed mixed patterns, with disparate patterns (P1 with P3) in 13%, confirming the high degree of heterogeneity of DA. There was a significant correlation between grade and survival, better than the correlation between survival and either the major or minor patterns evaluated separately. The median survival for G1, G2, and G3 were 22, 14, and 8 months; 1-year survival 68%, 44%, and 33%; 2-year was 67%, 11%, and 0%; and 3-year was 23%, 4%, and 0%, respectively (P = 0.0019). In a multivariate analysis, correlating survival with grade, tumor size, and lymph node status, the grade was the strongest independent predictor of survival. Odds ratio of dying of disease were 3.56 (P < 0.0001) in G3 versus G1, 1.79 (P = 0.058) in G2 versus G1, and 1.98 (P = 0.03) in G3 versus G2. Compared with this, the same odds ratio were 1.17 (P = 0.01) in tumors >2 cm versus < or =2 cm and 1.78 (P = 0.01) in cases with positive versus negative lymph nodes. The WHO grading scheme was not found to have as good a correlation with survival in this study, with WHO grade 2 showing a better survival than 1. The reproducibility of both the proposed grading system and that of WHO were found to be moderately good (with kappa values of 0.43 and 0.44, respectively), when 32 slides of DA were graded by four independent observers. The grading scheme for pancreatobiliary adenocarcinoma proposed here is highly applicable because it is practical and readily adoptable. It reflects biologic characteristics of ductal carcinoma (prominent tubule formation and tumor heterogeneity). Most importantly, it is clinically relevant with good prognostic value. Lastly, it is also applicable for use in research, by utilizing "patterns," even in small specimens like microa...
Background:Fine needle aspiration biopsy (FNAB) is a common and excellent procedure for the evaluation of thyroid lesions that require surgical resection. At times, the FNAB diagnosis can be difficult, particularly of follicular-patterned lesions. Previous studies have shown that some immunohistochemical (IHC) markers may be helpful in establishing more accurate diagnosis. In this study, our goal was to evaluate four of the recently investigated markers in differentiating benign from malignant thyroid nodules on FNABs.Materials and Methods:We performed IHC staining of galectin-3, Ret oncoprotein (Ret), HBME-1, and cytokeratin 19 (CK19), on cell block sections of thyroid FNAB cases that had corresponding surgical resections. They included 44 benign lesions (37 hyperplastic or cellular nodules, HN; and 7 follicular adenomas, FA) and 27 malignant tumors (6 follicular carcinoma, FC; 19 classic papillary carcinoma, PTC; and 2 follicular variant of papillary carcinoma, FVPC). The stains were done according to the standard avidin–biotin–peroxidase method.Results:Statistical analysis showed that immunoexpression was significantly higher in the malignant group for all four markers. The sensitivity for positive expression for all benign lesions versus malignant tumors was as follows: 10/44 (22.7%) versus 25/27 (92.6%) for galectin-3; 14/44 (31.8%) versus 23/27 (85%) for Ret; 12/44 (27.3%) versus 24/27 (88.8%) for HBME-1; and 13/44 (29.5%) versus 23/27 (85%) for CK19. The sensitivity and specificity was highest for galectin-3 (92.6% and 77.3%, respectively) followed by HMBE-1 (88.9% and 72.7%, respectively). When combining the markers' expressions, the panel of galectin-3 + HBME-1 showed the highest sensitivity and specificity (90.7% and 75%, respectively), but this was, however, lower than galectin-3 alone (92.3% and 77.3%, respectively).Conclusion:We conclude that galectin-3 is the best single marker in differentiating benign from malignant thyroid lesions with the highest sensitivity and specificity. The galectin-3 + HBME-1 was the best combination for distinguishing benign from malignant lesions. Because they were the best two independent and combined markers, we recommend the use of the galectin-3 + HBME-1 panel to enhance the diagnostic accuracy of follicular-patterned thyroid lesions on FNABs.
The 3-tiered FIGO grading system retained its superior prognostic power. However, available binary grading systems remain an attractive option by being highly reproducible and by eliminating the clinical ambiguity of intermediate grades of disease.
The pretreatment of bloody specimens with GAA did not appear to significantly affect high-risk HPV DNA testing in specimens with an ASCUS interpretation.
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