Atlas Of Differential Diagnosis In Neoplastic Hematopathology
Jacinda Saleeby
This atlas presents not only the differential diagnosis but also the detailed morphologic, immunophenotypic, and especially genetic characteristics of the majority of hematolymphoid malignancies. An expert hematopathologist here provides a valuable resource to understand, use, or interpret one or more of these diagnostic modalities with confidence. This new edition has a compact format with up-to-date information - especially on genetic aspects - and will be an indispensable reference for all professionals in the specialty. *Provides an unrivalled visual resource for differential diagnosis in neoplastic hematopathology *Enables specialist and trainee oncologists and pathologists alike to understand, use, and interpret diagnostic modalities with confidence *Supplies quick access to information via tables, algorithms, and composite figures
CML is characterized by marked leukocytosis (often >100 109/L) with neutrophils at various stages of maturation, mostly segmented forms, and myelocytes, accompanied by eosinophils and basophils. CNL also shows neutrophilia, but there is predominance of segmented forms with occasional bands. The neutrophils of CNL show prominent cytoplasmic granules. Leukocytosis with predominance of eosinophils is characteristic for CEL/HES. Neutrophilia and basophilia often present in PV, but it is not as pronounced as in CML. Mild leukocytosis may also be present in early PMF. Anemia and leukoerythroblastosis are seen typically in fibrotic stage of PMF. ET shows marked thrombocytosis, but normal WBC count or only mild leukocytosis. The differential diagnosis also includes other disorders associated with increased WBC count, B and T lymphoproliferations, CMML, reactive monocytosis, acute monoblastic leukemia, B- and T-ALL, AML as well as reactive processes (leukemoid reaction). Leukemoid reaction is defined as a persistent, reactive neutrophilic leukocytosis >50 109/L in response to infection, inflammation, or therapeutic agents such as growth factors and malignancy (there is no associated leukemia). The major causes of leukemoid reactions are severe infections, intoxications, malignancies, severe hemorrhage, or acute hemolysis [85]. A significant increase in the WBC in patients with malignancy (paraneoplastic leukemoid reaction) is often due to production of CSFs (e.g., G-CSF) by tumor cells. Lymphomas (with or without blood involvement) may also present with leukemoid reaction. Promyelocytic leukemoid reaction may accompany mycobacterial infections.
A leukemoid reaction is characterized by either (a) leukocytosis of 50.0 109/L or higher with a shift to the left, or (b) the presence of a considerable number of immature cells (metamyelocytes, myelocytes, promyelocytes, and even an occasional blast cell) in the peripheral blood, mimicking leukemia (Fig. 2). In the latter case, the WBC count may be above normal, normal, or rarely below normal. Depending on the predominant cell type, the leukemoid reaction may be neutrophilic, eosinophilic, or lymphocytic. Monocytic and basophilic leukemoid reactions, if they occur, are rare. Among the various types of leukemoid reactions, neutrophilic is the one most frequently encountered in clinical practice. In fact, it is so common that the term leukemoid reaction is presumed to refer to neutrophilic reaction unless specified otherwise. Neutrophilic leukemoid reaction may occur in many of the conditions associated with neutrophilia (Table 2). Cytoplasmic changes, such as toxic granulation, vacuolization, and Dhle bodies, along with a high neutrophil alkaline phosphatase (NAP) score, help to differentiate the leukemoid reaction from chronic myelogenous leukemia (CML), which is generally characterized by a large proportion of myelocytes, eosinophilia, basophilia, and a low NAP score. The diagnosis of CML is confirmed by the presence of Philadelphia chromosome or BCR-ABL gene rearrangement, both of which are absent in the leukemoid reaction. The leukemic hiatus, a characteristic of acute leukemia, is also absent in the leukemoid reaction. Eosinophilic leukemoid reactions usually occur in children and are generally caused by parasitic infections. Lymphocytic leukemoid reactions may occur in whooping cough, infectious lymphocytosis, infectious mononucleosis, and tuberculosis.
Acute splenic sequestration crisis is a rare complication of sickle cell disease in adults that typically presents with splenic enlargement, abdominal pain, and an acute drop in Hb. Acute splenic sequestration crisis most commonly occurs in adult patients with heterozygous sickle cell disease, although ASSC has been reported in patients with homozygous Hb S disease as well. This case demonstrates ASSC in a patient with homozygous Hb S disease who remained at-risk due to an abnormally high Hb F fraction. Furthermore, this case highlights that leukemoid reaction can be a feature of ASSC and does not necessarily represent severe infection. Due to significant mortality in patients with unrecognized ASSC, providers should consider this condition when caring for sickle cell disease patients with acute abdominal pain.
Due to its rapid development in recent years, hematopathology has become a very complicated discipline. The current development is mainly in two aspects: the new classification of lymphomas and leukemias and the new techniques.
The Revised European-American Classification of Lymphoid Neoplasms (REAL classification) and the World Health Organization (WHO) classification of hematologic neoplasms require not only morphologic criteria but also immunophenotyping and molecular genetics for the diagnosis of hematologic tumors. Immunophenotyping is performed by either flow cytometry or immunohistochemistry. There are many new monoclonal antibodies and new equipments accumulated in recent years that make immunophenotyping more or more accurate and helpful. There are even more new techniques invented in recent years in the field of molecular genetics. In cytogenetics, the conventional karyotype is supplemented and partly replaced by the fluorescence in situ hybridization (FISH) technique. The current development of gene expression profiling is even more powerful in terms of subtyping the hematologic tumors, which may help guiding the treatment and predict the prognosis. In molecular biology, the tedious Southern blotting technique is largely replaced by polymerase chain reaction (PCR). The recent development in reverse-transcriptase PCR and quantitative PCR makes these techniques even more versatile.
Because of these new developments, hematopathology has become too complicated to handle by a general pathologist. Many hospitals have to hire a newly trained hematopathologist to oversee peripheral blood, bone marrow and lymph node examinations. These young hematopathologists are geared to the new techniques, but most of them are inexperienced in morphology. No matter how well-trained a hematopathologist is, he or she still needs to see enough cases so that they can recognize the morphology and use the new techniques to substantiate the diagnosis. In other words, morphology is still the basis for the diagnosis of lymphomas and leukemias.
Therefore, a good color atlas is the most helpful tool for these young hematopathologists and for the surgical pathologists who may encounter a few cases of hematologic tumors from time to time. In a busy daily practice, it is difficult to refer to a comprehensive hematologic textbook all the time. There are a few hematologic color atlases on the market to show the morphology of the normal blood cells and hematologic tumor cells. These books are helpful but not enough, because tumor cell morphology is variable from case to case and different kinds of tumor cells may look alike and need to be differentiated by other parameters.
The best way to learn morphology is through the format of clinical case study. This format is also consistent with the daily practice of hematopathologists and with the pattern in all the specialty board examinations. Therefore, it is a good learning tool for the pathology residents, hematology fellows as well as medical students.
This proposed book will present 83 clinical cases with clinical history, morphology of the original specimen and a list of differential diagnoses. This is followed by further testing with pictures to show the test results. At the end, a correct diagnosis is rendered with subsequent brief discussion on how the diagnosis is achieved. A few useful references will be cited and a table will be provided for differential diagnosis in some cases.
The major emphasis is the provision of 500 color photos of peripheral blood smears, bone marrow aspirates, core biopsy, lymph node biopsy and biopsies of other solid organs that are involved with lymphomas and leukemias. Pictures of other diagnostic parameters, such as flow cytometric histograms, immunohistochemical stains, cytogenetic karyotypes, fluorescence in situ hybridization and polymerase chain reaction, will also be included.
A comprehensive approach with consideration of clinical, morphologic, immunophenotypic and molecular genetic aspects is the best way to achieve a correct diagnosis. After reading this book, the reader will learn to make a diagnosis not only based on the morphology alone but also in conjunction with other parameters.
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