Chronic lymphocytic leukemia/small lymphocytic lymphoma with cyclin D1 positive proliferation centers do not have CCND1 translocations or gains and lack SOX11 expression.

Cyclin D1 expression, usually absent in chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), has been described in the proliferation centers (PC) of some CLL/SLL. The prevalence of this finding is uncertain, as is the explanation for its occurrence and whether these cases have any other unique features. Cyclin D1 immunohistochemical staining was therefore investigated in 57 extramedullary CLL/SLL biopsies. In 6 cases, cyclin D1 immunofluorescence followed by CCND1 fluorescence in situ hybridization (FISH) and PC targeted analysis was performed using a Bioview Duet system. Excluding the prospectively selected cases that had the targeted FISH studies, cyclin D1+ PC were identified in 20% of cases. The cyclin D1+ CLL did not appear pathologically or phenotypically distinctive, though 46% had an interfollicular growth pattern. The cyclin D1+ PCs were SOX11- and lacked CCND1 translocations and gains in 5 of 5 informative cases. The recognition of cyclin D1 expression in PC of a significant minority of CLL/SLL can be a diagnostic aid and should not lead to the diagnosis of focal mantle cell lymphoma.

Brachyury, SOX-9, and podoplanin, new markers in the skull base chordoma vs chondrosarcoma differential: a tissue microarray-based comparative analysis.

The distinction between chondrosarcoma and chordoma of the skull base/head and neck is prognostically important; however, both have sufficient morphologic overlap to make delineation difficult. As a result of gene expression studies, additional candidate markers have been proposed to help in separating those entities. We sought to evaluate the performance of new markers: brachyury, SOX-9, and podoplanin alongside the more traditional markers glial fibrillary acid protein, carcinoembryonic antigen, CD24, and epithelial membrane antigen. Paraffin blocks from 103 skull base/head and neck chondroid tumors from 70 patients were retrieved (1969-2007). Diagnoses were made based on morphology and/or whole-section immunohistochemistry for cytokeratin and S100 protein yielding 79 chordomas (comprising 45 chondroid chordomas and 34 conventional chordomas), and 24 chondrosarcomas. A tissue microarray containing 0.6 mm cores of each tumor in triplicate was constructed using a manual array (MTA-1; Beecher Instruments). For visualization of staining, the ImmPRESS detection system (Vector Laboratories) with 2-diaminobenzidine substrate was used. Sensitivities and specificities were calculated for each marker. Core loss from the microarray ranged from 25 to 29% yielding 66-78 viable cases per stain. The classic marker, cytokeratin, still has the best performance characteristics. When combined with brachyury, accuracy improves slightly (sensitivity and specificity for detection of chordoma 98 and 100%, respectively). Positivity for both epithelial membrane antigen and AE1/AE3 had a sensitivity of 90% and a specificity of 100% for detecting chordoma in this study. SOX-9 is apparently common to both notochordal and cartilaginous differentiation, and is not useful in the chordoma-chondrosarcoma differential diagnosis. Glial fibrillary acid protein, carcinoembryonic antigen, CD24, and epithelial membrane antigen did not outperform other markers, and are less useful in the diagnosis of chordoma vs chondrosarcoma. Podoplanin still remains the only positive marker for chondrosarcoma, though its accuracy is less than previously reported.