Ⅰ. INTRODUCTION

Langerhans cell histiocytosis (LCH) is a rare disease originating from mononuclear histiocytes. Although its etiology is not yet fully defined, a prominent feature is the abnormal increase in histiocyte number. LCH is also known as Histiocytosis X, Hashimoto Pritzker syndrome, Langerhans cell granulomatosis, self-healing histiocytosis, type II histiocytosis, and nonlipid reticuloendotheliosis.¹

According to recent studies, LCH can be subcategorized as eosinophilic granuloma (limited to a single or multiple bones without visceral involvement), Hand-Schüller-Christian disease (chronic disseminated disease involving bone, skin, and viscera), and Letterer-Siwe disease (acute disseminated multi-system diseases that occur primarily in infants).²

This study presents a case of LCH in a 16-month-old girl. After performing a biopsy, the patient’s previous medical records were evaluated. The records described the presence of a yellowish plaque on her forehead since birth, a characteristic feature of LCH. Earlier knowledge of this medical history would have helped facilitate the diagnosis of LCH. This report aims to inform clinicians of the clinical and histopathological features of LCH in order to aid in the early diagnosis of this disease, which can occur in infancy.

Ⅱ. CASE REPORT

A 16-month-old girl was referred by a local medical clinic to Kyungpook National University Dental Hospital Oral and Maxillofacial Surgery department for prolonged swelling on the left buccal cheek area after being bumped by her grandfather. The oral examination revealed intraoral swelling and bleeding in the left buccal mucosa area (Fig. 1A). There was no limitation in mouth opening or abnormal jaw movements. PA view of the skull showed no fracture site or osteolytic lesions on the skull vault. Paranasal sinus computed tomography (PNS CT) with enhancement showed a 2.5-cm mass destroying the bone in the left mandibular body with a sclerotic margin. The radiological findings suggested a probable giant cell granuloma or LCH (Fig. 1B, C). Under chloral hydrate sedation, an incisional biopsy was performed on the lower left premolar buccal mucosa. Histopathology showed sheets of histiocytes dispersed with inflammatory cells, eosinophils, lymphocytes, and clusters of Langerhans cells resembling a granuloma. Immunohistochemical analysis showed that the specimen was positive for CD1a, CD68, and S100 and negative for CD34. Considering these findings, the final diagnosis was confirmed as LCH (Fig. 2A-F).

The patient was transferred to the pediatric oncology department of Kyungpook National University Hospital (KNUH) for chemotherapy. While transferring the patient, review of the patient’s past medical records at KNUH identified another characteristic of LCH: a walnut-sized yellowish plaque on the patient’s forehead present since birth. The patient was referred to the dermatology department for this symptom. The suggested diagnosis was nevus sebaceous, and a follow-up was performed in the dermatology department (Fig. 3A).

Imaging findings evaluated before chemotherapy did not reveal any LCH lesions involving other organs. A chemoport was inserted prior to the initiation of chemotherapy. The patient was given vinblastine 3 mg/week via intravenous injection and orally administered systemic prednisolone 12.5 mg/day for 25 weeks. The patient responded favorably to treatment, and at the 1-year follow-up, the PNS MRI reported that the enhancing mass on the left mandible had nearly disappeared (Fig. 3B, C). The patient visited the OMS department after two years of chemotherapy. No recurrence of LCH was observed on clinical radiological examination, and development of permanent teeth was good (Fig. 3D-F). The patient is being followed up every 6 months and there are no signs of recurrence in the lesion.

Ⅲ. DISCUSSION

Langerhans cells are derived from immature myeloid precursor cells in the bone marrow. Under normal conditions, these progenitor cells can differentiate into histiocytes, monocytes, and dendritic cell precursors.^3,4 LCH can occur both in children and adults. It is most frequently found between the ages of 1-4 years but can also occur in newborns, as well as in the 9th decade of life.⁵ The incidence is 4-5 per million children aged 0 to 15 years per year. The median age of diagnosis is 3.5 years, while the greatest incidence rate is observed before 1 year of age.5 The gender ratio is equal among all LCH subcategories.⁶

The clinical presentation of LCH is somewhat atypical but often manifests as skull and skin abnormalities.⁷ Although any organ or system can be affected by LCH, the skeleton (80%), skin (33%), and pituitary gland (25%) are most commonly involved.7 The most affected skeletal areas include the skull (27-43%), long bones of the upper extremities (14-15%), and jaws (7-10%).6 In the skull, the lesions present as round osteolytic areas in the radiographs.^2,6-9 Bone involvement is usually characterized by swelling and dull pain in the area, but sometimes patients express no symptoms.^6,10 When osteolysis occurs in the oral region, the mandibular molar area is most commonly affected and may lead to soft tissue swelling, excessive teeth mobility, and pathological mandibular bone fractures.^9,10 Cutaneous lesions are the second-most-common signs found in LCH.^6,7 Typical skin changes include seborrhoea-like dermatitis in the scalp area and dermatitis on the body, including skin erythema, inflammation, or the formation of yellow-brownish desquamating papulae.^2-4,6,8,10 In this patient, the radiographic examination showed no osteolysis on the skull, but the patient did have a medical history of a yellowish plaque on her forehead since birth. The patient also had gingival swelling and excessive tooth mobility, which are characteristic features of LCH.

Langerhans cells are differentiated from hematopoietic myeloid stem cells in the bone marrow, which are marked as CD34-positive.^7,11 A typical histopathological feature of LCH is the presence of lesional histiocytes with a Langerhans cell phenotype, accompanied by variable numbers of macrophages, T-lymphocytes, eosinophils, and multinucleated giant cells.^1,3 Langerhans cell nuclei show elaborate angular folds as well as a coffee-bean groove shape.11 In 1987, the Histiocyte Society working group defined the LCH diagnostic criteria as the presence of Birbeck granules by electron microscopy or the presence of CD1a (OKT6) by immunohistochemistry. CD1a is a well-known marker of epidermal Langerhans cells.¹¹ Immunohistochemically, the Birbeck granules in the Langerhans cells can be easily detected by Langerin (CD207) staining, a novel C-type lectin. Langerin induces the formation of Birbeck granules, which are specifically localized to the membrane surface and cytoplasm of Langerhans cells.¹² CD1a and/or Langerin positivity in the lesion is considered the gold standard for diagnosing LCH.^11-13

As the pathogenesis and etiology of LCH are not fully understand, and because treatment depends on the extent and severity of disease, the treatment of LCH remains controversial. The prognosis of LCH depends on the involved organs such as the liver, lung, spleen, and other hematopoietic systems.^3,7,14,15 The treatments to be considered should include chemotherapy, radiotherapy, and systemic corticosteroid administration.^4,14 If the lesion is restricted to a single bone, follow-up, surgical curettage, intralesional steroid injections, and local radiation therapy can be utilized.¹⁴ Biopsy of the lesion can also encourage spontaneous healing without curettage.¹⁵

LCH that occurs in the oral and maxillofacial area usually requires long-term treatment, follow-up monitoring of the patient’s dental development is important, as several studies have reported developmental dental disturbances after chemotherapy in children.^16,17

Ⅳ. CONCLUSION

In this case, an infant presented with long-term mandibular swelling. In addition to osteolytic lesions on the mandible, the patient had a walnut-sized yellowish plaque on the forehead from birth, which is the main clinical and radiological finding that can occur in LCH patients. A thorough understanding of the clinical, radiological, and histological characteristics of LCH manifesting may help clinicians in the early diagnosis of LCH. Additionally, dental follow- up after chemotherapy for LCH in pediatric patients is important to monitor tooth development and administer appropriate treatments.