Blood Res.  2024;59:18. 10.1007/s44313-024-00015-9.

Pathologic characteristics of histiocytic and dendritic cell neoplasms

• Yoon S

• KMID: 2562522
• DOI: http://doi.org/10.1007/s44313-024-00015-9

Abstract

Histiocytic and dendritic cell neoplasms comprise diverse tumors originating from the mononuclear phagocytic system, which includes monocytes, macrophages, and dendritic cells. The 5th edition of the World Health Organization (WHO) classification updating the categorization of these tumors, reflecting a deeper understanding of their pathogenesis. In this updated classification system, tumors are categorized as Langerhans cell and other dendritic cell neoplasms, histiocyte/macrophage neoplasms, and plasmacytoid dendritic cell neoplasms. Follicular dendritic cell neoplasms are classified as mesenchymal dendritic cell neoplasms within the stroma-derived neoplasms of lymphoid tissues. Each subtype of histiocytic and dendritic cell neoplasms exhibits distinct morphological characteristics. They also show a characteristic immunophenotypic profile marked by various markers such as CD1a, CD207/langerin, S100, CD68, CD163, CD4, CD123, CD21, CD23, CD35, and ALK, and hematolymphoid markers such as CD45 and CD43. In situ hybridization for EBV-encoded small RNA (EBER) identifies a particular subtype. Immunoprofiling plays a critical role in determining the cell of origin and identifying the specific subtype of tumors. There are frequent genomic alterations in these neoplasms, especially in the mitogen-activated protein kinase pathway, including BRAF (notably BRAFV600E), MAP2K1, KRAS, and NRAS mutations, and ALK gene translocation. This review aims to offer a comprehensive and updated overview of histiocytic and dendritic cell neoplasms, focusing on their ontogeny, morphological aspects, immunophenotypic profiles, and molecular genetics. This comprehensive approach is essential for accurately differentiating and classifying neoplasms according to the updated WHO classification.

Keyword

Mononuclear phagocyte system; Histiocytic and dendritic cell neoplasms; Histiocytosis; Immunophenotyping; Molecular genetics

Figure

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  Fig. 1 Overview of the origin and development of various cell types within the mononuclear phagocyte system, as well as those of stroma-derived/mesenchymal origin in lymphoid tissues, alongside their neoplastic counterparts. Abbreviations: BM, bone marrow; CMPs, common myeloid progenitors; CLPs, common lymphoid progenitors; GMPs, granulocyte–macrophage progenitors; cMoPs, common monocyte progenitors; CDPs, common dendritic cell progenitors; cDC, conventional dendritic cells; pDCs, plasmacytoid dendritic cells; moDC, monocyte-derived dendritic cell; JXG, juvenile xanthogranuloma; ECD, Erdheim-Chester disease; RDD, Rosai-Dorfman disease; ALK + H, ALK-positive histiocytosis; HS, histiocytic sarcoma; LCH, Langerhans cell histiocytosis; LCS, Langerhans cell sarcoma; IDDS, interdigitating dendritic cell sarcoma; IDDT, indeterminate dendritic cell tumor; MPDCP, mature plasmacytoid dendritic cell proliferation associated with myeloid neoplasm; BPDCN, blastic plasmacytoid dendritic cell neoplasm; SLO, secondary lymphoid organ; TLT, tertiary lymphoid tissue; FDC, follicular dendritic cell; FRC, fibroblastic reticular cell; FDCS, follicular dendritic cell sarcoma; EBV, Epstein Barr virus; FRCT, fibroblastic reticular cell tumor

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  Fig. 2 Tumor cells of LCH are round-to-oval histiocytes, with characteristic nuclear grooves and convolution, and prominent eosinophil infiltrates noted within the tumor microenvironment (A and B). In another LCH, tumor cells showing nuclear grooves are admixed with multinucleated giant cells of the osteoclast type, foamy histiocytes, and numerous small lymphocytes (C and D). In LCS, high-grade cytologic pleomorphism and confluent tumor necrosis are observed (E and F). In IDDS, the tumor cells appear as spindle to epithelioid cells, with a fascicular growth pattern, interspersed with small lymphocytes (G and H). LCH, Langerhans cell histiocytosis; LCS, Langerhans cell sarcoma; IDDS, interdigitating dendritic cell sarcoma

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  Fig. 3 JXG (A and B), noted as a well-circumscribed lesion (inset, B), consists of foamy histiocytes and Touton giant cells, mixed with lymphocytes. In ECD (C and D), a collection of foamy histiocytes intermingled with lymphocytes is observed. In RDD (E and F), prominent foamy histiocytes exhibiting emperipolesis are identified, accompanied by extensive plasma cell infiltration. At low magnification, the histiocytic clusters and lymphoplasmacytic tumor microenvironment create a contrasting light and dark pattern (inset, F). In ALK-positive histiocytosis (G and H), oval to spindle cells exhibit growth in fascicular and storiform patterns, interspersed with lymphocytes. Lastly, in HS (I-L), large pleomorphic tumor cells show high-grade cytologic atypia with increased mitosis and confluent tumor necrosis, displaying a storiform or whirling pattern that displaces the normal architecture of the lymph node. Abbreviations: JXG, juvenile xanthogranuloma; ECD, Erdheim-Chester disease; RDD, Rosai-Dorfman disease; HS, histiocytic sarcoma

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  Fig. 4 In BPDCN (A and B), immature blastic tumor cells infiltrate the dermis and subcutis, while sparing the epidermis. In FDCS (C and D), spindled and ovoid tumor cells, occasionally showing binucleation, grow in a fascicular pattern, interspersed with small lymphocytes. In EBV + FDSC, spindle-to-oval cells, resembling follicular dendritic cells, are either dispersed or form loose whorled fascicles, admixed with a rich and prominent lymphoplasmacytic infiltrate (E and F). Abbreviations: BPDCN, blastic plasmacytoid dendritic cell neoplasm; FDCS, follicular dendritic cell sarcoma; EBV, Epstein–Barr virus; EBV + FDCS, EBV-positive inflammatory follicular dendritic cell sarcoma

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  Fig. 5 Representative images of immunohistochemical expression in each subtype. Abbreviations: LCH, Langerhans cell histiocytosis; LCS, Langerhans cell sarcoma; IDDS, interdigitating dendritic cell sarcoma; ECD, Erdheim-Chester disease; RDD, Rosai-Dorfman disease; ALK + H, ALK-positive histiocytosis; HS, histiocytic sarcoma; BPDCN, blastic plasmacytoid dendritic cell neoplasm; FDCS, follicular dendritic cell sarcoma; EBV, Epstein Barr virus; EBV + FDCS, EBV-positive inflammatory follicular dendritic cell sarcoma

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  Fig. 6 Brief pathways affecting the pathogenesis of histiocytic and dendritic cell neoplasms. The MAPK pathway plays a pivotal role. Mutations in this pathway, especially the BRAF V600E mutation, are thought to originate from hematopoietic progenitors in the bone marrow, particularly in the pathogenesis of LCH and ECD. Additionally, gene mutations may occur in elements upstream of BRAF, such as RAS, or downstream, such as MAP2K1 (MEK1). Moreover, ALK gene translocation and CSF1R mutation, which affect the transmembrane RTK, can also be present in certain subtypes and are related to both MAPK and PI3K/AKT/mTOR pathways. The proliferation and accumulation of neoplastic histiocytes in tissues can lead to clinical symptoms such as inflammatory reactions, fibrosis, and tissue destruction. Abbreviations: RTK, receptor tyrosine kinase; BM, bone marrow; MAPK, mitogen-activated protein kinase; LCH, Langerhans cell histiocytosis; ECD, Erdheim-Chester disease

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  Fig. 7 Overall diagnostic process flow for the classification of histiocytic and dendritic cell neoplasms incorporates clinical presentations, morphology, immunohistochemistry, and molecular markers. Abbreviations: LC, Langerhans cell; XG, xanthogranuloma; IDDT, indeterminate dendritic cell tumor; LCH, Langerhans cell histiocytosis; JXG, juvenile xanthogranuloma; ECD, Erdheim-Chester disease; RDD, Rosai-Dorfman disease; IgG4-RD, IgG4-related disease; ALK + H, ALK-positive histiocytosis; IDDS, interdigitating dendritic cell sarcoma; HS, histiocytic sarcoma; LCS, Langerhans cell sarcoma; FDCS, follicular dendritic cell sarcoma; EBV, Epstein Barr virus; EBV + FDCS, EBV-positive inflammatory follicular dendritic cell sarcoma; FRCT, fibroblastic reticular cell tumor; BPDCN, blastic plasmacytoid dendritic cell neoplasm; HLM, hematolymphoid malignancies

Reference

1. Swerdlow SH. International Agency for Research on Cancer, World Health Organization. 2008. WHO classification of tumours of haematopoietic and lymphoid tissues. 4th ed. International Agency for Research on Cancer;Lyon, France:

2. Swerdlow SH. World Health Organization, International Agency for Research on Cancer. 2017. WHO classification of tumours of haematopoietic and lymphoid tissues. 4th ed. International Agency for Research on Cancer;Lyon:

3. Chan J. World Health Organization, International Agency for Research on Cancer. 2022. WHO classification of tumours. 5th ed. International Agency for Research on Cancer;Lyon, France:

4. Emile JF, Cohen-Aubart F, Collin M, et al. 2021; Histiocytosis. Lancet. 398(10295):157–70. https://doi.org/10.1016/S0140-6736(21)00311-1. DOI: 10.1016/S0140-6736(21)00311-1. PMID: 33901419.

5. Emile JF, Abla O, Fraitag S, et al. 2016; Revised classification of histiocytoses and neoplasms of the macrophage-dendritic cell lineages. Blood. 127(22):2672–81. https://doi.org/10.1182/blood-2016-01-690636. DOI: 10.1182/blood-2016-01-690636. PMID: 26966089. PMCID: PMC5161007.

6. McClain KL, Bigenwald C, Collin M, et al. 2021; Histiocytic disorders. Nat Rev Dis Primers. 7(1):73. https://doi.org/10.1038/s41572-021-00307-9. DOI: 10.1038/s41572-021-00307-9. PMID: 34620874. PMCID: PMC10031765.

7. Guilliams M, Ginhoux F, Jakubzick C, et al. 2014; Dendritic cells, monocytes and macrophages: a unified nomenclature based on ontogeny. Nat Rev Immunol. 14(8):571–8. https://doi.org/10.1038/nri3712. DOI: 10.1038/nri3712. PMID: 25033907. PMCID: PMC4638219.

8. eejit G Sr, Fleetwood AJ, Murphy AJ, Nagareddy PR. 2020; Origins and diversity of macrophages in health and disease. Clin Transl Immunol. 9(12):e1222. https://doi.org/10.1002/cti2.1222. DOI: 10.1002/cti2.1222. PMID: 33363732. PMCID: PMC7750014.

9. Hume DA, Irvine KM, Pridans C. 2019; The mononuclear phagocyte system: the relationship between monocytes and macrophages. Trends Immunol. 40(2):98–112. https://doi.org/10.1016/j.it.2018.11.007. DOI: 10.1016/j.it.2018.11.007. PMID: 30579704.

10. Jenkins SJ, Hume DA. 2014; Homeostasis in the mononuclear phagocyte system. Trends Immunol. 35(8):358–67. https://doi.org/10.1016/j.it.2014.06.006. DOI: 10.1016/j.it.2014.06.006. PMID: 25047416.

11. Germic N, Frangez Z, Yousefi S, Simon HU. 2019; Regulation of the innate immune system by autophagy: monocytes, macrophages, dendritic cells and antigen presentation. Cell Death Differ. 26(4):715–27. https://doi.org/10.1038/s41418-019-0297-6. DOI: 10.1038/s41418-019-0297-6. PMID: 30737475. PMCID: PMC6460400.

12. Auffray C, Sieweke MH, Geissmann F. 2009; Blood monocytes: development, heterogeneity, and relationship with dendritic cells. Annu Rev Immunol. 27:669–92. https://doi.org/10.1146/annurev.immunol.021908.132557. DOI: 10.1146/annurev.immunol.021908.132557. PMID: 19132917.

13. Collin M, McGovern N, Haniffa M. 2013; Human dendritic cell subsets. Immunology. 140(1):22–30. https://doi.org/10.1111/imm.12117. DOI: 10.1111/imm.12117. PMID: 23621371. PMCID: PMC3809702.

14. Sichien D, Lambrecht BN, Guilliams M, Scott CL. 2017; Development of conventional dendritic cells: from common bone marrow progenitors to multiple subsets in peripheral tissues. Mucosal Immunol. 10(4):831–44. https://doi.org/10.1038/mi.2017.8. DOI: 10.1038/mi.2017.8. PMID: 28198365.

15. Musumeci A, Lutz K, Winheim E, Krug AB. 2019; What makes a pDC: recent advances in understanding Plasmacytoid DC development and heterogeneity. Front Immunol. 10:1222. https://doi.org/10.3389/fimmu.2019.01222. DOI: 10.3389/fimmu.2019.01222. PMID: 31191558. PMCID: PMC6548821.

16. Rodrigues PF, Tussiwand R. 2020; Novel concepts in plasmacytoid dendritic cell (pDC) development and differentiation. Mol Immunol. 126:25–30. https://doi.org/10.1016/j.molimm.2020.07.006. DOI: 10.1016/j.molimm.2020.07.006. PMID: 32739721.

17. van Nierop K, de Groot C. 2002; Human follicular dendritic cells: function, origin and development. Semin Immunol. 14(4):251–7. https://doi.org/10.1016/s1044-5323(02)00057-x. DOI: 10.1016/S1044-5323(02)00057-X. PMID: 12163300.

18. Jarjour M, Jorquera A, Mondor I, et al. 2014; Fate mapping reveals origin and dynamics of lymph node follicular dendritic cells. J Exp Med. 211(6):1109–22. https://doi.org/10.1084/jem.20132409. DOI: 10.1084/jem.20132409. PMID: 24863064. PMCID: PMC4042641.

19. Krautler NJ, Kana V, Kranich J, et al. 2012; Follicular dendritic cells emerge from ubiquitous perivascular precursors. Cell. 150(1):194–206. https://doi.org/10.1016/j.cell.2012.05.032. DOI: 10.1016/j.cell.2012.05.032. PMID: 22770220. PMCID: PMC3704230.

20. Aguzzi A, Kranich J, Krautler NJ. 2014; Follicular dendritic cells: origin, phenotype, and function in health and disease. Trends Immunol. 35(3):105–13. https://doi.org/10.1016/j.it.2013.11.001. DOI: 10.1016/j.it.2013.11.001. PMID: 24315719.

21. D'Rozario J, Knoblich K, Lutge M, et al. 2023; Fibroblastic reticular cells provide a supportive niche for lymph node-resident macrophages. Eur J Immunol. 53(9):e2250355. https://doi.org/10.1002/eji.202250355. DOI: 10.1002/eji.202250355. PMID: 36991561. PMCID: PMC10947543.

22. Li L, Wu J, Abdi R, Jewell CM, Bromberg JS. 2021; Lymph node fibroblastic reticular cells steer immune responses. Trends Immunol. 42(8):723–34. https://doi.org/10.1016/j.it.2021.06.006. DOI: 10.1016/j.it.2021.06.006. PMID: 34256989. PMCID: PMC8324561.

23. Grois N, Fahrner B, Arceci RJ, et al. 2010; Central nervous system disease in Langerhans cell histiocytosis. J Pediatr. 156(6):873–881. DOI: 10.1016/j.jpeds.2010.03.001. PMID: 20434166.

24. Grois N, Prayer D, Prosch H, Lassmann H. Group CLC-o. 2005; Neuropathology of CNS disease in Langerhans cell histiocytosis. Brain. 128(Pt 4):829–38. https://doi.org/10.1093/brain/awh403. DOI: 10.1093/brain/awh403. PMID: 15705614.

25. McClain KL, Picarsic J, Chakraborty R, et al. 2018; CNS Langerhans cell histiocytosis: Common hematopoietic origin for LCH-associated neurodegeneration and mass lesions. Cancer. 124(12):2607–20. https://doi.org/10.1002/cncr.31348. DOI: 10.1002/cncr.31348. PMID: 29624648. PMCID: PMC6289302.

26. Phan TDA, Phung BG, Duong TT, et al. 2021; A study of pathological characteristics and BRAF V600E status in Langerhans cell histiocytosis of Vietnamese children. J Pathol Transl Med. 55(2):112–7. https://doi.org/10.4132/jptm.2020.11.30. DOI: 10.4132/jptm.2020.11.30. PMID: 33494131. PMCID: PMC7987525.

27. Shao H, Xi L, Raffeld M, et al. 2011; Clonally related histiocytic/dendritic cell sarcoma and chronic lymphocytic leukemia/small lymphocytic lymphoma: a study of seven cases. Mod Pathol. 24(11):1421–32. https://doi.org/10.1038/modpathol.2011.102. DOI: 10.1038/modpathol.2011.102. PMID: 21666687. PMCID: PMC3175277.

28. West DS, Dogan A, Quint PS, et al. 2013; Clonally related follicular lymphomas and Langerhans cell neoplasms: expanding the spectrum of transdifferentiation. Am J Surg Pathol. 37(7):978–86. https://doi.org/10.1097/PAS.0b013e318283099f. DOI: 10.1097/PAS.0b013e318283099f. PMID: 23759932.

29. Rezk SA, Spagnolo DV, Brynes RK, Weiss LM. 2008; Indeterminate cell tumor: a rare dendritic neoplasm. Am J Surg Pathol. 32(12):1868–76. https://doi.org/10.1097/PAS.0b013e31818593d6. DOI: 10.1097/PAS.0b013e31818593d6. PMID: 18813122.

30. Joo JW, Chung T, Cho YA, Kim SK. 2018; Recurrent indeterminate dendritic cell tumor of the skin. J Pathol Transl Med. 52(4):243–7. https://doi.org/10.4132/jptm.2018.03.27. DOI: 10.4132/jptm.2018.03.27. PMID: 29621879. PMCID: PMC6056357.

31. Xue T, Jiang XN, Wang WG, Zhou XY, Li XQ. 2018; Interdigitating dendritic cell sarcoma: clinicopathologic study of 8 cases with review of the literature. Ann Diagn Pathol. 34:155–60. https://doi.org/10.1016/j.anndiagpath.2018.03.008. DOI: 10.1016/j.anndiagpath.2018.03.008. PMID: 29660568.

32. Dehner LP. 2003; Juvenile xanthogranulomas in the first two decades of life: a clinicopathologic study of 174 cases with cutaneous and extracutaneous manifestations. Am J Surg Pathol. 27(5):579–93. https://doi.org/10.1097/00000478-200305000-00003. DOI: 10.1097/00000478-200305000-00003. PMID: 12717244.

33. Chang KTE, Tay AZE, Kuick CH, et al. 2019; ALK-positive histiocytosis: an expanded clinicopathologic spectrum and frequent presence of KIF5BALK fusion. Mod Pathol. 32(5):598–608. https://doi.org/10.1038/s41379-018-0168-6. DOI: 10.1038/s41379-018-0168-6. PMID: 30573850.

34. Ozkaya N, Rosenblum MK, Durham BH, et al. 2018; The histopathology of Erdheim-Chester disease: a comprehensive review of a molecularly characterized cohort. Mod Pathol. 31(4):581–97. https://doi.org/10.1038/modpathol.2017.160. DOI: 10.1038/modpathol.2017.160. PMID: 29192649. PMCID: PMC6718953.

35. Abla O, Jacobsen E, Picarsic J, et al. 2018; Consensus recommendations for the diagnosis and clinical management of Rosai-Dorfman-Destombes disease. Blood. 131(26):2877–90. https://doi.org/10.1182/blood-2018-03-839753. DOI: 10.1182/blood-2018-03-839753. PMID: 29720485. PMCID: PMC6024636.

36. Menon MP, Evbuomwan MO, Rosai J, Jaffe ES, Pittaluga S. 2014; A subset of Rosai-Dorfman disease cases show increased IgG4-positive plasma cells: another red herring or a true association with IgG4-related disease? Histopathology. 64(3):455–9. https://doi.org/10.1111/his.12274. DOI: 10.1111/his.12274. PMID: 24215263. PMCID: PMC3947184.

37. Kemps PG, Picarsic J, Durham BH, et al. 2022; ALK-positive histiocytosis: a new clinicopathologic spectrum highlighting neurologic involvement and responses to ALK inhibition. Blood. 139(2):256–80. https://doi.org/10.1182/blood.2021013338. DOI: 10.1182/blood.2021013338. PMID: 34727172. PMCID: PMC8759533.

38. Lucas N, Duchmann M, Rameau P, et al. 2019; Biology and prognostic impact of clonal plasmacytoid dendritic cells in chronic myelomonocytic leukemia. Leukemia. 33(10):2466–80. https://doi.org/10.1038/s41375-019-0447-3. DOI: 10.1038/s41375-019-0447-3. PMID: 30894665.

39. Xiao W, Chan A, Waarts MR, et al. 2021; Plasmacytoid dendritic cell expansion defines a distinct subset of RUNX1-mutated acute myeloid leukemia. Blood. 137(10):1377–91. https://doi.org/10.1182/blood.2020007897. DOI: 10.1182/blood.2020007897. PMID: 32871587. PMCID: PMC7955409.

40. Zalmai L, Viailly PJ, Biichle S, et al. 2021; Plasmacytoid dendritic cells proliferation associated with acute myeloid leukemia: phenotype profile and mutation landscape. Haematologica. 106(12):3056–66. https://doi.org/10.3324/haematol.2020.253740. DOI: 10.3324/haematol.2020.253740. PMID: 33054115. PMCID: PMC8634182.

41. Cota C, Vale E, Viana I, et al. 2010; Cutaneous manifestations of blastic plasmacytoid dendritic cell neoplasm-morphologic and phenotypic variability in a series of 33 patients. Am J Surg Pathol. 34(1):75–87. https://doi.org/10.1097/PAS.0b013e3181c5e26b. DOI: 10.1097/PAS.0b013e3181c5e26b. PMID: 19956058.

42. Wu A, Pullarkat S. 2016; Follicular dendritic cell sarcoma. Arch Pathol Lab Med. 140(2):186–90. https://doi.org/10.5858/arpa.2014-0374-RS. DOI: 10.5858/arpa.2014-0374-RS. PMID: 26910224.

43. Van Baeten C, Van Dorpe J. 2017; Splenic Epstein-Barr Virus-associated inflammatory Pseudotumor. Arch Pathol Lab Med. 141(5):722–7. https://doi.org/10.5858/arpa.2016-0283-RS. DOI: 10.5858/arpa.2016-0283-RS. PMID: 28447898.

44. Andriko JW, Kaldjian EP, Tsokos M, Abbondanzo SL, Jaffe ES. 1998; Reticulum cell neoplasms of lymph nodes: a clinicopathologic study of 11 cases with recognition of a new subtype derived from fibroblastic reticular cells. Am J Surg Pathol. 22(9):1048–58. https://doi.org/10.1097/00000478-199809000-00002. DOI: 10.1097/00000478-199809000-00002. PMID: 9737236.

45. Pileri SA, Grogan TM, Harris NL, et al. 2002; Tumours of histiocytes and accessory dendritic cells: an immunohistochemical approach to classification from the International lymphoma study group based on 61 cases. Histopathology. 41(1):1–29. https://doi.org/10.1046/j.1365-2559.2002.01418.x. DOI: 10.1046/j.1365-2559.2002.01418.x. PMID: 12121233.

46. Allen CE, Merad M, McClain KL. 2018; Langerhans-cell histiocytosis. N Engl J Med. 379(9):856–68. https://doi.org/10.1056/NEJMra1607548. DOI: 10.1056/NEJMra1607548. PMID: 30157397. PMCID: PMC6334777.

47. Shanmugam V, Craig JW, Hornick JL, Morgan EA, Pinkus GS, Pozdnyakova O. 2017; Cyclin D1 Is expressed in neoplastic cells of langerhans cell histiocytosis but not reactive langerhans cell proliferations. Am J Surg Pathol. 41(10):1390–6. https://doi.org/10.1097/PAS.0000000000000897. DOI: 10.1097/PAS.0000000000000897. PMID: 28622183.

48. Sahm F, Capper D, Preusser M, et al. 2012; BRAFV600E mutant protein is expressed in cells of variable maturation in Langerhans cell histiocytosis. Blood. 120(12):e28–34. https://doi.org/10.1182/blood-2012-06-429597. DOI: 10.1182/blood-2012-06-429597. PMID: 22859608.

49. Valladeau J, Ravel O, Dezutter-Dambuyant C, et al. 2000; Langerin, a novel C-type lectin specific to Langerhans cells, is an endocytic receptor that induces the formation of Birbeck granules. Immunity. 12(1):71–81. https://doi.org/10.1016/s1074-7613(00)80160-0. DOI: 10.1016/S1074-7613(00)80160-0. PMID: 10661407.

50. Sung YE, Lee YS, Lee J, Lee KY. 2018; Erdheim-Chester disease involving lymph nodes and liver clinically mimicking lymphoma: a case report. J Pathol Transl Med. 52(3):183–90. https://doi.org/10.4132/jptm.2017.10.16. DOI: 10.4132/jptm.2017.10.16. PMID: 29281781. PMCID: PMC5964286.

51. Ravindran A, Goyal G, Go RS, Rech KL, Mayo Clinic Histiocytosis Working G. 2021; Rosai-Dorfman disease displays a unique monocyte-macrophage phenotype characterized by expression of OCT2. Am J Surg Pathol. 45(1):35–44. https://doi.org/10.1097/PAS.0000000000001617. DOI: 10.1097/PAS.0000000000001617. PMID: 33177341.

52. Garces S, Medeiros LJ, Patel KP, et al. 2017; Mutually exclusive recurrent KRAS and MAP2K1 mutations in Rosai-Dorfman disease. Mod Pathol. 30(10):1367–77. https://doi.org/10.1038/modpathol.2017.55. DOI: 10.1038/modpathol.2017.55. PMID: 28664935. PMCID: PMC5837474.

53. Julia F, Dalle S, Duru G, et al. 2014; Blastic plasmacytoid dendritic cell neoplasms: clinico-immunohistochemical correlations in a series of 91 patients. Am J Surg Pathol. 38(5):673–80. https://doi.org/10.1097/PAS.0000000000000156. DOI: 10.1097/PAS.0000000000000156. PMID: 24441662.

54. Lee YJ, Kim Y, Park SH, Jo JC. 2023; Plasmacytoid dendritic cell neoplasms. Blood Res. 58(S1):90–5. https://doi.org/10.5045/br.2023.2023052. DOI: 10.5045/br.2023.2023052. PMID: 37105563. PMCID: PMC10133850.

55. Facchetti F, Cigognetti M, Fisogni S, Rossi G, Lonardi S, Vermi W. 2016; Neoplasms derived from plasmacytoid dendritic cells. Mod Pathol. 29(2):98–111. https://doi.org/10.1038/modpathol.2015.145. DOI: 10.1038/modpathol.2015.145. PMID: 26743477.

56. Sukswai N, Aung PP, Yin CC, et al. 2019; Dual expression of TCF4 and CD123 is highly sensitive and specific for blastic plasmacytoid dendritic cell neoplasm. Am J Surg Pathol. 43(10):1429–37. https://doi.org/10.1097/PAS.0000000000001316. DOI: 10.1097/PAS.0000000000001316. PMID: 31261288.

57. Wang W, Khoury JD, Miranda RN, et al. 2021; Immunophenotypic characterization of reactive and neoplastic plasmacytoid dendritic cells permits establishment of a 10-color flow cytometric panel for initial workup and residual disease evaluation of blastic plasmacytoid dendritic cell neoplasm. Haematologica. 106(4):1047–55. https://doi.org/10.3324/haematol.2020.247569. DOI: 10.3324/haematol.2020.247569. PMID: 32241840. PMCID: PMC8017819.

58. Grogg KL, Lae ME, Kurtin PJ, Macon WR. 2004; Clusterin expression distinguishes follicular dendritic cell tumors from other dendritic cell neoplasms: report of a novel follicular dendritic cell marker and clinicopathologic data on 12 additional follicular dendritic cell tumors and 6 additional interdigitating dendritic cell tumors. Am J Surg Pathol. 28(8):988–98. https://doi.org/10.1097/01.pas.0000112536.76973.7f. DOI: 10.1097/01.pas.0000112536.76973.7f. PMID: 15252304.

59. Pan ST, Cheng CY, Lee NS, Liang PI, Chuang SS. 2014; Follicular Dendritic cell Sarcoma of the inflammatory Pseudotumor-like variant presenting as a Colonic Polyp. Kor J Pathol. 48(2):140–5. https://doi.org/10.4132/KoreanJPathol.2014.48.2.140. DOI: 10.4132/KoreanJPathol.2014.48.2.140. PMID: 24868227. PMCID: PMC4026805.

60. Emile JF, Diamond EL, Helias-Rodzewicz Z, et al. 2014; Recurrent RAS and PIK3CA mutations in Erdheim-Chester disease. Blood. 124(19):3016–9. https://doi.org/10.1182/blood-2014-04-570937. DOI: 10.1182/blood-2014-04-570937. PMID: 25150293. PMCID: PMC4224196.

61. Haroche J, Charlotte F, Arnaud L, et al. 2012; High prevalence of BRAF V600E mutations in Erdheim-Chester disease but not in other non-Langerhans cell histiocytoses. Blood. 120(13):2700–3. https://doi.org/10.1182/blood-2012-05-430140. DOI: 10.1182/blood-2012-05-430140. PMID: 22879539.

62. Diamond EL, Durham BH, Haroche J, et al. 2016; Diverse and targetable kinase alterations drive histiocytic neoplasms. Cancer Discov. 6(2):154–65. https://doi.org/10.1158/2159-8290.CD-15-0913. DOI: 10.1158/2159-8290.CD-15-0913. PMID: 26566875. PMCID: PMC4744547.

63. O'Malley DP, Agrawal R, Grimm KE, et al. 2015; Evidence of BRAF V600E in indeterminate cell tumor and interdigitating dendritic cell sarcoma. Ann Diagn Pathol. 19(3):113–6. https://doi.org/10.1016/j.anndiagpath.2015.02.008. DOI: 10.1016/j.anndiagpath.2015.02.008. PMID: 25787243.

64. Hervier B, Haroche J, Arnaud L, et al. 2014; Association of both Langerhans cell histiocytosis and Erdheim-Chester disease linked to the BRAFV600E mutation. Blood. 124(7):1119–26. https://doi.org/10.1182/blood-2013-12-543793. DOI: 10.1182/blood-2013-12-543793. PMID: 24894769.

65. Chakraborty R, Burke TM, Hampton OA, et al. 2016; Alternative genetic mechanisms of BRAF activation in Langerhans cell histiocytosis. Blood. 128(21):2533–7. https://doi.org/10.1182/blood-2016-08-733790. DOI: 10.1182/blood-2016-08-733790. PMID: 27729324. PMCID: PMC5123197.

66. Badalian-Very G, Vergilio JA, Degar BA, et al. 2010; Recurrent BRAF mutations in Langerhans cell histiocytosis. Blood. 116(11):1919–23. https://doi.org/10.1182/blood-2010-04-279083. DOI: 10.1182/blood-2010-04-279083. PMID: 20519626. PMCID: PMC3173987.

67. Davies H, Bignell GR, Cox C, et al. 2002; Mutations of the BRAF gene in human cancer. Nature. 417(6892):949–54. https://doi.org/10.1038/nature00766. DOI: 10.1038/nature00766. PMID: 12068308.

68. Chakraborty R, Hampton OA, Shen X, et al. 2014; Mutually exclusive recurrent somatic mutations in MAP2K1 and BRAF support a central role for ERK activation in LCH pathogenesis. Blood. 124(19):3007–15. https://doi.org/10.1182/blood-2014-05-577825. DOI: 10.1182/blood-2014-05-577825. PMID: 25202140. PMCID: PMC4224195.

69. Heritier S, Emile JF, Barkaoui MA, et al. 2016; BRAF mutation correlates with high-risk langerhans cell histiocytosis and increased resistance to first-line therapy. J Clin Oncol. 34(25):3023–30. https://doi.org/10.1200/JCO.2015.65.9508. DOI: 10.1200/JCO.2015.65.9508. PMID: 27382093. PMCID: PMC5321082.

70. Brown NA, Furtado LV, Betz BL, et al. 2014; High prevalence of somatic MAP2K1 mutations in BRAF V600E-negative Langerhans cell histiocytosis. Blood. 124(10):1655–8. https://doi.org/10.1182/blood-2014-05-577361. DOI: 10.1182/blood-2014-05-577361. PMID: 24982505.

71. Nelson DS, Quispel W, Badalian-Very G, et al. 2014; Somatic activating ARAF mutations in Langerhans cell histiocytosis. Blood. 123(20):3152–5. https://doi.org/10.1182/blood-2013-06-511139. DOI: 10.1182/blood-2013-06-511139. PMID: 24652991.

72. Berres ML, Lim KP, Peters T, et al. 2015; BRAF-V600E expression in precursor versus differentiated dendritic cells defines clinically distinct LCH risk groups. J Exp Med. 212(2):281. https://doi.org/10.1084/jem.2013097701202015c. DOI: 10.1084/jem.2013097701202015c. PMID: 25646268. PMCID: PMC4322054.

73. Hogstad B, Berres ML, Chakraborty R, et al. 2018; RAF/MEK/extracellular signal-related kinase pathway suppresses dendritic cell migration and traps dendritic cells in Langerhans cell histiocytosis lesions. J Exp Med. 215(1):319–36. https://doi.org/10.1084/jem.20161881. DOI: 10.1084/jem.20161881. PMID: 29263218. PMCID: PMC5748846.

74. Bigenwald C, Le Berichel J, Wilk CM, et al. 2021; BRAF(V600E)-induced senescence drives Langerhans cell histiocytosis pathophysiology. Nat Med. 27(5):851–61. https://doi.org/10.1038/s41591-021-01304-x. DOI: 10.1038/s41591-021-01304-x. PMID: 33958797. PMCID: PMC9295868.

75. Massoth LR, Hung YP, Ferry JA, et al. 2021; Histiocytic and dendritic cell sarcomas of Hematopoietic origin share targetable genomic alterations distinct from follicular dendritic cell sarcoma. Oncologist. 26(7):e1263–72. https://doi.org/10.1002/onco.13801. DOI: 10.1002/onco.13801. PMID: 33904632. PMCID: PMC8265357.

76. Durham BH, Lopez Rodrigo E, Picarsic J, et al. 2019; Activating mutations in CSF1R and additional receptor tyrosine kinases in histiocytic neoplasms. Nat Med. 25(12):1839–42. https://doi.org/10.1038/s41591-019-0653-6. DOI: 10.1038/s41591-019-0653-6. PMID: 31768065. PMCID: PMC6898787.

77. Durham BH, Roos-Weil D, Baillou C, et al. 2017; Functional evidence for derivation of systemic histiocytic neoplasms from hematopoietic stem/progenitor cells. Blood. 130(2):176–80. https://doi.org/10.1182/blood-2016-12-757377. DOI: 10.1182/blood-2016-12-757377. PMID: 28566492. PMCID: PMC5510787.

78. Milne P, Bigley V, Bacon CM, et al. 2017; Hematopoietic origin of Langerhans cell histiocytosis and Erdheim-Chester disease in adults. Blood. 130(2):167–75. https://doi.org/10.1182/blood-2016-12-757823. DOI: 10.1182/blood-2016-12-757823. PMID: 28512190. PMCID: PMC5524529.

79. Egan C, Lack J, Skarshaug S, et al. 2021; The mutational landscape of histiocytic sarcoma associated with lymphoid malignancy. Mod Pathol. 34(2):336–47. https://doi.org/10.1038/s41379-020-00673-x. DOI: 10.1038/s41379-020-00673-x. PMID: 32929178. PMCID: PMC9161669.

80. Sapienza MR, Fuligni F, Agostinelli C, et al. 2014; Molecular profiling of blastic plasmacytoid dendritic cell neoplasm reveals a unique pattern and suggests selective sensitivity to NF-kB pathway inhibition. Leukemia. 28(8):1606–16. https://doi.org/10.1038/leu.2014.64. DOI: 10.1038/leu.2014.64. PMID: 24504027. PMCID: PMC4294271.

81. Cisse B, Caton ML, Lehner M, et al. 2008; Transcription factor E2-2 is an essential and specific regulator of plasmacytoid dendritic cell development. Cell. 135(1):37–48. https://doi.org/10.1016/j.cell.2008.09.016. DOI: 10.1016/j.cell.2008.09.016. PMID: 18854153. PMCID: PMC2631034.

82. Griffin GK, Sholl LM, Lindeman NI, Fletcher CD, Hornick JL. 2016; Targeted genomic sequencing of follicular dendritic cell sarcoma reveals recurrent alterations in NF-kappaB regulatory genes. Mod Pathol. 29(1):67–74. https://doi.org/10.1038/modpathol.2015.130. DOI: 10.1038/modpathol.2015.130. PMID: 26564005.

83. Go H, Jeon YK, Huh J, et al. 2014; Frequent detection of BRAF(V600E) mutations in histiocytic and dendritic cell neoplasms. Histopathology. 65(2):261–72. https://doi.org/10.1111/his.12416. DOI: 10.1111/his.12416. PMID: 24720374.