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Numerous non-neoplastic and neoplastic conditions manifest with distinctive features in blood. Although automated complete blood count ( CBC) data are essential, CBC information alone is insufficient for diagnosis. Consequently, morphologic review of blood smears is still relevant in the era of sophisticated automated analyzer systems. Pathologist interpretation of the peripheral blood smear, in conjunction with CBC and clinical information, can provide rapid diagnostic information and guide cost-effective targeted laboratory testing. Pathologist review of blood smears can be used to diagnose cases in which the clinical findings are misleading or nonspecific. Here, we discuss a selection of cases in which the pathologist examination of the blood smear can aid in rapid and accurate diagnosis and guide appropriate treatment. Exemplary non-neoplastic disorders with distinctive morphologic blood features of RBC, neutrophils, monocytes, and lymphocytes will be highlighted. The differential diagnostic considerations in blood smears with RBC destruction will be presented, expanding beyond microangiopathic hemolytic anemia. Lymphocyte morphologic assessment guides differential diagnosis including the identification of rare germline disorders. In each case presented, the integration of morphologic features guided additional testing with confirmation of the diagnosis. Peripheral blood smear review is timely and cost effective, even in an era of sophisticated automated laboratory testing. [ABSTRACT FROM AUTHOR]

An increased white blood cell count, or leukocytosis, is a common laboratory finding. Appropriate specimen evaluation depends on which lineages are increased and the morphologic findings on peripheral blood smear review to guide further testing. The presence of blasts is concerning for acute leukemia and may require bone marrow biopsy. Lymphocytosis may be morphologically divided into polymorphic and monomorphic populations. Polymorphic lymphocytosis is most consistent with a reactive process, while monomorphic populations are concerning for lymphoproliferative neoplasm. The differential can be further narrowed based on morphologic findings. Myeloid leukocytosis can occur in a number of reactive conditions as well as myeloid malignancies. The types of cells present and morphology can help to guide additional workup. This study provides guidance for the appropriate evaluation and further workup of leukocytosis. [ABSTRACT FROM AUTHOR]