INTRODUCTION
Langerhans cell histiocytosis (LCH), characterized by abnormal proliferation of mononuclear phagocytic cells (Langerin-positive histiocytes), is rare [1]. LCH may originate in any organ and shows a varied clinical presentation ranging from single indolent lesions to aggressive multisystem disease [2]. Although gastric involvement is occasionally observed in pediatric patients with systemic LCH [3,4], localized gastric LCH without systemic involvement is extremely rare in adults. Owing to its rarity, the clinical characteristics and outcomes of localized gastric LCH remain unclear. We present a case series of seven patients diagnosed with localized gastric LCH at a single tertiary hospital.
METHODS
Patients
We retrospectively reviewed the medical records of seven patients who underwent stomach biopsies via esophagogastroduodenoscopy (EGD) at our hospital between September 1997 and December 2023. All patients had histopathologically confirmed gastric LCH, and no patient showed multisystemic involvement. Clinicopathological data were obtained via retrospective review of medical records using the intranet resources of Samsung Medical Center. The follow-up period was calculated from the date of diagnosis to the date of the last followup EGD. Overall survival time was calculated from the date of diagnosis to the date of all-cause death or cutoff date (December 29, 2023). Survival status was confirmed with the National Health Insurance System database using the cutoff date. The study protocol was approved by the Institutional Review Board of Samsung Medical Center (approval number: 2024-03-087-001). This study was performed in accordance with the Declaration of Helsinki guidelines. Written informed consent was waived by the IRB due to the retrospective nature of the study.
Histopathological evaluation
Specimens were fixed in 10% formalin, embedded in paraffin blocks, and stained using hematoxylin and eosin. LCH was diagnosed in specimens that showed clusters of histiocytic cells with pale cytoplasm and prominent intranuclear grooves on microscopic examination and cells with immunoreactivity for both S-100 and CD1a on immunohistochemical analysis (except in one case of an outside referral in which S-100 staining was infeasible owing to unavailability of an unstained specimen).
RESULTS
Clinicopathological characteristics of patients with localized gastric LCH
Table 1 summarizes the clinicopathological characteristics of patients with localized gastric LCH. All lesions were detected in the antrum or low-body, without any lesions in the proximal stomach. Endoscopically, the lesions presented as an erosion or a raised erosion in all patients (Fig. 1). All lesions measured ≤0.5 cm. Immunohistochemical analysis showed cells with immunopositivity for S-100 and CD1a in all patients, except for the patient described in Case #5, who underwent only CD1a testing. Among the four patients who underwent pre-treatment positron emission tomography-computed tomography (PETCT), no patient showed high fluorodeoxyglucose (FDG) uptake.
Treatment outcomes in patients with localized gastric LCH
Table 2 summarizes the treatment outcomes in patients with localized gastric LCH. Endoscopic resection was performed in only one patient, and the others underwent only routine surveillance. The endoscopically resected specimen tested negative for a tumor. The first follow-up EGD was performed 4–6 months after the initial diagnosis in 83.0% (5/6) of patients. Among the six patients who underwent follow-up, two (33.3%) showed metachronous recurrence at a location distinct from the initial site. Endoscopically, recurrent lesions appeared as erosions. Five of six patients underwent >3-year follow-up (two patients underwent follow-up for up to 109 months). The final EGD showed no evidence of disease in any patient, including in those with recurrence. We observed no deaths during follow-up; however, survival data were unavailable in one patient who emigrated.
Detailed case description
Case 1
A 30-year-old man was referred to our hospital for further evaluation of atypical cells with histiocytic differentiation observed during EGD performed for evaluation of dyspepsia symptoms. The patient had an unremarkable medical history and denied alcohol or tobacco use. The initial EGD performed at another hospital showed an erosion (0.3 cm) involving the posterior wall (PW)-greater curvature (GC) side of the antrum (Fig. 1A). Microscopic examination of the specimen revealed clusters of histiocytic cells with pale cytoplasm and prominent intranuclear grooves in the lamina propria, interspersed with lymphocytes and eosinophils (Fig. 2A). Immunohistochemical analysis revealed cells with strong immunoreactivity for both S-100 (Fig. 2B) and CD1a (Fig. 2C). CT and PET-CT did not show any evidence of multisystem involvement; therefore, the patient was diagnosed with localized gastric LCH. The 6-month follow-up EGD showed complete disappearance of the erosion, and follow-up biopsy was consistent with chronic gastritis. However, follow-up EGD performed thereafter showed recurrent erosion in the GC side of low-body and biopsy findings were consistent with gastric LCH. The 12-month followup EGD showed spontaneous and complete disappearance of this recurrent lesion, and the patient remained in remission during the 52-month follow-up.
Case 2
A previously healthy 33-year-old woman underwent EGD at a local clinic for evaluation of epigastric soreness. The patient denied any alcohol or tobacco use. EGD revealed an erosion (0.3 cm) in the GC side of low-body (Fig. 1B), and biopsy findings were consistent with gastric LCH. The 4-month followup EGD showed spontaneous disappearance of the lesion, and no recurrence was observed at the 43-month follow-up.
Case 3
A 35-year-old woman with an unremarkable medical history was referred to our hospital for evaluation of abnormalities observed during EGD and abdominopelvic (AP) CT performed for evaluation of abdominal pain, fever, and chills. APCT revealed mesenteric lymphadenitis. EGD showed an erosion (0.3 cm) in the anterior wall (AW) of the antrum (Fig. 1C), and biopsy findings were consistent with LCH. The patient was lost to follow-up owing to pregnancy; however, she has survived for >5 years (cutoff date: December 2023) based on data obtained from the National Insurance System.
Case 4
A 38-year-old man with a history of asthma underwent EGD during routine medical evaluation. The patient had quit smoking 5 years previously and admitted to a 20-year history of alcohol consumption once a month. EGD showed a raised erosion (0.5 cm) in the PW of the antrum (Fig. 1D), and biopsy findings were consistent with LCH. Endoscopic mucosal resection (EMR) with precutting was performed within 2 weeks; the resected specimen showed no residual tumor. PET-CT performed 9 days after EMR showed no evidence of distant metastases. The first follow-up EGD one year after EMR showed a clean scar without recurrence. However, the follow-up EGD performed 18 months after EMR showed an erosion in the low-body GC, and biopsy findings were consistent with LCH. The 6-month follow-up EGD revealed LCH lesions at another location (GC side of distal antrum), and the one-year followup EGD revealed LCH lesions at the AW of the angle. EGDs performed thereafter continued to show multifocal erosions; however, biopsies showed negative findings for LCH. The patient remained symptom-free in an overall good condition at the 72-month follow-up.
Case 5
A previously healthy 44-year-old current smoker with a 20-year history of alcohol consumption underwent regular surveillance EGD for an esophageal subepithelial tumor. EGD showed a raised erosion (0.5 cm) at the AW-lesser curvature (AW-LC) side of low body (Fig. 1E). Biopsy findings were consistent with LCH, and PET-CT did not show any signs of systemic involvement. Follow-up EGD performed 4 months later showed spontaneous disappearance of the lesion, and he showed no evidence of LCH at the 109-month follow-up.
Case 6
A 50-year-old woman with an unremarkable medical history was referred to our hospital for evaluation of an erosion (0.5 cm) in the AW-LC side of low-body (Fig. 1F) detected on EGD performed during routine medical examination. Biopsy findings were consistent with LCH. The patient denied a history of smoking or alcohol consumption. CT and PET-CT revealed no abnormalities. The 6-month follow-up EGD showed spontaneous disappearance of the lesion. The patient was lost to follow-up thereafter; however, she has survived for >10 years (cutoff date: December 2023) based on data from the National Insurance System.
Case 7
A 59-year-old man with a history of surgery for prostate cancer 2 years prior to presentation underwent EGD during routine medical examination. He denied smoking but had a 30-year history of alcohol consumption. EGD showed a raised erosion (0.5 cm) at the AW-LC side of low-body (Fig. 1G), and biopsy findings were consistent with LCH. CT and PET-CT showed no abnormalities. The 4-month follow-up EGD revealed only a whitish scar at the site of the lesion. The patient was diseasefree at the time of the 109-month follow-up.
DISCUSSION
LCH, a rare idiopathic disease characterized by the abnormal proliferation of Langerhans cells, may involve a single or multiple organs [1]. Gastrointestinal involvement is usually observed at initial presentation as a component of multisystemic disease in 2.0%–10.0% of pediatric patients with multisystemic LCH [3,5]. Studies have reported an association between LCH and clinical symptoms, such as bloody diarrhea and malabsorption, with an unfavorable prognosis in pediatric patients [5,6]. In contrast, localized gastrointestinal LCH is reportedly asymptomatic in adults. However, owing to its rarity, the clinicopathological characteristics and outcomes of localized gastric LCH remain unclear. To date, only 11 case reports in the published English or Korean literature have discussed this condition (Table 3). To our knowledge, this is the first and largest case series that describes localized gastric LCH in adults, with a sufficiently long follow-up duration.
In this study, we observed distinctive characteristics of gastric LCH. Endoscopically, gastric LCH presented as a small (<0.5 cm) or raised erosion in the low body or antrum (Fig. 1); notably, the proximal stomach was spared even in cases of recurrence. Previous studies (Table 3) have reported that endoscopically LCH presented as slightly elevated lesions in 54.5% (6/11), erosions in 18.2% (2/11), polyps in 18.2% (2/11), and masslike lesions in 9.1% (1/11) of patients. Histopathologically, a gastric erosion indicates focally enhanced mucosal inflammation [7], and elevated or polypoid lesions may indicate locally aggregated tumor cells [8]. Therefore, the endoscopic morphology of erosions or slight elevation of lesions may be attributable to the histopathology of gastric LCH, which consists of clonal expansion of Langerhans cells interspersed with other inflammatory cells, such as eosinophils and lymphocytes [4,9].
Owing to its extreme rarity, the necessity or extent of staging workup in patients with gastric LCH remains unclear. In the present study, no patient who underwent pre-treatment PETCT showed high FDG uptake in the biopsy-proven affected areas of the stomach. Therefore, in our opinion, PET-CT has a limited diagnostic role in patients with gastric LCH. It is important to determine lesion distribution (localized vs. multisystem LCH) to ensure selection of an appropriate treatment strategy [10]. Reportedly, bones (39.0%), lungs (32.0%), and skin (15.0%) are the most common sites of involvement in adults with LCH [11]. Therefore, imaging modalities that can accurately evaluate the bones, lungs, and skin would be useful for staging workup in patients with LCH. The current international expert consensus on adult LCH recommends baseline PET-CT and organ-specific CT imaging for all patients with LCH [10]. Taking these aspects into account, it may be considered that patients with gastric LCH undergo a baseline staging workup, ideally including AP-CT, chest CT, and PET-CT. In cases where PET-CT is unavailable, it may be reasonable to consider substituting it with a bone scan to assess bone involvement.
With regard to the therapeutic strategy and follow-up outcomes, only one patient in our study underwent endoscopic resection. The resected specimen did not contain tumor cells, which may be attributable to the fact that all tumor cells were completely removed during the initial biopsy or the disease resolved spontaneously. The other six patients who underwent only regular surveillance eventually showed spontaneous resolution, except for one patient who was lost to follow-up. Among the six patients who underwent follow-up, five were followedup for >36 months and two (33.3%) showed recurrence. However, spontaneous resolution was observed even in patients with recurrence. Based on the National Insurance System Database, all patients survived at the time of the cutoff date (December 2023). The excellent prognosis of patients with localized gastric LCH in our study is consistent with that reported by previous studies (Table 3). Only one patient presented with a large mass and multi-organ involvement [12], and currently, no study has reported LCH-induced mortality. Of the 11 patients with LCH reported in the literature, nine were recurrence-free and one was symptom-free throughout the follow-up period.
In summary, localized gastric LCH, a rare condition with an unclear etiology, endoscopically presents as small erosions in the distal part of the stomach. Although occasional recurrences may occur, lesions most likely eventually disappear without treatment unless patients show mass formation or systemic involvement. Therefore, careful and regular surveillance may be sufficient in most cases of localized gastric LCH.
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