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.

Background:The distinction of lung adenocarcinoma (ADC) from squamous cell carcinoma (SCC) has important therapeutic implications. Napsin A is a recently developed marker, which has shown high specificity for lung tissue in the surgical pathology specimens. In this study, we have evaluated whether the use of a panel of novel multiplex cocktails of TTF-1 + Napsin A and p63 + CK5 for dual color immunostaining will improve the diagnostic accuracy of lung adenocarcinoma and squamous cell carcinoma in fine needle aspiration (FNA) specimens, usually with relatively scant microfragments of diagnostic material.Materials and Methods:Formalin-fixed, paraffin-embedded, adequately cellular FNA cell blocks with a confirmed diagnosis of either ADC (n = 22), SCC (n = 20) or poorly differentiated carcinoma (PDC; n = 7), from a total of 49 consecutive cases, were studied. All these cases had subsequently confirmed diagnosis in biopsies or resection specimens. The sections were immunostained with two color methods of TTF-1 + Napsin A and p63 + CK5 multiplex cocktails. The presence of one or more unequivocal individual tumor cells with convincing brown nuclear TTF-1 and red cytoplasmic Napsin A staining, and cells with brown nuclear p63 and membranous / cytoplasmic CK5 staining were interpreted as ‘positive’.Results: All 20 FNA cell blocks from SCC cases were positive for dual stain p63 + CK5 and negative for dual stain TTF-1 + Napsin A. The sensitivity and specificity of the dual immunoexpressions of p63 + CK5 for SCC of lung FNAs were both 100%. All 22 ADC cases were positive with dual stain of TTF-1 + Napsin A and negative for dual stain of p63 + CK5. On follow-up of the surgical pathology specimens, 22 cases were confirmed as ADC. The sensitivity of the dual immunoexpression of TTF-1 + Napsin A for ADC of lung FNAs was 100% and the specificity was also 100%. Of the seven PDC cases, five cases that were positive for dual stain p63 + CK5 and negative for dual stain TTF-1 + Napsin A could be categorized as SCC. Two of the seven (2 / 7) PDC cases were positive for dual stain TTF-1 + Napsin A and negative for dual stain p63 + CK5, consistent with ADC.Conclusions:Simultaneous coordinate or individual immunostaining for Napsin A / TTF-1 in ADC and p63 / CK5 in SCC demonstrated high sensitivity and specificity. The panel with multiplex Napsin A / TTF-1 and p63 / CK5 dual color immunostains could specifically subcategorize PDC into ADC and SCC in lung FNA specimens. Multiplex dual color Napsin A / TTF-1 and p63 / CK5 immunostaining is especially recommended for evaluation of FNA specimens with relatively scant cellularity.

The pretreatment of bloody specimens with GAA did not appear to significantly affect high-risk HPV DNA testing in specimens with an ASCUS interpretation.

Malignant ascites may be the first presentation of an unsuspected cancer. Pancreas and ovary are among the organs that are usually evaluated as a source of primary. The purpose of this study is to investigate a panel of immunohistochemical stains to help differentiate pancreatic from ovarian carcinoma. We evaluated the immunohistochemical staining of eight commercially available antibodies MUC1, MUC2, MUC5ac, Wilm's tumor susceptibility gene 1 (WT1), cytokeratin 7 (CK7), CK20, CA125, and CA19.9 in 25 effusion specimens with evidence of metastatic carcinoma including 14 ovarian serous carcinomas, 9 pancreatic adenocarcinomas, and 2 unknown primaries. Primary ovarian serous carcinomas were positive for WT-1 (100%), CK7 (93%), CK20 (43%), CA125 (100%), CA19.9 (50%), MUC1 (100%), MUC2 (0%), and MUC5ac (0%). Primary pancreatic carcinomas were positive for MUC5ac (100%), MUC1 (100%), CA19.9 (100%), CK7 (78%), CK20 (22%), CA125 (89%), WT-1 (0%), and MUC 2 (0%). The combination of MUC5ac positivity/WT-1 negativity was seen in 100% of pancreatic carcinoma, whereas MUC5ac negativity/WT-1 positivity in 100% of ovarian serous carcinoma. It appears that the combination of MUC5ac and WT-1 stains is useful in distinguishing pancreatic ductal from ovarian serous carcinoma in body fluid cytology.

Pancreatic ductal adenocarcinoma (PDCA) is characterized by well-defined tubular units in the vast majority of the cases; however, variations in this theme do occur. It is important to recognize the morphologic spectrum of PDCA to avoid misdiagnosis especially in small specimens and also in metastatic foci. Here, we document a morphologic variant of PDCA that is characterized by a distinctive pattern of infiltrating cribriform nests in a distinctive “microcystic” or “secretory” pattern. Twenty-four cases of PDCA have been identified in a review of 505 cases diagnosed with PDCA. Histologically, this pattern was characterized by infiltrating nests of tumor cells with large vacuoles and “signet-ring” like appearance imparting a cribriform growth pattern. The vacuoles were one to five cells in size, often merging to form multilocular spaces separated by a thin rim of cell membrane. Many of these spaces contained CA19.9 positive granular secretory material. The nuclei were often pushed to the periphery and compressed in a pattern resembling adipocytes, although the nuclei were often densely hyperchromatic and displayed significant atypia. Especially in biopsies from the peripancreatic fat and peritoneum, these neoplastic cells had been misdiagnosed as degenerating adipocytes, and in the lymph nodes, they had been misinterpreted as lipogranulomas. Clinical findings of the patients were similar to that of conventional PDCA, except higher incidence of history of smoking (83% vs. 60%; p=0.034). In conclusion, vacuolated cell adenocarcinoma is a distinct morphologic variant of PDCA, and the presence of this peculiar pattern in a metastatic site, although not specific, should raise the suspicion of a PDCA.

FNAB is an effective tool for the diagnosis and triage of patients with head and neck masses that can be further improved with an onsite immediate adequacy evaluation and triage performed by a pathologist.