Original Article Congenital Self-Healing Langerhans Cell Histiocytosis: Clinical and Pathological Characteristics

Int J Clin Exp Pathol 2019;12(6):2275-2278 www.ijcep.com /ISSN:1936-2625/IJCEP0090794

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

Yu Pan1, Xianfeng Zeng2, Juan Ge1, Xiaoyan Liu1, Ying Chen1, Donghua Zhou1

1Department of Pathology, Southern Medical University Affiliated Maternal and Child Health Hospital of Foshan, Foshan 528000, Guangdong, P. R. China; 2Department of Neurology, The First People’s Hospital of Foshan, Fos- han, Guangdong, P. R. China Received January 3, 2019; Accepted March 22, 2019; Epub June 1, 2019; Published June 15, 2019

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.

Keywords: Congenital self-healing, langerhans cell histiocytosis, prognosis, CD1a, S-100

Introduction Materials and methods

Langerhans cell histiocytosis (LCH) is a disor- All the resected specimens were fixed in 10% der with a broad spectrum of forms with diverse neutral formalin, conventional dehydrated, em- clinical presentations, ranging from self-healing bedded in paraffin, made into 4 µm paraffin, to systematic forms [1]. Depending on clinical and eventually HE (hematoxylin and eosin) presentations, it is further distinguished into staining. including Letterer-Siwe disease, Hand-Schüller- Christian disease, eosinophilic granuloma, and Paraffin sections were stained by immunohisto- a congenital self-healing form [2]. chemical study carried out according to the manufacturer’s protocols. The following prima- Congenital Self-Healing Langerhans Cell His- ry antibodies were used: CD1a, S-100, CD68, tiocytosis (CSHLCH) also called Congenital se- and Ki67 which all from DAKO (Glostrup, Den- lf-healing reticulohistiocytosis or Hashimoto- mark). Immunoreactivity was detected using Pritzker disease, is rare, characterized by cuta- the Dako labeled streptavidin-biotin detection neous lesions at birth or in the neonatal period, kit according to the manufacturer’s recom- and absence of systemic lesions. It is known mended procedures. that the lesions of CSHLCH may regress spontaneously within weeks to months [3, 4]. Result

Here, we reported seven cases of Congenital In searches of the archival files spanning long self-healing Langerhans cell histiocytosis at periods in the Foshan Women and Children birth or in the neonatal period, and the clinico- Hospital, Foshan, People’s Republic of China, pathological characteristics of it are listed seven cases of CSHLCH could be recruited. based on the literature. Birth weight, length and Apgar score of all Congenital self-healing langerhans cell histiocytosis

made. No recurrence had been observed.

Discussion

Congenital Self Healing Lan- gerhans Cell Histiocytosis (CS- HLCH) 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 Figure 1. One of our 7 cases of CSHLCH. A: The lesion is located in the der- of cutaneous lesions and lack mis. H&E × 40. B: It shows a dense infiltrate of histiocytic cells mixed with of systemic involvement are eosinophils, Histiocytes had folded nuclei and eosinophilic cytoplasm, and essential for the diagnosis of some kidney-shaped nuclei. H&E × 400. C: Immunohistochemical staining CSHLCH [6-8]. The diagnosis for S-100 is positive. H&E × 200. D: Immunohistochemical staining for CD1a is confirmed by immunohisto- is positive. H&E × 200. chemical positivity with S-100 and CD1a. Electron microsco- infants were within normal range. Physical py will reveal the characteristic Birbeck gran- examination revealed no hepatosplenomegaly ules [9], but is usually not needed [10]. Exact or lymphadenopathy. Skull, chest and long etiology of CSHLCH is unclear. Strenger V. et al. bone X-rays and abdominal ultrasound were [5] showed that Langerhans cell proliferation normal. A complete blood count creatinine, bili- may be induced either by viral infection or rubin, liver and kidney function tests, urine and defective immunity [11]. stool examination, viral serologies such as TORCH, VDRL, and HIV were negative. In our 7 cases of CSHLCH, 28.6% (2/7) of the cutaneous lesions were multiple, 71.4% (5/7) Skin biopsy was performed and the histologic were solitary, indicated that CSHLCH had a examination of the skin section, routinely classical clinical picture: it is almost a sing- stained with hematoxylin-eosin. All the resect- le cutaneous lesion. The lesions measured ed specimens were fixed in 10% neutral forma- 0.5~4.5 cm, and it seemed to mostly occur in lin, conventional dehydrated, embedded in par- males. All of the lesions regressed within one to affin, made into 4 μm paraffin, and eventually four months, a mean period of 2.5 months and H&E (hematoxylin and eosin) staining. Mic- excluding the cases of loss to follow-up, no roscopically, in the dermis, a dense infiltrate of recurrences were observed. Since the lesions histiocytic cells mixed with numerous eosino- regress spontaneously, clinical findings are no- phils. Histiocytes had folded nuclei and eosino- nspecific and it can be supposed that some philic cytoplasm, and some kidney-shaped cases were not diagnosed, suggesting that the nuclei with prominent nucleoli, mitotic figures morbidity of CSHLCH was underestimated [12]. were rare (Figure 1A and 1B). These histiocytes Our cases provided an additional frequency. were immunohistochemically positive for CD1a, Microscopically, in the dermis, there was a S-100 (Figure 1C and 1D). dense infiltrate of histiocytic cells mixed with numerous eosinophils. Histiocytes had folded The clinicopathological characteristics, clini- nuclei and eosinophilic cytoplasm, and some cal course and outcome of our 7 cases of kidney-shaped nuclei with prominent nucleoli. Congenital Self-Healing Langerhans Cell His- Mitotic figures were rare. These histiocytes tiocytosis are presented in Table 1. Based up- were immunohistochemically positive for CD1a, on this, the final diagnosis of CSHLCH was and S-100. The main differential diagnosis

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Table 1. Summary of our 7 cases of CSHLCH Age at onset Age at Systemic No. Sex Site Size (cm) Clinical course and outcome of rash diagnosis involvement 1 2 w 1-year-old M On the skin of Diameter 1.0 None A solitary red-brown papule with crust; two back months later, the skin lesion resolved spontaneously; lost to follow-up 2 At birth 8 d M Multiple on skin Diameter 0.5 to 1.0 None Multiple red papules, partially blistered; three of the entire body months later, the skin lesion resolved spontaneously; lost to follow-up 3 1 d 5 d M On Left upper Diameter 1.0 None A solitary skin colored papule with crust; one arm 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 Diameter 1.0 to 2.2 None Multiple black papules with crust; three months of the entire body 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. includes juvenile xanthogranuloma, hemangio- Disclosure of conflict of interest ma, infantile fibrous hamartoma. The characteristics of routine histology and immunohisto- None. chemistry, such as S-100 and CD1a staining, can exclude those diseases [13]. Abbreviations

There is no specific treatment for CSHLCH. The HE, hematoxylin and eosin stain; CSHLCH, Co- conduct recommended by the Histiocyte So- ngenital Self Healing Langerhans Cell Histio- ciety consists of awaiting spontaneous regres- cytosis. sion [14, 15]. If the cutaneous lesions persist, topical nitrogen mustard or topical corticoste- Address correspondence to: Dr. Donghua Zhou, roids may be effective [16]. Most CSHLCH are Department of Pathology, Southern Medical Uni- limited to the skin, but there are reports of versity Affiliated Maternal and Child Health Hospital cutaneous lesions accompanied with ophthal- of Foshan, 11 Renminxi Road, Chancheng District, mic and pulmonary involvement [17-19]. Since Foshan 528000, Guangdong, P. R. China. E-mail: there are reports of recurrence, it needs long- [email protected] term follow-up to detect possible systemic involvement [20, 21]. References

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