Indolent B-Lineage Precursor Populations Identified by Flow Cytometry and Immunohistochemistry in Benign Lymph Nodes.

OBJECTIVES: In this retrospective study, we report a series of benign lymph nodes showing small populations of normal B-cell precursors characterized by flow cytometry and immunohistochemistry. METHODS: Ten cases identified during clinical flow cytometry practice were retrospectively reanalyzed with particular attention to hematogone categorization and enumeration. Immunohistochemical staining was performed on five excisional lymph node biopsy specimens to characterize the morphologic correlate. RESULTS: Populations of hematogones ranging from 0.13% to 1.86% (median, 0.51%) of all viable leukocytes were demonstrated in 10 benign lymph node samples from eight different patients ranging in age from 17 to 45 years (median, 37.5). These hematogones showed a characteristic immunophenotype (CD19+/CD10+) and maturational pattern by flow cytometry, with progression from stage 1 (median, 0.03%) to stage 2 (median, 0.19%) to stage 3 (median, 0.26%) seen in all cases. Immunohistochemical staining on five excisional biopsy specimens demonstrated a distinct perisinusoidal distribution of CD10+/CD20+ cells with a subset of TdT+ cells, providing a morphologic correlate. CONCLUSIONS: To our knowledge, this is the first study to characterize distinct hematogone populations within benign lymph nodes by both flow cytometry and immunohistochemistry. Recognizing these normal B-cell precursor populations is important to avoid their miscategorization as a CD10+ B-cell neoplasm.

B-cell posttransplant lymphoproliferative disorder isolated to the central nervous system is Epstein-Barr virus positive and lacks p53 and Myc expression by immunohistochemistry.

In this retrospective study from one institution, we performed a clinicopathological study of a cohort of patients with posttransplant lymphoproliferative disorder (PTLD) confined to the central nervous system. We also identified a comparison cohort of patients with de novo primary diffuse large B-cell lymphoma of the central nervous system. We performed a detailed morphologic review, evaluated Epstein-Barr virus (EBV) by in situ hybridization, and interpreted a panel of immunohistochemical stains in a subset of cases including Hans classification markers (CD10, BCL6, MUM1), p53, CD30, Myc, and BCL2. All 17 of the posttransplant and none of 11 de novo cases were EBV positive (P < .005). Morphologic patterns identified in the PTLD cases were monomorphic diffuse large B-cell lymphoma pattern (10 patients) and "T-cell-rich" pattern (7 patients). The monomorphic posttransplant cases were more likely to be Myc negative (P = .015) and CD30 positive (P < .005) than the de novo cases, and showed a similarly low rate of p53 positivity by immunohistochemistry. No prognostic factors for overall survival were identified. Central nervous system PTLD is EBV positive, typically lacks p53 and Myc expression by immunohistochemistry, and can present with numerous background T lymphocytes.

Analysis of Peripheral T-cell Lymphoma Diagnostic Workup in the United States.

BACKGROUND: With increased understanding of the unique entities, subtype-specific approaches for peripheral T-cell lymphoma (PTCL) are emerging, and more precise diagnoses are becoming increasingly important. PATIENTS AND METHODS: We analyzed the approach to the histopathologic diagnosis of PTCL using data from the comprehensive oncology measures of peripheral T-cell lymphoma (COMPLETE) study. The COMPLETE trial is a large prospective cohort study of patients with newly diagnosed PTCL in the United States. RESULTS: A total of 499 patients were enrolled from 40 academic and 15 community-based centers. Baseline assessment forms were collected for 493 patients, of which 435 (88%) were available for analysis. The most common diagnoses were PTCL, not otherwise specified (PTCL-NOS), anaplastic large cell lymphoma, and angioimmunoblastic T-cell lymphoma (AITL). A mean of 10 markers (range, 0-21) was assessed per patient. CD30 was assessed frequently but not uniformly in cases that were not anaplastic large cell lymphoma. Only 17% of PTCL-NOS cases were assessed for PD1. CXCL13 was a relatively sensitive marker in AITL, expressed in 84% of tested cases; however, only 3% of PTCL-NOS cases were tested. T follicular helper cell marker assessment differed between academic and community practices, with PD1 more often evaluated by academic centers in cases of AITL (62% vs. 12%; P = .01). CONCLUSION: The diagnostic workup for PTCL in the United States varies widely and often lacks important phenotypic information to fully characterize the lymphoma. Gaps in testing of selected markers should be filled, given the impending revision to the World Health Organization classification. The accuracy of diagnosis will become increasingly important as we enter the era of targeted treatment for PTCL.