Agnieszka Sebastian-Rusin

Eugeniusz Baran

Joanna Maj

Piotr Dziegiel

Rafal Bialynicki-Birula

Zdzislaw Wozniak

Hrčak - Portal of scientific journals of Croatia

35Acta Dermatovenerol Croat                 2010;18(1):35-37                         CLINICAL ARTICLEMulticentric Reticulohistiocytosis with S100 Protein Positive Staining: A Case Report  Rafal Bialynicki-Birula1, Agnieszka Sebastian-Rusin1, Joanna Maj1,  Zdzislaw Wozniak1, Eugeniusz Baran1, Piotr Dziegiel2 1Department of Dermatology, Venereology and Allergology, 2Department of Histology, Wroclaw Medical University, Wroclaw, Poland Corresponding author:Rafal Bialynicki-Birula, MDDepartment of Dermatology, Venereology and AllergologyWroclaw Medical UniversityChalubinskiego 150-368 WroclawPolandrafalb@derm.am.wroc.plReceived: November 22, 2009Accepted: January 8, 2010SUMMARY Multicentric reticulohistiocytosis is a very rare systemic disease that affects skin, mucosa and joints. We reported a case of a woman with multicentric reticulohistiocytosis who presented typical skin syndromes and arthralgia. Immunohistochemical analysis showed positive staining for S100 protein, which was reported negative in the majority of previously presented cases. Other immunohistochemical markers (CD68(+), CD1a(-), lagerin (-) and complete histologic and clinical picture were specific enough to make the definitive diagnosis of multicentric reticulohistiocytosis. The patient was administered prednisone just when arthritis appeared and we believe that this therapy protected her from the development of destructive arthritis. No autoimmune disease or internal malignancy was observed during 12-month follow up. KEY WORDS: histiocytosis, non-Langerhans cell, S100 proteinINTRODUCTION Multicentric reticulohistiocytosis (MR) is a rare systemic disorder of unknown etiology, classified as a non-Langerhans cell histiocytosis. It mainly affects skin, mucosa and synovia, and usually causes destructive symmetric arthritis. MR often affects internal organs and can also coexist with autoimmune diseases and/or malignancy (1). Goltz and Laymon (2) introduced MR as a new nosologic entity in 1954. CASE REPORT A 30-year-old Caucasian woman was admit-ted to the Wroclaw Department of Dermatology because of dark-red nodules that appeared on the skin of her hands. The diameters of the lesions were between 2 and 7 mm. The nodules were hard, painless and had a tendency to linear arrange-ment like Koebner phenomenon (Fig. 1). There were additional small nodules localized along the proximal nail fold, known as a ‘coral beads’ sign. Moreover, there were numerous small papules symmetrically located on the face, in particular on the dorsal part of the nose. No erosions, ulcers or scales were observed.  Histology of the biopsy specimens obtained from the skin of the nose and hands showed very 36 ACTA DERMATOVENEROLOGICA CROATICAsimilar patterns characterized by abundant infiltra-tion of histiocytes with homogeneous copious eo-sinophilic cytoplasm and multinucleated giant cells (large histiocytes) with finely granulated cytoplasm of ‘ground glass’ appearance (Fig. 2). The dermis was infiltrated throughout its thickness and there were no changes seen in the epidermis covering the lesion.  An admixture of scattered chronic in-flammatory cells was seen.  Immunohistochemical analysis showed a very strong expression of CD68, positive staining for S100 protein (Fig. 3) and complete absence of CD1a labeling and lagerin (antibodies supplied by DAKO: CD68 code N1577, S-100 – N1573, CD1a – N1616; antibody supplied by Nocastra: NCL – lagerin; staining procedure: EnVision + System-HRP [DAB]). Electron microscopy did not demon-strate Birbeck granules.  The clinical features, histologic and immuno-histologic pictures indicated a definitive diagnosis of multicentric reticulohistiocytosis. Radiologic, biochemical and serologic tests re-vealed no involvement of internal organs including joints and bones, autoimmune disease or malig-nancy. Rheumatoid factor and antinuclear anti-bodies were negative. Erythrocyte sedimentation rate and cholesterol concentration were within the normal range. About half a year after the first skin lesions, the patient presented again for arthralgia. She felt strong pain in the shoulders, elbows, knees and hands joints. Medium doses of prednisone (40 mg/d) were used and complete remission of the joint symptoms was achieved in about two weeks. Skin lesions showed gradual but moderate improve-ment. Selected skin lesions were also treated with hypodermic injections of steroids, however, with-out clinical response. The patient has been con-tinuously followed up.DISCUSSION We describe this case because of the very low incidence of multicentric reticulohistiocytosis in Polish population. The authors found no report from Poland in the English literature. The world-Figure 1. Clinical presentation with dark-red nod-ules on the skin of the hands. Small nodules local-ized over the proximal nail folds are known as a ‘coral beads’ sign.Figure 2. Skin biopsy. Abundant infiltration of his-tiocytes with homogenous copious eosinophilic cytoplasm and multinucleated giant cells (large histiocytes) with finely granulated cytoplasm of ‘ground glass’ appearance. The epidermis cov-ering the lesion remained unchanged. Scattered chronic inflammatory cells present in the der-mis (hematoxylin-eosin staining) (magnification X100).Figure 3. Skin biopsy. Positive staining of histio-cytes for S-100 protein (antibodies from DAKO: S-100 – N1573) (magnification X200).Bialynicki-Birula  et al.    Acta Dermatovenerol CroatMulticentric Reticulohistiocytosis     2010;18(1):35-3737ACTA DERMATOVENEROLOGICA CROATICAwide incidence of the disease is also very low. Barrow and Holubar (5) found only 33 patients described in medical literature worldwide in the 1954-1969 period, whereas Luz et al. (1) found 96 case reports published during the 1977-2001 pe-riod. We consider it worthy of emphasizing the very gentle course of the disease during 12 months and positive staining for S100 protein in our patient. The morphology and localization of skin lesions were typical. Arthritis in MR is symmetric and de-structive (3). Hand joints, knees, wrists and hips are usually affected, but all joints can be involved (1). In 40%-60% of cases, joint pain occurs before skin lesions; however, skin manifestations may sometimes precede arthralgia for years. In our pa-tient, joint symptoms occurred about 6 months af-ter skin lesions and short therapy with steroids led to complete remission of joint pain. We assume that, thanks to early treatment, destructive arthritis may never get chance to develop. In patients suffering from MR many autoim-mune diseases have been observed. According to previous reports, comorbidity of MR and rheu-matoid arthritis, dermatomyositis, Sjögren’s syn-drome, scleroderma, primary biliary cirrhosis (4), diabetes mellitus, hypothyroidism (5), vasculitis, celiac disease, and systemic lupus erythemato-sus (6) has been reported. The association of MR and internal malignancy (about 20%-30%) is also widely known. The role of MR as a paraneoplastic syndrome is discussed because of the very wide spectrum of malignancy types it can be connected with. The oncologic process can occur prior to or simultaneously with MR. In several cases, the treatment of malignancy resulted in complete re-mission of MR (7). Because of the rare incidence of MR and its unclear etiopathogenesis, there are no specific therapeutic guidelines. The use of prednisone, hydroxychloroquine, cyclophosphamide, chloram-bucil, methotrexate and azathioprine has been mentioned in the literature (1). Recent reports on treatment using anti-TNF agents like etanercept and infliximab in combination with traditional im-munosuppressants seem to be promising (8,9). In our patient, we used only prednisone because the course of the disease was mild and the ini-tial remission of the joint symptoms showed some promise. In most reports, staining for S100 protein was negative (1). Only Miettinen and Fetsch (10) observed focal expression in a few cases in a se-ries of 44 biopsies and Weber et al. (11) revealed S100 protein in one case. It is hard to assess whether positive staining for this marker can be considered decisive for definitive diagnosis. In our patient, definitive diagnosis was based on other pronounced features of MR.References1.   Luz FB, Gaspar NK, Gaspar AP, Ramos-e-Sil-va M. Multicentric reticulohistiocytosis. J Eur Acad Dermatol Venereol 2001;15:524-31.2.   Goltz RW, Laymon CW. Multicentric reticulo-histiocytosis of the skin and synovia; reticulo-histiocytoma or ganglioneuroma. AMA Arch Derm Syphilol 1954;69:717-31.3.   Hsiung SH, Chan EF, Elenitsas R, Kolasinski SL, Schumacher HR, Werth VP. Multicentric reticulohistiocytosis presenting with clinical features of dermatomyositis. J Am Acad Der-matol 2003;48(Suppl):S11-S14.4.   Takahashi M, Mizutani H, Nakamura Y, Shimi-zu . A case of multicentric reticulohistiocytosis, systemic sclerosis and Sjögren syndrome. J Dermatol 1997;24:530-4.5.   Barrow MV, Holubar K. Multicentric reticulo-histiocytosis: a review of 33 patients. Medicine 1969;48:287-305.6.   Trotta F, Castellino G, Lo Monaco A. Multi-centric reticulohistiocytosis. Best Pract Res Clin Rheumatol 2004;18:759-72.7.   Valencia IC, Colsky A, Berman B. Multicentric reticulohistiocytosis associated with recur-rent breast carcinoma. J Am Acad Dermatol 1998;39(5 Pt 2):864-6.8.   Sellam J, Deslandre CJ, Dubreuil F, Arfi S, Ka-han A. Refractory multicentric reticulohistiocy-tosis treated by infliximab: two cases. Clin Exp Rheumatol 2005;23:97-9.9.   Kovach BT, Calamia KT, Walsh JS, Gins-burg WW. Treatment of multicentric reticulo-histiocytosis with etanercept. Arch Dermatol 2004;140:919-21.10. Miettinen M, Fetsch JF. Reticulohistiocytoma (solitary epithelioid histiocytoma): a clinicopat-hologic and immunohistochemical study of 44 cases. Am J Surg Pathol 2006;30:521-8.11. Weber L, Hesse G, Feller A. Multicenter skin tumor of the interdigitating dendritic cell. Hau-tarzt 1988;39:28-33.Bialynicki-Birula  et al.    Acta Dermatovenerol CroatMulticentric Reticulohistiocytosis     2010;18(1):35-37

Multicentric Reticulohistiocytosis with S100 Protein Positive Staining: A Case Report

Abstract

Similar works

Full text

Available Versions

Hrčak - Portal of scientific journals of Croatia