[Langerhans cell histiocytosis of gastrointestinal tract: a clinicopathological analysis of twelve cases].

Objective

To investigate the clinicopathological, immunophenotypic, and molecular characteristics of gastrointestinal Langerhans cell histiocytosis (LCH).

Methods

A total of 12 patients diagnosed with gastrointestinal LCH from July 2021 to September 2025 were retrieved from the pathological archive database of the First Affiliated Hospital, Zhejiang University School of Medicine, among whom 10 cases were external consultation specimens. Clinical data of these patients were collected, lesion locations, endoscopic findings, histopathologic features, treatment strategies, and follow-up outcomes were systematically analyzed for all cases. Immunohistochemical staining was performed to detect the expression of CD1a, Langerin, S-100, cyclin D1, BRAF V600E and so on, followed by a comprehensive review of relevant literatures.

Results

A total of 12 patients were enrolled, including 9 males and 3 females, with an age of 34.5 (26.0, 51.0) years. Lesions predominantly involved the upper gastrointestinal tract (11 out of 12 cases, gastric involvement observed in 10 cases). Endoscopically, 6 of 12 cases presented as polypoid lesions, 3 of 12 cases were flat/depressed lesions and no obvious mucosal lesions were identified in the remaining 3 patients. The key histological findings were sheets of tumor cells displaying reniform or coffee bean-shaped nuclei, and the adjacent stroma was associated with mixed inflammatory cell infiltration, with eosinophils as a prominent constituent. Immunophenotypically, all 12 cases were positive for CD1a, Langerin and S-100; cyclin D1 was positive in 8 out of 10 cases, and BRAF V600E was positive in 6 out of 10 cases. One case showed BRAF V600E point mutation by ARMS-PCR. All patients were diagnosed via biopsy and subsequently received local treatment or regular follow-up observation. The follow-up duration ranged from 3 to 54 months. All patients remained disease-free during follow-up, except for one case that developed multifocal lesions within the same system.

Conclusions

Gastrointestinal LCH follows an indolent clinical course with a favorable prognosis. Characteristic histopathologic features include tumor cells with reniform or coffee bean-shaped nuclei and stromal infiltration by eosinophils. The triple immunohistochemistry panel consisting of CD1a, Langerin and S-100 serves as the cornerstone for definitive diagnosis, whereas combined assessment of cyclin D1 and BRAF V600E help confirm the neoplastic nature of the lesion.