{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T11:53:19Z","timestamp":1783338799003,"version":"3.54.6"},"reference-count":32,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2017,4,24]],"date-time":"2017-04-24T00:00:00Z","timestamp":1492992000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer Cytopathology"],"published-print":{"date-parts":[[2017,8]]},"abstract":"<jats:sec><jats:title>BACKGROUND<\/jats:title><jats:p>Histiocytic sarcoma (HS) is a rare malignant neoplasm showing morphologic and immunophenotypic features of histiocytes. Molecular characteristics of HS and fine\u2010needle aspiration (FNA) criteria for its diagnosis have not been established.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>A case series of HS in 8 FNA samples from 6 patients was reviewed along with histopathologic and clinical data. Immunohistochemistry was performed on cell blocks (3 cases), core biopsies (5 cases), and surgical specimens (4 cases). Targeted\u2010exome next\u2010generation sequencing (NGS) was performed on surgical resection specimens in 4 cases.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>Four patients had a known history of hematolymphoid malignancy. Cytomorphologic features included variably cellular smears composed of large epithelioid cells with reniform nuclei and abundant vacuolated cytoplasm, in an inflammatory background, with occasional cytophagocytosis and lymphoglandular bodies. Marked pleomorphism, multinucleated monster cells, and binucleated histiocytoid cells with partially overlapping, eccentrically placed nuclei resembling Pac\u2010Man were common. Most cases expressed histiocytic markers CD68 (6 of 7 cases), CD163 (5 of 5 cases), and PU.1 (3 of 4 cases). In 3 cases, NGS analysis revealed alterations in lysine methyltransferase 2D (<jats:italic>KMT2D<\/jats:italic>)\/mixed\u2010lineage leukemia 2 (<jats:italic>MLL2<\/jats:italic>), a gene involved in chromatin regulation and previously implicated in the pathogenesis of follicular lymphoma.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS<\/jats:title><jats:p>Although diagnosing HS with FNA alone is extremely challenging, the presence of pleomorphic and epithelioid large cells with binucleation and\/or multinucleation in an inflammatory background should prompt the diagnosis of HS with judicious use of confirmatory histiocytic lineage markers. The detection of recurrent <jats:italic>KMT2D<\/jats:italic>\/<jats:italic>MLL2<\/jats:italic> alterations implicates epigenetic regulation in the pathogenesis of HS and supports the notion of transdifferentiation from a genetically similar but phenotypically distinct tumor of a different lineage. <jats:bold><jats:italic>Cancer Cytopathol<\/jats:italic> 2017;125:604\u201014<\/jats:bold>. \u00a9 <jats:italic>2017 American Cancer Society<\/jats:italic>.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncy.21851","type":"journal-article","created":{"date-parts":[[2017,4,24]],"date-time":"2017-04-24T11:02:51Z","timestamp":1493031771000},"page":"604-614","source":"Crossref","is-referenced-by-count":37,"title":["Histiocytic sarcoma: New insights into FNA cytomorphology and molecular characteristics"],"prefix":"10.1002","volume":"125","author":[{"given":"Yin P.","family":"Hung","sequence":"first","affiliation":[{"name":"Department of Pathology Brigham and Women's Hospital and Harvard Medical School Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott B.","family":"Lovitch","sequence":"additional","affiliation":[{"name":"Department of Pathology Brigham and Women's Hospital and Harvard Medical School Boston Massachusetts"},{"name":"Center for Advanced Molecular Diagnostics Brigham and Women's Hospital and Harvard Medical School Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8241-5976","authenticated-orcid":false,"given":"Xiaohua","family":"Qian","sequence":"additional","affiliation":[{"name":"Department of Pathology Brigham and Women's Hospital and Harvard Medical School Boston 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