Dermatologica Sinica

: 2020  |  Volume : 38  |  Issue : 3  |  Page : 176--179

Non-Langerhans cell histiocytosis with peripheral joint destruction and mediastinal lymph node invasion: The continuous feature spectrum of clinical multicentric reticulohistiocytosis and microscopical xanthoma disseminatum

Yi-Hsiang Yu, Chih-Hung Lee, Shang-Hung Lin 
 Department of Dermatology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan

Correspondence Address:
Shang-Hung Lin
Department of Dermatology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, No. 123, Dapi Road, Niaosong Dist, Kaohsiung City 83301


The non-Langerhans cell histiocytoses (non-LCH) are rare and benign histiocytic disorders. We present a 61-year-old female with progressive skin-colored nodules on the face and extremities. The skin biopsy showed dermal infiltration of foamy histiocytes. Further imaging study showed erosive arthritis and lymphadenopathy. The microscopical feature of anterior mediastinal lymph node was similar to that in the skin. Thus, the diagnosis is non-LCH with joints and lymph nodes involvement. This patient presented both the clinical manifestations of multicentric reticulohistiocytosis (MRH) and histologic findings of xanthoma disseminatum (XD), indicating the plausible association and the shared disease spectrum of MRH and XD.

How to cite this article:
Yu YH, Lee CH, Lin SH. Non-Langerhans cell histiocytosis with peripheral joint destruction and mediastinal lymph node invasion: The continuous feature spectrum of clinical multicentric reticulohistiocytosis and microscopical xanthoma disseminatum.Dermatol Sin 2020;38:176-179

How to cite this URL:
Yu YH, Lee CH, Lin SH. Non-Langerhans cell histiocytosis with peripheral joint destruction and mediastinal lymph node invasion: The continuous feature spectrum of clinical multicentric reticulohistiocytosis and microscopical xanthoma disseminatum. Dermatol Sin [serial online] 2020 [cited 2020 Oct 20 ];38:176-179
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Histiocytic disorders represent a heterogeneous group of diseases derived from the proliferation of histiocytes. In 1987, the Histiocyte Society first described the classification of histiocytosis with three categories: Langerhans cell or non-Langerhans cell-related and malignant histiocytoses.[1] The non-Langerhans cell histiocytoses (non-LCH) refer to a family of histiocytosis characterized by the absence of Langerhans cells or do not meet the criteria for the diagnosis of LCH.[2] LCH can affect any organ of the body, and the most common sites are the bones, skin, and lymph nodes. However, non-LCH are mostly localized to the skin and mucosa, and systemic manifestations are uncommon. Here, we present an extremely rare case of cutaneous non-LCH with joints and lymph nodes involvement.

 Case Report

This 61-year-old female started to develop extensive itchy skin-colored nodules on the face, neck, and limbs 7 months ago. She also experienced joint deformity and joint pain over her fingers, wrists, and elbows. She lost her body weight at 10 kg in 7 months. Physical examination showed numerous discrete-to-confluent, skin-colored, and mild shiny papulonodules on the forehead, nasolabial folds, chin, neck, and dorsal hands [Figure 1]a and [Figure 1]b. Our tentative diagnosis was multicentric reticulohistiocytosis (MRH) and leprosy due to the presence of papulonodular cutaneous lesions along with peripheral arthritis. Laboratory data revealed elevated lactate dehydrogenase (505 U/L), slightly elevated total cholesterol (239 mg/dL), and normal triglyceride level (118 mg/dL). The anti-dsDNA, anti-extractable nuclear antigen screen, rheumatoid factor, and serum paraproteins were all within normal limits. The skin biopsy from the hand showed many infiltrative foamy and vacuolated histiocytes with amphophilic cytoplasm and round nuclei in the dermis [Figure 1]d and [Figure 1]e. However, the absence of multinucleated eosinophilic histiocytes unfavored the diagnosis of MRH. In addition, there was no extracellular lipid in the adipophilin stain. The histiocytes were positive for CD68, negative for adipophilin, negative for S100, and negative for CD1a [Figure 1]f. The Fite's acid-fast stain did not show leprosy bacilli. Therefore, the diagnosis was established as non-LCH based on histopathology and immunohistochemistry.{Figure 1}

Further examination of hand X-ray showed irregular subchondral bone with osteolysis of the phalanges and joint space narrowing of both the hands [Figure 1]c. We arranged systemic workup for malignancy surveys due to unintentional weight loss in few months. There are no specific findings from cardiac echography, renal echography, panendoscopy, and colonfiberscopy. Of note, chest computed tomography reported a 4.7-cm soft-tissue mass at the anterior mediastinum with lymphadenopathy [Figure 1]g. Surgical removal of the lymph node by mediastinoscope revealed abundant foamy histiocytes. Immunohistochemical staining of the histiocytes was also positive for CD68, negative for S100, and negative for CD1a. The morphology and immunohistochemistry features were similar and remnant as that in skin biopsy. Taken together, the diagnosis was non-LCH with joints and lymph nodes involvement. The skin lesions and joint mobility improved significantly by oral prednisolone at 20 mg/day over 1 year of follow-up. The bony destruction was stable, and soft-tissue swelling resolved. Her joint mobility and deformity also improved.


The non-LCH consists of a heterogeneous of disorders with different clinical presentations, pathogenesis, and morphology. This case presented clinical, pathological, and immunohistochemical findings that are consistent with non-LCH. The case also showed a rare extension of the proliferative histiocytes to the lymph nodes and associated with peripheral joint destruction in non-LCH.

Currently, several variants of non-LCH tend to occur in a cutaneous and generalized distribution over the body, such as the subgroup of cutaneous non-LCH with a major systemic component. In the classification, this subgroup of disorders is further subdivided into the xanthogranuloma (XG) family: xanthoma disseminatum (XD) and non-XG family: MRH.[3] Clinically, approximately 60% of patients may develop polyarthralgia and joint damage in MRH.[4] On the other hand, it is uncommon for the lesion extending into bone or joint in XD, and only three cases were reported in the last 20 years.[5],[6],[7] Besides, lymph nodes involvement was extremely rare in XD and MRH.[8]

MRH patients are usually 50–60-year-old women. Lesions are reddish-brown papules, nodules, or tumors and predominate on the face, forearm, and hands. Arthropathy and synovitis are the features of MRH, which often causes destructive arthritis. MRH is also associated with autoimmune disease. In about 25% of the patients, MRH is associated with malignancy.[9] The histiocytes of MRH bear copious pink histiocytes and multinucleated giant cells, with eosinophilic, finely granular, and ground-glass cytoplasm. The histiocytes and multinucleate giant cells are positive for CD68 and CD163 but negative for CD1a and S100. They reacted variably with factor XIIIa[10] [Table 1].{Table 1}

The characteristic histologic feature of XD is the presence of scalloped macrophages with foamy cells in early lesions, while the late lesions have a mixture of macrophages, foamy cells, and Touton giant cells. Immunohistochemical staining of histiocytes is positive for CD68 and factor XIIIa but negative for CD1a and S100 protein.[11] Therefore, XD cannot easily be excluded due to the histologic and immunohistochemical pictures of abundant foamy histiocyte infiltration in our case. However, clinically, XD patients are younger with male predominance. XD typically shows widespread brown-to-yellow papules and nodules involving the face and trunk, including the fflexural regions. The mucosa sites are often affected. Respiratory, ocular, and central nervous system involvement could be found in patients, but the diabetes insipidus is usually mild and transient.[12],[13] Importantly, the skeletal involvement in patients with XD is rare.

In the present case, papulonodular skin lesions distribution of the face, neck, and dorsal hands with severe polyarthritis were consistent with the clinical features in the diagnosis of MRH. However, based on the microscopical pathology, our patient was in favor of XD due to the presence of numerous foamy histiocytes and a lack of eosinophilic histiocytes and ground-glass multinucleate giant cell. This is the interesting part that the diagnosis of non-LCH is based on histopathology, and further differentiation of different subgroups is supported by immunophenotypic and the clinical presentations. Therefore, clinicopathologic overlap makes it difficult to place some patients exactly into one definite entity.[14],[15] To our knowledge, there were few similarly documented cases presenting as the combination of generalized xanthoma and destructive arthritis consistent with MRH.[16],[17],[18],[19] One similar case had an association with double cancers.[18] Interestingly, recently, two cases reported a good response to adalimumab;[19] some people thought these are variants of MRH. However, none of these patients developed lymphadenopathy. Our case is the only case with prominent foamy histiocytic infiltration of lymph nodes and could be considered as a clinical variant of non-LCH group.

Generally, the non-LCH is a self-limiting disease but may persist for years. The patients with non-LCH may have extracutaneous manifestations. Prompt recognition and treatment is recommended to avoid irreversible inflammation period.[20],[21] Currently, there is no standard treatment for these cases, and various immunosuppressant agents including systemic steroids, methotrexate, and tumor necrosis factor-alpha blocker of adalimumab have been tried with different results. In our experience, progressive joint destruction in this patient with non-LCH benefits from systemic steroid.


We report a case presenting MRH clinically but XD microscopically. Not only skin and joints but also mediastinal lymph nodes could be involved in patients with non-LCH. Appropriate treatment and prolonged follow-up are mandatory.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understand that her name and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

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Conflicts of interest

There are no conflicts of interest.


1Histiocytosis syndromes in children. Writing Group of the Histiocyte Society. Lancet 1987;1:208-9.
2Weitzman S, Jaffe R. Uncommon histiocytic disorders: The non-Langerhans cell histiocytoses. Pediatr Blood Cancer 2005;45:256-64.
3Emile JF, Abla O, Fraitag S, Horne A, Haroche J, Donadieu J, et al. Revised classification of histiocytoses and neoplasms of the macrophage-dendritic cell lineages. Blood 2016;127:2672-81.
4Selmi C, Greenspan A, Huntley A, Gershwin ME. Multicentric reticulohistiocytosis: A critical review. Curr Rheumatol Rep 2015;17:511.
5Khandpur S, Manchanda Y, Sharma VK, Singh MK, Tandon N. Rare association of xanthoma disseminatum with skeletal involvement. Australas J Dermatol 2003;44:190-3.
6Gupta P, Khandpur S, Vedi K, Singh MK, Walia R. Xanthoma disseminatum associated with inflammatory arthritis and synovitis – A rare association. Pediatr Dermatol 2015;32:e1-4.
7Taniguchi Y, Nishino T, Sugaya H, Hajime M, Ochiai N, Yamazaki M. Osteoarticular lesion in xanthoma disseminatum treated with total hip arthroplasty: A case report. J Med Case Rep 2019;13:51.
8West KL, Sporn T, Puri PK. Multicentric reticulohistiocytosis: A unique case with pulmonary fibrosis. Arch Dermatol 2012;148:228-32.
9Toz B, Büyükbabani N, İnanç M. Multicentric reticulohistiocytosis: Rheumatology perspective. Best Pract Res Clin Rheumatol 2016;30:250-60.
10Tajirian AL, Malik MK, Robinson-Bostom L, Lally EV. Multicentric reticulohistiocytosis. Clin Dermatol 2006;24:486-92.
11Zelger B, Cerio R, Orchard G, Fritsch P, Wilson-Jones E. Histologic and immunohistochemical study comparing xanthoma disseminatum and histiocytosis X. Arch Dermatol 1992;128:1207-12.
12Caputo R, Veraldi S, Grimalt R, Gianotti R, Tosti A, Varotti C, et al. The various clinical patterns of xanthoma disseminatum. Considerations on seven cases and review of the literature. Dermatology 1995;190:19-24.
13Zak IT, Altinok D, Neilsen SS, Kish KK. Xanthoma disseminatum of the central nervous system and cranium. AJNR Am J Neuroradiol 2006;27:919-21.
14Chu AC. The confusing state of the histiocytoses. Br J Dermatol 2000;143:475-6.
15Stinco G, Patriarca M, Di Loreto C, Patrone P. A histiocytic disorder that does not easily fit into the classification of the juvenile xanthogranuloma family. Int J Dermatol 2013;52:849-55.
16Matiz C, Ferguson PJ, Zaenglein A, Groh B, Bingham CA. Papular xanthomas and erosive arthritis in a 3 year old girl, is this a new MRH variant&? Pediatr Rheumatol Online J 2009;7:15.
17Andrew R, Nuara A, McCollough M, Kelly E. Papular xanthomas with destructive arthritis. J Am Acad Dermatol 2013;69:e309-10.
18Ge JS, Hung SJ, Hsu YH, Hung JS. Rare case of multicentric reticulohistiocytosis presenting as epidermotropic papular xanthoma and double primary cancers. J Dermatol 2018;45:e138-9.
19Sin CZ, Cheng YP, Tsai TF. Papular xanthoma with destructive arthritis (a variant of multicentric reticulohistiocytosis): Reports of two cases. Dermatologica Sinica 2019;37:174-5.
20Park HY, Cho DH, Kang HC, Yun SJ. A case of xanthoma disseminatum with spontaneous resolution over 10 years: Review of the literature on long-term follow-up. Dermatology 2011;222:236-43.
21Tariq S, Hugenberg ST, Hirano-Ali SA, Tariq H. Multicentric reticulohistiocytosis (MRH): Case report with review of literature between 1991 and 2014 with in depth analysis of various treatment regimens and outcomes. Springerplus 2016;5:180.