Myeloid/Lymphoid Neoplasms Associated With Eosinophilia and Rearrangements of PDGFRA, PDGFRB, or FGFR1 or With PCM1-JAK2

2020 ◽  
Author(s):  
Olga Pozdnyakova ◽  
Attilio Orazi ◽  
Katalin Kelemen ◽  
Rebecca King ◽  
Kaaren K Reichard ◽  
...  
Keyword(s):  
Myeloid Leukemia ◽  
Clinical Laboratory ◽  
Myeloproliferative Neoplasms ◽  
Molecular Genetic ◽  
Lymphoblastic Lymphoma ◽  
Therapeutic Implications ◽  
Lymphoid Neoplasms ◽  
Diagnosis And Classification ◽  
T Lymphoblastic Lymphoma

Abstract Objectives To summarize cases submitted to the 2019 Society for Hematopathology/European Association for Haematopathology Workshop under the category of myeloid/lymphoid neoplasms with eosinophilia and PDGFRA, PDGFRB, or FGFR1 or with PCM1-JAK2 rearrangements, focusing on recent updates and relevant practice findings. Methods The cases were summarized according to their respective gene rearrangement to illustrate the spectrum of clinical, laboratory, and histopathology manifestations and to explore the appropriate molecular genetic tests. Results Disease presentations were heterogeneous, including myeloproliferative neoplasms (MPNs), myelodysplastic syndromes (MDSs), MDS/MPN, acute myeloid leukemia, acute B- or T-lymphoblastic lymphoma/acute lymphoblastic lymphoma (ALL/LBL), or mixed-lineage neoplasms. Frequent extramedullary involvement occurred. Eosinophilia was common but not invariably present. With the advancement of RNA sequencing, cryptic rearrangements were recognized in genes other than PDGFRA. Additional somatic mutations were more frequent in the FGFR1-rearranged cases. Cases with B-ALL presentations differed from Philadelphia-like B-ALL by the presence of an underlying MPN. Cases with FLT3 and ABL1 rearrangements could be potential candidates for future inclusion in this category. Conclusions Accurate diagnosis and classification of this category of myeloid/lymphoid neoplasms has important therapeutic implications. With the large number of submitted cases, we expand our understanding of these rare neoplasms and improve our ability to diagnose these genetically defined disorders.

scholarly journals T-Cell Lymphoblastic Lymphoma Arising in the Setting of Myeloid/Lymphoid Neoplasms with Eosinophilia: LMO2 Immunohistochemistry as a Potentially Useful Diagnostic Marker

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 3102
Author(s):  
Magda Zanelli ◽  
Giuseppe G. Loscocco ◽  
Elena Sabattini ◽  
Maurizio Zizzo ◽  
Francesca Sanguedolce ◽  
...  
Keyword(s):  
Immunohistochemical Analysis ◽  
Lymphoblastic Lymphoma ◽  
Correct Identification ◽  
Lim Domain ◽  
Therapeutic Implications ◽  
Molecular Features ◽  
Lymphoid Neoplasms ◽  
Low Degree ◽  
Molecular Patterns ◽  
T Lymphoblastic Lymphoma

Background: Rarely, T-lymphoblastic lymphoma (T-LBL) may develop in the setting of myeloid/lymphoid neoplasms with eosinophilia (M/LNs-Eo), a group of diseases with gene fusion resulting in overexpression of an aberrant tyrosine kinase or cytokine receptor. The correct identification of this category has relevant therapeutic implications. LIM domain only 2 (LMO2) is overexpressed in most T-LBL, but not in immature TdT-positive T-cells in the thymus and in indolent T-lymphoblastic proliferations (iT-LBP). Methods and Results: We retrospectively evaluated 11 cases of T-LBL occurring in the context of M/LNs-Eo. Clinical, histological, immunohistochemical and molecular features were collected and LMO2 immunohistochemical staining was performed. The critical re-evaluation of these cases confirmed the diagnosis of T-LBL with morphological, immunohistochemical and molecular features consistent with T-LBL occurring in M/LNs-Eo. Interestingly, LMO2 immunohistochemical analysis was negative in 9/11 cases, whereas only 2 cases revealed a partial LMO2 expression with a moderate and low degree of intensity, respectively. Conclusions: LMO2 may represent a potentially useful marker to identify T-LBL developing in the context of M/LNs-Eo. In this setting, T-LBL shows LMO2 immunohistochemical profile overlapping with cortical thymocytes and iT-LBP, possibly reflecting different molecular patterns involved in the pathogenesis of T-LBL arising in the setting of M/LNs-Eo.

scholarly journals Co-occurrence of immature T-lymphoblastic lymphoma and acute myeloid leukemia—microenvironment-dependent lineage differentiation derived from a common progenitor?

2021 ◽  
Author(s):  
Edit Porpaczy ◽  
Wolfgang R. Sperr ◽  
Renate Thalhammer ◽  
Gerlinde Mitterbauer-Hohendanner ◽  
Leonhard Müllauer ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Next Generation Sequencing ◽  
Myeloid Leukemia ◽  
Genetic Alterations ◽  
Lymphoblastic Lymphoma ◽  
Simultaneous Occurrence ◽  
Next Generation ◽  
T Lymphoblastic Lymphoma ◽  
Generation Sequencing ◽  
Acute Myeloid

AbstractMixed phenotype acute leukemia (MPAL) is an uncommon disease characterized by currently only limited knowledge concerning biology, clinical presentation, and treatment outcome. We here describe a most unusual case of simultaneous occurrence of T-lymphoblastic lymphoma in cervical and mediastinal lymph nodes and acute myeloid leukemia in the bone marrow (BM) successfully treated with allogeneic stem cell transplantation (SCT). Although the blasts in both locations showed additional aberrant expression of other lineage markers (even B-cell markers), diagnostic criteria of MPAL were not fulfilled either in the LN or in the BM. We performed next generation sequencing (NGS) with the objective to look for common genetic aberrations in both tissues. Histology, immunohistochemistry, flow cytometry, AML-associated genetic alterations (FLT3, NPM1, KIT D816V, CEPBA), and clonal T-cell receptor β and γ gene rearrangements were performed according to routine diagnostic workflows. Next generation sequencing and Sanger sequencing were additionally performed in BM and LN. Somatic mutation in the EZH2 gene (p.(Arg684Cys)) was detected in the BM by NGS, and the same mutation was found in the LN. Since an identical genetic aberration (EZH2 mutation) was detected in both locations, a common progenitor with regional dependent differentiation may be involved.

scholarly journals Papillary Lesions of the Breast: An Update

2016 ◽  
Vol 140 (7) ◽  
pp. 628-643 ◽  
Author(s):  
Shi Wei
Keyword(s):  
English Language ◽  
Molecular Genetic ◽  
Prognostic Significance ◽  
Molecular Techniques ◽  
Biological Behavior ◽  
Genetic Characteristics ◽  
Decision Tools ◽  
Diagnosis And Classification ◽  
Papillary Lesions

Context.—Papillary lesions of the breast, characterized by the presence of arborescent fibrovascular cores that support epithelial proliferation, constitute a heterogeneous group of neoplasms with overlapping clinical manifestation and histomorphologic features, but may have divergent biological behavior. These lesions are exclusively intraductal neoplasms, although an invasive carcinoma may rarely have a predominantly papillary architecture. Although recognition of a papillary architecture is typically not challenging, the histologic distinction of these entities is not always straightforward. Historically, different terminologies and variable criteria have been proposed for a given entity by various authorities. The difficulty in classifying these lesions has been further confounded by the scarcity of data and the heterogeneity across different studies with regard to the molecular genetic characteristics of this group of lesions. Objective.—To provide an overview focusing on the current concepts in the diagnosis and classification of papillary lesions of the breast incorporating recent molecular genetic advances. Data Sources.—Data were obtained from pertinent peer-reviewed English-language literature. Conclusions.—The recent evolution of molecular techniques has enhanced our knowledge of the pathogenesis of papillary carcinomas of the breast. This, along with emerging outcome studies, has led to prognosis-based reclassification of some of these entities. Additional studies focusing on the molecular signatures are needed to identify potential decision tools to further stratify these lesions with respect to prognostic significance.

Acute Leukemia Immunohistochemistry: A Systematic Diagnostic Approach

2008 ◽  
Vol 132 (3) ◽  
pp. 462-475
Author(s):  
Randall J. Olsen ◽  
Chung-Che Chang ◽  
Jennifer L. Herrick ◽  
Youli Zu ◽  
Aamir Ehsan
Keyword(s):  
Flow Cytometry ◽  
Relevant Literature ◽  
General Strategy ◽  
Acute Leukemias ◽  
Fixed Tissue ◽  
Genetic Studies ◽  
Therapeutic Implications ◽  
Formalin Fixed Tissue ◽  
Diagnosis And Classification

Abstract Context.—The diagnosis and classification of leukemia is becoming increasingly complex. Current classification schemes incorporate morphologic features, immunophenotype, molecular genetics, and clinical data to specifically categorize leukemias into various subtypes. Although sophisticated methodologies are frequently used to detect characteristic features conferring diagnostic, prognostic, or therapeutic implications, a thorough microscopic examination remains essential to the pathologic evaluation. Detailed blast immunophenotyping can be performed with lineage- and maturation-specific markers. Although no one marker is pathognomonic for one malignancy, a well-chosen panel of antibodies can efficiently aid the diagnosis and classification of acute leukemias. Objective.—To review important developments from recent and historical literature. General immunohistochemical staining patterns of the most commonly encountered lymphoid and myeloid leukemias are emphasized. The goal is to discuss the immunostaining of acute leukemias when flow cytometry and genetic studies are not available. Data Sources.—A comprehensive review was performed of the relevant literature indexed in PubMed (National Library of Medicine) and referenced medical texts. Additional references were identified in the reviewed manuscripts. Conclusions.—Immunophenotyping of blasts using an immunohistochemical approach to lymphoid and myeloid malignancies is presented. Initial and subsequent additional antibody panels are suggested to confirm or exclude each possibility in the differential diagnosis and a general strategy for diagnostic evaluation is discussed. Although the use of immunohistochemistry alone is limited and evaluation by flow cytometry and genetic studies is highly recommended, unavoidable situations requiring analysis of formalin-fixed tissue specimens arise. When performed in an optimized laboratory and combined with a careful morphologic examination, the immunohistochemical approach represents a useful laboratory tool for classifying various leukemias.

scholarly journals Diagnostic Workup of Small B Cell Lymphomas: A Laboratory Perspective

Lymphoma ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-15 ◽  
Author(s):  
Kathryn Rizzo ◽  
Mehdi Nassiri
Keyword(s):  
B Cell ◽  
Correct Diagnosis ◽  
Molecular Genetic ◽  
B Cell Lymphoma ◽  
Lymphoid Cells ◽  
B Cell Lymphomas ◽  
Genetic Features ◽  
Diagnosis And Classification ◽  
Biomarker Evaluation

Small B cell lymphoma is a morphological designation to a group of B cell lymphomas which are composed of a clonal population of small lymphoid cells. The subtypes of this category have diagnostically distinct characteristics and different clinical behaviors and treatment. Correct diagnosis and classification of these subsets depend on the integration of morphologic, immunophenotypic, and molecular genetic features. In this paper, differential diagnosis of this category of tumors and a practical approach based on biomarker evaluation are discussed.

scholarly journals Diagnosis and classification of hematologic malignancies on the basis of genetics

Blood ◽  
2017 ◽  
Vol 130 (4) ◽  
pp. 410-423 ◽  
Author(s):  
Justin Taylor ◽  
Wenbin Xiao ◽  
Omar Abdel-Wahab
Keyword(s):  
B Cell ◽  
Clinical Management ◽  
Myeloid Leukemia ◽  
Myeloproliferative Neoplasms ◽  
Lymphoblastic Leukemia ◽  
Hematologic Malignancies ◽  
Genetic Alterations ◽  
B Cell Lymphomas ◽  
Acute Leukemias

Abstract Genomic analysis has greatly influenced the diagnosis and clinical management of patients affected by diverse forms of hematologic malignancies. Here, we review how genetic alterations define subclasses of patients with acute leukemias, myelodysplastic syndromes (MDS), myeloproliferative neoplasms (MPNs), non-Hodgkin lymphomas, and classical Hodgkin lymphoma. These include new subtypes of acute myeloid leukemia defined by mutations in RUNX1 or BCR-ABL1 translocations as well as a constellation of somatic structural DNA alterations in acute lymphoblastic leukemia. Among patients with MDS, detection of mutations in SF3B1 define a subgroup of patients with the ring sideroblast form of MDS and a favorable prognosis. For patients with MPNs, detection of the BCR-ABL1 fusion delineates chronic myeloid leukemia from classic BCR-ABL1− MPNs, which are largely defined by mutations in JAK2, CALR, or MPL. In the B-cell lymphomas, detection of characteristic rearrangements involving MYC in Burkitt lymphoma, BCL2 in follicular lymphoma, and MYC/BCL2/BCL6 in high-grade B-cell lymphomas are essential for diagnosis. In T-cell lymphomas, anaplastic large-cell lymphoma is defined by mutually exclusive rearrangements of ALK, DUSP22/IRF4, and TP63. Genetic alterations affecting TP53 and the mutational status of the immunoglobulin heavy-chain variable region are important in clinical management of chronic lymphocytic leukemia. Additionally, detection of BRAFV600E mutations is helpful in the diagnosis of classical hairy cell leukemia and a number of histiocytic neoplasms. Numerous additional examples provided here demonstrate how clinical evaluation of genomic alterations have refined classification of myeloid neoplasms and major forms of lymphomas arising from B, T, or natural killer cells.

scholarly journals Acute myeloid leukemia with T lymphoblastic lymphoma: a case report and literature review

2021 ◽  
Vol 49 (5) ◽  
pp. 030006052110161
Author(s):  
Yan Gao ◽  
Xian-Qi Feng ◽  
Shan-Shan Liu ◽  
Yu-Jie Xu ◽  
Chun-Xia Mao ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Marrow Cell ◽  
Final Diagnosis ◽  
Lymphoblastic Lymphoma ◽  
Standard Chemotherapy ◽  
Cell Percentage ◽  
T Lymphoblastic Lymphoma ◽  
Cluster Of Differentiation ◽  
Acute Myeloid

Acute myeloid leukemia (AML) with T lymphoblastic lymphoma (T-LBL) is a hematologic tumor of two origins, myeloid and lymphoblastic, and is relatively rare in the same patient. We report a rare case of AML with T-LBL. After the patient was diagnosed, he received standard chemotherapy, which decreased the primitive bone marrow cell percentage from 84% to 5%; however, the enlarged superficial lymph nodes showed no obvious change in size. Immunohistochemistry revealed the following: cluster of differentiation (CD)3 (+), CD5 (+), CD7 (+), transmission disequilibrium test (TDT) (+), myeloperoxidase (MPO) (−), and lysozyme (Lys) (−). The lymph node morphology and immunohistochemical results indicated T-LBL. Therefore, the final diagnosis was AML with T-LBL, with both diseases occurring independently and concurrently.

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