Preface: Diagnostic Hematopathology: Aiming at a Moving Target

Abstract

The field of hematopathology is an ever-changing discipline: as our clinical colleagues develop and implement increasingly sophisticated therapies, we pathologists are constantly refining our ability to effectively diagnose the diseases they are treating. Many current therapies aim to target oncogenic pathways deregulated in particular neoplasms, requiring us to interrogate diseases with tools that tease out these specific pathways. While these ancillary tools often inform us about the tumor biologies, they add to the large amounts of (sometimes contradictory) data that we must digest and synthesize in each case. The goal of this issue is to present the current state-of-the-art diagnostic approaches in several particular areas of hematopathology. I have chosen areas that my colleagues and I feel are particularly challenging, have undergone changes and refinements, and/or have been influenced by evolving concepts in our field. This issue thus both provides guidelines to apply in practice as well as reviews current changes to the field of hematopathology.Splenic B-cell lymphomas/leukemias, nodal peripheral T-cell lymphomas, histiocytic and dendritic neoplasms, systemic mastocytosis, and diseases affecting the bone marrow of pediatric patients are not frequently encountered by most pathologists. Such unfamiliar diagnostic arenas can be particularly challenging; for example, nodal T-cell lymphomas and pediatric bone marrow neoplasms are notorious for their difficult differential diagnosis with reactive processes. This issue provides practical diagnostic approaches to these diseases that integrate salient morphologic and clinical features with the appropriate use of ancillary testing. Such approaches are designed to help the pathologist correctly diagnose and classify these relatively uncommon neoplasms and avoid potential pitfalls. Conversely, plasma cell neoplasms and bone marrow interpretation in cytopenic patients represent areas in diagnostic hematopathology that are relatively commonly encountered by the practicing pathologist: anemia is the most common indication for bone marrow sampling in most practices and plasma cell myeloma is one of the most common hematologic malignancies. Again, the authors in this issue provide guidance on how pathologists should handle these scenarios and indicate what diagnostic information is currently necessary to provide our clinical colleagues so that they can develop an appropriate treatment plan for each patient.As the field of hematopathology continues to advance, the diagnostic criteria of certain diseases have changed. In particular, definitions of acute myeloid leukemia with myelodysplasia-related changes, chronic lymphocytic leukemia/small lymphocytic leukemia, and Burkitt lymphoma have undergone modifications in the 2008 WHO Classification of Tumours of Hematopoietic and Lymphoid Tissues. These changes reflect evolving concepts in hematopathology, where disease categorization is increasingly driven by our understanding of tumor biology and, in some cases, clinical behavior and/or response to therapy. The authors in this issue review the rationale behind the refinements to these diagnostic categories and suggest the appropriate use of ancillary studies to correctly classify the disease entities. The topic of B-cell proliferations related to herpesviruses (EBV and HHV8) reviews several recent changes in the classification of virus-associated lymphomas and lymphoproliferative disorders and also compares and contrasts the various diseases caused by herpesviruses. Finally, the current state-of-the-art diagnostic approach to “conventional” follicular lymphoma is described and new disease variants are reviewed: these variants reflect our increasing realization that the category of follicular lymphoma is likely more complex and heterogeneous than previously thought.Each topic has been organized in order to maximize its practical utility: there are summary lists of key features as well as challenging pitfalls for each disease or disease category. Most of the topics are organized so as to present the clinical, morphologic, phenotypic, and genetic features of each disease, with sections on differential diagnosis and prognosis. Differential diagnoses are put forth either as lists for each entity (with key distinguishing features) or as tables summarizing a disease category. Approaches to pediatric bone marrow interpretation and the diagnosis of myelodysplasia in cytopenic patients are organized differently: the differential diagnoses and diagnostic algorithms are presented for particular scenarios based on the basic bone marrow appearance and clinical findings. All articles are extensively illustrated with images that underscore the salient features of the diseases discussed in the text and provide up-to-date references.I am deeply indebted to the all authors who have contributed to this issue. Their collective wealth of experience in these challenging areas of diagnostic pathology is truly an invaluable resource. I hope that this issue will serve as both an update on the current state of diagnostic hematopathology and also a useful resource to pathologists in their daily practice. The field of hematopathology is an ever-changing discipline: as our clinical colleagues develop and implement increasingly sophisticated therapies, we pathologists are constantly refining our ability to effectively diagnose the diseases they are treating. Many current therapies aim to target oncogenic pathways deregulated in particular neoplasms, requiring us to interrogate diseases with tools that tease out these specific pathways. While these ancillary tools often inform us about the tumor biologies, they add to the large amounts of (sometimes contradictory) data that we must digest and synthesize in each case. The goal of this issue is to present the current state-of-the-art diagnostic approaches in several particular areas of hematopathology. I have chosen areas that my colleagues and I feel are particularly challenging, have undergone changes and refinements, and/or have been influenced by evolving concepts in our field. This issue thus both provides guidelines to apply in practice as well as reviews current changes to the field of hematopathology. Splenic B-cell lymphomas/leukemias, nodal peripheral T-cell lymphomas, histiocytic and dendritic neoplasms, systemic mastocytosis, and diseases affecting the bone marrow of pediatric patients are not frequently encountered by most pathologists. Such unfamiliar diagnostic arenas can be particularly challenging; for example, nodal T-cell lymphomas and pediatric bone marrow neoplasms are notorious for their difficult differential diagnosis with reactive processes. This issue provides practical diagnostic approaches to these diseases that integrate salient morphologic and clinical features with the appropriate use of ancillary testing. Such approaches are designed to help the pathologist correctly diagnose and classify these relatively uncommon neoplasms and avoid potential pitfalls. Conversely, plasma cell neoplasms and bone marrow interpretation in cytopenic patients represent areas in diagnostic hematopathology that are relatively commonly encountered by the practicing pathologist: anemia is the most common indication for bone marrow sampling in most practices and plasma cell myeloma is one of the most common hematologic malignancies. Again, the authors in this issue provide guidance on how pathologists should handle these scenarios and indicate what diagnostic information is currently necessary to provide our clinical colleagues so that they can develop an appropriate treatment plan for each patient. As the field of hematopathology continues to advance, the diagnostic criteria of certain diseases have changed. In particular, definitions of acute myeloid leukemia with myelodysplasia-related changes, chronic lymphocytic leukemia/small lymphocytic leukemia, and Burkitt lymphoma have undergone modifications in the 2008 WHO Classification of Tumours of Hematopoietic and Lymphoid Tissues. These changes reflect evolving concepts in hematopathology, where disease categorization is increasingly driven by our understanding of tumor biology and, in some cases, clinical behavior and/or response to therapy. The authors in this issue review the rationale behind the refinements to these diagnostic categories and suggest the appropriate use of ancillary studies to correctly classify the disease entities. The topic of B-cell proliferations related to herpesviruses (EBV and HHV8) reviews several recent changes in the classification of virus-associated lymphomas and lymphoproliferative disorders and also compares and contrasts the various diseases caused by herpesviruses. Finally, the current state-of-the-art diagnostic approach to “conventional” follicular lymphoma is described and new disease variants are reviewed: these variants reflect our increasing realization that the category of follicular lymphoma is likely more complex and heterogeneous than previously thought. Each topic has been organized in order to maximize its practical utility: there are summary lists of key features as well as challenging pitfalls for each disease or disease category. Most of the topics are organized so as to present the clinical, morphologic, phenotypic, and genetic features of each disease, with sections on differential diagnosis and prognosis. Differential diagnoses are put forth either as lists for each entity (with key distinguishing features) or as tables summarizing a disease category. Approaches to pediatric bone marrow interpretation and the diagnosis of myelodysplasia in cytopenic patients are organized differently: the differential diagnoses and diagnostic algorithms are presented for particular scenarios based on the basic bone marrow appearance and clinical findings. All articles are extensively illustrated with images that underscore the salient features of the diseases discussed in the text and provide up-to-date references. I am deeply indebted to the all authors who have contributed to this issue. Their collective wealth of experience in these challenging areas of diagnostic pathology is truly an invaluable resource. I hope that this issue will serve as both an update on the current state of diagnostic hematopathology and also a useful resource to pathologists in their daily practice.