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B‐cell lymphomas with atypical presentation or immunophenotype pose diagnostic challenges. Conventional ancillary tests (cytogenetics, FISH) can help, but have technical limitations. New technologies such as mate‐pair sequencing (MPSeq) offer a route around these technical limitations. [ABSTRACT FROM AUTHOR]

Rearrangement of MYC is associated with a poor prognosis in patients with diffuse large B cell lymphoma ( DLBCL) and B cell lymphoma unclassifiable ( BCLU), particularly in the setting of double hit lymphoma ( DHL). However, little is known about outcomes of patients who demonstrate MYC rearrangement without evidence of BCL2 or BCL6 rearrangement (single hit) or amplification (>4 copies) of MYC. We identified 87 patients with single hit lymphoma ( SHL), 22 patients with MYC-amplified lymphoma ( MYC amp) as well as 127 DLBCL patients without MYC rearrangement or amplification ( MYC normal) and 45 patients with DHL, all treated with either R- CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) or intensive induction therapy. For SHL and MYC amp patients, the 2-year progression-free survival rate ( PFS) was 49% and 48% and 2-year overall survival rate ( OS) was 59% and 71%, respectively. SHL patients receiving intensive induction experienced higher 2-year PFS (59% vs. 23%, P = 0·006) but similar 2-year OS as compared with SHL patients receiving R- CHOP. SHL DLBCL patients treated with R- CHOP, but not intensive induction, experienced significantly lower 2-year PFS and OS ( P < 0·001 for both) when compared with MYC normal patients. SHL patients appear to have a poor prognosis, which may be improved with receipt of intensive induction. [ABSTRACT FROM AUTHOR]

Background: Double-hit lymphomas (DHLs) are collectively defined as B-cell non-Hodgkin lymphomas harboring rearrangements of MYC as well as B-cell lymphoma 2 (BCL2) and/or B-cell lymphoma 6 (BCL6). To the authors' knowledge, the impact of specific oncogene rearrangements on outcomes of patients with DHL who are treated with immunochemotherapy has not been previously described. Methods: The authors identified patients whose diagnostic tissue specimens underwent metaphase karyotyping or fluorescence in situ hybridization for MYC as well as both BCL2 and BCL6 rearrangements. Cohorts were defined by the presence (+) or absence (-) of rearrangements: MYC+/BCL2+/BCL6- (BCL2-DHL), MYC+/BCL2-/BCL6+ (BCL6-DHL), and MYC+/BCL2+/BCL6+ (triple-hit lymphoma; THL). Results: A total of 117 patients were included in the current analysis (76 BCL2-DHL patients, 16 BCL6-DHL patients, and 25 THL patients). Compared with patients with BCL2-DHL, those with BCL6-DHL were more likely to be classified as having a non-germinal center cell of origin, presented with extranodal disease, and appeared to achieve higher rates of complete response despite receiving intensive induction therapy less frequently. However, patients with BCL6-DHL experienced a shorter median overall survival if achieving an initial complete response compared with patients with BCL2-DHL. Patients with THL experienced survival outcomes similar to those of patients with BCL2-DHL. Conclusions: Recognition of the specific oncogene rearrangements may be of prognostic value and potentially guide future therapeutic strategies for patients with DHL. [ABSTRACT FROM AUTHOR]

Aim To assess the validity and potential clinical utility of evaluating MYC expression by immunohistochemistry ( IHC) in mantle cell lymphoma ( MCL). Methods and results MYC IHC was scored on a tissue microarray containing 62 MCLs and 29 controls by two pathologists. Inter-observer correlation was high (intra-class correlation of 0.98). MYC IHC scores correlated with MYC expression (Spearman's rank correlation 0.69, P < 0.0001) and weakly with Ki67 proliferation index (Spearman's rank correlation 0.30, P = 0.03). Six blastic MCLs did not have higher mean MYC IHC scores or MYC mRNA expression than non-blastic MCLs. None of 57 cases assessed, including all of the blastic cases, showed MYC rearrangement by fluorescence in-situ hybridization. Multivariate analysis with backward selection from potential predictors including age, lactate dehydrogenase, leukocyte count, MIPI score, ECOG performance status, blastic morphology and Ki67 index showed that MYC IHC score is an independent predictor of progression-free survival (hazard ratio 2.34, 95% CI 1.42-3.88, P = 0.0009) and overall survival (hazard ratio 1.90, 95% CI 1.05-3.43, P = 0.034). Conclusions We show that a new monoclonal anti- MYC antibody can enable accurate and reproducible visual assessment of MYC expression that is independently predictive of clinical outcomes in MCL. [ABSTRACT FROM AUTHOR]

Summary Intensive chemotherapy regimens are not feasible in many adults with mantle cell lymphoma (MCL). We sought to build upon our previous experience with a non-intensive regimen, modified R-hyperCVAD chemotherapy (rituximab, cyclophosphamide, vincristine, doxorubicin, dexamethasone) with maintenance rituximab (MR), by the incorporation of bortezomib (VcR-CVAD) and the extension of MR beyond 2 years. Patients with previously untreated MCL received VcR-CVAD chemotherapy every 21 d for six cycles. Patients achieving at least a partial response to induction chemotherapy received rituximab consolidation (375 mg/m2 × 4 weekly doses) and MR (375 mg/m2 every 12 weeks × 20 doses). The primary end points were overall and complete response (CR), and secondary endpoints were progression-free (PFS) and overall survival (OS). Thirty patients were enrolled, with a median age of 61 years. All patients had advanced stage disease, and 60% had medium/high MCL International Prognostic Index risk factors. A CR or unconfirmed CR was achieved in 77% of patients. After a median follow-up of 42 months, the 3-year PFS and OS were 63% and 86%, respectively. The observed 3-year PFS and OS with VcR-CVAD in MCL were comparable to reported outcomes with more intensive regimens. A cooperative group trial (E1405) is attempting to replicate these promising results. [ABSTRACT FROM AUTHOR]

Distinguishing merkel cell carcinoma (MCC), small cell lung carcinoma (SCLC) metastatic to the skin, and atypical basal cell carcinoma (BCC) can be problematic in some cases. Significant differences in the biology of these tumors necessitate that they need to be distinguished from one another. We evaluated the immunophenotypic characteristics of 22 MCCs, nine SCLCs, and 19 BCCs using antibodies to cytokeratin 20 (CK20), thyroid transcription factor-1 (TTF-1), CD117, and DNA topoisomerase II-α (topo II). Nineteen of 22 MCCs stained with the antibody to CK20, none stained with anti-TTF-1, and 13 stained with anti-CD117. No SCLC stained with anti-CK20, all stained with anti-TTF-1, and eight stained with anti-CD117. No BCC stained with any of the three markers. The proliferative index (PI), determined by the expression of topo II, was similar for SLCLs (mean 58.5 ± 9.0%) and MCCs (mean 45.2 ± 12.4%) and was lowest in BCCs (mean 25.0 ± 8.7%). CK20 and TTF-1 appear to be reliable in distinguishing MCC from SCLC. CD117 is expressed in both MCC and SCLC, limiting its diagnostic utility. CK20, TTF-1, and CD117 are not expressed in BCC. The high PI seen in MCCs suggests a role for topoisomerase II inhibitors in their treatment. Yang DT, Holden JA, Florell SR. CD117, CK20, TTF-1, and DNA topoisomerase II-α antigen expression in small cell tumors. [ABSTRACT FROM AUTHOR]

The anticoagulant activity of warfarin sodium is monitored by the prothrombin time (PT) using the international normalized ratio (INR). Standard oral anticoagulant therapy monitoring requires frequent patient visits to physicians' offices and/or laboratories to optimize warfarin dosage. Home PT monitoring by patients can increase testing frequency and may thus decrease complications associated with oral anticoagulant therapy. Clinical studies suggest that home PT monitoring is more effective than uncoordinated management and is as effective as care through specialized anticoagulation clinics for keeping INRs within a therapeutic range. There are accurate and reliable instruments available, but paramount to the success of home PT monitoring is sound patient selection, appropriate patient training, and consistent quality control., (Copyright 2004 Wiley-Liss, Inc.)