We studied 28 cases of lymphoepithelioma-like carcinoma of the bladder, one case in the renal pelvis, and one in the urethra. The mean age of the patients was 67.6 years with 21 (70%) males. Seventeen cases (56.7%) were pure with the remaining mixed with other patterns of carcinoma, including invasive urothelial carcinoma (n ¼ 10), invasive adenocarcinoma (n ¼ 3), and squamous cell carcinoma (n ¼ 2). The surface demonstrated carcinoma in situ (CIS) in six cases, noninvasive high-grade papillary urothelial carcinoma in three cases, and in situ adenocarcinoma in one case. In 19/30 (66%) cases, there was a heavy lymphocytic infiltrate and in the remaining 11/30 (34%) cases a mixed inflammatory infiltrate. None of the 26 cases labeled for EBV-encoded RNA by in situ hybridization. Tumor stages at presentation were: seven cases T1 (23%); 14 cases T2 (47%); seven cases T3 (23%); and two cases T4 (7%). Treatment consisted of radical cystectomy in 13/30 cases (43%); partial cystectomy in 4/30 cases (13%); nephrectomy in one case (3%), and transurethral resection often followed by radiation or chemotherapy in 12/30 (40%) cases. The mean follow up for patients without progression was 31 months. Eight of 27 cases with follow-up (30%) cases had tumor recurrence, with seven patients having metastases. In cases treated with cystectomy, the 5-year actuarial recurrence-free risk was 59% (62 and 57%, for pure and mixed cases, respectively). Lymphoepithelioma-like carcinoma, whether in pure or mixed form, has a similar prognosis to ordinary urothelial carcinoma when treated by cystectomy. Of the three pure cases treated by chemotherapy, two were free of disease at 4 and 65 months and the third had recurrent disease at 17 months. Given the association of lymphoepithelioma-like carcinoma with urothelial carcinoma in 47% of our cases and its propensity for multifocality, partial cystectomy would typically be ill advised for lymphoepithelioma-like carcinoma.

The prognostic significance of Paneth cell-like neuroendocrine differentiation in adenocarcinoma of the prostate has not yet been established. We studied 36 cases of adenocarcinoma of the prostate showing Paneth cell-like neuroendocrine differentiation, including needle biopsy specimens (n = 27), radical prostatectomies (n = 8), and transurethral resection specimens (n = 1). Paneth cell-like neuroendocrine cells (NECs) were observed as either patchy isolated cells or diffusely involving glands or nests. With Gleason pattern 3, a patchy pattern of NECs was seen in 18/19 cases with only 1/19 (5.3%) case showing diffuse NECs. All the 4 Gleason pattern 4 cases had patchy NECs. Of the 21 cases with Gleason pattern 5, 18 (85.7%) had diffuse NECs with the remaining 3 exhibiting patchy NECs. Radical prostatectomy was performed in 16/36 (44.4%). Tumor was organ confined in 10/16 cases (62.5%). Extraprostatic extension (EPE) with positive surgical margins was seen in 6/16 cases (37.5%). In 4 cases, seminal vesicles were positive for cancer. Pelvic lymph nodes were free of tumor in all cases. The actuarial prostate specific antigen progression-free risk at 5 years and 7 years was 92% and 80%, respectively. Only 2 patients progressed after radical prostatectomy and they both had Gleason score 7 cancer with extraprostatic extension and seminal vesicle invasion. Of the 16 radical prostatectomy cases, 8 (50%) had a Gleason pattern 5 component either on needle biopsy or at radical prostatectomy, with nests, cords, or single cells containing Paneth cell-like neuroendocrine differentiation. Five of these 6 cases with Gleason pattern 5 and available follow-up information had no evidence of progression with mean and median follow-ups of 46 months. Radiation therapy either as monotherapy or combined with hormonal therapy was used to treat patients in 13/36 cases. Overall only 2 patients progressed, one with clinical T2 and the other T3 disease. Of the 5 cases with Gleason pattern 5 composed in part or totally by NECs treated by radiation therapy, all are without evidence of recurrence with a mean and median follow-up of 47 and 45 months, respectively. Of the remaining 5 cases with available follow-up treated with watchful waiting, hormone therapy, or cryotherapy, 4 had Gleason pattern 5 tumor with NECs. Of these 4 cases, 3 had no progression with a mean and median follow-up of 42.5 and 60.5 months, respectively. Despite the cells' bland histologic appearance, strictly applying the Gleason grading system one would have to assign a Gleason pattern 5 to these foci with no glandular differentiation. The current study demonstrates that applying the Gleason score to these foci does not accurately reflect their clinical behavior. In cases with Paneth cell-like NECs, only the conventional adenocarcinoma component should be assigned a Gleason score. In cases in which the entire tumor is composed of Paneth cell-like cells and areas of the tumor lack glandular differentiation, the tumors should not be assigned a Gleason score and a comment shou...

Based on gene expression profiling, diffuse large B-cell lymphomas arising in immunocompetent patients can be divided into germinal center and activated B-cell types. Since little is known about acquired immunodeficiency syndrome associated diffuse large B-cell lymphomas, we tested whether the protein expression of germinal center and activated B-cell markers differed between acquired immunodeficiency syndrome (AIDS) vs non-AIDS diffuse large B-cell lymphomas. We immunohistochemically stained tissue microarrays of 39 de novo diffuse large B-cell lymphomas: 12 AIDS associated and 27 non-AIDS, with germinal center (BCL6, CD10, CyclinH) and activated B-cell markers (MUM1, CD138, PAK1, CD44, BCL2). We scored each case for percent positive cells (0-19% ¼ 0; 20-49% ¼ 1; 50-100% ¼ 2). The activated B-cell and germinal center summation scores of each case were used as (x, y) coordinate data points to construct two-dimensional contour-frequency plots. The contour plot of non-AIDS diffuse large B-cell lymphomas showed two distinct clusters: a cluster with a high germinal center phenotype (cluster 1) and a cluster with a high activated B-cell phenotype (cluster 3). In contrast, the AIDS-related diffuse large B-cell lymphomas formed a single aggregate (cluster 2) (P ¼ 0.02, Fisher exact test). When the contour plots of the AIDS-related and the non-AIDS cases were superimposed, cluster 2 of the AIDS cases expressed an intermediate germinal center/activated B-cell phenotype compared to clusters 1 and 3 of the non-AIDS diffuse large B-cell lymphomas. Our results confirm that non-AIDS diffuse large B-cell lymphomas segregate into two groups with either germinal center or activated B-cell phenotype. We report the new finding that the AIDS status of the patient predicts the immunophenotype of the diffuse large B-cell lymphomas. We also describe a novel method for displaying immunohistochemical expression data using twodimensional contour-frequency plots. Materials and methods Lymphoma SamplesWe performed a retrospective study of 56 diffuse large B-cell lymphomas (23 AIDS-related and 33 non-AIDS) that were retrieved from the archives of

Morphologic features of Burkitt lymphoma (BL) and diffuse large B-cell lymphoma (DLBCL) overlap. No single phenotypic marker or molecular abnormality is pathognomonic. We tested a panel of 8 germinal center (GC) and activated B-cell (ABC) markers for their ability to separate BL and DLBCL. We diagnosed 16 BL and 39 DLBCL cases from 21 patients with AIDS and 34 without AIDS based on traditional morphologic criteria, Ki-67 proliferative index, and c-myc rearrangement (fluorescence in situ hybridization). After immunohistochemically staining tissue microarrays of BL and DLBCL for markers of GC (bcl-6, CD10, cyclin H) and ABC (MUM1, CD138, PAK1, CD44, bcl-2), we scored each case for the percentage of positive cells. Hierarchical clustering yielded 2 major clusters significantly associated with morphologic diagnosis (P < .001). For comparison, we plotted the sum of the GC scores and ABC scores for each case as x and y data points. This revealed a high-GC/low-ABC group and a low-GC/high-ABC group that were associated significantly with morphologic diagnosis (P < .001). Protein expression of multiple GC and ABC markers can separate BL and DLBCL.

Morphologic features of Burkitt lymphoma (BL) and diffuse large B-cell lymphoma (DLBCL) overlap. No single phenotypic marker or molecular abnormality is pathognomonic. We tested a panel of 8 germinal center (GC) and activated B-cell (ABC) markers for their ability to separate BL and DLBCL. We diagnosed 16 BL and 39 DLBCL cases from 21 patients with AIDS and 34 without AIDS based on traditional morphologic criteria, Ki-67 proliferative index, and c-myc rearrangement (fluorescence in situ hybridization). After immunohistochemically staining tissue microarrays of BL and DLBCL for markers of GC (bcl-6, CD10, cyclin H) and ABC (MUM1, CD138, PAK1, CD44, bcl-2), we scored each case for the percentage of positive cells. Hierarchical clustering yielded 2 major clusters significantly associated with morphologic diagnosis (P < .001). For comparison, we plotted the sum of the GC scores and ABC scores for each case as x and y data points. This revealed a high-GC/low-ABC group and a low-GC/high-ABC group that were associated significantly with morphologic diagnosis (P < .001). Protein expression of multiple GC and ABC markers can separate BL and DLBCL.