Dermatology Department of Xinhua HospitalShanghai 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.

MH RH

CD68 + +

HAM56 + +

S100 - -

FxⅢ - +

HHF35 - +

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 hepaticdysfunction, 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 a subtypes of non-LCH, and Rosai-Ⅱ

Dorfman disease belongs to class b Ⅱsubtypes 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.

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