Primary Langerhans Cell Histiocytosis of the Maxilla: Case Report

Abstract

A 5-year-old boy presented with a two-month history of right facial swelling that persisted after resolution of an initial febrile illness, with no response to anti-inflammatory therapy. Contrast-enhanced MRI revealed expansive bone destruction of the anterior wall of the right maxillary sinus, cortical discontinuity, and a soft-tissue mass that appeared hypointense on T1WI, hyperintense on T2WI, and exhibited ring-like enhancement. The lesion was surgically resected via a Colles approach with maxillary sinus fenestration. Histopathology confirmed Langerhans cell histiocytosis, and immunohistochemistry was positive for CD1a, S-100, Langerin, and CD68, with a Ki-67 proliferation index of 15%; special stains for acid-fast bacilli, PAS, and silver were negative. Postoperative chemotherapy with vincristine or vindesine was administered. This case underscores the importance of considering Langerhans cell histiocytosis in pediatric patients with refractory facial swelling and destructive bone lesions, and highlights the value of combined surgical and chemotherapeutic management.

Introduction

Langerhans cell histiocytosis (LCH) is a rare disorder characterized by the abnormal clonal proliferation and infiltration of immature bone marrow–derived dendritic cells and reticular cells. ¹ Because these proliferating cells share similar morphological features with normal mucosal and cutaneous Langerhans cells and express the same antigens—CD1a, S-100, and CD207—the condition is uniformly classified as LCH. Its underlying pathogenesis remains unclear. ² Approximately 60% of patients present with single or multiple bone lesions, and the incidence is higher in children than in adults. ³ According to the Histiocyte Society classification system, LCH is categorized as either single-system LCH (SS-LCH), involving one organ or system (single site or multiple sites within the same system), or multisystem LCH (MS-LCH), involving two or more organ systems. ⁴ Here, we describe a case of LCH initially presenting as a maxillary bone lesion, treated in our department and followed for five years. Our goal is to improve clinical recognition of this condition and help reduce diagnostic errors.

Case Presentation

The patient was a 5-year-old boy admitted to the Department of Otorhinolaryngology–Head and Neck Surgery at Linyi People’s Hospital on December 8, 2020, with a two-month history of right facial swelling. Two months earlier, he had developed a fever of unknown origin accompanied by cough. His temperature returned to normal after anti-inflammatory treatment, but his parents subsequently observed progressive swelling on the right side of his face. The swelling was not associated with noticeable tenderness, skin ulceration, purulent or bloody nasal discharge, nasal obstruction, facial numbness, or dental pain, and it did not respond to anti-inflammatory therapy. Throughout the course of illness, the child remained in good spirits, slept well, and experienced no significant weight changes. He had been previously healthy and denied any family history of genetic disorders.

Physical Examination

Mild swelling was noted on the right side of the face, with indistinct borders, soft consistency, and no significant tenderness. Both nasal cavities were patent, with no visible masses in the middle nasal meatus. Routine blood tests and chest radiography showed no significant abnormalities.

Laboratory Tests

White blood cell count: 6.73×109/L; Red blood cell count: 4.41×1012/L; Hemoglobin: 118g/L (↓); Platelet count: 471×109/L (↑); Fibrinogen: 4.12g/L (↑); Cardiac enzyme spectrum: α-hydroxybutyrate dehydrogenase: 186U/L (↑); Other tests were normal; Liver function, kidney function, electrolytes, urine and stool routine, and other coagulation tests were normal; Immunoglobulins (A, G, M), thyroid function, growth hormone, and PRO-BNP results were normal.

Ultrasound and Imaging Examinations

Preoperative superficial facial ultrasonography revealed hypoechoic nodules in the corresponding region of the right face. Maxillofacial CT demonstrated a soft-tissue mass adjacent to the anterior wall of the right maxillary sinus, containing patchy high-density areas and associated with moth-eaten bone destruction of the surrounding structures, along with mucosal thickening of the right maxillary sinus. Contrast-enhanced MRI of the paranasal sinuses showed expansive bone destruction of the anterior wall of the right maxillary sinus and interruption of the lateral cortical bone. A soft-tissue mass was present, demonstrating low signal intensity on T1-weighted imaging and high signal intensity on T2-weighted imaging, with ring-like enhancement after contrast administration. Mucosal thickening of the right maxillary sinus was also noted, while the remaining sinus cavities appeared unremarkable. These findings suggested a bone-origin lesion with associated infection involving the anterior wall of the right maxillary sinus (Figure 1).

Figure 1.

Preoperative CT manifestations of the patient: Preoperative CT and MRI showed a mass on the anterior wall of the right maxillary sinus, with bone destruction of the anterior wall of the maxillary sinus. (A): Preoperative axial CT image (soft tissue window); (B): Preoperative axial CT image (bone window); (C): Preoperative MRI coronal image; (D): Preoperative MRI sagittal image (T1W1)

Pathological Examination

Intraoperative frozen-section analysis revealed numerous mononuclear and multinucleated giant cells within the sampled tissue, accompanied by hemorrhage and extensive necrosis. The findings suggested a lesion potentially originating from bone tissue or a soft-tissue tumor. Routine postoperative histopathological examination demonstrated proliferative histiocytes with prominent eosinophilic infiltration. The final pathological diagnosis was Langerhans cell histiocytosis of the right facial region. Immunohistochemistry: CD1a (+), S-100 (+), Langerin (+), CK (–), CD68 (+), Ki-67/MIB-1 (15%), CD3 (T cells +), CD20 (B cells +), CD30 (–). Special stains: Acid-fast stain (–), PAS stain (–), and silver stain (–) (Figure 2).

Figure 2.

Pathological examination results: Patchy distribution of monocytes, accompanied by lymphocyte infiltration, and Langerhans cells appear brown. (A): HE × 100; (B): HE × 400; (C): CD1a cell positive; Immunohistochemical staining × 400; (D): S-100 cell positive; Immunohistochemical staining × 40

Diagnosis and Differential Diagnosis

The patient was male, and imaging revealed an orbital space-occupying lesion involving the maxilla.Histopathological findings,together with immunohistochemical results—CD1a (+), S-100 (+), Langerin (+), CD68 (+), and Ki-67/MIB-1 (15%)—were consistent with Langerhans cell histiocytosis. According to the diagnostic criteria outlined in the Guidelines for the Evaluation and Treatment of Langerhans Cell Histiocytosis (Histiocyte Society, 2009), ⁴ the clinical, radiologic, and pathological features in this case met the requirements for an unequivocal diagnosis of LCH.

Treatment

After admission, the patient underwent a series of evaluations to exclude surgical contraindications. On the third hospital day, he underwent right Kocher orbital floor tumor resection, maxillary sinus fenestration, and endoscopic maxillary sinusotomy under general anesthesia. A labiogingival sulcus incision was made, and the subcutaneous tissues were dissected. The tumor appeared gray-yellow and granular, adhered closely to the underlying bone, was soft in consistency, and lacked a capsule (Figure 3). Intraoperative frozen-section analysis revealed numerous mononuclear and multinucleated giant cells, accompanied by hemorrhage and extensive necrosis, suggesting a lesion potentially originating from bone tissue or a soft-tissue tumor. Surgical exploration showed that the tumor extended superiorly to the infraorbital foramen, laterally toward the buccal fat pad, inferiorly to the gingival margin, and medially toward the frontal process of the maxilla. The lateral segment of the maxillary bone was resected. Following removal of the lateral maxillary lesion, partial destruction of the anterior wall of the maxillary sinus with tumor invasion was observed. The tumor was excised completely, the affected bone was burred down, and the surgical field was expanded. The maxillary sinus mucosa appeared edematous but showed no evidence of tumor infiltration. Endoscopic maxillary sinusotomy was then performed, and a piece of Nasacort-soaked cotton was placed within the sinus. The estimated intraoperative blood loss was approximately 50 ml. Postoperatively, piperacillin–tazobactam (2.25 g) was administered intravenously for 5 days for infection prophylaxis. Following discharge, the patient received chemotherapy in the pediatric hematology department. Each chemotherapy cycle lasted 20 days, and treatment was completed in February 2022. In total, 24 cycles were administered, including five doses of vincristine (1 mg each) and nineteen doses of vincristine (2.19 mg each).

Figure 3.

Intraoperative endoscopic view (A): The tumor is located at the anterior wall of the maxillary sinus, and the bone of the anterior wall of the maxillary sinus is partially damaged; (B): After the tumor and the partially damaged bone of the anterior wall of the maxillary sinus are removed, the changes occur

Treatment Outcome, Follow-Up, and Outcome

The patient was followed up continuously until August 2025. No facial deformity or depression was observed, and the clinical symptoms had markedly improved. CT imaging of the paranasal sinuses revealed no evidence of lesion recurrence. The previously eroded and surgically resected bone had gradually remodeled and healed. Overall, the patient achieved complete clinical remission (Figure 4).

Figure 4.

Postoperative CT manifestations of the patient (A): Horizontal CT image at 1 month after surgery; (B): Horizontal CT image at 8 months after surgery; (C): Horizontal CT image at 14 months after surgery;(D): Horizontal CT image at 30 months after surgery;(E): Horizontal CT image at 42 months after surgery; (F): Horizontal CT image at 54 months after surgery

Discussion

Langerhans cell histiocytosis (LCH) is a myeloid-derived inflammatory disorder characterized by abnormal proliferation of CD1a- and Langerin (CD207)-positive cells, forming granulomatous lesions accompanied by local inflammatory cell infiltration. ⁵ Recent advances in understanding LCH pathogenesis have identified BRAF V600E mutations in approximately 50-60% of pediatric LCH cases, with additional MAPK pathway alterations (MAP2K1, ARAF) in BRAF-wildtype tumors. ⁶ These findings support the neoplastic nature of LCH and have therapeutic implications. Vemurafenib and other BRAF inhibitors have shown promising results in refractory MS-LCH, though their role in SS-LCH remains limited. ⁷

Studies indicate that over 50% of reported cases occur in patients younger than 10 years, with an estimated incidence of approximately 5 per 100,000 in children. ⁸ The pathogenesis of LCH remains unclear, with current hypotheses focusing on either inflammatory responses or neoplastic proliferation.In the present case, the patient was diagnosed with SS-LCH with unifocal bone involvement based on comprehensive evaluation.^9,10 Prior to admission, chest radiography and abdominal ultrasonography showed no abnormalities. During the 5-year follow-up period, no other organ involvement was identified, confirming the single-system classification. SS-LCH typically has a favorable prognosis compared to MS-LCH, which is consistent with the excellent outcome observed in this patient. ¹

The clinical manifestations of LCH are highly variable and depend on the affected site and the extent of involvement. Commonly affected regions include the bones, skin, and pituitary gland, as well as the lungs, lymph nodes, and central nervous system. ¹¹ Among patients with skeletal involvement, 60%–70% have lesions in the head and neck region. Radiographically, X-rays often reveal irregular osteolytic lesions, while cranial CT scans demonstrate circular or oval “worm-eaten” defects. On MRI, affected skull lesions typically show isointense or slightly hypointense signals on T1-weighted imaging and hyperintense signals on T2-weighted imaging, with moderate homogeneous or heterogeneous enhancement after contrast administration. ¹² In the present case, CT imaging revealed worm-eaten defects in the maxilla, extending into the subcutaneous tissues. Contrast-enhanced MRI demonstrated a lesion in the right maxillary region with low signal intensity on T1WI and high signal intensity on T2WI, showing marked enhancement on post-contrast imaging, consistent with previously reported imaging characteristics of LCH.

The histopathological diagnosis of LCH is primarily based on morphological assessment and immunohistochemistry to identify characteristic Langerhans cell infiltration. Langerhans cells are large, elongated cells with long cytoplasmic dendritic processes and contain distinctive Birbeck granules. Microscopically, these cells are often diffusely distributed and may present in reticular, fascicular, or patchy patterns. ¹³ Pathological examination remains the most reliable method for confirming LCH. Key immunohistochemical markers for diagnosing LCH include CD207, CD1a, S-100, and CD68/PGM-1. CD207 is a specific lectin expressed by Langerhans cells, while CD1a is a membrane glycoprotein; co-expression of these markers is the most common manifestation of clonal proliferation and is regarded as the “gold standard” for diagnosis according to the latest pediatric LCH guidelines. ¹ Notably, Ki-67 proliferation index has been proposed as a potential prognostic marker in recent studies, with higher indices correlating with more aggressive disease. ¹⁴ In this case, immunohistochemistry revealed S-100 (+), CD207 (+), CD1a (+), vimentin (+), CD68 (+), and Ki-67/MIB-1 (15%), fulfilling the diagnostic criteria for LCH. The 15% Ki-67 index supported the decision for adjuvant chemotherapy.

Currently, no universally accepted standard treatment exists for LCH. Management is guided by the lesion’s extent and severity, and may include surgical resection, radiotherapy, chemotherapy, or targeted therapy. For single-system LCH (SS-LCH), surgery is generally the first-line treatment. In cases where complete surgical excision is not feasible, adjuvant radiotherapy or chemotherapy may be indicated. In this case, the patient underwent surgical resection with preservation of facial appearance. Although the tumor was completely removed under microscopic guidance, the proximity to critical anatomical structures precluded a truly complete excision. Consequently, adjuvant chemotherapy was administered in the pediatric hematology department. After five years of follow-up, the child remains in good health, with stable facial appearance and no nasal or other abnormal symptoms.

LCH is a rare clinical disorder that often presents with an insidious onset in children, lacking specific symptoms and exhibiting complex, variable manifestations. Long-term outcomes in pediatric SS-LCH are generally favorable, with recent large cohort studies reporting >90% survival rates. ¹⁵ However, recurrence rates of 10-20% have been reported, particularly in patients with incomplete surgical resection or multifocal disease^[16-17]. Our 5-year follow-up with documented bone remodeling supports the excellent prognosis of appropriately managed maxillary SS-LCH. Given the recurrent nature of pediatric LCH and the unpredictable disease course, prompt biopsy is essential to establish a definitive diagnosis and guide individualized treatment. In conclusion, early detection and timely, appropriate management are crucial for improving patient outcomes in LCH.