Dermatology Department of Xinhua Hospital Shanghai Jiaotong University, Medical school Hong Yu Cases report

Case 1 Red hemorrhagic papules with multiple organs involved

A 2-year-old boy hospitalized in Pediatric Department in our hospital was consulted because of skin rash The lesions of the skin: Needle size of fresh colored papules over the patient’s head and face, with a few greasy scaly brown patches on the scalp A few needle size red hemorrhagic papules on the trunk, among them on the back there is one papule as large as a millet

History The patient was admitted for recurrent fever in 4 months on 09/09/17 Physical examination hepatosplenomegaly, enlargement of lymph nodes of neck and groin areas;

Laboratory examination: Blood routing test: WBC 2.45*109/L↓ ， HB 49 g/L↓ ， PLT 69*109/L↓ ； Albumin ↓ No abnormal detection for ANA ， HBsAg ， HCV, HIV ；

Bone marrow smear suspected the diagnosis of Langerhans cell histiocytosis No microorganism evidence in blood and cerebrospinal fluid B Ultrasound ： hepatosplenomegaly ， enlargement of lymph nodes of mesentery No abnormal findings of skull by CT and MRI ， No abnormal detection of chest by X-ray;

Histiopathology examination Skin biopsy revealed ： Mononuclear and multinucleated histiocytes infiltrate densely in the dermis, with some inflammatory cells, such as lymphocytes, neutrophils and eosinophils. A few of the mononulcear cells were with reni-form nuclei, and multinucleated cells had ground- glass appearing cytoplasm.

Immunochemical stain: All the histiocytes: VIM （＋） some mononuclear histiocytes: both CD1a and S100 were positive Some mono and all the multinucleated cells: Both CD68 and PAS were positive

Prognosis After chemotherapy, the skin lesions have been improved, most of the papules over the head and face were disappeared, however, the patient is still in severe condition, with a high fever, anemia, hypoproteinemia and hepatosplenomegaly, and he obviously has a bulging abdomen.

Langerhans cell histiocytosis(LCH) accompany with or not multicentric reticulohistiocytosis(MH) / reticulohistiocytoma(RH) What is the diagnosis?

Diagnosis of LCH is based on classical clinical findings and histologic/immunohistochemical criteria. Previously absolute criteria for diagnosis depended on finding CD1a or Birbeck granules. Currently, the presence of Birbeck granules is assumed by immunohistochemical demonstration of langerin (CD207). Positivity of one or both of these markers now defines the langerhans cell phenotype.

LCH is a granulomatous lesion containing Langerhans cells as well as normal inflammatory cells and multinucleated giant cells (MGC). The MGC were recently reported to be osteoclast-like and able to produce cytokines that can cause osteolysis; and in bone lesions, the osteoclast-like MGCs were only CD68(+), in the nonostotic sites, they coexpressed CD1a. Then, the multinucleated cells in our case Can not be explained by LCH.

Multicentric reticulohistiocytosis(MH) multiple cutaneous nodules associated with a destructive polyarthritis, which can be seen in approximately 20% to 50% patients. Reticulohistiocytoma(RH) flesh or yellow-brown colored nodule

Both of them have similar histological features, but the immunochemical profiles are different as the table; and the phenotype of RH is identical to xanthogranuloma. MHRH CD HAM S100-- Fx Ⅲ -+ HHF Large multinucleated giant cells with distinctive eosinophilic granular cytoplasm.

The preferred diagnosis LCH with RH

Cases 2 yellow papules with multi-organs involved

A 15-month-old boy was hospitalized in our department with a working diagnosis of LCH. History hemorrhagic macules and papules on his chest and abdomen since 8-month-old accompanied by fever At 12 months of age, he developed yellow papules, initially on the forehead and spreading over the rest of his face and scalp. At the same time, the lesions of the trunk became more numerous.

Skin biopsy revealed: A dense dermal infiltrate of foamy histiocytes, among them Touton giant cells At the periphery of the biopsy specimen were mononuclear histiocytes with kidney-shaped nuclei in the papillary dermis

Immunohistochemical staining : Histiocytes near the center of the specimen was positive for CD68 Whereas the infiltrate at the periphery was reactive for CD1a and S100

The patient’s general condition progressively deteriorated as he developed anemia, hepatosplenomegaly with hepatic dysfunction, xanthochromia, and generalized lymphadenopathy. The patient died from disseminated intravascular coagulopathy on day 12 of his hospital admission, having received no systemic therapy.

What is the diagnosis: Langerhans cell histiocytosis or Juvenile xanthogranuloma or both mixed / overlapped

Prefer to think: LCH overlapped JXG

In the last decade, there have been several reports of JXG developing from LCH. Six children with LCH developed JXG within several months or years after having received systemic or topical therapy. In addition, there is a 2-year-old boy with Juvenile multiple xanthogranuloma on his skin and Langerhans cell histiocytosis on his tibia.

Some authors thought there is a cell lineage relationship between RH and adult xanthogranuloma, both of them are class Ⅱ a subtypes of non-LCH, and Rosai- Dorfman disease belongs to class Ⅱ b subtypes of non-LCH.

However, there has been a report about coexistence of LCH and cutaneous Rosai- Dorfman disease in a Chinese child. To me, many quandaries are yet to be resolved in regard to this seeming overlap of histiocytic disorders.

Refernces 1. Weitzman S, Egeler RM.Langerhans cell histiocytosis: updateWeitzman SEgeler RM for the pediatrician. Curr Opin Pediatr Feb;20(1): Dermnet NZ Non-Langerhans cell histiocytosis da Costa CE ； Annels NE ； Faaij CM ； Forsyth RG ； Hogendoornda Costa CE Annels NE Faaij CM Forsyth RG Hogendoorn PC PC ； Egeler RM Presence of osteoclast-like multinucleated giant Egeler RM cells in the bone and nonostotic lesions of Langerhans cell histiocytosis. Journal of Experimental Medicine 2005:201(no.5) 4.Hoeger PH, Diaz C, Malone M, et al. Juvenile xanthogranuloma as a sequel to Langerhans cell histiocytosis: a report of three cases. Clin Exp Dermatol 2001;26:391-4.

5. Patrizi A, Neri I, Bianchi F, et al. Langerhans cell histiocytosis and juvenile xanthogranuloma: two case reports. Dermatology 2004;209: Pe´rez-Gala S, Torrelo A, Colmenero I, et al. Juvenile multiple xanthogranuloma in a patient with Langerhans cell histiocytosis. Actas Dermo-Sif 2006;97: Shani-Adir A, Chou P, Morgan E, et al. A child with both Langerhans and non-Langerhans cell histiocytosis. Pediatr Dermatol 2002;19: Kong YY, Kong JC, Shi DR. Cutaneous Rosai-Dorfman disease: a clinical and histopathologic study of 25 cases in China. Am J Surg Pathol 2007;31:

9.Zelger B, Cerio R, Soyer HP, Misch K, Orchard G,Zelger BCerio RSoyer HPMisch KOrchard G Wilson-Jones E Reticulohistiocytoma and multicentricWilson-Jones E reticulohistiocytosis. Histopathologic and immunophenotypic distinct entities. Am J Dermatopathol Dec;16(6): Barnhill RL, Neil Crowson A, Busam KJ, Granter SR textbook of dermatopathology, McGraw-hill health professions division, 1997: Hong Yu, Jinchen Kong, Yan Gu ， Bo Ling, Zhengjun Xi, Zhirong Yao.A child with coexistent juvenile xanthogranuloma and Langerhans’ cell histiocytosis. Journal of American Academy of Dermatology vol.62 No.2,2010: