Abstract
Rosai–Dorfman disease (RDD) or sinus histiocytosis with massive lymphadenopathy is a rare histiocytic proliferation that is generally considered to be reactive with a benign clinical course. The etiology of RDD is very poorly understood. Recent studies have shown frequent BRAF, NRAS, KRAS, and PIK3CA activating mutations in several histiocytic neoplasms highlighting the emerging importance of the RAF/MEK/ERK pathway in the pathogenesis of these diseases. Here we report a case of Rosai–Dorfman disease involving the submandibular salivary gland with a KRAS K117N missense mutation discovered by next-generation sequencing. These results suggest that at least a subset of RDD cases may be clonal processes. Further mutational studies on this rare histiocytic disease should be undertaken to better characterize its pathogenesis as well as open up potential avenues for therapy.
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References
Swerdlow SH. WHO classification of tumours of haematopoietic and lymphoid tissues. Geneva: World Health Organization; 2008.
Weitzman S, Jaffe R. Uncommon histiocytic disorders: the non-Langerhans cell histiocytoses. Pediatr Blood Cancer. 2005;45(3):256–64. doi:10.1002/pbc2246.
Paulli M, Bergamaschi G, Tonon L, et al. Evidence for a polyclonal nature of the cell infiltrate in sinus histiocytosis with massive lymphadenopathy (Rosai–Dorfman disease). Br J Haematol. 1995;91(2):415–8.
Middel P, Hemmerlein B, Fayyazi A, Kaboth U, Radzun HJ. Sinus histiocytosis with massive lymphadenopathy: evidence for its relationship to macrophages and for a cytokine-related disorder. Histopathology. 1999;35(6):525–33.
Badalian-Very G, Vergilio J-A, Degar BA, et al. Recurrent BRAF mutations in Langerhans cell histiocytosis. Blood. 2010;116(11):1919–23. doi:10.1182/blood-2010-04-279083.
Chakraborty R, Hampton OA, Shen X, et al. Mutually exclusive recurrent somatic mutations in MAP2K1 and BRAF support a central role for ERK activation in LCH pathogenesis. Blood. 2014;124(19):3007–15. doi:10.1182/blood-2014-05-577825.
Emile J-F, Diamond EL, Hélias-Rodzewicz Z, et al. Recurrent RAS and PIK3CA mutations in Erdheim–Chester disease. Blood. 2014;124(19):3016–9. doi:10.1182/blood-2014-04-570937.
Go H, Jeon YK, Huh J, et al. Frequent detection of BRAF(V600E) mutations in histiocytic and dendritic cell neoplasms. Histopathology. 2014;65(2):261–72. doi:10.1111/his.12416.
Haroche J, Charlotte F, Arnaud L, et al. High prevalence of BRAF V600E mutations in Erdheim–Chester disease but not in other non-Langerhans cell histiocytoses. Blood. 2012;120(13):2700–3. doi:10.1182/blood-2012-05-430140.
Goodnight JW, Wang MB, Sercarz JA, Fu YS. Extranodal Rosai–Dorfman disease of the head and neck. Laryngoscope. 1996;106(3 Pt 1):253–6.
Güven G, Ilgan S, Altun C, Gerek M, Gunhan O. Rosai Dorfman disease of the parotid and submandibular glands: salivary gland scintigraphy and oral findings in two siblings. Dentomaxillofac Radiol. 2007;36(7):428–33. doi:10.1259/dmfr/39858276.
Hyman DM, Diamond EL, Vibat CRT, et al. Prospective blinded study of BRAFV600E mutation detection in cell-free DNA of patients with systemic histiocytic disorders. Cancer Discov. 2015;5(1):64–71. doi:10.1158/2159-8290.CD-14-0742.
Chen T-D, Lee L. Rosai–Dorfman disease presenting in the parotid gland with features of IgG4-related sclerosing disease. Arch Otolaryngol Head Neck Surg. 2011;137(7):705–8. doi:10.1001/archoto.2011.52.
Dahlgren M, Smetherman DH, Wang J, Corsetti RL. Rosai–Dorfman disease of the breast and parotid gland. J La State Med Soc. 2008;160(1):35–8.
Juskevicius R, Finley JL. Rosai–Dorfman disease of the parotid gland: cytologic and histopathologic findings with immunohistochemical correlation. Arch Pathol Lab Med. 2001;125(10):1348–50. doi:10.1043/0003-9985(2001)125<1348:RDDOTP>2.0.CO;2.
Norman L, Bateman AC, Watters GW, Singh V, Spedding AV. Rosai–Dorfman disease presenting as a parotid mass. J Laryngol Otol. 1997;111(11):1091–3.
Dalia S, Sagatys E, Sokol L, Kubal T. Rosai–Dorfman disease: tumor biology, clinical features, pathology, and treatment. Cancer Control. 2014;21(4):322–7.
Dion E, Graef C, Miquel A, et al. Bone involvement in Erdheim–Chester disease: imaging findings including periostitis and partial epiphyseal involvement. Radiology. 2006;238(2):632–9. doi:10.1148/radiol.2382041525.
Thawerani H, Sanchez RL, Rosai J, Dorfman RF. The cutaneous manifestations of sinus histiocytosis with massive lymphadenopathy. Arch Dermatol. 1978;114(2):191–7.
Cohen-Barak E, Rozenman D, Schafer J, et al. An unusual co-occurrence of Langerhans cell histiocytosis and Rosai–Dorfman disease: report of a case and review of the literature. Int J Dermatol. 2014;53(5):558–63. doi:10.1111/ijd.12051.
O’Malley DP, Duong A, Barry TS, et al. Co-occurrence of Langerhans cell histiocytosis and Rosai–Dorfman disease: possible relationship of two histiocytic disorders in rare cases. Mod Pathol. 2010;23(12):1616–23. doi:10.1038/modpathol.2010.157.
Sachdev R, Shyama J. Co-existent Langerhans cell histiocytosis and Rosai–Dorfman disease: a diagnostic rarity. Cytopathology. 2008;19(1):55–8. doi:10.1111/j.1365-2303.2006.00428.x.
Wang K-H, Cheng C-J, Hu C-H, Lee W-R. Coexistence of localized Langerhans cell histiocytosis and cutaneous Rosai–Dorfman disease. Br J Dermatol. 2002;147(4):770–4.
Pineles SL, Liu GT, Acebes X, et al. Presence of Erdheim–Chester disease and Langerhans cell histiocytosis in the same patient: a report of 2 cases. J Neuroophthalmol. 2011;31(3):217–23. doi:10.1097/WNO.0b013e31820a204e.
Venkataraman G, McClain KL, Pittaluga S, Rao VK, Jaffe ES. Development of disseminated histiocytic sarcoma in a patient with autoimmune lymphoproliferative syndrome and associated Rosai–Dorfman disease. Am J Surg Pathol. 2010;34(4):589–94. doi:10.1097/PAS.0b013e3181d5ddf8.
Agarwal A, Pathak S, Gujral S. Sinus histiocytosis with massive lymphadenopathy–a review of seven cases. Indian J Pathol Microbiol. 2006;49(4):509–15.
Krzemieniecki K, Pawlicki M, Margañska K, Parczewska J. The Rosai–Dorfman syndrome in a 17-year-old woman with transformation into high-grade lymphoma. A rare disease presentation. Ann Oncol. 1996;7(9):977.
Zaletel K, Gaberšček S. Hashimoto’s thyroiditis: from genes to the disease. Curr Genomics. 2011;12(8):576–88. doi:10.2174/138920211798120763.
Kim KH, Suh KS, Kang DW, Kang DY. Mutations of the BRAF gene in papillary thyroid carcinoma and in Hashimoto’s thyroiditis. Pathol Int. 2005;55(9):540–5.
Jaiswal S, Fontanillas P, Flannick J, Manning A, Grauman PV, Mar BG, Lindsley RC, Mermel CH, Burtt N, Chavez A, Higgins JM, Moltchanov V, Kuo FC, Kluk MJ, Henderson B, Kinnunen L, Koistinen HA, Ladenvall C, Getz G, Correa A, Banahan BF, Gabriel S, Kathiresan S, Stringham HM, McCarthy MI, Boehnke M, Tuomilehto J, Haiman C, Groop L, Atzmon G, Wilson JG, Neuberg D, Altshuler D, Ebert BL. Age-related clonal hematopoiesis associated with adverse outcomes. N Engl J Med. 2014;371(26):2488–98. doi:10.1056/NEJMoa1408617 (Epub 2014 Nov 26).
Nelson DS, van Halteren A, Quispel WT, et al. MAP2K1 and MAP3K1 mutations in Langerhans cell histiocytosis. Genes Chromosomes Cancer. 2015;54(6):361–8. doi:10.1002/gcc.22247.
Dhillon AS, Hagan S, Rath O, Kolch W. MAP kinase signalling pathways in cancer. Oncogene. 2007;26(22):3279–90. doi:10.1038/sj.onc.1210421.
Zhao Y, Adjei AA. The clinical development of MEK inhibitors. Nat Rev Clin Oncol. 2014;11(7):385–400. doi:10.1038/nrclinonc.2014.83.
Diamond EL, Durham BH, Haroche J, et al. Diverse and targetable kinase alterations drive histiocytic neoplasms. Cancer Discov. 2015;. doi:10.1158/2159-8290.CD-15-0913.
Smith G, Bounds R, Wolf H, Steele RJC, Carey FA, Wolf CR. Activating K-Ras mutations outwith “hotspot” codons in sporadic colorectal tumours–implications for personalised cancer medicine. Br J Cancer. 2010;102(4):693–703. doi:10.1038/sj.bjc.6605534.
Dulak AM, Stojanov P, Peng S, et al. Exome and whole-genome sequencing of esophageal adenocarcinoma identifies recurrent driver events and mutational complexity. Nat Genet. 2013;45(5):478–86. doi:10.1038/ng.2591.
Papaemmanuil E, Gerstung M, Malcovati L, et al. Clinical and biological implications of driver mutations in myelodysplastic syndromes. Blood. 2013;122(22):3616–27. doi:10.1182/blood-2013-08-518886 (quiz 3699).
Stolze B, Reinhart S, Bulllinger L, Fröhling S, Scholl C. Comparative analysis of KRAS codon 12, 13, 18, 61, and 117 mutations using human MCF10A isogenic cell lines. Sci Rep. 2015;5:8535. doi:10.1038/srep08535.
Su F, Bradley WD, Wang Q, et al. Resistance to selective BRAF inhibition can be mediated by modest upstream pathway activation. Cancer Res. 2012;72(4):969–78. doi:10.1158/0008-5472.CAN-11-1875.
Gatalica Z, Bilalovic N, Palazzo JP, et al. Disseminated histiocytoses biomarkers beyond BRAFV600E: frequent expression of PD-L1. Oncotarget. 2015;6(23):19819–25.
Carrasco DR, Fenton T, Sukhdeo K, et al. The PTEN and INK4A/ARF tumor suppressors maintain myelolymphoid homeostasis and cooperate to constrain histiocytic sarcoma development in humans. Cancer Cell. 2006;9(5):379–90. doi:10.1016/j.ccr.2006.03.028.
Hayase E, Kurosawa M, Yonezumi M, Suzuki S, Suzuki H. Aggressive sporadic histiocytic sarcoma with immunoglobulin heavy chain gene rearrangement and t(14;18). Int J Hematol. 2010;92(4):659–63. doi:10.1007/s12185-010-0704-8.
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The authors gratefully acknowledge the contributions of all the staff of the Molecular Pathology Laboratory of New York Presbyterian Hospital/Weill Cornell Medicine in specimen processing and data collection. No major sources of funding.
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Shanmugam, V., Margolskee, E., Kluk, M. et al. Rosai–Dorfman Disease Harboring an Activating KRAS K117N Missense Mutation. Head and Neck Pathol 10, 394–399 (2016). https://doi.org/10.1007/s12105-016-0709-6
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DOI: https://doi.org/10.1007/s12105-016-0709-6