Integrative analysis of clinicopathological features defines novel prognostic models for mantle cell lymphoma in the immunochemotherapy era: a report from The North American Mantle Cell Lymphoma Consortium.

BACKGROUND: Patients with mantle cell lymphoma (MCL) exhibit a wide variation in clinical presentation and outcome. However, the commonly used prognostic models are outdated and inadequate to address the needs of the current multidisciplinary management of this disease. This study aims to investigate the clinical and pathological features of MCL in the immunochemotherapy era and improve the prognostic models for a more accurate prediction of patient outcomes. METHODS: The North American Mantle Cell Lymphoma Project is a multi-institutional collaboration of 23 institutions across North America to evaluate and refine prognosticators for front-line therapy. A total of 586 MCL cases diagnosed between 2000 and 2012 are included in this study. A comprehensive retrospective analysis was performed on the clinicopathological features, treatment approaches, and outcomes of these cases. The establishment of novel prognostic models was based on in-depth examination of baseline parameters, and subsequent validation in an independent cohort of MCL cases. RESULTS: In front-line strategies, the use of hematopoietic stem cell transplantation was the most significant parameter affecting outcomes, for both overall survival (OS, p < 0.0001) and progression-free survival (PFS, p < 0.0001). P53 positive expression was the most significant pathological parameter correlating with inferior outcomes (p < 0.0001 for OS and p = 0.0021 for PFS). Based on the baseline risk factor profile, we developed a set of prognostic models incorporating clinical, laboratory, and pathological parameters that are specifically tailored for various applications. These models, when tested in the validation cohort, exhibited strong predictive power for survival and showed a stratification resembling the training cohort. CONCLUSIONS: The outcome of patients with MCL has markedly improved over the past two decades, and further enhancement is anticipated with the evolution of clinical management. The innovative prognostic models developed in this study would serve as a valuable tool to guide the selection of more suitable treatment strategies for patients with MCL.

Trends in Bone Marrow Sampling and Core Biopsy Specimen Adequacy in the United States and Canada: A Multicenter Study.

OBJECTIVES: To assess bone marrow (BM) sampling in academic medical centers. METHODS: Data from 6,374 BM samples obtained in 32 centers in 2001 and 2011, including core length (CL), were analyzed. RESULTS: BM included a biopsy (BMB; 93%) specimen, aspirate (BMA; 92%) specimen, or both (83%). The median (SD) CL was 12 (8.5) mm, and evaluable marrow was 9 (7.6) mm. Tissue contraction due to processing was 15%. BMB specimens were longer in adults younger than 60 years, men, and bilateral, staging, and baseline samples. Only 4% of BMB and 2% of BMB/BMA samples were deemed inadequate for diagnosis. BM for plasma cell dyscrasias, nonphysician operators, and ancillary studies usage increased, while bilateral sampling decreased over the decade. BM-related quality assurance programs are infrequent. CONCLUSIONS: CL is shorter than recommended and varies with patient age and sex, clinical circumstances, and center experience. While pathologists render diagnoses on most cases irrespective of CL, BMB yield improvement is desirable.

A Simple and Effective Method for Flow Cytometric Study of Lymphoid Malignancies Using Needle Core Biopsy Specimens.

OBJECTIVES: We developed a simple and effective rinsing technique (RT) of needle biopsies to produce cell suspensions for flow cytometry (FCM) and evaluated whether the RT is comparable to the conventional tissue cell suspension (TCS) technique. METHODS: We retrieved 93 needle core biopsy cases employing the RT for FCM and 25 needle biopsy cases using TCS for FCM. RESULTS: The diagnostic concordance between the FCM results and the morphologic diagnoses of both groups was compared. The diagnostic concordance was comparable in the RT group (92.6%) to the TCS group (71.4%). Furthermore, the diagnostic concordance in the RT group was associated with number of isolated cells. The diagnostic accuracy increased significantly when the cell number was above 30,000 in the RT group. CONCLUSIONS: The RT for FCM not only maximizes the tissue utilization, but also is a simple and effective method to obtain cell suspension as compared to traditional cell suspension technique. © 2018 International Clinical Cytometry Society.

Flow Cytometric Characteristics of Extrathymic Thymocytes in Adenoid Tissue: A Case Report and Comparison to Normal Thymus and Thymoma.

BACKGROUND: Normal thymocyte precursors in secondary lymphoid organs have previously been described. It is important to recognize normal thymocyte precursors by flow cytometry to differentiate them from T-cell lymphoblastic leukemia. METHODS: A 3-year-old boy status 2 years postallogenic cardiac transplant underwent adenoidectomy to exclude post-transplant lymphoproliferative disorder. Microscopic, immunohistochemical, and flow cytometry analyses of the adenoid were performed. RESULTS: By flow cytometry, a population of CD45+(dim)/CD7+(bright)/CD3- cells were observed at 1.0% of lymphocytes. These cells expressed CD10, partial CD34 and exhibited acquisition of CD4 followed by CD8. Within the brighter CD45+ lymphocytes, a population of CD3-/CD4+/CD8+ thymocytes and a similarly sized population of CD4+/CD8+ cells exhibiting acquisition of low-density CD3 were identified. By immunostaining, clusters of TdT+/CD1a+/CD4+/CD8+ T-cells were identified in the interfollicular areas. Compared to normal thymus, thymocytes in the adenoid tissue lacked the classic CD4xCD8 winged differentiation profile but showed a normal early precursor pattern. CONCLUSIONS: Thymocytes in adenoid show a similar differentiation pattern to thymus and thymoma. However, the classic winged pattern of common thymocyte differentiation may not be readily apparent in thymocytes differentiating outside of the thymus. Recognition of the early thymocyte precursor antigen acquisition profile can be crucial to correct interpretation. © 2017 International Clinical Cytometry Society.

Flow cytometric characteristics of extrathymic thymocytes in adenoid tissue: A case report and comparison to normal thymus and thymoma.

BACKGROUND: Normal thymocyte precursors in secondary lymphoid organs have previously been described. It is important to recognize normal thymocyte precursors by flow cytometry to differentiate them from T-cell lymphoblastic leukemia. METHODS: A 3-year-old boy status 2 years post-allogenic cardiac transplant underwent adenoidectomy to exclude post-transplant lymphoproliferative disorder. Microscopic, immunohistochemical, and flow cytometry analyses of the adenoid were performed. RESULTS: By flow cytometry, a population of CD45+(dim)/CD7+(bright)/CD3- cells were observed at 1.0% of lymphocytes. These cells expressed CD10, partial CD34, and exhibited acquisition of CD4 followed by CD8. Within the brighter CD45+ lymphocytes, a population of CD3-/CD4+/CD8+ thymocytes and a similarly sized population of CD4+/CD8+ cells exhibiting acquisition of low-density CD3 were identified. By immunostaining, clusters of TdT+/CD1a+/CD4+/CD8+ T-cells were identified in the interfollicular areas. Compared to normal thymus, thymocytes in the adenoid tissue lacked the classic CD4xCD8 winged differentiation profile but showed a normal early precursor pattern. CONCLUSIONS: Thymocytes in adenoid show a similar differentiation pattern to thymus and thymoma. However, the classic winged pattern of common thymocyte differentiation may not be readily apparent in thymocytes differentiating outside of the thymus. Recognition of the early thymocyte precursor antigen acquisition profile can be crucial to correct interpretation. © 2017 International Clinical Cytometry Society.