Langerhans cell histiocytosis (LCH) and Langerhans cell sarcoma (LCS) are clonal proliferations of Langerhans-type cells. Unlike in LCH, the pathophysiology and clinical course of LCS are unclear due to its rarity. Here, we report the case of a 73-year-old male patient who was diagnosed with cutaneous LCH and pulmonary LCS at the same time. Pathological review of these 2 tumors revealed similar immunohistochemical findings. However, the tumor cells in LCS had more aggressive cytological features than those in LCH. Results of BRAF mutation analysis using real-time PCR were negative for both tumors. In whole-exome sequencing (WES), stop-gain mutations in TP53 gene were discovered only in LCS cells. The mechanism of development of LCS from various progenitor cells is currently unclear. According to the results of the WES study, changes in TP53 gene might have contributed to the malignant features of LCS.

Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Vardiman JW: WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues, ed 4. Lyon, International Agency for Research on Cancer (IARD), 2008.
Badalian-Very G, Vergilio JA, Degar BA, MacConaill LE, Brandner B, Calicchio ML, Kuo FC, Ligon AH, Stevenson KE, Kehoe SM, Garraway LA, Hahn WC, Meyerson M, Fleming MD, Rollins BJ: Recurrent BRAF mutations in Langerhans cell histiocytosis. Blood 2010;116:1919-1923.
Sahm F, Capper D, Preusser M, Meyer J, Stenzinger A, Lasitschka F, Berghoff AS, Habel A, Schneider M, Kulozik A, Anagnostopoulos I, Mullauer L, Mechtersheimer G, von Deimling A: BRAFV600E mutant protein is expressed in cells of variable maturation in Langerhans cell histiocytosis. Blood 2012;120:e28-e34.
Howard JE, Dwivedi RC, Masterson L, Jani P: Langerhans cell sarcoma: a systematic review. Cancer Treat Rev 2015;41:320-331.
Lee JS, Ko GH, Kim HC, Jang IS, Jeon KN, Lee JH: Langerhans cell sarcoma arising from Langerhans cell histiocytosis: a case report. J Korean Med Sci 2006;21:577-580.
Tugrul Saribeyoglu E, DA, Bilgic B, Solakoglu S, Agop Citak SA, Devecioglu O: A patient with Langerhans cell sarcoma arising from Langerhans cell histiocytosis (abstract). Pediatr Blood Cancer 2009;53:1.
Berres ML, Merad M, Allen CE: Progress in understanding the pathogenesis of Langerhans cell histiocytosis: back to histiocytosis X? Br J Haematol 2015;169:3-13.
Brown NA, Furtado LV, Betz BL, Kiel MJ, Weigelin HC, Lim MS, Elenitoba-Johnson KS: High prevalence of somatic MAP2K1 mutations in BRAF V600E-negative Langerhans cell histiocytosis. Blood 2014;124:1655-1658.
Nelson DS, van Halteren A, Quispel WT, van den Bos C, Bovee JV, Patel B, Badalian-Very G, van Hummelen P, Ducar M, Lin L, MacConaill LE, Egeler RM, Rollins BJ: MAP2K1 and MAP3K1 mutations in Langerhans cell histiocytosis. Genes Chromosomes Cancer 2015;54:361-368.
Zwerdling T, Won E, Shane L, Javahara R, Jaffe R: Langerhans cell sarcoma: case report and review of world literature. J Pediatr Hematol Oncol 2014;36:419-425.
Go H, Jeon YK, Huh J, Choi SJ, Choi YD, Cha HJ, Kim HJ, Park G, Min S, Kim JE: Frequent detection of BRAF(V600E) mutations in histiocytic and dendritic cell neoplasms. Histopathology 2014;65:261-272.
Mourah S, Lorillon G, Meignin V, Vercellino L, de Margerie-Mellon C, Pages C, Goldwirt L, How-Kit A, Tost J, Lebbe C, Tazi A: Dramatic transient improvement of metastatic BRAF(V600E)-mutated Langerhans cell sarcoma under treatment with dabrafenib. Blood 2015;126:2649-2652.
da Costa CE, Szuhai K, van Eijk R, Hoogeboom M, Sciot R, Mertens F, Bjorgvinsdottir H, Debiec-Rychter M, de Krijger RR, Hogendoorn PC, Egeler RM, Annels NE: No genomic aberrations in Langerhans cell histiocytosis as assessed by diverse molecular technologies. Genes Chromosomes Cancer 2009;48:239-249.
Karai LJ, Sanik E, Ricotti CA, Susa J, Sinkre P, Aleodor AA: Langerhans cell sarcoma with lineage infidelity/plasticity: a diagnostic challenge and insight into the pathobiology of the disease. Am J Dermatopathol 2015;37:854-861.
Ratei R, Hummel M, Anagnostopoulos I, Jahne D, Arnold R, Dorken B, Mathas S, Benter T, Dudeck O, Ludwig WD, Stein H: Common clonal origin of an acute B-lymphoblastic leukemia and a Langerhans' cell sarcoma: evidence for hematopoietic plasticity. Haematologica 2010;95:1461-1466.
Furmanczyk PS, Lisle AE, Caldwell RB, Kraemer KG, Mercer SE, George E, Argenyi ZB: Langerhans cell sarcoma in a patient with hairy cell leukemia: common clonal origin indicated by identical immunoglobulin gene rearrangements. J Cutan Pathol 2012;39:644-650.
Chen W, Jaffe R, Zhang L, Hill C, Block AM, Sait S, Song B, Liu Y, Cai D: Langerhans cell sarcoma arising from chronic lymphocytic lymphoma/small lymphocytic leukemia: lineage analysis and BRAF V600E mutation study. N Am J Med Sci 2013;5:386-391.
Ambrosio MR, De Falco G, Rocca BJ, Barone A, Amato T, Bellan C, Lazzi S, Leoncini L: Langerhans cell sarcoma following marginal zone lymphoma: expanding the knowledge on mature B cell plasticity. Virchows Arch 2015;467:471-480.
Kato M, Seki M, Yoshida K, Sato Y, Oyama R, Arakawa Y, Kishimoto H, Taki T, Akiyama M, Shiraishi Y, Chiba K, Tanaka H, Mitsuiki N, Kajiwara M, Mizutani S, Sanada M, Miyano S, Ogawa S, Koh K, Takita J: Genomic analysis of clonal origin of Langerhans cell histiocytosis following acute lymphoblastic leukaemia. Br J Haematol 2016;175:169-172.
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