The "hyperplastic polyp" is considered a benign lesion with no malignant potential, whereas "serrated adenoma" is a precursor of adenocarcinoma. The morphologic complexity of the serrated adenoma varies from being clearly adenomatous to being difficult to distinguish from hyperplastic polyp, which creates a need for more detailed morphologic analysis of all serrated polyps. We evaluated 24 morphologic variables in 289 serrated polyps from the colon and rectum. Cluster analysis and discriminant analysis were performed. A subset of polyps was immunostained for hMLH1 and hMSH2. Major differences were found between right-sided and left-sided polyps. A distinct group of serrated polyps with abnormal proliferation was identified throughout the colon and rectum. These polyps demonstrated decreased expression of hMHL1 and hMSH2 compared with polyps with normal proliferation. Left-sided serrated polyps with normal proliferation further clustered into three groups: vesicular cell-type, goblet cell-type, and mucin-poor-type. We recommend evaluation of the localization, size, and morphologic features when serrated polyps are included in colorectal carcinogenesis research. Polyps with abnormal proliferation are similar to the polyps in "hyperplastic polyposis" and, because of their decreased expression of hMLH1 and hMSH2, may be the subset of polyps associated with the development of colorectal carcinoma via the microsatellite instability pathway.

Whereas L26 (anti-CD20) is well established as a B-cell marker of high specificity for use in paraffin-embedded tissues and JCB117 (anti-CD79a) is increasingly used, a comparable additional pan-B-cell antibody has hitherto not yet been identified. Here we have studied the use of a novel anti-pan-B-cell marker Pax-5 for use in diagnostic pathology. Pax-5 encodes for BSAP (Pax-5), a B-cell-specific transcription factor, the expression of which is detectable as early as the pro-B-cell stage and subsequently in all further stages of B-cell development until the plasma cell stage where it is downregulated. Pax-5 is essential for B-lineage commitment in the fetal liver, whereas in adult bone marrow this transcription factor is required for progression of B-cell development beyond the early pro-B (pre-BI) cell stage. Among the B-cell genes that are present in early B-cell development and are upregulated by Pax-5 are CD19 and Igalpha (CD79a). We have tested a commercially available anti-Pax-5 antibody (anti-BSAP, clone 24) in a series of 592 routinely fixed and paraffin wax-embedded biopsies, including lymph nodes, bone marrow, and various other organs containing lymphoid tissues. Pax-5 protein (BSAP) was detected in all cases of precursor and mature B-cell non-Hodgkin lymphomas/leukemias. In addition, in 97% of classic Hodgkin lymphomas, Reed-Sternberg cells expressed Pax-5. However, Pax-5 was not detected in any of the multiple myelomas, solitary plasmacytomas, and 4% of diffuse large B-cell lymphomas. Among those diffuse large B-cell lymphomas not expressing Pax-5 were only those with terminal B-cell differentiation. All T-cell non-Hodgkin lymphomas, including ALCL and lymphoblastic lymphomas and leukemias, were negative. There was a strong association between Pax-5 and CD20 expression. We conclude that anti-Pax-5 is an excellent pan-B and pan-pre-B-cell marker. We have found that anti-Pax-5 is superior to anti-CD20 in the diagnosis of pre-B acute lymphoblastic leukemia and classic Hodgkin lymphoma versus ALCL of T and "null" cell type. It was also useful in differential diagnosis between lymphoplasmacytic lymphoma and plasmacytoma. Even though there is an excellent correlation between CD20 and Pax-5 expression, anti-Pax-5 exceeds the specificity and sensitivity of L26 (anti-CD20) because of its earlier expression in B-cell differentiation and its ability to detect all committed B cells, including classic Hodgkin lymphoma.