Pleomorphic adenoma is the most common benign tumor of the salivary glands. It has marked histological diversity with epithelial, myoepithelial and mesenchymal-type cells arranged in a variety of architectural and differentiation patterns. Pleomorphic adenoma gene 1 (PLAG1), shown to be consistently rearranged in pleomorphic adenomas, is activated by chromosomal translocations involving 8q12, the chromosome region that is most frequently affected in these tumors. In this study, we evaluated PLAG1 involvement in salivary gland tumorigenesis by determining the frequency of its alterations in a selected group of 20 salivary gland tumors: 16 pleomorphic adenomas and four carcinomas ex-pleomorphic adenoma, having in common the presence of karyotypic chromosome 8 deviations, either structural, with 8q12 rearrangements, or numerical, with gain of chromosome 8. PLAG1 status was analyzed using in situ hybridization techniques, on metaphase cells, by fluorescence detection and/or interphase cells in paraffin sections, by chromogenic detection. Except for one pleomorphic adenoma case (5%) that lacked PLAG1 involvement, 17 tumors (85%), (14 pleomorphic adenomas and three carcinomas ex-pleomorphic adenoma) showed intragenic rearrangements of PLAG1 and the remaining two cases (10%), (one pleomorphic adenoma and one carcinoma ex-pleomorphic adenoma), had chromosome trisomy 8 only. To further investigate the role of PLAG1 on pleomorphic adenomas tumorigenesis, as well as the putative morphogenesis mechanism, we attempted to identify the cell types (epithelial vs myoepithelial) carrying 8q12/PLAG1 abnormalities by a combined phenotypic/genotypic analysis in four cases (three pleomorphic adenoma and one carcinoma ex-pleomorphic adenoma) characterized by 8q12 translocations and PLAG1 rearrangement. In these cases, both cells populations carried PLAG1 rearrangements. This finding further supports the pluripotent single-cell theory, which postulates that the tumor-initiated, modified myoepithelial cell, evolves into the varied somatic cell phenotypes present in pleomorphic adenoma, and reinforces the role of PLAG1 on the tumorigenesis of benign and malignant pleomorphic adenoma.

This review presents a pattern recognition approach for the diagnosis of malignant effusions. The cytomorphologic features of reactive mesothelial proliferation, mesothelioma and metastatic carcinoma are presented. In addition, the role of ancillary studies in challenging cases and the importance of integrating clinical findings are stressed. An algorithmic approach to the workup of serous effusions as well as pitfalls for false-positive diagnosis are discussed.

The presence of persistent circulating leukemia cells, or engrafted into extramedullary tissues, is a bad prognostic factor for patients with acute leukemia. However, little is known about the mechanisms that regulate the exit of leukemia cells from the bone marrow (BM) microenvironment. We reveal that vascular endothelial growth factor receptor 1 (FLT-1) modulates acute leukemia distribution within the BM, along VEGF and PlGF gradients, regulating leukemia survival and exit into the peripheral circulation.

BACKGROUNDThe authors attempted to resolve the dilemma posed by the lack of unanimity concerning the optimal immunohistochemical (IHC) method for determining and scoring estrogen receptor (ER) and progesterone receptor (PR).METHODSSections for IHC were prepared from paraffin embedded tumor samples from 402 patients with lymph node positive breast carcinoma who had biochemical receptor values (obtained with the dextran‐coated charcoal [DCC] method) and who were enrolled in a prospective, randomized trial (National Surgical Adjuvant Breast and Bowel Project protocol B‐09). IHC receptors were scored independently by two observers according to percent, intensity, and any‐or‐none algorithms. Results from these evaluations and from two computer‐assisted evaluations, DCC, and common pathologic characteristics were analyzed for optimum splits for positive reactions in univariate and multivariate analyses using a tree‐structured model. Concordance, sensitivity, and specificity were determined between the DCC method and all other methods.RESULTSInterobserver agreement and concordance between the DCC method and the other methods and among the methods were high. Univariate analyses revealed that a positive ER score obtained with all methods was related significantly to overall survival (OS) at 5 years and at 10 years. Results related to PR scores and disease‐free survival and recurrence‐free survival were less consistent. In multivariate analysis, it also was found that all methods for scoring ER predicted a better prognosis for OS in patients with an unfavorable lymph node status at 5 years and 10 years. Patients in a favorable lymph node status group were discriminated further by nuclear grade.CONCLUSIONSAll IHC methods for scoring ER appeared valid as prognostic indicators of OS in patients with positive lymph nodes. The any‐or‐none IHC method, by virtue of its simplicity, represents an appropriate choice for practical use. Cancer 2005. © 2004 American Cancer Society.