Gastric Langerhans Cell Histiocytosis is Easily Ignored or Misdiagnosed in Stomach Biopsy and Indicates a Poor Outcome in Multisystem Langerhans Cell Histiocytosis

Abstract

Langerhans cell histiocytosis (LCH) is a histiocytic neoplasm that affects almost every organ of the human body. Digestive system involvement is uncommon and gastric involvement is extremely rare. It is difficult to diagnose gastric LCH during stomach biopsy because of its rarity. The prognosis of LCH with gastric involvement is also unclear due to limited evidence from large-scale studies. Here, we present five new specimens of gastric LCH. The patients initially presented with digestive symptoms. Similar pathological features, including histiocyte-like tumor cells and an inflammatory background, were observed in our five patients, which were also similar to previously reported specimens. The diagnosis of LCH was confirmed using immunohistochemistry and molecular analysis. Helicobacter pylori infection was observed in one patient. Two patients exhibited multiorgan or multisystem disease, including infiltration into the ileocecal junction, skin, bone, tonsil, and nasopharynx synchronously or metachronously. BRAF p.V600E mutation was identified in four patients. In summary, gastric involvement is associated with favorable prognosis in patients with single-system LCH. However, gastric LCH may serve as an unfavorable prognostic indicator in patients with multisystem LCH and risk organ involvement. These patients can initially present with the digestive symptoms. In such specimens, gastric LCH is easily ignored or misdiagnosed as signet-ring cell carcinoma, reactive lymphoid hyperplasia, or other hematolymphoid tumors. Pathologists should be on guard when encountering similar lesions during stomach biopsy and immunohistochemistry is recommended.