Mantle cell lymphoma (MCL) typically expresses B-cell antigens and CD5 and overexpresses bcl-1 protein. However, unusual cases of bcl-1+ and CD5-MCL have been observed, posing a practical challenge for correct diagnosis and management. We identified 25 cases (48 samples) of bcl-1+ and CD5- lymphoma. CD5 expression was assessed by flow cytometric analysis alone (1 case), immunohistochemical analysis alone (17 cases), or dual flow cytometric/immunohistochemical methods (7 cases). The morphologic features were consistent with MCL with centrocytic cytomorphology in 20 cases and blastic variant in 5 cases. The t(11;14) was confirmed in 8 of 11 cases by fluorescence in situ hybridization of paraffin-embedded tissue. Cytogenetic analysis revealed the t(11;14) within a complex karyotype in 2 additional cases. These data show that MCL may lack CD5 expression. Evaluation of bcl-1 expression by immunohistochemical analysis or molecular genetics may be indicated if MCL is suspected clinically or morphologically despite a lack of CD5 expression.

Coexpression of CD5 and CD10 is highly unusual in B-cell lymphomas and may pose a diagnostic challenge. We report 42 cases of B-cell lymphoma with simultaneous expression of CD5 and CD10. They made up approximately 0.4% of all B-cell lymphomas seen during the study period and included the following cases: large B-cell lymphoma (LBCL), 14 (33%); follicular lymphoma (FL), 10 (24%); mantle cell lymphoma (MCL), 9 (21%); chronic lymphocytic leukemia, 4 (10%); acute precursor B-cell lymphoblastic leukemia/lymphoma, 2 (5%); and other low-grade B-cell lymphomas, 3 (7%). All MCLs had overexpression of bcl-1 or the t(11;14) and were CD43+. All FLs had typical histomorphologic features and were bcl-2+ and bcl-6+ but CD43-. Of 14 LBCLs, 5 were histologically high-grade. Six (43%) of 14 patients with LBCL died within 10 months of diagnosis of CD5+CD10+ lymphoma (median survival, 4 months), including all 3 patients with stage IV disease and 2 of 5 with histologically high-grade lymphoma. Our findings indicate that coexpression of CD5 and CD10 is rare but occurs in diverse subtypes of B-cell lymphoma. Investigation of bcl-1, bcl-6, and CD43 and morphologic evaluation may resolve the potential confusion in diagnosis and lead to the recognition of the correct lymphoma subtype.

PURPOSE TP53 missense mutations may help to identify prostate cancer (PCa) with lethal potential. Here, we pre-analytically, analytically and clinically validated a robust immunohistochemistry (IHC) assay to detect subclonal and focal TP53 missense mutations in PCa. EXPERIMENTAL DESIGN The p53 IHC assay was performed in a CLIA-accredited laboratory on the Ventana Benchmark immunostaining system. p53 protein nuclear accumulation was defined as any p53 nuclear labeling in >10% of tumor cells. 54 formalin fixed paraffin embedded (FFPE) cell lines from the NCI-60 panel and 103 FFPE PCa tissues (88 primary adenocarcinomas, 15 metastases) with known TP53 mutation status were studied. DU145 and VCaP xenografts were subjected to varying fixation conditions to investigate the effects of pre-analytic variables. Clinical validation was performed in two partially overlapping radical prostatectomy (RP) cohorts. RESULTS p53 nuclear accumulation by IHC was 100% sensitive for detection of TP53 missense mutations in the NCI-60 panel (25/25 missense mutations correctly identified). Lack of p53 nuclear accumulation was 86% (25/29) specific for absence of TP53 missense mutation. In FFPE prostate tumors, the positive predictive value (PPV) of p53 nuclear accumulation for underlying missense mutation was 84% (38/45), while the negative predictive value (NPV) was 97% (56/58). In a cohort of men who experienced biochemical recurrence after RP, the multivariable hazard ratio for metastasis among cases with p53 nuclear accumulation compared to those without was 2.55 (95% CI: 1.1–5.91). CONCLUSIONS IHC is widely available method to assess for the presence of deleterious and heterogeneous TP53 missense mutations in clinical PCa specimens.

CD103 is characteristically expressed in hairy cell leukemia (HCL), a B-lymphoproliferative disorder highly responsive to treatment with purine analogs. Other CD103+ diseases are rare and do not respond well to the same therapy, including HCL variant (HCLv) and splenic marginal zone B-cell lymphoma (SMZL) variants. We analyzed 215 cases of CD103+ B-lymphoproliferative disorders to further delineate their immunophenotypic features. Flow cytometric analysis revealed that 78.6% of all cases expressed CD25 and CD103, characteristic of classical HCL. Cases analyzed immunohistochemically were also invariably positive for annexin-A1; a subset coexpressed CD10 (33/169 [19.5%]) or BCL1 (26/65 [36.9%]). In contrast, 21.4% of cases lacked CD25, a subset of which was analyzed and was invariably negative for annexin-A1, CD10, and BCL1. The CD25- cases had variable morphologic features ranging from HCLv and SMZL to prolymphocytic leukemia and diffuse large B-cell lymphoma. Clinically, patients with CD25- disease tended to be older (P= .001), typically had leukocytosis (P= .014), and did not respond well to cladribine or pentostatin. We suggest categorizing CD103+ B-lymphoproliferative disorders into 2 groups. While HCL coexpresses CD25 and annexin-A1, diseases lacking CD25 and annexin-A1 behave clinically differently and can be separated from HCL on diagnosis.

p53 inactivation in the primary tumor (but not PTEN loss) may be predictive of inferior outcomes to novel hormonal therapies in CRPC.