Absent Cyclin D1 Expression in Myeloid Sarcomas Distinguishes From Malignant Histiocytic Neoplasms: When Morphologic Ambiguity is Deceptive.
| Title: | Absent Cyclin D1 Expression in Myeloid Sarcomas Distinguishes From Malignant Histiocytic Neoplasms: When Morphologic Ambiguity is Deceptive. |
|---|---|
| Authors: | Lee AM; Division of Laboratory Medicine-Hematopathology Section, University of Alabama at Birmingham, Birmingham, AL.; Seth N; Department of Pathology and Laboratory Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, New York, NY.; Tam W; Department of Pathology and Laboratory Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, New York, NY.; Jiang L; Department of Laboratory Medicine and Pathology, Division of Hematopathology, Mayo Clinic, Jacksonville, FL.; Abeykoon JP; Department of Medicine, Division of Hematology, Mayo Clinic, Rochester, MN.; Yi D; Department of Medicine, Division of Hematology, Mayo Clinic, Rochester, MN.; King RL; Department of Laboratory Medicine and Pathology, Division of Hematopathology, Mayo Clinic, Rochester, MN.; Reichard KK; Department of Laboratory Medicine and Pathology, Division of Hematopathology, Mayo Clinic, Rochester, MN.; Go RS; Department of Medicine, Division of Hematology, Mayo Clinic, Rochester, MN.; Goyal G; Division of Hematology-Medical Oncology, University of Alabama at Birmingham, Birmingham, AL.; Morlote DM; Division of Laboratory Medicine-Hematopathology Section, University of Alabama at Birmingham, Birmingham, AL.; Rech KL; Department of Laboratory Medicine and Pathology, Division of Hematopathology, Mayo Clinic, Rochester, MN.; Ravindran A; Division of Laboratory Medicine-Hematopathology Section, University of Alabama at Birmingham, Birmingham, AL.; Department of Laboratory Medicine and Pathology, Division of Hematopathology, Mayo Clinic, Rochester, MN. |
| Corporate Authors: | Histio-Care Network |
| Source: | The American journal of surgical pathology [Am J Surg Pathol] 2026 Jun 15. Date of Electronic Publication: 2026 Jun 15. |
| Publication Model: | Ahead of Print |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: Wolters Kluwer Health, Inc Country of Publication: United States NLM ID: 7707904 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1532-0979 (Electronic) Linking ISSN: 01475185 NLM ISO Abbreviation: Am J Surg Pathol Subsets: MEDLINE |
| Imprint Name(s): | Publication: : Philadelphia, PA : Wolters Kluwer Health, Inc.; Original Publication: New York, Masson. |
| Abstract: | Myeloid sarcoma (MS) is a tumor mass involving any extramedullary site composed of myeloid-lineage blasts with myeloid, myelomonocytic, or monocytic differentiation. Distinguishing MS from malignant histiocytic neoplasms (MHNs) is diagnostically challenging due to morphologic and immunophenotypic overlap, particularly for MS with monocytic differentiation, which can mimic MHNs, especially the subtypes of histiocytic sarcoma and interdigitating dendritic cell sarcoma, leading to potential misdiagnosis and inappropriate management. Cyclin D1 overexpression is implicated in MHNs, but its utility in differentiating these entities has not been systematically characterized. We evaluated cyclin D1 immunostaining in 43 MS cases and 30 MHNs. The median age at MS diagnosis was 59 years (range: 0.1 to 90), while the median age at MHN diagnosis was 62 years (range: 9 to 90), with heterogeneous sites of involvement. Cyclin D1 evaluation showed 100% MHNs with strong cyclin D1 positivity in ≥50% tumor cells, compared with 7% MS with weak-to-intermediate positivity in a minor subset of tumor cells. Additional immunohistochemical evaluation showed no difference in PU.1 expression in MHNs (93%) versus MS (84%) but demonstrated a higher proportion of OCT2-positivity in MHNs over MS (52% vs. 23%, P |
| Competing Interests: | Conflicts of Interest and Source of Funding: G.G. has served on the advisory board of Opna Bio, Seagen, Sobi, and Electra, and received consulting fees from Recordati and Pharmassentia, outside the scope of the submitted work. The remaining authors declare no conflicts of interest. |
| References: | Loscocco GG, Vannucchi AM. Myeloid sarcoma: more and less than a distinct entity. Ann Hematol. 2023;102:1973–1984.; Naresh KNCW, Medeiros JL. Myeloid sarcoma. In: WHO Classification of Tumours Editorial Board, ed. WHO Classification of Tumours: Haematolymphoid Tumours. 5th ed. Vol 11. International Agency for Research on Cancer; 2024.; Wang HQ, Li J. Clinicopathological features of myeloid sarcoma: report of 39 cases and literature review. Pathol Res Pract. 2016;212:817–824.; Khoury JD, Solary E, Abla O, et al. The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: myeloid and histiocytic/dendritic neoplasms. Leukemia. 2022;36:1703–1719.; Ravindran A, Dasari S, Ruan GJ, et al. Malignant histiocytosis comprises a phenotypic spectrum that parallels the lineage differentiation of monocytes, macrophages, dendritic Cells, and Langerhans cells. Mod Pathol. 2023;36:100268.; Emile JF, Abla O, Fraitag S, et al. Revised classification of histiocytoses and neoplasms of the macrophage-dendritic cell lineages. Blood. 2016;127:2672–2681.; Ruan GJ, Zanwar S, Ravindran A, et al. Clinical characteristics, molecular aberrations, treatments, and outcomes of malignant histiocytosis. Am J Hematol. 2024;99:871–879.; Oskarsdottir AR, Ravindran A, Koster MJ, et al. Cyclin D1 overexpression with cytoplasmic localization distinguishes Erdheim-Chester disease from reactive histiocytic infiltrates. Am J Surg Pathol. 2026;50:273–282.; Ravindran A, Rech KL. How I diagnose Rosai-Dorfman disease. Am J Clin Pathol. 2023;160:1–10.; Hershkovitz-Rokah O, Abeykoon JP, Ravindran A, et al. Histiocyte Society blueprint for non-Langerhans cell histiocytosis research: unraveling complex diseases through collaboration. Haematologica. 2025;110:2603–2619.; Arber DA, Orazi A, Hasserjian RP, et al. International consensus classification of myeloid neoplasms and acute leukemias: integrating morphologic, clinical, and genomic data. Blood. 2022;140:1200–1228.; Brenner AK, Bruserud O. S100 proteins in acute myeloid leukemia. Neoplasia. 2018;20:1175–1186.; Elliott CJ, McCarthy KP, Carter RL, et al. Granulocytic sarcoma: misleading immunohistological staining with MT1 and S100 protein antibodies. J Clin Pathol. 1989;42:188–190.; Tamburini J. S100 proteins in AML: differentiation and beyond. Blood. 2017;129:1893–1894.; Rothenberg EV, Hosokawa H, Ungerback J. Mechanisms of action of hematopoietic transcription factor PU.1 in initiation of T-cell development. Front Immunol. 2019;10:228.; Ungureanu IA, Cohen-Aubart F, Heritier S, et al. PU.1 is a useful nuclear marker to distinguish between histiocytosis and histiocyte-rich tumours. Histopathology. 2023;83:320–325.; Gibson SE, Dong HY, Advani AS, et al. Expression of the B cell-associated transcription factors PAX5, OCT-2, and BOB.1 in acute myeloid leukemia: associations with B-cell antigen expression and myelomonocytic maturation. Am J Clin Pathol. 2006;126:916–924.; Kiruthiga KG, Younes S, Natkunam Y. Strong coexpression of transcription factors PU.1 and Oct-2 in Rosai-Dorfman disease. Am J Clin Pathol. 2022;158:672–677.; Ravindran A, Goyal G, Go RS; Mayo Clinic Histiocytosis Working G. Rosai-Dorfman disease displays a unique monocyte-macrophage phenotype characterized by expression of OCT2. Am J Surg Pathol. 2021;45:35–44.; Ungureanu IA, Cohen-Aubart F, Heritier S, et al. OCT2 expression in histiocytoses. Virchows Arch. 2023;483:81–86.; Chatterjee D, Vishwajeet V, Saikia UN, et al. CyclinD1 Is useful to differentiate Langerhans cell histiocytosis from reactive Langerhans cells. Am J Dermatopathol. 2019;41:188–192.; Yamamoto T, Ebisuya M, Ashida F, et al. Continuous ERK activation downregulates antiproliferative genes throughout G1 phase to allow cell-cycle progression. Curr Biol. 2006;16:1171–1182.; Almond LM, Charalampakis M, Ford SJ, et al. Myeloid sarcoma: presentation, diagnosis, and treatment. Clin Lymphoma Myeloma Leuk. 2017;17:263–267.; Shahin OA, Ravandi F. Myeloid sarcoma. Curr Opin Hematol. 2020;27:88–94.; Cardona-Benavides IJ, Cristobal-Vargas S, De Ramon C, et al. Exploring the role of cyclin D1 in the pathogenesis of multiple myeloma beyond cell cycle regulation. Mol Oncol. 2025;19:3175–3192.; Lu K, Zhang M, Qin H, et al. Disruption of cyclin D1 degradation leads to the development of mantle cell lymphoma. Acta Pharm Sin B. 2024;14:2977–2991.; Diamantidis MD. Myeloid sarcoma: novel advances regarding molecular pathogenesis, presentation and therapeutic options. J Clin Med. 2024;13:6154. |
| Contributed Indexing: | Keywords: histiocytic sarcoma; interdigitating dendritic cell sarcoma; malignant histiocytosis; myeloid sarcoma |
| Entry Date(s): | Date Created: 20260615 Latest Revision: 20260615 |
| Update Code: | 20260615 |
| DOI: | 10.1097/PAS.0000000000002570 |
| PMID: | 42290298 |
| Database: | MEDLINE |
Journal Article