CLINICAL AND LABORATORY INVESTIGATIONS
Langerhans cell histiocytosis first presenting in the skin in adults: frequent association with a second haematological malignancy
J.R. Edelbroek, M.H. Vermeer, P.M. Jansen,
T.J. Stoof,
M.M.D. van der Linden,
B. Horváth,
J. van Baarlen,
R. Willemze,
P.M. Jansen
Pathology, Leiden University Medical Center, Leiden, the Netherlands
Search for more papers by this authorT.J. Stoof
Department of Dermatology, Vrije Universiteit Medical Center, Amsterdam, the Netherlands
Search for more papers by this authorM.M.D. van der Linden
Department of Dermatology, Academic Medical Center, Amsterdam, the Netherlands
Search for more papers by this authorB. Horváth
Department of Dermatology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
Search for more papers by this authorJ. van Baarlen
Laboratorium Pathologie Oost-Nederland, Enschede, the Netherlands
Search for more papers by this authorJ.R. Edelbroek, M.H. Vermeer, P.M. Jansen,
T.J. Stoof,
M.M.D. van der Linden,
B. Horváth,
J. van Baarlen,
R. Willemze,
P.M. Jansen
Pathology, Leiden University Medical Center, Leiden, the Netherlands
Search for more papers by this authorT.J. Stoof
Department of Dermatology, Vrije Universiteit Medical Center, Amsterdam, the Netherlands
Search for more papers by this authorM.M.D. van der Linden
Department of Dermatology, Academic Medical Center, Amsterdam, the Netherlands
Search for more papers by this authorB. Horváth
Department of Dermatology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
Search for more papers by this authorJ. van Baarlen
Laboratorium Pathologie Oost-Nederland, Enschede, the Netherlands
Search for more papers by this authorRein Willemze. E-mail: [email protected]
Funding sources None.
Conflicts of interest None declared.
Summary
Background Langerhans cell histiocytosis (LCH) in adults first presenting in the skin is rare. Guidelines for staging, treatment and follow-up are lacking.
Objectives To better define staging procedures, treatment results and clinical course in adult patients with LCH first presenting in the skin.
Methods Eighteen adult patients with LCH first presenting in the skin were collected from five centres collaborating in the Dutch Cutaneous Lymphoma Group. Clinical records and (skin) biopsy specimens were reviewed and follow-up data were obtained. A literature search on adult patients with LCH presenting in the skin was performed.
Results Staging procedures showed extracutaneous disease in three of 16 patients who were adequately staged. One patient had a histologically confirmed lytic LCH bone lesion, while two patients had a myelodysplastic syndrome. During follow-up two of 18 patients developed extracutaneous localizations of LCH. Five patients developed a second haematological malignancy, including (myelo)monocytic leukaemia (two cases), histiocytic sarcoma (one case), diffuse large B-cell lymphoma (one case) and peripheral T-cell lymphoma (one case). Review of the literature revealed six other adult patients with a second haematological malignancy preceding or following a diagnosis of LCH.
Conclusions The results of the present study suggest an increased risk of a second haematological malignancy in adult patients with LCH presenting in the skin. Extensive staging at presentation and long-term follow-up are therefore warranted in such patients.
References
- 1 Guyot-Goubin A, Donadieu J, Barkaoui M et al. Descriptive epidemiology of childhood Langerhans cell histiocytosis in France, 2000–2004. Pediatr Blood Cancer 2008; 1: 3–4.
- 2 Aricò M, Girschikofsky M, Généreau T et al. Langerhans cell histiocytosis in adults. Report from the International Registry of the Histiocyte Society. Eur J Cancer 2003; 16: 2341–8.
- 3 Broadbent V, Gadner H, Komp DM, Ladisch S. Histiocytosis syndromes in children: II. Approach to the clinical and laboratory evaluation of children with Langerhans cell histiocytosis. Clinical Writing Group of the Histiocyte Society. Med Pediatr Oncol 1989; 6: 492–5.
- 4
Axiotis CA,
Merino MJ,
Duray PH.
Langerhans cell histiocytosis of the female genital tract.
Cancer
1991; 67: 1650–60.
10.1002/1097-0142(19910315)67:6<1650::AID-CNCR2820670629>3.0.CO;2-T CAS PubMed Web of Science® Google Scholar
- 5 Nethercott JR, Murray AH, Medwidsky W, Chalvardjian A. Histiocytosis X in two adults. Arch Dermatol 1983; 119: 157–61.
- 6 Berman B, Chang DL, Shupack JL. Histiocytosis X: treatment with topical nitrogen mustard. J Am Acad Dermatol 1980; 3: 23–9.
- 7 Neumann C, Kolde G, Bonsmann G. Histiocytosis X in an elderly patient. Ultrastructure and immunocytochemistry after PUVA photochemotherapy. Br J Dermatol 1988; 119: 385–91.
- 8 Claudy AL, Larbre B, Colomb M et al. Letterer–Siwe disease and subacute monocytic leukemia. J Am Acad Dermatol 1989; 21: 1105–6.
- 9 Wright AL, Tucker WF, Slater DN, Harrington CI. Letterer–Siwe disease in the ninth decade. J Am Acad Dermatol 1985; 12: 369–71.
- 10 Wollina U, Kaatz M, Krönert C et al. Cutaneous Langerhans cell histiocytosis with subsequent development of haematological malignancies. Report of two cases. Acta Dermatovenereol Alp Panonica Adriat 2006; 15: 79–84.
- 11 Yamashita H, Nagayama M, Kawashima M et al. Langerhans-cell histiocytosis in an adult patient with multiple myeloma. Clin Exp Dermatol 1992; 17: 275–8.
- 12 Querings K, Starz H, Balda BR. Clinical spectrum of cutaneous Langerhans’ cell histiocytosis mimicking various diseases. Acta Derm Venereol (Stockh) 2006; 86: 39–43.
- 13 Billings S, Hans C, Schapiro BL et al. Langerhans cell histiocytosis associated with myelodysplastic syndrome in adults. J Cutan Pathol 2006; 33: 171–4.
- 14 Padula A, Medeiros LJ, Silva EG, Deavers MT. Isolated vulvar Langerhans cell histiocytosis: report of two cases. Int J Gynecol Pathol 2004; 23: 278–83.
- 15 Voelklein K, Horny H-P, Marzusch K, Dietl J. Primary Langerhans cell histiocytosis of the vulva. Gynecol Obstet Invest 1993; 36: 189–90.
- 16 Jiang W, Li L, He YM, Yang KX. Langerhans cell histiocytosis of the female genital tract: a literature review with additional three case studies in China. Arch Gynecol Obstet 2012; 285: 99–103.
- 17 Foley S, Panting K, Bell H et al. Rapid resolution of primary vulval adult Langerhans cell histiocytosis with very potent topical corticosteroids. Australas J Dermatol 2011; 52: e8–14.
- 18 Kwong YL, Chan AC, Chan TK. Widespread skin-limited Langerhans cell histiocytosis: complete remission with interferon alfa. J Am Acad Dermatol 1997; 36: 628–9.
- 19 Caputo R, Gianotti R, Monti M. Nodular ‘pure’ mucocutaneous histiocytosis X in an adult. Arch Dermatol 1987; 123: 1274–5.
- 20 Lair G, Marie I, Cailleux N et al. Langerhans histiocytosis in adults: cutaneous and mucous lesion regression after treatment with thalidomide. Rev Med Interne 1998; 19: 196–8.
- 21 O’Kane D, Jenkinson H, Carson J. Langerhans cell histiocytosis associated with breast carcinoma successfully treated with topical imiquimod. Clin Exp Dermatol 2009; 34: e829–32.
- 22 Aihara M, Hasegawa T, Okuyama Y et al. Langerhans cell histiocytosis treated with narrow-band ultraviolet B. J Dermatol 2011; 38: 151–4.
- 23 Shahidi-Dadras M, Saeedi M, Shakoei S, Ayatollahi A. Langerhans cell histiocytosis: an uncommon presentation, successfully treated by thalidomide. Indian J Dermatol Venereol Leprol 2011; 77: 587–90.
- 24 Monk BE, McKee PH, du Vivier A. Histiocytosis X of the scalp and face. J R Soc Med 1984; 77: 613–15.
- 25 Conias S, Strutton G, Stephenson G. Adult cutaneous Langerhans cell histiocytosis. Australas J Dermatol 1998; 39: 106–8.
- 26 Guitart J, Micali G, Norton SA. A young adult with a recalcitrant scalp folliculitis. Langerhans’ cell histiocytosis (LCDH) presenting as scalp folliculitis in an adult. Arch Dermatol 1995; 131: 719–20, 722–3.
- 27 Moravvej H, Yousefi M, Barikbin B. An unusual case of adult disseminated cutaneous Langerhans cell histiocytosis. Dermatol Online J 2006; 12: 13.
- 28 Li R, Lin T, Gu H, Zhou Z. Successful thalidomide treatment of adult solitary perianal Langerhans cell histiocytosis. Eur J Dermatol 2010; 20: 391–2.
- 29 Singh A, Prieto VG, Czelusta A et al. Adult Langerhans cell histiocytosis limited to the skin. Dermatology 2003; 207: 157–61.
- 30 Hancox JG, James AP, Madden C et al. Adult onset folliculocentric Langerhans cell histiocytosis confined to the scalp. Am J Dermatopathol 2004; 26: 123–6.
- 31 Santillan A, Montero AJ, Kavanagh JJ et al. Vulvar Langerhans cell histiocytosis: a case report and review of the literature. Gynecol Oncol 2003; 91: 241–6.
- 32 Lookingbill DP. Histiocytosis X confined to the skin of the scalp. J Am Acad Dermatol 1984; 10: 968–9.
- 33 Sander CS, Kaatz M, Elsner P. Successful treatment of cutaneous Langerhans cell histiocytosis with thalidomide. Dermatology 2004; 208: 149–52.
- 34 Steen AE, Steen KH, Bauer R, Bieber T. Successful treatment of cutaneous Langerhans cell histiocytosis with low-dose methotrexate. Br J Dermatol 2001; 145: 137–40.
- 35 Solano T, España A, Sola J, López G. Langerhans cell histiocytosis on the vulva. Gynecol Oncol 2000; 78: 251–4.
- 36 Lichtenwald DJ, Jakubovic HR, Rosenthal D. Primary cutaneous Langerhans cell histiocytosis in an adult. Arch Dermatol 1991; 127: 1545–8.
- 37 Chang SE, Koh GJ, Choi JH et al. Widespread skin-limited adult Langerhans cell histiocytosis: long-term follow-up with good response to interferon alpha. Clin Exp Dermatol 2002; 27: 135–7.
- 38 Chi DH, Sung KJ, Koh JK. Eruptive xanthoma-like cutaneous Langerhans cell histiocytosis in an adult. J Am Acad Dermatol 1996; 34: 688–9.
- 39 Pather S, Moodley JM, Bramdev A. Isolated Langerhans cell histiocytosis of the vulva: a case report. J Obstet Gynaecol Res 2001; 27: 111–15.
- 40 Pan Z, Sharma S, Sharma P. Primary Langerhans cell histiocytosis of the vulva: report of a case and brief review of the literature. Indian J Pathol Microbiol 2009; 52: 65–8.
- 41 Baldo A, Vitiello A, Argenziano G et al. Pure cutaneous relapsing Langerhans cell histiocytosis in an adult. Eur J Dermatol 1998; 8: 501–2.
- 42 Rose PG, Johnston GC, O’Toole RV. Pure cutaneous histiocytosis X of the vulva. Obstet Gynecol 1984; 64: 587–90.
- 43 Triantafyllidou O, Giannakopoulos K, Pergialiotis V et al. Pure vulvar Langerhans cell histiocytosis: a case report and literature review. Eur J Gynaecol Oncol 2009; 30: 691–4.
- 44 Fernandes LB, Guerra JG, Costa MB et al. Langerhans cells histiocytosis with vulvar involvement and responding to thalidomide therapy – case report. An Bras Dermatol 2011; 86: S78–81.
- 45 Cardoso JC, Cravo M, Cardoso R et al. Langerhans cell histiocytosis in an adult: good response of cutaneous lesions to acitretin. Clin Exp Dermatol 2010; 35: 627–30.
- 46 Wang P, Wang X, Hong J, Wang Z. Extensive cutaneous Langerhans cell histiocytosis in an elderly woman. J Dermatol 2011; 38: 794–7.
- 47 Venizelos ID, Mandala E, Tatsiou ZA et al. Primary Langerhans cell histiocytosis of the vulva. Int J Gynecol Pathol 2006; 25: 48–51.
- 48 Modi D, Schulz EJ. Skin ulceration as sole manifestation of Langerhans-cell histiocytosis. Clin Exp Dermatol 1991; 16: 212–15.
- 49 Ishigaki H, Hatta N, Yamada M et al. Localised vulva Langerhans cell histiocytosis. Eur J Dermatol 2004; 14: 412–14.
- 50 Meunier L, Marck Y, Ribeyre C, Meynadier J. Adult cutaneous Langerhans cell histiocytosis: remission with thalidomide treatment. Br J Dermatol 1995; 132: 168.
- 51 Misery L, Larbre B, Lyonnet S et al. Remission of Langerhans cell histiocytosis with thalidomide treatment. Clin Exp Dermatol 1993; 18: 487.
- 52 Fernandez Flores A, Mallo S. Langerhans cell histiocytosis of vulva. Dermatol Online J 2006; 12: 15.
- 53 Imafuku S, Shibata S, Tashiro A, Furue M. Cutaneous Langerhans cell histiocytosis in an elderly man successfully treated with narrowband ultraviolet B. Br J Dermatol 2007; 157: 1277–9.
- 54 Hashimoto K, Kagetsu N, Taniguchi Y et al. Immunohistochemistry and electron microscopy in Langerhans cell histiocytosis confined to the skin. J Am Acad Dermatol 1991; 25: 1044–53.
- 55 Taverna JA, Stefanato CM, Wax FD, Demierre MF. Adult cutaneous Langerhans cell histiocytosis responsive to topical imiquimod. J Am Acad Dermatol 2006; 54: 911–13.
- 56
Iwatsuki K,
Tsugiki M,
Yoshizawa N
et al.
The effect of phototherapies on cutaneous lesions of histiocytosis X in the elderly.
Cancer
1986; 57: 1931–6.
10.1002/1097-0142(19860515)57:10<1931::AID-CNCR2820571007>3.0.CO;2-G CAS PubMed Web of Science® Google Scholar
- 57 Campanati A, Simonetti O, Marconi B et al. Purely cutaneous Langerhans’ cell histiocytosis in an adult woman. Acta Derm Venereol (Stockh) 2009; 89: 299–301.
- 58 Stefanato CM, Andersen WK, Calonje E et al. Langerhans cell histiocytosis in the elderly: a report of three cases. J Am Acad Dermatol 1998; 39: 375–8.
- 59 Aoki M, Aoki R, Akimoto M, Hara K. Primary cutaneous Langerhans cell histiocytosis in an adult. Am J Dermatopathol 1998; 20: 281–4.
- 60 Goldberg NS, Bauer K, Rosen ST et al. Histiocytosis X. Flow cytometric DNA content and immunohistochemical and ultrastructural analysis. Arch Dermatol 1986; 122: 446–50.
- 61 Black A, Bershow A, Allen PS, Crowson AN. Seventy-nine-year-old man with Langerhans cell histiocytosis treated with cladribine. J Am Acad Dermatol 2011; 65: 681–3.
- 62 Watson LC, Mendelsohn SS, Nash J. Adult-onset Langerhans cell histiocytosis associated with severe abscesses. Clin Exp Dermatol 1995; 20: 415–18.
- 63 Holme SA, Mills CM. Adult primary cutaneous Langerhans’ cell histiocytosis mimicking nodular prurigo. Clin Exp Dermatol 2002; 27: 250–1.
- 64 Vogel CA, Aughenbaugh W, Sharata H. Excimer laser as adjuvant therapy for adult cutaneous Langerhans cell histiocytosis. Arch Dermatol 2008; 144: 1287–90.
- 65 Shinmi K, Nagai Y, Matsushima Y et al. Adult case of Langerhans cell histiocytosis. J Dermatol 2007; 34: 275–7.
- 66 Cambazard F, Misery L, Kanitakis J et al. Acute monoblastic leukemia and histiocytosis X: a case report and review of the literature. Eur J Dermatol 1991; 1: 11–17.
- 67 Munn S, Chu AC. Langerhans cell histiocytosis of the skin. Hematol Oncol Clin North Am 1998; 12: 269–86.
- 68 Egeler RM, Neglia JP, Aricò M et al. The relation of Langerhans cell histiocytosis to acute leukemia, lymphomas, and other solid tumors. The LCH-Malignancy Study Group of the Histiocyte Society. Hematol Oncol Clin North Am 1998; 12: 369–78.
- 69 Egeler RM, Neglia JP, Puccetti DM et al. Association of Langerhans cell histiocytosis with malignant neoplasms. Cancer 1993; 3: 865–73.
- 70 Ghosn MG, Haddad AC, Nassar MN et al. Acute myeloid leukemia and Langerhans’ cell histiocytosis: multiple theories for an unusual presentation. Leuk Res 2010; 3: 406–8.
- 71 Feldman AL, Berthold F, Arceci RJ et al. Clonal relationship between precursor T-lymphoblastic leukaemia/lymphoma and Langerhans-cell histiocytosis. Lancet Oncol 2005; 6: 435–7.
- 72 Baumgartner I, von Hochstetter A, Baumert B et al. Langerhans’-cell histiocytosis in adults. Med Pediatr Oncol 1997; 1: 9–14.
