Introduction: Myeloid sarcoma (MS) is a rare extramedullary tumor consisting of blasts of granulocytic, monocytic, erythroid, or megakaryocytic lineage that disrupts the architecture of the involved tissue. MS shows vast clinical, morphologic, immunophenotypic, and genetic heterogeneity posing a diagnostic dilemma, especially in small biopsy specimens such as fine-needle aspiration (FNA) and core biopsy. The objective of this study is to highlight the morphologic features of MS in cytological preparations and investigate the efficacy of pathologist-performed rapid on-site evaluation (ROSE) in assuring accurate triage. Methods: A retrospective review was performed for cases of MS with concurrent cytology and ROSE results from 2006 to 2017. FNA smears and touch preparations were reviewed, and the results of ROSE, immunohistochemistry (IHC), flow cytometric immunophenotyping (FCI), cytogenetics/FISH, and histology were analyzed. Results: A total of 15 cases were found including 6 (40%) with monocytic morphology comprising promonocytes and monoblasts and 9 (60%) with conventional myeloblastic morphology. The most common genetic subgroup was KMT2A-rearranged MS (33.3%) followed by extramedullary blast crisis of chronic myeloid leukemia (26.6%). ROSE provided sufficient preliminary information and ensured the procurement of adequate tissue for histology, IHCs, FCI, and cytogenetics/FISH, leading to an accurate and complete diagnosis of MS in all cases. Discussion/Conclusion: MS is a rare malignancy that shows pronounced clinical, morphologic, immunophenotypic, and genetic heterogeneity that often overlaps with other neoplastic and non-neoplastic entities. Features including the presence of classic myeloblasts, promonocytes, monoblasts, nucleated red blood cells, left-shifted granulocytes, cytoplasmic granules, and pseudopods are helpful hints in cytological preparations. In the modern era where pathologists are increasingly expected to do extensive diagnostic, molecular, and therapeutic biomarker testing on tissue that is historically diminishing in size, ROSE is a highly effective tool to ensure effective triage of MS aiding in an accurate, timely, and complete diagnosis.

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