Abstract
Large-scale normative data are lacking for benign lymph nodes assessed by flow cytometry immunophenotyping. Initial diagnostics are increasingly moving toward fine needle aspiration (FNA). ...We used a novel informatics approach to gather large-scale normative data for benign lymph node flow cytometry and compare the performance of flow cytometry immunophenotyping from samples obtained by excisional biopsy vs FNA. We hypothesized that a large normative immunophenotyping dataset will demonstrate comparability between excisional biopsies and FNA flow cytometry immunophenotyping results. Custom text-parsing software was created to extract clinical, diagnostic, and flow cytometry data from 382 consecutive excisional biopsies and 309 consecutive FNAs carrying a benign diagnosis and spanning the last 15 years. Antigens normalized to B- and T-cell content were compared between excisional biopsy and FNAs by t-test corrected for multiple comparisons by false discovery rate. As expected, raw numbers of events were lower in the FNA as compared to the excisional biopsies (86.0% vs 82%). Excisional biopsy vs FNA samples had a significantly lower proportion of events in the monocyte gate (6.5% vs 4.3%). FNAs were enriched for CD3+ T cell events (70.1% vs 59.4%) and with proportionately fewer CD19+ B cells events (23.8% vs 32.7%). Nevertheless, normalized B-cell subsets (eg, %CD19/CD10+, %CD19/CD5+) and T-cell subsets (eg, CD4:CD8 ratio) did not significantly differ between excisional biopsy and FNA specimens with minor exceptions. In conclusion, excisional biopsy and FNA samples differ in overall yield as well as T-cell content, likely due to peripheral blood contamination, but nevertheless produce comparable immunophenotyping results with respect to B- and T-cell subsets in benign lymph nodes. Informatics approaches enlarge normative datasets and in the current study led to the first large-scale quantitative comparison of normative data between different tissue-sampling methods.
Iron overload and transfusion dependance portend poor risk in myelodysplastic syndromes (MDS); bone marrow macrophages store iron and limit oxidative damage through heme oxygenase-1 (HO1). We ...assessed iron stores and macrophage HO1 expression in MDS using image analysis of intact diagnostic bone marrow biopsies and qualitative scoring of marrow aspirate iron among 129 cytopenic patients, 67 with MDS and 62 similarly aged patients with benign cytopenias. Using double immunofluorescence and sequential iron and immunohistochemistry staining, we showed that marrow iron colocalizes with HO1 and H-ferritin to CD163 + macrophages. Marrow iron was elevated in MDS independent of transfusion status, a finding of potential utility in distinguishing benign cytopenia from MDS. Among MDS patients only, CD163 + macrophage density and HO1 and H-ferritin expression by CD163 + macrophages increased in tandem with marrow iron. High HO1 was significantly associated with shorter overall survival among MDS patients independent of IPSSR and history of transfusion.
Professionalism and physician well-being are important topics in academic medicine. Lapses in professional judgment may lead to disciplinary action and put patient’s health at risk. Within medical ...education, students and trainees are exposed to professionalism in the institution’s formal curriculum and hidden curriculum. Development of professionalism starts early in medical school. Trainees entering graduate medical education already have developed professional behavior. As a learned behavior, development of professional behavior is modifiable. In addition to role modeling by faculty, other modalities are needed. Use of case vignettes based on real-life issues encountered in trainee and faculty behavior can serve as a basis for continued development of professionalism in trainees. Based on the experience of program directors and pathology educators, case vignettes were developed in the domains of service, research, and education and subdivided into the areas of duty, integrity, and respect. General and specific questions pertaining to each case were generated to reinforce model behavior and overcome professionalism issues encountered in the hidden curriculum. To address physician burnout, cases were generated to provide trainees with the skills to deal with burnout and promote well-being.
Primary cutaneous lymphomas are defined as non-Hodgkin lymphomas that present in the skin with no evidence of extracutaneous disease at the time of diagnosis. Mycosis fungoides is the most common ...type of primary cutaneous T-cell lymphoma, representing almost 50% of primary cutaneous T-cell lymphomas, and primary cutaneous CD30
T-cell lymphoproliferative disorders are the second most common group (30%). Transformed mycosis fungoides is usually CD30
and can involve multiple nodal sites; other primary cutaneous CD30
T-cell lymphoproliferative disorders can also involve draining regional nodes. Nodal involvement by CD30
T-cell lymphoproliferative disorders can mimic classical Hodgkin lymphoma, which can aberrantly express T-cell antigens. The aim of this article is to briefly review salient clinical, histologic, immunophenotypic, and molecular features that can be used to distinguish lymph node involvement by CD30
cutaneous T-cell lymphomas and lymphoproliferative disorders from classical Hodgkin lymphoma, a clinically important differential diagnosis that represents a challenging task for the pathologist.
Summary CD81 is a tetraspanin cell surface protein that regulates CD19 expression in B lymphocytes and enables hepatitis C virus infection of human cells. Immunohistologic analysis in normal ...hematopoietic tissue showed strong staining for CD81 in normal germinal center B cells, a cell type in which its increased expression has not been previously recognized. High-dimensional flow cytometry analysis of normal hematopoietic tissue confirmed that among B- and T-cell subsets, germinal center B cells showed the highest level of CD81 expression. In more than 800 neoplastic tissue samples, its expression was also found in most non-Hodgkin lymphomas. Staining for CD81 was rarely seen in multiple myeloma, Hodgkin lymphoma, or myeloid leukemia. In hierarchical cluster analysis of diffuse large B-cell lymphoma, staining for CD81 was most similar to other germinal center B cell–associated markers, particularly LMO2. By flow cytometry, CD81 was expressed in diffuse large B-cell lymphoma cells independent of the presence or absence of CD10, another germinal center B-cell marker. The detection of CD81 in routine biopsy samples and its differential expression in lymphoma subtypes, particularly diffuse large B-cell lymphoma, warrant further study to assess CD81 expression and its role in the risk stratification of patients with diffuse large B-cell lymphoma.
Biopsies from patients with inborn error of immunity (IEI) may pose a diagnostic challenge due to the abnormal anatomy of their lymphoid organs and the tendency for the development of ...lymphoproliferations in various organs, some of which may lead to the wrong impression of malignant lymphoma which may prompt aggressive unnecessary treatment. In this article we will review typical histologic findings in various IEI's described in the literature and discuss the appropriate approach to the diagnosis of lymphoproliferations in these patients by presenting illustrative cases.
The aim of this article is to briefly review salient clinical, histologic, immunophenotypic, and molecular features that can be used to distinguish lymph node involvement by CD30+ cutaneous T-cell ...lymphomas and lymphoproliferative disorders from classical Hodgkin lymphoma, a clinically important differential diagnosis that represents a challenging task for the pathologist. Patients presenting with involvement of regional lymph nodes have a good prognosis that is similar to that of patients with only skin lesions.2-5 Advanced-stage MF including systemic lymphadenopathy, however, has a poorer prognosis, and large cell transformation is associated with worse outcomes within this group.6 GROSS PATHOLOGY When excisional lymph node biopsy is performed, involved lymph nodes may demonstrate effacement of the nodal architecture, and a nodular appearance or fibrosis. If present, sinusoidal involvement by the large cells favors CD30+ T-LPDs.7 Architecturally, the presence of thick fibrous bands is most consistent with CHL nodular sclerosis subtype, although cases of nodal involvement by primary cutaneous T-cell lymphoma with extensive fibrosis in a nodular pattern have been described (Figure, A).7 Flow cytometry shows an increased CD4:CD8 ratio in both cases. Standard gene rearrangement studies performed according to the BIOMED-2 protocol demonstrate immunoglobulin gene rearrangement in a subset of CHL cases,17 whereas T-cell receptor gene rearrangement supports T-cell lymphoma origin (Table 1).1,2,3,7 Comparing molecular studies from the different patient's specimens (skin biopsies versus lymph node) is valuable, as identifying clonal peaks of identical size supports involvement by the same process.
PDF
