Congenital self-healing langerhans cell histiocytosis: clinical and pathological characteristics

Abstract

Introduction: Congenital Self-Healing Langerhans Cell Histiocytosis (CSHLCH) is rare, characterized by cutaneous lesions at birth or in the neonatal period, and absence of systemic lesions. Materials and methods: Skin biopsy was performed and the histologic examination of the skin section, routinely stained with hematoxylin-eosin. Paraffin sections were stained by immunohistochemical study which were carried out according to the manufacturer’s protocols. Result: Seven cases of CSHLCH were recruited. 28.6% (2/7) of the cutaneous lesions were multiple, 71.4% (5/7) were solitary. Skin biopsy was performed and the histologic examination of the skin section, routinely stained with hematoxylin-eosin. Microscopically, in the dermis, a dense infiltrate of histiocytic cells mixed with numerous eosinophils. These histiocytes were immunohistochemically positive for CD1a and S-100. All of the cutaneous lesions regress spontaneously, and lack of systemic involvement, the final diagnosis of Congenital Self-Healing Langerhans Cell Histiocytosis were made. No recurrence had been observed. Conclusion: The cutaneous lesions of CSHLCH may regress spontaneously. Spontaneous resolution of cutaneous lesions and lack of systemic involvement are essential for the diagnosis of CSHLCH. It needs long-term follow-up.

Introduction

Langerhans cell histiocytosis (LCH) is a disorder with a broad spectrum of forms with diverse clinical presentations, ranging from self-healing to systematic forms [1]. Depending on clinical presentations, it is further distinguished into including Letterer-Siwe disease, Hand-Schüller-Christian disease, eosinophilic granuloma, and a congenital self-healing form [2].

Congenital Self-Healing Langerhans Cell Histiocytosis (CSHLCH) also called Congenital self-healing reticulohistiocytosis or Hashimoto-Pritzker disease, is rare, characterized by cutaneous lesions at birth or in the neonatal period, and absence of systemic lesions. It is known that the lesions of CSHLCH may regress spontaneously within weeks to months [3,4].

Here, we reported seven cases of Congenital self-healing Langerhans cell histiocytosis at birth or in the neonatal period, and the clinicopathological characteristics of it are listed based on the literature.

Materials and methods

All the resected specimens were fixed in 10% neutral formalin, conventional dehydrated, embedded in paraffin, made into 4 μm paraffin, and eventually HE (hematoxylin and eosin) staining.

Paraffin sections were stained by immunohistochemical study carried out according to the manufacturer’s protocols. The following primary antibodies were used: CD1a, S-100, CD68, and Ki67 which all from DAKO (Glostrup, Denmark). Immunoreactivity was detected using the Dako labeled streptavidin-biotin detection kit according to the manufacturer’s recommended procedures.

Result

In searches of the archival files spanning long periods in the Foshan Women and Children Hospital, Foshan, People’s Republic of China, seven cases of CSHLCH could be recruited. Birth weight, length and Apgar score of all infants were within normal range. Physical examination revealed no hepatosplenomegaly or lymphadenopathy. Skull, chest and long bone X-rays and abdominal ultrasound were normal. A complete blood count creatinine, bilirubin, liver and kidney function tests, urine and stool examination, viral serologies such as TORCH, VDRL, and HIV were negative.

Skin biopsy was performed and the histologic examination of the skin section, routinely stained with hematoxylin-eosin. All the resected specimens were fixed in 10% neutral formalin, conventional dehydrated, embedded in paraffin, made into 4 μm paraffin, and eventually H&E (hematoxylin and eosin) staining. Microscopically, in the dermis, a dense infiltrate of histiocytic cells mixed with numerous eosinophils. Histiocytes had folded nuclei and eosinophilic cytoplasm, and some kidney-shaped nuclei with prominent nucleoli, mitotic figures were rare (Figure 1A and 1B). These histiocytes were immunohistochemically positive for CD1a, S-100 (Figure 1C and 1D).

Figure 1.

One of our 7 cases of CSHLCH. A: The lesion is located in the dermis. H&E × 40. B: It shows a dense infiltrate of histiocytic cells mixed with eosinophils, Histiocytes had folded nuclei and eosinophilic cytoplasm, and some kidney-shaped nuclei. H&E × 400. C: Immunohistochemical staining for S-100 is positive. H&E × 200. D: Immunohistochemical staining for CD1a is positive. H&E × 200.

The clinicopathological characteristics, clinical course and outcome of our 7 cases of Congenital Self-Healing Langerhans Cell Histiocytosis are presented in Table 1. Based upon this, the final diagnosis of CSHLCH was made. No recurrence had been observed.

Table 1.

Summary of our 7 cases of CSHLCH

No.	Age at onset of rash	Age at diagnosis	Sex	Site	Size (cm)	Systemic involvement	Clinical course and outcome
1	2 w	1-year-old	M	On the skin of back	Diameter 1.0	None	A solitary red-brown papule with crust; two months later, the skin lesion resolved spontaneously; lost to follow-up
2	At birth	8 d	M	Multiple on skin of the entire body	Diameter 0.5 to 1.0	None	Multiple red papules, partially blistered; three months later, the skin lesion resolved spontaneously; lost to follow-up
3	1 d	5 d	M	On Left upper arm	Diameter 1.0	None	A solitary skin colored papule with crust; one month later, the skin lesion resolved spontaneously; followed-up 8 years, no recurrence
4	At birth	10 d	M	On Right buttocks	Diameter 4.5	None	A red papule with erosion; four months later, the skin lesion resolved spontaneously; followed-up 3 years, no recurrence
5	At birth	6 d	F	Multiple on skin of the entire body	Diameter 1.0 to 2.2	None	Multiple black papules with crust; three months later, the skin lesion resolved spontaneously; followed-up 2 year, died from other causes
6	At birth	4 d	F	On left heel	Diameter 1.0	None	A solitary skin-colored papule with crust; two months later, the skin lesion resolved spontaneously; followed-up 9 years, no recurrence
7	At birth	1 m	M	On left thigh	Diameter 2.0	None	A solitary dark-red papule with crust; three months later, the skin lesion resolved spontaneously; followed-up 1 year, no recurrence

CSHLCH, Congenital Self-Healing Langerhans Cell Histiocytosis; NO., Patient Number; w, week; M, Male; F, Female; d, day; m, month.

Discussion

Congenital Self Healing Langerhans Cell Histiocytosis (CSHLCH) was first reported by Hashimoto and Pritzker in 1973 [5], is a rare disorder. Cutaneous lesions range from papules to vesicles, pustules and ulcers, with onset at birth or in the neonatal period. It is known that cutaneous lesions of CSHLCH may regress spontaneously [6,7], and systemic involvement should be ruled out. Spontaneous resolution of cutaneous lesions and lack of systemic involvement are essential for the diagnosis of CSHLCH [6-8]. The diagnosis is confirmed by immunohistochemical positivity with S-100 and CD1a. Electron microscopy will reveal the characteristic Birbeck granules [9], but is usually not needed [10]. Exact etiology of CSHLCH is unclear. Strenger V. et al. [5] showed that Langerhans cell proliferation may be induced either by viral infection or defective immunity [11].

In our 7 cases of CSHLCH, 28.6% (2/7) of the cutaneous lesions were multiple, 71.4% (5/7) were solitary, indicated that CSHLCH had a classical clinical picture: it is almost a single cutaneous lesion. The lesions measured 0.5~4.5 cm, and it seemed to mostly occur in males. All of the lesions regressed within one to four months, a mean period of 2.5 months and excluding the cases of loss to follow-up, no recurrences were observed. Since the lesions regress spontaneously, clinical findings are nonspecific and it can be supposed that some cases were not diagnosed, suggesting that the morbidity of CSHLCH was underestimated [12]. Our cases provided an additional frequency. Microscopically, in the dermis, there was a dense infiltrate of histiocytic cells mixed with numerous eosinophils. Histiocytes had folded nuclei and eosinophilic cytoplasm, and some kidney-shaped nuclei with prominent nucleoli. Mitotic figures were rare. These histiocytes were immunohistochemically positive for CD1a, and S-100. The main differential diagnosis includes juvenile xanthogranuloma, hemangioma, infantile fibrous hamartoma. The characteristics of routine histology and immunohistochemistry, such as S-100 and CD1a staining, can exclude those diseases [13].

There is no specific treatment for CSHLCH. The conduct recommended by the Histiocyte Society consists of awaiting spontaneous regression [14,15]. If the cutaneous lesions persist, topical nitrogen mustard or topical corticosteroids may be effective [16]. Most CSHLCH are limited to the skin, but there are reports of cutaneous lesions accompanied with ophthalmic and pulmonary involvement [17-19]. Since there are reports of recurrence, it needs long-term follow-up to detect possible systemic involvement [20,21].

Conclusion

Congenital Self-Healing Langerhans Cell Histiocytosis (CSHLCH) is a rare disorder. It is known that cutaneous lesions of CSHLCH may regress spontaneously. Spontaneous resolution of cutaneous lesions and lack of systemic involvement are essential for the diagnosis of CSHLCH. It needslong-term follow-up.

Disclosure of conflict of interest

None.

Abbreviations

HE

hematoxylin and eosin stain

CSHLCH

Congenital Self Healing Langerhans Cell Histiocytosis