The Comparative Sensitivity of Immunohistochemical Markers of Megakaryocytic Differentiation in Acute Megakaryoblastic Leukemia

Klairmont, Matthew M; Hoskoppal, Deepthi; Yadak, Nour; Choi, John K.

doi:10.1093/ajcp/aqy074

Cited by 11 publications

(9 citation statements)

References 8 publications

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“…A distinct feature of this case was very bright and homogeneous coexpression of CD41 and CD42b (Figure A–B). This pattern is seen far less frequently in true AMKL, which more commonly demonstrates a broader range of CD41/CD42b intensity, usually spread over more than 1 decalog . It should be noted that platelet satellitism is not restricted to PBFC and can occur in BMFC as well .…”

Section: Discussionmentioning

confidence: 92%

Peripheral blood flow cytometry for the diagnosis of pediatric acute leukemia: Highly reliable with rare exceptions

Cheng

Klairmont

Choi

2018

Pediatric Blood & Cancer

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Background: Recent data have demonstrated the high sensitivity and specificity of peripheral blood flow cytometry (PBFC) for the diagnosis of pediatric leukemia; however, diagnostically significant immunophenotypic discrepancies between PBFC and bone marrow (BM) evaluation, which result in different lineage assignment and treatment protocols, can rarely occur. Here, we sought to further characterize the performance of PBFC for pediatric leukemia and highlight the exceptions when PBFC can result in misdiagnosis. Methods: An institutional database was searched between 2012 and 2016 for cases of acute leukemia with concurrent PBFC and BM evaluation. Immunophenotyping results from the peripheral blood and BM using four or eight color flow cytometry, as well as BM cytochemical staining and immunohistochemistry, were compared. Results: Two hundred ninety PBFC samples with concurrent BM evaluation were identified. Based on the final immunophenotypic classification, the cases were distributed as follows: 108 B-lymphoblastic leukemia (B-ALL), 57 T-lymphoblastic leukemia (T-ALL), 116 acute myeloid leukemia (AML), and 9 mixed-phenotype acute leukemia (MPAL). Among all cases, five had a diagnostically significant discrepancy between PBFC and BM evaluation. In three cases, the immunophenotype by PBFC was consistent with early T-cell precursor ALL (ETP-ALL), whereas BM evaluation demonstrated MPAL. Two cases were suspicious for acute megakaryoblastic leukemia (AMKL) and MPAL, T/myeloid by PBFC but were diagnosed as B-ALL and T-ALL in the BM. Conclusion: Immunophenotypic classification by PBFC is accurate (>98%) in almost all cases of pediatric leukemia with the rare exceptions of suspected ETP-ALL, MPAL, and AMKL. These PBFC diagnoses should be confirmed with BM immunophenotyping. K E Y W O R D S acute lymphoblastic leukemia, acute myeloid leukemia, early T-cell precursor acute lymphoblastic leukemia, mixed-phenotype acute leukemia, pediatric leukemia, peripheral blood flow cytometry

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Section: Discussionmentioning

confidence: 92%

Peripheral blood flow cytometry for the diagnosis of pediatric acute leukemia: Highly reliable with rare exceptions

Cheng

Klairmont

Choi

2018

Pediatric Blood & Cancer

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“…Our obtained results conform with recent studies about the diagnosis of acute leukemia and Non-Hodgkin lymphomas methods. [ 63 – 67 ]…”

Section: Discussionmentioning

confidence: 99%

Biomarkers involved in evaluation of platelets function in South-Eastern Romanian patients with hematological malignancies subtypes

et al. 2021

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At present, various researches presented how subtypes of hematological malignancies are related to stages of the immune response, because the activated immune system represents a promising form in cancer treatment. This study explores the relationship between the adaptive immune system (T cells), and the coagulation system (platelets, platelet membrane glycoproteins, platelets derivate microparticles) which seems to play an important role in host immune defense of patients with acute myeloblastic leukemia (AML) or B cell lymphoma (BCL), 2 of the most common hematological malignancies subtypes. Blood samples (n = 114) obtained from patients with AML or BCL were analyzed for platelet membrane glycoproteins (CD42b, CD61), glycoprotein found on the surface of the T helper cells (CD4 + ), protein complex-specific antigen for T cells (CD3 + ), platelet-derived microparticles (CD61 PMP) biomarkers by flow cytometry, and hematological parameters were quantified by usual methods. In patients with AML, the means of the percentage of the expressions of the molecules on platelet surfaces (CD61 and CD42b, P < .01; paired T test) were lower as compared to both control subgroups. The expression of cytoplasmic granules content (CD61 PMP) had a significantly higher value in patients with AML reported to controlling subgroups ( P < .01; paired T test), which is suggesting an intravascular activation of platelets. The platelet activation status was presented in patients with low stage BCL because CD61 and CD42b expressions were significantly higher than control subgroups, but the expression of CD 61 PMP had a significantly decreased value reported to control subgroups (all P < .01; paired T test). T helper/inducer lineage CD4 + and T lymphoid lineage CD3 + expressions presented significant differences between patients with AML or low stage BCL reported to control subgroups (all P < .01; paired T test). Platelet–lymphocyte interactions are involved in malignant disorders, and CD61, CD42b present on platelet membranes, as functionally active surface receptors mediate the adhesion of active platelets to lymphocytes, endothelial cells, and cancer cells.

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Section: Methodsmentioning

confidence: 99%

“…Histologic descriptions for control autopsies were recorded from finalized autopsy reports. IHC was performed on a single representative block from each case, consisting of left and/ or right ventricle, using a modified protocol described by Klairmont et al 45 Staining for CD42b was performed on a BOND III Immunostainer (Leica Biosystems, Buffalo Grove, IL, USA). Pretreatment (heatinduced epitope retrieval) at low pH (ER1; Leica Biosystems) was performed for 30 min, followed by incubation with antihuman CD42b rabbit monoclonal antibody (clone SP219; ABCAM, Waltham, MA, USA), diluted 1:1000 for 1 h. Detection was performed using DAB Refine Polymer Detection Kit (Leica Biosystems).…”

Section: H I S T O L O G Y a N D I M M U N O H I S T O C H E M I S T ...mentioning

confidence: 99%

Cardiac megakaryocytes in SARS‐CoV‐2‐positive autopsies

et al. 2022

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Thromboembolic phenomena are an important complication of infection by severe acute respiratory coronavirus 2 (SARS‐CoV‐2). Increasing focus on the management of the thrombotic complications of Coronavirus Disease 2019 (COVID‐19) has led to further investigation into the role of platelets, and their precursor cell, the megakaryocyte, during the disease course. Previously published postmortem evaluations of patients who succumbed to COVID‐19 have reported the presence of megakaryocytes in the cardiac microvasculature. Our series evaluated a cohort of autopsies performed on SARS‐CoV‐2‐positive patients in 2020 (n = 36) and prepandemic autopsies performed in early 2020 (n = 12) and selected to represent comorbidities common in cases of severe COVID‐19, in addition to infectious and noninfectious pulmonary disease and thromboembolic phenomena. Cases were assessed for the presence of cardiac megakaryocytes and correlated with the presence of pulmonary emboli and laboratory platelet parameters and inflammatory markers. Cardiac megakaryocytes were detected in 64% (23/36) of COVID‐19 autopsies, and 40% (5/12) prepandemic autopsies, with averages of 1.77 and 0.84 megakaryocytes per cm2, respectively. Within the COVID‐19 cohort, autopsies with detected megakaryocytes had significantly higher platelet counts compared with cases throughout; other platelet parameters were not statistically significant between groups. Although studies have supported a role of platelets and megakaryocytes in the response to viral infections, including SARS‐CoV‐2, our findings suggest cardiac megakaryocytes may be representative of a nonspecific inflammatory response and are frequent in, but not exclusive to, COVID‐19 autopsies.

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The Comparative Sensitivity of Immunohistochemical Markers of Megakaryocytic Differentiation in Acute Megakaryoblastic Leukemia

Abstract: CD42b can reliably be used as a solitary first-line marker for blasts of megakaryocytic lineage, whereas CD61 may be reserved for infrequent cases that are CD42b negative. There is no role for the routine use of vWF when CD42b and CD61 are available.

Cited by 11 publications

References 8 publications

Peripheral blood flow cytometry for the diagnosis of pediatric acute leukemia: Highly reliable with rare exceptions

Peripheral blood flow cytometry for the diagnosis of pediatric acute leukemia: Highly reliable with rare exceptions

Biomarkers involved in evaluation of platelets function in South-Eastern Romanian patients with hematological malignancies subtypes

Cardiac megakaryocytes in SARS‐CoV‐2‐positive autopsies

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