Revisiting Bone Marrow Core Biopsy Adequacy Criteria in the Era of Extensive Ancillary Testing.

BACKGROUND: Bone marrow core biopsy is a routine component of comprehensive marrow evaluation, and adequacy criteria have been recommended. However, the effectiveness of these adequacy criteria for diagnostic bone marrow evaluation needs to be reassessed in the current era of extensive ancillary testing. We aimed to determine the impact of core biopsy length and intertrabecular area of evaluable bone marrow on overall adequacy for diagnostic marrow evaluation at our tertiary care institution. METHODS: Five hundred sequential cases of iliac crest bone marrow sampling were identified by retrospective re-view at our tertiary care institution. In this cohort, 470 core biopsies were obtained for histologic evaluation. Data including gross core biopsy length, number of intertrabecular 40x high power fields of evaluable marrow, and other pathologic/clinical parameters were compiled. RESULTS: The mean core biopsy length was 1.2 cm, and only 23% measured the recommended ≥ 1.5 cm. However, 96% of the core biopsies were interpretable and contributed to the comprehensive bone marrow evaluation. Notably, 100% of biopsies with ≥ 5.5 intertrabecular areas were contributory. Ancillary testing including immunophenotypic, cytogenetic, and/or molecular studies were performed in > 99% of cases. CONCLUSIONS: When histology was integrated with ancillary testing, the overall diagnosis was substantially limited in only 0.4% of cases and material deemed entirely insufficient in 0.4%. The number of intertrabecular 40x areas of evaluable marrow is a better predictor of adequacy than core biopsy length, and adequacy criteria should be revised in this era of extensive ancillary testing.

Complex karyotype in patients with mantle cell lymphoma predicts inferior survival and poor response to intensive induction therapy.

BACKGROUND: Risk stratification of newly diagnosed patients with mantle cell lymphoma (MCL) primarily is based on the MCL International Prognostic Index (MIPI) and Ki-67 proliferative index. Single-center studies have reported inferior outcomes in patients with a complex karyotype (CK), but this remains an area of controversy. METHODS: The authors retrospectively reviewed 483 patients from 5 academic centers in the United States and described the effect of a CK on survival outcomes in individuals with MCL. RESULTS: A CK was found to be associated with inferior overall survival (OS) (4.5 vs 11.6 years; P<.01) and progression-free survival (PFS) (1.9 vs 4.4 years; P<.01). In patients who underwent high-intensity induction followed by autologous stem cell transplantation (ASCT) in first remission, a CK was associated with poor OS (5.1 vs 11.6 years; P = .04) and PFS (3.6 vs 7.8 years; P<.01). Among patients with a CK, high-intensity induction had no effect on OS (4.5 vs 3.8 years; P = .77) nor PFS (2.3 vs 1.5 years; P = .46). Similarly, ASCT in first remission did not improve PFS (3.5 vs 1.2 years; P = .12) nor OS (5.1 vs 4.0 years; P = .27). On multivariable analyses with Ki-67 and MIPI, only CK was found to be predictive of OS (hazard ratio [HR], 1.98; 95% confidence interval [95% CI], 1.12-3.49 [P = .02]), whereas both CK (HR, 1.91; 95% CI, 1.17-3.12 [P = .01]) and Ki-67 >30% (HR, 1.86; 95% CI, 1.06-3.28 [P = .03]) were associated with inferior PFS. Multivariable analysis did not identify any specific cytogenetic abnormalities associated with inferior survival. CONCLUSIONS: CK appears to be independently associated with inferior outcomes in patients with MCL regardless of the intensity of induction therapy and receipt of ASCT. Cytogenetics should be incorporated into the workup of a new diagnosis of MCL and novel therapeutic approaches should be investigated for patients with CK. Cancer 2018;124:2306-15. © 2018 American Cancer Society.

Performance comparison of capillary and agarose gel electrophoresis for the identification and characterization of monoclonal immunoglobulins.

The objective of this study was to compare gel- and capillary-based serum protein electrophoresis methods to identify and characterize monoclonal immunoglobulins (M proteins). Five reviewers interpreted 149 consecutively ordered serum specimens following agarose gel electrophoresis (AGE), capillary electrophoresis (CE), immunofixation electrophoresis (IFE), and subtraction immunotyping (IT). As a screening test for detecting M proteins, AGE and CE displayed similar sensitivity (91% and 92%, respectively). CE was less specific (74%) than AGE (81%). An analysis of interinterpreter agreement revealed that interpretations were more consistent using gel-based methods than capillary-based methods, with 80% of the gel interpretations being in complete (5/5) agreement compared with 67% of the capillary interpretations. After implementing the capillary-based methods, the number of tests per reportable result increased (from 1.58 to 1.73). CE is an analytically suitable alternative to AGE, but laboratories implementing it will need to continue IFE testing to characterize all M proteins detected by CE.

Transformation in Low-grade B-cell Neoplasms.

Low-grade B-cell leukemias/lymphomas are a diverse group of indolent lymphoproliferative disorders that are typically characterized by good patient outcomes and long life expectancies. A subset of cases, however, undergo histologic transformation to a higher-grade neoplasm, a transition associated with a more aggressive clinical course and poor survival. Transformation of follicular lymphoma to diffuse large B-cell lymphoma and Richter transformation of chronic lymphocytic leukemia/small lymphocytic lymphoma are best characterized in the literature. This article reviews clinical and pathologic characteristics of these most common forms of transformation, with an emphasis on salient histologic, immunophenotypic, and genetic features.

Karyotypic abnormalities associated with Epstein-Barr virus status in classical Hodgkin lymphoma.

Classical Hodgkin lymphoma (CHL) is morphologically characterized by scattered malignant Hodgkin/Reed-Sternberg (HRS) cells that are far outnumbered by surrounding reactive hematolymphoid cells. Approximately half of all cases of CHL are associated with infection by Epstein-Barr virus (EBV), an oncogenic herpesvirus that expresses a number of proteins thought to contribute to transformation. While a small number of published studies have attempted to identify recurrent cytogenetic abnormalities in CHL, no large case series have explored karyotypic differences between EBV-positive and EBV-negative tumors. Here, we report a two-institution retrospective investigation of cytogenetic features characterizing CHL. In our cohort, cases of EBV-negative CHL were characterized by more complex routine karyotypes than their EBV-positive counterparts (24.6 versus 15.6 independent aberrations per case, P = 0.009). The increased complexity of EBV-negative cases was driven by a number of features suggestive of genomic instability, including a larger number of independent chromosomal breakpoints (P = 0.03) and apparently aneuploid autosomes (P = 0.008). Compelling but nonsignificant trends also suggest a larger modal number and increased marker chromosomes in EBV-negative cases (P = 0.13 and 0.06, respectively). While some of these differences are related to histologic subtype, others appear independent of histology. Finally, a significant subset of EBV-positive tumors has a surprisingly simple karyotype relative to what is normally seen in CHL, an observation suggesting considerable biological and genetic diversity in this disease.

Clonal karyotypic abnormalities associated with reactive lymphoid hyperplasia.

Cytogenetic abnormalities are important in the diagnosis and prognosis of hematolymphoid neoplasms. Although many recurrent karyotypic abnormalities are well-defined and known to underlie pathophysiologic processes contributing to malignancy, the significance of other cytogenetic changes is less clear. This uncertainty reflects an incomplete understanding of the frequency with which karyotypic abnormalities arise in benign processes. Numerous case reports and a small number of retrospective series have noted clonal cytogenetic changes in association with reactive-appearing lymph nodes. However, the incidence of such abnormalities has varied widely in published series. Here, we report the largest retrospective series of karyotypic abnormalities in association with reactive lymphoid hyperplasia published to date. Clonal karyotypic abnormalities were present in 6.3% of reactive lymph nodes with informative karyotypes and 5.1% of all reactive lymphoid tissues. These data suggest that karyotypic abnormalities are less frequently found in association with reactive lymphoid tissue than previously reported and provide a clearer picture of the baseline incidence of cytogenetic changes in benign lymphoid processes.