Rare Tumors 2010; volume 2:e34

Photodynamic therapy for may be involved. 1 The clinical expression and the prognosis principally depend on the clini - Correspondence: Arjen F. Nikkels, Department of multi-resistant cutaneous cal type and the number of organs affected. 2 Dermatology, CHU of Sart Tilman, University of Langerhans cell histiocytosis First-line treatment for the cutaneous lesions Liège, B-4000 Liège, Belgium. relies on topical corticosteroids. Topical E-mail: [email protected] Valérie Failla, Odile Wauters, chemotherapy (nitrogen mustard, carmustine) Key words: Langerhans cell histiocytosis, photo - Marie Caucanas, Nazli Nikkels-Tassoudji, or PUVA-therapy are interesting second-line dynamic therapy, childhood. Arjen F. Nikkels options. Systemic chemotherapy is reserved for severe and refractory cutaneous involve - Department of Dermatology, University Contributions: all authors provided substantial ment. Hospital of Liège, Liège, Belgium contributions to the conception and design, Notwithstanding, some cases fail to respond acquisition of data, or analysis and interpretation and require alternative therapy. Photodynamic of data, to the drafting of the article or revising it therapy (PDT) is an FDA-recognized treatment critically for important intellectual content. All option for superficial basal cell carcinoma, authors provided final approval of the version to Abstract Bowen’s disease and actinic keratosis. 3-6 The be published. preferential accumulation of the photosensi - Langerhans cell histiocytosis is a rare group tizing agents in hypermetabolic cells (i.e. pre- Conflict of interest: the authors report no con - of proliferative disorders. Beside cutaneous cancerous and cancerous cells) explains the flicts of interest. involvement, other internal organs can be selectiveness of PDT. The spectrum of other Received for publication: 9 February 2010. affected. The treatment of cutaneous lesions is cutaneous oncological conditions effectively Revision received: 27 April 2010. difficult and relies on topical corticosteroids, 7 treated by PDT is continuously increasing. Accepted for publication: 29 April 2010. carmustine, nitrogen mustard, and pho - The presence of an oligoclonal proliferation of tochemotherapy. Systemic steroids and vin - LCs in LCH was the rationale for PDT treat - This work is licensed under a Creative Commons blastine are used for recalcitrant skin lesions. ment. This paper reports the first successful Attribution 3.0 License (by-nc 3.0). However, some cases fail to respond. An 18- PDT treatment of multi-resistant scalp month old boy presented a CD1a +, S100a + Langerhans cell histiocytosis in a young boy. ©Copyright V. Failla et al., 2010 Langerhans cell histocytosis with cutaneous Licensee PAGEPress, Italy Rare Tumors 2010; 2:e34 and severe scalp involvement. Topical corticos - doi:10.4081/rt.2010.e34 teroids and nitrogen mustard failed to improve the skin lesions. Systemic corticosteroids and Case Report vinblastine improved the truncal involvement tion of histiocytic disorders. 2 The clinical score but had no effect on the scalp lesions. Methyl- An 18-month old boy visited the dermatology for disease activity was 2 (clinical findings: 2, aminolevulinate (MAL) based photodynamic department for erythematous and squamous laboratory evaluation: 0, radiological studies: therapy (PDT) resulted in a significant regres - lesions of the trunk and the scalp. The lesions 0). 2 sion of the scalp lesions. Control histology appeared at the age of eight months and pro - No regression of the skin lesions was revealed an almost complete clearance of the gressively spread over the trunk and scalp. A observed following topical applications of very tumor infiltrate. Clinical follow-up after six pediatrician proposed a diagnosis of atopic potent corticosteroids (clobetasol propionate months showed no recurrence. dermatitis. The child was otherwise healthy, 0.05% cream, Dermovate©, GSK), but the itch - Although spontaneous regression of cuta - did not take any medication and presented a ing sensations were partially relieved. neous Langerhans cell histiocytosis is normal development. There were no signs of Subsequent treatment with topical nitrogen observed, the rapid effect of photodynamic growth retardation. There was no particular therapy after several failures of other treat - family medical history. mustard (10 mg/50 mL H 20, 3 times/week, for ment suggests that photodynamic therapy was Skin examination revealed infiltrated, three weeks (Mustargen©)) also failed to successful. As far as we know this is the first sometimes purpuric, papular and slightly squa - improve the skin lesions. PUVA therapy was report of photodynamic therapy for refractory mous, ill-defined lesions on the trunk. These not performed, as efficacy on the hairy scalp is skin lesions. Larger series are needed to deter - lesions were neither pruritic nor painful. limited. Systemic corticosteroids (40 mine whether photodynamic therapy deserves Severe inflammatory and crusting lesions mg/m²/day) also failed. Finally, following sys - a place in the treatment of multiresistant cuta - were evidenced on the scalp and behind the temic vinblastine (Velbe©), a partial regres - neous Langerhans cell histiocytosis. ears (Figure 1). These lesions were painful sion of the truncal lesions was observed but and itchy, and the child used to scratch them. the aspect of the scalp lesions did not improve. Further clinical examination was unremark - During the second chemotherapy course, fever able. No adenopathies were evidenced. A cuta - and neutropenia with a bilateral interstitial Introduction neous biopsy was performed under local anes - pneumopathy suddenly appeared, necessitat - thesia. Histology suggested LCH. Immuno- ing interruption of treatment. The pulmonary Langerhans cell histiocytosis (LCH) is a histochemical staining revealed a CD1a +, lesions resolved and four months later, a sub - rare group of proliferative disorders. The S100a + infiltrate with a proliferative KI67 frac - sequent treatment combining vinblastine and prevalence is estimated between 1 and 2 per tion of 15%, confirming the diagnosis of LCH. corticosteroids (once every two weeks for six 1,000,000. The male:female ratio is 2:1. Usually Electron microscopy to ascertain the presence months) was started. The truncal lesions pro - LCH affects young children, particularly of Birbeck granules was not performed. An gressively disappeared but the scalp and ear between the ages of one and three years. LCH extensive internal workup, including ultra - lesions resisted. A new skin biopsy of the scalp presents an oligoclonal proliferation of sound, blood sampling, chest radiography and was performed, revealing S-100a + and CD1a + Langerhans cells (LC). The etiology has not chest CT scan, was normal. The final diagnosis Langerhans cell histiocytosis. The KI67 growth been elucidated. LCH affects the skin in 40% of was a cutaneous LCH (multifocal single organ fraction was 5%. Finally, a methyl-aminolevuli - the cases, but almost any other internal organ disease), according to the current classifica - nate (MAL)-based photodynamic therapy was

[page 94 ] [Rare Tumors 2010; 2:e34] Case Report performed under total anesthesia. Previously, a cream containing 15% urea was applied once daily for 15 days to diminish the hyperkeratot - ic character of the scalp lesions. MAL (Metvix© cream 5%, Galderma) was applied under occlusion, using a plastic film, for three hours. Red light LED illumination was per - formed using an Aktilite© light source (634 nm, 74 J/cm 2) for eight minutes. Post-treat - ment crusting was limited using an antibiotic ointment (mupiro cine, Bactroban©) twice daily for one week. The child did not complain of any pain or itching after the treatment. No Figure 1. Langerhans cell histiocytosis Figure 2. Aspect of the scalp one month involving the scalp. after PDT. painkillers were required. Two weeks after PDT treatment, a significant reduction of the inflammation and crusting was noted. Four al therapy only if required. However, treatment Effective therapies for cases unresponsive to weeks later, there was an almost complete is recommended as isolated cutaneous LCH in the above include cytosine arabinoside and healing (Figure 2). A control biopsy revealed a infants is not always a benign disorder and the cladribine. Intravenous cladribine (2- complete histological clearing and only some evolution is not always predictable. 10 chlorodeoxyadenosine, 2CDA), a purine ana - residual CD1a + LC on immunohistological Topical corticosteroids (potent or very log, has also been proven effective. 15 Emerging examination. After a follow-up of six months potent) are recommended as first-line treat - therapies include monoclonal antibodies the scalp was still recurrence free. ment. 2 Surgery may be considered for isolated against the CD1a or CD52 epitopes found on and small lesions. When these fail, topical Langerhans cells. Although normal epidermal chemotherapy can be used: daily applications Langerhans cells do not express CD52, patho - of nitrogen mustard (0.02% mechlorethamine logical LCH cells express CD52, suggesting Discussion hydrochloride, mustine), an alkylating cytosta - that alemtuzumab may represent a new, tar - tic agent 12 often bring clinical improvement geted therapy for LCH. 24 Langerhans cell histiocytosis is rarely within ten days. 13 After induction treatment, PDT permits selective destruction of cells encountered and encompasses a group of dis - topical chemotherapy can be considered as accumulating the topical photosensitizer MAL orders characterized by the proliferation and maintenance therapy. 14 Although adverse and subsequently activated by a light source. 7 infiltration of Langerhans cells, potentially effects are minimal in the short-term, the pos - Through a non-elucidated selectivity mecha - affecting almost every organ. 2,8 The diagnosis sibility of long-term cutaneous carcinogenicity nism, a ten-fold higher intracellular concentra - of cutaneous LCH is suggested by histopathol - is not excluded. 13 Carmustine (bis-chloroni - tion of the photosensitizer is achieved in ogy and confirmed by a positive immunohisto - trosourea, BCNU) is another mustard gas- metabolically more active cells, such as the chemical signal for the CD1a, S100a and related α-chloro-nitrosourea compound used keratinocytes of actinic keratosis. This selec - CD207 (Langerin) antigens. 1,9 Electron as an alkylating agent for cutaneous LCH. 15 tivity is not only restricted to epithelial cells, as microscopy evidences the pathognomical New treatments include imiquimod, a topical endothelial cells, lymphocytes, as well as glan - intracytoplasmic Birbeck granules, but is not interferon-inducing agent. A case of LCH was dular cells may also be effectively targeted, routinely performed. 1,9 The skin lesions are effectively treated with topical imiquimod, hence expanding the therapeutic potential of polymorphous, but macular, papular and vesic - resulting in clinical and histological clear - PDT. 7 This case furthermore suggests that the ular elements covered by slight brown crusts ance. 16 Oral 8-methoxypsoralen (8-MOP) plus LCH cells are capable of concentrating the pho - are characteristic clinical features. 9,10 The ultraviolet A (PUVA) therapy (3 times per week tosensitizer, whereas the normal epidermal LC usual localizations include the face, the front for two months, 1-2 times per week mainte - are not affected. The rationale behind PDT for and the scalp, the trunk and the large folds. nance PUVA) is an interesting treatment LCH was the selective accumulation of the Bone disease usually affects one single bone option, in particular offering treatment to photosensitizer in metabolically more active with pain, swelling, deformation, fracture, etc. patients presenting extensive cutaneous dis - cells. In our patient, the large area involved, Cranial, mandibular, vertebral, and the pelvic ease. 17-19 Low-dose methotrexate (20 mg week - the pain inherent in the illumination phase bones are the most frequently affected. Lung ly) successfully treated multiresistant cuta - and the young age of the child, prompted us to disease typically presents as a reticulo-micron - neous LCH. 20,21 In some patients with multire - perform PDT under total anesthesia. As no pre - odular syndrome with dyspnea, a dry cough sistant cutaneous LCH, subcutaneous interfer - vious experience is available on PDT in LCH, a and fever. Hematologic disease is polymor - on- α2b achieved long remission periods. 15 Oral standard treatment procedure was chosen. It is phous and may evolve to pancytopenia. Other thalidomide (N-phtalimidoglutarimide, 200 clear that specific PDT protocols for LCH signs, such as diabetes insipidia, hepatosple - mg/d) was effective for mucocutaneous LCH should be developed according to future clini - nomegalia, sclerosing cholangitis, median oti - after four weeks of treatment with total clear - cal experience. The child did not experience tis may be observed. ing after three months. Maintenance therapy any post-procedure pain and did not ask for Treatment is directed towards decreasing using 100 mg/d can be recommended to pre - pain reducing medication. The time course of the activity and proliferation of the histiocytes vent recurrent disease. Hence, thalidomide the crusting was similar to superficial basal and to relieve symptoms such as itching and monotherapy represents an effective, safe and cell carcinoma treatments. stinging, as well as to improve the esthetic well-tolerated treatment option that may be In summary, as far as we know, this case aspects and quality of life. 11 As the prognosis of considered as first-line therapy for mucocuta - presents the first successful PDT treatment of isolated cutaneous involvement is favorable neous LCH. 21-23 Systemic chemotherapy includ - multiresistant cutaneous LHC. More experi - and as auto-resolution may be expected, it is ing mercaptopurine and vinblastine, with or ence should be gathered to determine the recommended to start with the simplest treat - without prednisone and/or methotrexate, may appropriate role of PDT in the management of ment and progress to systemic or intervention - be used in case of extensive internal disease. 19 cutaneous LHC.

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