Abstract
Langerhans cell histiocytosis (LCH) is a rare histiocytic disease that predominantly affects young children, with adult cases being exceedingly uncommon. The most frequently affected sites in LCH are bones, lungs, and the pituitary gland, in whom gastrointestinal involvement is scarce. Primary isolated gastric LCH is rarely seen and typically manifests as a polypoid lesion. This article presented a case of LCH in an adult patient, while endoscopic examination revealed an erosive lesion on the greater curvature of the gastric antrum, confirmed by immunohistochemistry. We further discuss the pathogenesis, endoscopic and histopathological characteristics, immunohistochemical findings, relevant differential diagnoses, and current treatment strategies. This report aims to raise clinicians’ awareness of the various endoscopic presentations for LCH and emphasizes the importance of thorough histopathological evaluation to obtain an accurate diagnosis and avoid oversight or misdiagnosis.
1 Introduction
LCH is a malignant histiocytic disease derived from myeloid dendritic cells (), classified as a rare disease. The incidence rate in children is approximately 3–5 per million, while in adults, it is 1–2 per million (). The male-to-female ratio is 2.1:1. Although LCH can affect multiple organs or systems throughout the body, gastrointestinal involvement is rare in adults (, ), accounting for only about 2% in all LCH patients. Gastrointestinal LCH most frequently involves the colon and rectum, which typically presents as a single colorectal polyp (, ). Isolated gastric LCH is seldom seen. Most affected patients are either asymptomatic or only mild gastrointestinal symptoms. Under endoscopy, most cases manifest as solitary polyps or submucosal protruding lesions, while fewer cases present with erosive or ulcerative changes. They are prone to misdiagnosis or missed diagnosis due to their non-specific manifestations (). We reported an adult case of isolated gastric LCH presenting with an erosive lesion in the gastric antral mucosa and reviewed the relevant literature on isolated gastric LCH to enhance clinicians’ understanding about this disease.
2 Clinical data
2.1 Previous medical history
A 37-year-old male was admitted due to “Upper abdominal distension for four years and diarrhea for one year”. Four years ago, the patient experienced epigastric distension without obvious causes, accompanied by acid reflux and hiccups. The patient denied cough, dyspnea, and chest pain, as well as polyuria, nocturia, and cognitive impairment. An external gastroscopy examination suggested atrophic gastritis. Although the patient received acid-suppressing and stomach-protecting drugs, his symptoms showed no significant improvement. One year ago, he developed intermittent diarrhea, with pasty stools occurring 3–4 times per day. One month before admission, follow-up gastroscopy and colonoscopy were performed at local hospital. There were no abnormalities in colonoscopy, while gastroscopy showed one 0.5 cm × 0.5 cm erosion of the anterior wall mucosa on the greater curvature side of the gastric antrum. A preliminary diagnosis suggested chronic atrophic gastritis with erosion. A biopsy was obtained from the greater curvature mucosa of the gastric antrum. Pathological examination showed diffuse heterogeneous cells within the local mucosa, which were consistent with a malignant tumor and prone to a low-adhesive carcinoma. It was recommended to perform immunohistochemistry for further diagnosis.
2.2 Current hospitalization data
To further clarify the diagnosis, the patient was evaluated at the Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences on December 11, 2024. His medical history was the same as above described, with no significant personal or family history. Physical examination revealed no generalized skin rash, no tremor of the extremities, steady gait without ataxia, and normal muscle tone. Physical examination showed no abnormalities. Blood tests (including complete blood count, liver and kidney functions, electrolytes, lactate dehydrogenase, autoantibodies, and endocrine assessment such as pituitary function and serum osmolality) were all within normal limits. Bone marrow puncture and biopsy showed no significant abnormalities. Pathological consultation of the gastric mucosal lesion from the external hospital demonstrated the infiltration of atypical cells among the glandular structures in the mucosal layer. These nuclei exhibited oval or slightly irregular morphology. Some of the nuclei showed nuclear grooves and thin nuclear chromatin. There were also a small number of lymphocytes and eosinophils presenting in the background (Figures 1A, B). Immunohistochemical staining results were as follows: Langerin+, CD1a+, S100+, BRAF V600E+, Vimentin+, CD68+, CD4+, a small amount of cyclin D1 positivity, and Ki67 positive rate approximately 30% (Figures 1C–H). Negative markers included: Desmin-, SOX10-, CD56- (Figure 1I), HMB45-, CD79a-, CK-, CD19-, MUM1-, CD138-, P40-, CD38-, CD20-, SYN-, SMA-, and PAX5-. Conclusion: Langerhans cell histiocytosis (involving the anterior wall of the greater curvature of the gastric antrum). No abnormalities were identified on cranial CT, chest CT, abdominal ultrasound, and echocardiography. Fluorodeoxyglucose-positron emission tomography-CT (FDG-PET-CT) scan showed a slightly increased metabolic activity (SUVmax ≈ 2.7) on the anterior wall of the greater curvature of the gastric antrum. The arrow pointed to the location of the lesion (Figure 2). No abnormalities were found in other organs, and final diagnosis should be combined with gastroscopic pathological results. After systematic examination ruled out multi-systemic diseases, the final diagnosis was isolated gastric LCH.
Figure 1
Figure 2
3 Discussion
LCH is a dendritic cell tumor caused by clonal proliferation of Langerhans cells (). It was previously regarded as an inflammatory lesion until 2010, when recurrent somatic BRAF V600E mutations () were identified in the majority of LCH patients, proving its malignant nature. Regarding the pathogenesis of LCH, it is currently believed to be a clonal disease caused by the activation of RAS-RAF-MEK-ERK pathway (). Approximately 50% patients have BRAF V600E mutations (Figure 3). Another 50% patients, MAP2K1 mutations are up to 50%, which are the members of mitogen-activated protein kinase (MAPK). While there is a mutually exclusive relationship between BRAF V600E mutations and MAP2K1 mutations (, ). Additional a few mutations have already been reported in literature, such as BRAF in-frame deletions, ARAF, NRAS, and KRAS mutations (, ). They both lead to a nearly universal activation of MAPK-ERK pathway in downstream, which in turn upregulates cyclin D1 expression. Researches on the prognostic significance of different mutations are also being explored.
Figure 3
LCH is a heterogeneous disease that can affect multiple systems throughout the body (). The most commonly affected sites include bones, lungs, and the central nervous system (CNS). The clinical manifestations show different characteristics depending on the involved organs. Bone lesions mainly present as osteolytic changes; lung involvements may cause cough, chest pain, and dyspnea; and the pituitary gland is the most frequently affected site in the CNS, mainly leading to central diabetes insipidus. Based on different patterns of lesion distribution, LCH can be classified as single-system unifocal LCH, single-system multifocal LCH, and multi-system LCH (). Currently, there is no standard treatments for adult LCH. Generally, single system single-site involvement can be followed up or conducts a local treatment, such as the surgical resection. For single-system multiple-lesion or multi-system involvement, systemic treatments are recommended, primarily consisting of chemotherapy or targeted agents (). The commonly used chemotherapy drugs comprise cytarabine monotherapy, cytarabine combined with methotrexate or clatbine monotherapy, etc. Patients with BRAF V600E mutations may benefit from BRAF inhibitors, for example vemurafenib (, ).
The incidence rate of LCH in adults is low, and isolated gastric involvement is exceedingly rare (). Previous reports on isolated gastric LCH are limited. A comprehensive literature analysis indicates that male patients are predominant in adult LCH (), while female patients are more frequently affected in isolated gastric LCH (, –), suggesting potential differences in gender distribution among the different subtypes of LCH. The median age of onset for isolated gastric LCH ranges from 46.5 to 56 years (, ), which is consistent with the general population of adult LCH. The patient in this case was a 37-year-old male, with a relatively young age at the onset, possibly due to early detection.
In isolated gastric LCH, approximately 50% of patients may be asymptomatic (), only detected during endoscopic examination. Some patients may present with non-specific gastrointestinal symptoms, for instance abdominal distension, abdominal pain, nausea, diarrhea, or heartburn. The most commonly affected sites of isolated gastric LCH are the gastric body, the gastric antrum, and the junction between the gastric body and gastric antrum (). It rarely invades the entire stomach. Most patients exhibit a single lesion. The area of endoscopic lesions ranges from 0.2 cm × 0.3 cm to 1.0 cm × 1.0 cm (). Endoscopic manifestations exhibit diverse characteristics and are categorized into submucosal protruding and non-protruding lesions. Protruding lesions primarily consist of solitary polyps or simple submucosal protrusions, while non-protruding lesions mainly contain erosive or ulcerative lesions. Nozaki et al. () reported a case of a middle-aged man that a red lesion with superficial bulging in the gastric body was found during endoscopy and resembled the early gastric cancer. The final diagnosis was isolated gastric LCH. Nihei et al. () described a middle-aged female who exhibited atrophy and erosion of the gastric fundus mucosa that mimicked a signet ring cell carcinoma. The patient underwent a subtotal gastrectomy, and the postoperative pathological diagnosis confirmed isolated gastric LCH. Moreover, there was also a case of gastric LCH presenting as granulomatous lesions () in literature, thus highlighting the importance of differential diagnosis from other granulomatous diseases in stomach. Given the non-specific endoscopic manifestations, clinicians should carefully evaluate the diverse pathological morphology to avoid missed or incorrect diagnoses. In our case, gastroscopy revealed an erosive lesion on the greater curvature of the gastric antrum, suggesting chronic atrophic gastritis with erosion. The local hospital initially suspected a poorly differentiated carcinoma, but consultation with the pathology department of our hospital ascertained as isolated gastric LCH.
The diagnosis of LCH primarily relies on the histopathology and immunohistochemistry of the lesioned tissue. In isolated gastric LCH, the cytological morphology under light microscopy and immunohistochemical features generally correspond to those of LCH affecting other organs. Langerhans cells are relatively large and exhibit round or oval shapes. Their nuclei are irregular and are like kidney-shaped or coffee bean-shaped, with folded nuclear membranes and indistinct nucleoli. There is a prominent infiltration of reactive inflammatory cells in the background, such as neutrophils, eosinophils, lymphocytes, and multinucleated giant cells, etc. (). For immunohistochemical characteristics, tumor cells specifically express langerin, CD1a, and S-100 (). Notably, studies have reported Cyclin D1 overexpression in 30%–70% of LCH cases (, ), which may be attributed to the activation of RAS-RAF-MEK-ERK pathway (). The histological findings showed typical cell morphology of LCH (Figures 1A, B) and immunohistochemistry testified the positivity of the genes mentioned above in this patient (Figures 1C–H), corresponding to the previous literature reports. It is worth noting that an atypical case of gastric LCH has also been documented. The case described an endoscopic spherical mass on the lesser curvature of the gastric body (). Microscopic examination revealed Langerhans cells with significant atypia, obvious nucleoli, and easily visible mitotic figures. Despite these atypical morphological features, immunohistochemistry conformed to the LCH phenotype, showing strong positivity to S-100, CD1a, and langerin. The patient experienced a rapid disease progression and died two months after tumor resection. The cell morphology was highly malignant under the microscope, which penetrated into the perigastric lymph nodes and other organs around. The progression of disease was rapid, which was different from the conventional features of LCH. Therefore, for atypical cases with high-grade cytological atypia and aggressive behavior, we should be alert to the possibility of malignant transformation from LCH into Langerhans cell sarcoma (LCS). In such scenarios, the expression of CD56 plays a critical role in differential diagnosis. Although both LCH and LCS typically express S-100, CD1a, and langerin; CD56 positivity is highly suggestive of LCS and generally absent in classical LCH. This case displays CD56 negativity (Figure 1I) without the atypical cellular morphological features like LCS patients.
Furthermore, gastric LCH must be differentiated from other histiocytic diseases (), for example, LCS, Rosai-Dorfman disease (RDD), and Erdheim-Chester disease (ECD); as well as non-histiocytic tumors (), including poorly differentiated carcinoma, malignant melanoma, and mastocytosis, etc.
According to the literature, BRAF V600E mutation rate in isolated gastric LCH ranges from 66.7% to 90.9% (, ), which is significantly higher than that of LCH in other sites. To our knowledge, another few LCH-related mutations, such as MAP2K1, ARAF, and NRAS mutations, have not been reported in isolated gastric LCH. Those patients may have a different gene mutation spectrum by contrast other sites of LCH, warranting further investigation. Another study has suggested that the mutation rate of BRAF V600E was associated with the multi-system involvement and a poor prognosis in pediatric LCH (). Interestingly, we find that BRAF V600E mutation rate is high in isolated gastric LCH among adults, however, the clinical prognosis generally appears favorable. The apparent discrepancy between the high mutation frequency and favorable prognosis may be explained by several factors. First, the BRAF V600E mutation itself does not uniformly predict aggressive behavior; rather, clinical outcomes depend on disease extent and organ involvement. Second, and most importantly, the cellular context in which the BRAF V600E mutation arises—rather than the mere presence of the mutation itself—appears to be the key determinant of clinical behavior. In the landmark study by Berres et al (), the mutation was detected in circulating CD11c+ dendritic cells, CD14+ monocytes, and BM CD34+hematopoietic progenitors in all high-risk LCH patients, whereas it was restricted to lesional CD207+ DCs in low-risk patients. These observations support a model in which high-risk LCH arises from somatic mutation of a hematopoietic progenitor, while low-risk disease results from mutation of a tissue-restricted precursor DC. Therefore, in the case of isolated gastric LCH—which by definition is unifocal and single-system—the disease is likely derived from a tissue-restricted precursor rather than a multipotent hematopoietic stem cell, explaining its excellent prognosis despite a high BRAF V600E mutation rate. Third, the small number of reported cases limits the ability to draw definitive conclusions. Further research is needed to clarify the discrepancy between the high mutation rate and clinical prognosis in gastric LCH. Combined with this patient, BRAF V600E was positive in the local tissue by immunohistochemistry, but BRAF V600E mutation test was not performed, due to the limited specimen of pathological tissue. Regarding the impact on interpretation of the BRAF testing, Acosta-Medina et al. () has demonstrated that IHC has a sensitivity of 82.4% and a specificity of 96.4% compared with NGS as the gold standard. Given the high specificity of IHC, we consider the positive result sufficient for clinical purposes in our case. Nevertheless, we acknowledge that molecular testing should be pursued whenever tissue is available.
Isolated gastric LCH most commonly presents as a solitary polypoid lesion (, ). For a unifocal lesion, the treatment mainly involves observation or endoscopic resection of the lesion, while multifocal lesions are recommended chemotherapy or targeted therapy. The 5-year overall survival rate exceeds 90% for adult patients with single-system LCH (, ). Existing data indicate that isolated gastric LCH has a favorable prognosis similar to single-system LCH at other sites. A study of 13 cases of gastrointestinal LCH (including 8 gastric cases) found that endoscopic morphology correlated with patients’ prognosis. The progression-free survival rate of submucosal protruding lesions was significantly better than that of non-protruding lesions (). These endoscopic characteristics may provide a basis for guiding treatment and predicting prognosis. Based on these findings, we speculate that close follow-up observation is sufficient for polyps or submucosal protruding lesions under endoscopy, while ulcerative lesions might require the earlier intervention. Although this requires validation in large cohorts. Kim et al. () studied seven patients with gastric LCH presenting as superficial erosions (diameter < 0.5cm) or protruding lesions with erosion under endoscopy. Only one patient underwent endoscopic resection, while the other six patients were managed with regular surveillance and eventually showed spontaneous regression of the disease. Accordingly, they proposed that careful periodic monitoring may be sufficient for isolated gastric LCH. Most importantly, the International Expert Consensus Recommendations () state that for unifocal LCH, “observation or local therapies such as surgical excision” are both acceptable first-line options. This patient had a single 0.5 cm × 0.5 cm erosive lesion on the gastric antrum mucosa. Taken together, we recommend close surveillance, with endoscopic resection reserved for cases of progression. For unifocal disease, initial follow-up imaging is recommended every 3–6 months, and surveillance intervals may be extended once disease stability is confirmed. Our patient has been kept under close surveillance by the gastroenterology team. One year after diagnosis (March 2026), repeated endoscopy confirmed a stable lesion with no evidence of progression. The patient’s gastrointestinal symptoms have resolved following symptomatic management then.
4 Conclusion
Isolated gastric LCH in adults is making it prone to miss diagnosis and misdiagnosis due to its extremely low incidence and lack of specific clinical manifestations. In clinical practices, if erosive or ulcerative lesions are found under gastroscopy, which shows a large amount of inflammatory cells infiltration in pathology, and which are ineffective against standard therapy, the possibility of LCH should be considered. For atypical cases with obvious cellular atypia, LCS must be ruled out. BRAF V600E mutation appears more prevalent in isolated gastric LCH compared to LCH involving other organs, however, larger-scale studies are required to elucidate its molecular pathological changes more comprehensively. For single-system unifocal patients without symptoms, it is recommended active surveillance or endoscopic resection of the lesion; whereas patients with multi-system multifocal involvement should receive chemotherapy or targeted therapy. The overall prognosis of isolated gastric LCH is generally favorable. Notably, the progression-free survival rate for endoscopic submucosal protruding lesions is better than that of non-protruding lesions, which may indicate a correlation with clinical prognosis and merits further investigation in larger cohorts.
Statements
Data availability statement
The datasets used and analyzed during the current study are available from the corresponding author request.
Ethics statement
Ethical approval was not required for this kind of study involving humans in accordance with the local legislation and institutional requirements. Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.
Author contributions
XN: Investigation, Conceptualization, Writing – review & editing, Data curation, Writing – original draft, Formal analysis. YT: Writing – original draft, Conceptualization, Writing – review & editing, Investigation, Data curation. YW: Conceptualization, Writing – review & editing, Writing – original draft, Data curation. KW: Conceptualization, Writing – original draft, Data curation. LW: Conceptualization, Writing – review & editing, Writing – original draft, Supervision. QS: Writing – review & editing, Supervision. SY: Supervision, Visualization, Validation, Writing – review & editing. SD: Writing – review & editing, Validation, Visualization, Supervision.
Funding
The authors declared that financial support was not received for this work or its publication.
Conflict of interest
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References
1
AllenCEMeradMMcClainKL. Langerhans-cell histiocytosis. N Engl J Med. (2018) 379:856–68. doi: 10.1056/NEJMra1607548
2
MinkovM. Multisystem Langerhans cell histiocytosis in children: current treatment and future directions. Paediatr Drugs. (2011) 13:75–86. doi: 10.2165/11538540-000000000-00000
3
WangLYangFDingYLuLLiHCuiYet al. Gastrointestinal Langerhans cell histiocytosis with unifocal, single-system involvement in adults: cases report and literature review. J Clin Lab Anal. (2022) 36(12):e24765. doi: 10.1002/jcla.24765
4
MatsubaraYKobayashiMHijikataYOtaYHirataYLimLAet al. Gastrointestinal lesion in adult-onset Langerhans cell histiocytosis. Int J Clin Oncol. (2020) 25(11):1945–50. doi: 10.1007/s10147-020-01739-1
5
HuSGrahamRPChoiWTWenKWPutraJChenWet al. Clinicopathologic features of gastrointestinal tract Langerhans cell histiocytosis. Mod Pathol. (2024) 37(9):100543. doi: 10.1016/j.modpat.2024.100543
6
TherrienAEl HaffafZWartelle-BladouCCôté-DaigneaultJNguyenBN. Langerhans cell histiocytosis presenting as Crohn's disease: a case report. Int J Colorectal Dis. (2018) 33:1501–4. doi: 10.1007/s00384-018-3066-y
7
ZhaoJLiYZhangYMeiXLiuWLiY. Isolated Langerhans cell histiocytosis in the stomach of adults: four-case series and literature review. J Hematop. (2024) 17:63–9. doi: 10.1007/s12308-024-00584-9
8
EmileJFAblaOFraitagSHorneAHarocheJDonadieuJet al. Revised classification of histiocytoses and neoplasms of the macrophage-dendritic cell lineages. Blood. (2016) 127(22):2672–81. doi: 10.1182/blood-2016-01-690636
9
Badalian-VeryGVergilioJADegarBAMacConaillLEBrandnerBCalicchioMLet al. Recurrent BRAF mutations in Langerhans cell histiocytosis. Blood. (2010) 116(11): 1919–23. doi: 10.1182/blood-2010-04-279083
10
SahmFCapperDPreusserMMeyerJStenzingerALasitschkaFet al. BRAFV600E mutant protein is expressed in cells of variable maturation in Langerhans cell histiocytosis. Blood. (2012) 120(12):e28–34. doi: 10.1182/blood-2012-06-429597
11
BrownNAFurtadoLVBetzBLKielMJWeigelinHCLimMSet al. High prevalence of somatic MAP2K1 mutations in BRAF V600E-negative Langerhans cell histiocytosis. Blood. (2014) 124(10):1655–8. doi: 10.1182/blood-2014-05-577361
12
AlayedKMedeirosLJPatelKPZuoZLiSVermaSet al. BRAF and MAP2K1 mutations in Langerhans cell histiocytosis: a study of 50 cases. Hum Pathol. (2016) 52:61–7. doi: 10.1016/j.humpath.2015.12.029
13
ChakrabortyRBurkeTMHamptonOAZinnDJLimKPAbhyankarHet al. Alternative genetic mechanisms of BRAF activation in Langerhans cell histiocytosis. Blood. (2016) 128(21):2533–7. doi: 10.1182/blood-2016-08-733790
14
NelsonDSQuispelWBadalian-VeryGvan HalterenAGvan den BosCBovéeJVet al. Somatic activating ARAF mutations in Langerhans cell histiocytosis. Blood. (2014) 123(20):3152–5. doi: 10.1182/blood-2013-06-511139
15
EmileJFAblaOFraitagSHorneAHarocheJDonadieuJet al. Revised classification of histiocytoses and neoplasms of the macrophage-dendritic cell lineages. Blood. (2016) 127(22):2672–81. doi: 10.1182/blood-2016-01-690636
16
GoyalGHeaneyMLCollinMCohen-AubartFVaglioADurhamBHet al. Erdheim-Chester disease: consensus recommendations for evaluation, diagnosis, and treatment in the molecular era. Blood. (2020) 135(22):1929–45. doi: 10.1182/blood.2019003507
17
LinHChangLLangMLiuZZDuanMHZhouDBet al. Long-term follow-up of methotrexate and cytarabine in adult patients with Langerhans cell histiocytosis. Br J Haematol. (2025) 206(2):576–84. doi: 10.1111/bjh.19830
18
EmileJFCohen-AubartFCollinMFraitagSIdbaihAAbdel-WahabOet al. Histiocytosis. Lancet. (2021) 398(10295):157–70. doi: 10.1016/S0140-6736(21)00311-1
19
DiamondELSubbiahVLockhartACBlayJYPuzanovIChauIet al. Vemurafenib for BRAF V600-mutant Erdheim-Chester disease and Langerhans cell histiocytosis: analysis of data from the histology-independent, phase 2, open-label VE-BASKET study. JAMA Oncol. (2018) 4(3):384–8. doi: 10.1001/jamaoncol.2017.5029
20
KimTSAhnSMinYWLeeHLeeJHRheePLet al. Clinical characteristics and outcomes in patients with localized gastric Langerhans cell histiocytosis: a case series. Korean J Helicobacter Up Gastrointest Res. (2024) 24(2):175–81. doi: 10.7704/kjhugr.2024.0019
21
Badalian-VeryGVergilioJADegarBARodriguez-GalindoCRollinsBJ. Recent advances in the understanding of Langerhans cell histiocytosis. Br J Haematol. (2012) 156:163–72. doi: 10.1111/j.1365-2141.2011.08915.x
22
ShangQChangLLangMLiuZZLinHZhaoJHet al. Manifestations and outcomes of digestive tract involvement in adult Langerhans cell histiocytosis. Ann Hematol. (2024) 103(11):4459–66. doi: 10.1007/s00277-024-06034-x
23
GotesmanMGetachewRMoralesSZangwillKMGershmanGLeeSet al. A case of Langerhans cell histiocytosis with multifocal, single-system GI tract involvement and literature review. J Pediatr Hematol Oncol. (2020) 42(6):e491–3. doi: 10.1097/MPH.0000000000001662
24
SinghiADMontgomeryEA. Gastrointestinal tract Langerhans cell histiocytosis: a clinicopathologic study of 12 patients. Am J Surg Pathol. (2011) 35:305–10. doi: 10.1097/PAS.0b013e31820654e4
25
LeeSJHwangCSHuhGYLeeCHParkDY. Gastric Langerhans cell histiocytosis: case report and review of the literature. J Pathol Transl Med. (2015) 49:421–3. doi: 10.4132/jptm.2015.05.19
26
NozakiYOshiroHNakajimaA. Image of the month. Langerhans cell histiocytosis of the stomach mimicking early gastric cancer. Clin Gastroenterol Hepatol. (2010) 8:A18. doi: 10.1016/j.cgh.2010.01.009
27
NiheiKTerashimaKAoyamaKImaiYSatoH. Benign histiocytosis X of stomach. Previously undescribed lesion. Acta Pathol Jpn. (1983) 33:577–88. doi: 10.1111/j.1440-1827.1983.tb00364.x
28
GroismanGMRoshJRHarpazN. Langerhans cell histiocytosis of the stomach. A cause of granulomatous gastritis and gastric polyposis. Arch Pathol Lab Med. (1994) 118(12):1232–5.
29
ChertoffJChungJAtayaA. Adult Langerhans cell histiocytosis masquerading as hidradenitis suppurativa. Am J Respir Crit Care Med. (2017) 195:e34–6. doi: 10.1164/rccm.201610-2082IM
30
SalamaHAJaziehARAlhejaziAYAbsiAAlshiebanSAlzahraniMet al. Highlights of the management of adult histiocytic disorders: Langerhans cell histiocytosis, Erdheim-Chester disease, Rosai-Dorfman disease, and hemophagocytic lymphohistiocytosis. Clin Lymphoma Myeloma Leuk. (2021) 21(1):e66–75. doi: 10.1016/j.clml.2020.08.007
31
ChatterjeeDVishwajeetVSaikiaUNRadotraBDeDBansalD. CyclinD1 is useful to differentiate Langerhans cell histiocytosis from reactive Langerhans cells. Am J Dermatopathol. (2019) 41:188–92. doi: 10.1097/DAD.0000000000001250
32
Ben RejebSCharfiLSahraouiGBoujelbenNMradKDoghriR. Cyclin D1: potential utility as marker for Langerhans cell histiocytosis. J Immunoassay Immunochem. (2021) 42:370–9. doi: 10.1080/15321819.2020.1870132
33
ShanmugamVCraigJWHornickJLMorganEAPinkusGSPozdnyakovaO. Cyclin D1 is expressed in neoplastic cells of Langerhans cell histiocytosis but not reactive Langerhans cell proliferations. Am J Surg Pathol. (2017) 41:1390–6. doi: 10.1097/PAS.0000000000000897
34
TerraccianoLKocherTCathomasGBubendorfLLehmannFS. Langerhans cell histiocytosis of the stomach with atypical morphological features. Pathol Int. (1999) 49:553–6. doi: 10.1046/j.1440-1827.1999.00909.x
35
GoyalGYoungJRKosterMJTobinWOVassalloRRyuJHet al. The Mayo Clinic Histiocytosis Working Group consensus statement for the diagnosis and evaluation of adult patients with histiocytic neoplasms: Erdheim-Chester disease, Langerhans cell histiocytosis, and Rosai-Dorfman disease. Mayo Clin Proc. (2019) 94(10):2054–71. doi: 10.1016/j.mayocp.2019.02.023
36
WuRZhaoYWuXGuiHLiuXLiuZ. Isolated Langerhans cell histiocytosis of the stomach in adults: an analysis of clinicopathologic characteristics and molecular genetics. Med (Baltimore). (2024) 103:e40950. doi: 10.1097/MD.0000000000040950
37
HéritierSEmileJFBarkaouiMAThomasCFraitagSBoudjemaaSet al. BRAF mutation correlates with high-risk Langerhans cell histiocytosis and increased resistance to first-line therapy. J Clin Oncol. (2016) 34(25):3023–30. doi: 10.1200/JCO.2015.65.9508
38
BerresMLLimKPPetersTPriceJTakizawaHSalmonHet al. BRAF-V600E expression in precursor versus differentiated dendritic cells defines clinically distinct LCH risk groups. J Exp Med. (2015) 212(2):281. doi: 10.1084/jem.2013097701202015c
39
Acosta-MedinaAAAbeykoonJPGoRSRavindranASchramSMGoyalGet al. BRAF testing modalities in histiocytic disorders: comparative analysis and proposed testing algorithm. Am J Clin Pathol. (2023) 160(5):483–9. doi: 10.1093/ajcp/aqad076
40
AblaOWeitzmanS. Treatment of Langerhans cell histiocytosis: role of BRAF/MAPK inhibition. Hematol Am Soc Hematol Educ Program. (2015) 2015:565–70. doi: 10.1182/asheducation-2015.1.565
41
HarocheJCohen-AubartFEmileJFArnaudLMaksudPCharlotteFet al. Dramatic efficacy of vemurafenib in both multisystemic and refractory Erdheim-Chester disease and Langerhans cell histiocytosis harboring the BRAF V600E mutation. Blood. (2013) 121(9):1495–500. doi: 10.1182/blood-2012-07-446286
42
HuMGoyalGAbeykoonJPAcosta-MedinaAARuanGJYoungJRet al. Clinical features and outcomes of non-pulmonary unifocal adult Langerhans cell histiocytosis. Blood Cancer J. (2022) 12(6):89. doi: 10.1038/s41408-022-00685-7
43
GoyalGTaziAGoRSRechKLPicarsicJLVassalloRet al. International expert consensus recommendations for the diagnosis and treatment of Langerhans cell histiocytosis in adults. Blood. (2022) 139(17):2601–21. doi: 10.1182/blood.2021014343
Summary
Keywords
adult, BRAF V600E, isolated gastric, Langerhans cell histiocytosis, Langerhans cells
Citation
Ning X, Tao Y, Wang Y, Wan K, Wang L, Sun Q, Yi S and Deng S (2026) Isolated gastric Langerhans cell histiocytosis: a case report and literature review. Front. Oncol. 16:1724994. doi: 10.3389/fonc.2026.1724994
Received
14 October 2025
Revised
25 July 2026
Accepted
05 August 2026
Published
25 August 2026
Volume
16 - 2026
Edited by
Jean El Cheikh, American University of Beirut Medical Center, Lebanon
Reviewed by
Ahad Ahmed Kodipad, Nationwide Children’s Hospital, United States
Firas Kreidieh, American University of Beirut Medical Center, Lebanon
Updates
Copyright
© 2026 Ning, Tao, Wang, Wan, Wang, Sun, Yi and Deng.
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*Correspondence: Shuhua Yi, yishuhua@ihcams.ac.cn; Shuhui Deng, dengshuhui@ihcams.ac.cn
†These authors have contributed equally to this work and share first authorship
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