Case Of Langerhans Cell Histiocytosis Research Articles

A case of langerhans cell histiocytosis accompanying hypothalamus, mastoid bone and liver involvement

A case of langerhans cell histiocytosis accompanying hypothalamus, mastoid bone and liver involvement

Isolated Langerhans cell histiocytosis in the stomach of adults: four-case series and literature review

Langerhans cell histiocytosis (LCH) of the stomach is rare. Moreover, it is usually found in pediatric patients with systemic diseases and may be associated with a poor prognosis. Solitary gastric LCH in adults is extremely rare and is often misdiagnosed or missed. The aim of our study was to review cases of gastric LCH and explore the characteristics of the disease further. A retrospective study of all patients admitted with solitary gastric LCH was conducted between 2013 and 2023. Clinical manifestations, endoscopic and pathological features, immunophenotypes, and molecular changes were collected from medical records. We examined four cases (one female, three males) of gastric LCH. The affected patients were between 33 and 70 years of age. Endoscopically, three patients presented with a solitary polyp or elevated lesions, whereas one patient showed no abnormalities. Under a microscope, all cases showed abnormal proliferation of histiocytoid cells infiltrating in a nested or sheet-like fashion. The tumor cells were medium-sized, with a slightly eosinophilic cytoplasm, irregular or renal-shaped nuclei, folded nuclear membranes, visible nuclear grooves, and the infiltration of inflammatory cells in the background. Immunohistochemically, all lesions expressed CD1a, S-100, langerin, and cyclinD1. One case showed diffuse BRAF V600E positivity. Follow-up data were available for all patients from 4 to 36 months, and all patients were alive without recurrence or progress at the time of manuscript preparation. Combined with previously reported data, solitary adult gastric LCH is more common in male patients, most of whom are asymptomatic or exhibit only mild gastrointestinal symptoms, with a good prognosis. Endoscopy often reveals solitary polyps or protruding lesions; rare cases may progress to multifocal/multisystem lesions, necessitating long-term close follow-up.

Localisation hépatique isolée d’une histiocytose langerhansienne : à propos d’un cas

Langerhans cell histiocytosis (LCH) is a disease whose physiopathology remains unclear, involving both inflammatory processes and clonal proliferation. It is observable at any given age, although about ten times more frequent in children than adults. Hepatic involvement is not rare, mostly part of a systemic disease, and linked to a poor prognosis. We report here a case of LCH with solitary hepatic involvement in a 74year-old patient. This case demonstrated molecular anomaly of the MAPK pathway, BRAF N486_P490del. Through this observation, we precise the epidemiological and histological aspects and diagnostic criteria of this rare disease.

Persistent purple erythematous rash: Langerhans cell histiocytosis

Langerhans cell histiocytosis (LCH) is an uncommon yet serious inflammatory neoplasia that frequently affects children. Skin and bone manifestations are frequent and may be isolated or associated with visceral or systemic disorders. Diagnosis is clinicopathologic, established upon typical clinical findings and immunohistochemical and histological analyses of a biopsy taken from the lesions. Prognosis depends on onset age and the quantity of affected organs. Treatment is often necessary for LCH if systemic involvement exists. Herein, we report a rare case of multifocal LCH of late onset. Key words: Histiocytosis, Langerhans cell histiocytosis, Inflammation, Systemic manifestations

Dermoscopy and reflectance confocal microscopy finding of different anatomic sites of Langerhans cell histiocytosis.

Recognizing Langerhans cell histiocytosis (LCH) might be a challenge due to its rarity. Reflectance confocal microscopy (RCM) and dermoscopy were emergent promising non-invasive technique as auxiliary tools in diagnosis of different skin conditions. However, the RCM and dermoscopic features of LCH had been less investigated. To reveal the common RCM and dermoscopic features of LCH. Forty cases of LCH were retrospectively analyzed according to age, locations, clinical, RCM, and dermoscopic features from September 2016 to December 2022. To reveal the differences and common in clinical, RCM, and dermoscopic features that occur in different anatomic location. In the study, sites of predilection include the trunk 31/40 (77.5%), extremity 21/40 (52.5%), face 14/40 (35%), scalp 11/40 (27.5%), vulvar 4/40 (10%), and nail 2/40 (5%). All LCHs had the common RCM features. There were significant differences in clinical and dermoscopic features for age and lesion anatomic site. The common dermoscopic features for scalp, face, trunk, and extremity were the erythematous scaly rash, purplish-red globules or patches, scar-like streaks with ectatic vessels. While the features for nail LCH were purpuric striae, onycholysis and purulent scaly rash, and the erosive erythematous plaque and purulent scaly rash for vulvar LCH. The common RCM features of all LCH showed a focal highly reflective dense image in the surface keratin layer, epidermis architectural disarray, obscuration of dermo-epidermal junction, numerous polygonal, large, medium reflective, short dendrites cells in the epidermis, and dermis. All LCH involving the vulvar and nail did not manifest skin lesions. RCM and dermoscopy showed promising value for diagnosis and differentiation of LCH.

Identification of Germline, Ancestry-Specific Variants for Langerhans Cell Histiocytosis in Hispanic Patients

Background: Langerhans cell histiocytosis (LCH) is an inflammatory myeloid neoplasia characterized by lesions including pathogenic CD207+ dendritic cells among an inflammatory infiltrate with recurrent, mutually exclusive somatic activating mutations in MAPK pathway genes in ~85% of LCH lesions. Our group and others have reported that Hispanic populations are more likely to develop LCH, particularly high-risk LCH, than non-Hispanic counterparts. Our group previously identified and validated a risk SNP in SMAD6 associated with a 3-fold increase in LCH risk that was also enriched in those of Hispanic ancestry; however, germline risk factors have yet to be fully elucidated in the higher-risk Hispanic population. Methods: Using targeted SMAD6 sequence data from 466 cases with LCH and aggregate data for 15,694 non-cancer controls from gnomAD v2.1.1, we evaluated 49 SNPs previously associated with case status to identify those that were enriched specifically in Hispanic populations. We conducted an additional genome-wide association study (GWAS) on 98 LCH cases and 1,158 controls, all inferred to be Hispanic based on global genomic ancestry. The GWAS was adjusted for the first 3 PCs. Population genetics were assessed in Ensembl, ancestry inference was conducted Admixture software (reference panel 1000 Genomes, Phase 3), and statistical analyses were conducted with PLINK, Stata, and SAS software. Results: In the population genetics analysis of the SMAD6 SNPs, the top 4 SNPs (Figure 1) have a lower minor allele frequency (MAF) of 2-9% across all populations. However, in Hispanic populations, the alternate/risk allele in the top 4 SNPs is increased (MAF range 15-23%). Furthermore, the LD between the top four SNPs is enriched among Hispanic populations (range of r 2: 0.51-0.92; Table 1), suggesting that Hispanic patients may have different risk loci compared to others. In the LCH GWAS of Hispanic patients, there were no statistically significant SNPs; however, this pilot study of our ongoing analyses identified 5 LCH risk loci in Hispanic patients that had suggestive significant associations ( P=1.0x10 -5). Strikingly, these loci differed from the SNPs identified in our GWAS of all patients. Conclusions: Using multiple approaches, we have identified LCH risk variants that were identified in Hispanic patients. These Hispanic ancestry-specific risk SNPs were more strongly associated with case status in Hispanic patients than the risk SNPs from our GWAS of all patients. This indicates that the ancestry-specific SNPs may contribute to the increased risk of LCH, particularly high-risk LCH, that is seen in Hispanic populations compared to populations of other ancestries. Our ongoing work involves assessing these SNPs for association with patient and clinical characteristics and outcomes in Hispanic patients. In addition, we are determining how these Hispanic ancestry-specific variants affect risk of LCH in patients of other ancestries, identifying additional ancestry-specific risk SNPs in patients of other ancestries, and examining the effects of global and ancestry-specific risk SNPs on LCH risk.

Expanded Assessments of Germline Genetic Variants Identify Additional Risk Loci for Langerhans Cell Histiocytosis

Introduction: Langerhans cell histiocytosis (LCH) is an inflammatory myeloid neoplasia characterized by lesions including pathogenic CD207+ dendritic cells among an inflammatory infiltrate. Sequencing studies have identified recurrent, mutually exclusive somatic activating mutations in MAPK pathway genes in ~85% of LCH lesions, including BRAF V600E in 50-65%. Despite advances to elucidate the somatic mutational landscape underlying LCH pathogenesis, germline risk factors remain largely unknown. We previously conducted the first genome-wide association study (GWAS) of LCH and identified and validated a risk variant in SMAD6 (rs12438941, G->A) associated with a 3-fold increase in LCH risk. Our current objective is to further elucidate the role of SMAD6 variation on LCH risk and identify novel LCH susceptibility loci. Methods: Independent of our discovery GWAS, we sequenced SMAD6 in 466 additional LCH cases and compared them to aggregate-level SMAD6 data from ~15,694 non-cancer controls in gnomAD v2.1.1. Targeted sequencing of SMAD6 was conducted among these cases with ~200x coverage at the Avera Institute of Human Genetics. In parallel, we conducted a GWAS of 319 of those cases and leveraged controlled-access data from 9,921 controls in the ADDHealth study. Genotyping of the 319 cases was also performed at the Avera Institute for Human Genetics on the Illumina Infinium Global Screening Array. We evaluated the role of common variants (minor allele frequency >5%) on LCH risk and applied principal components analysis to account for potential population stratification. A genome-wide threshold of significance was applied at P-value<5.0x10 -8, and threshold of suggestive significance at P-value<1.0x10 -6. Analyses were conducted in Plink and STATAv17.1. Results: The case-control study of targeted SMAD6 identified novel SMAD6 variants associated with LCH risk ( P-values ranging from 4.54x10 -28 to 2.9x10 -4), including our original GWAS locus. All cases with two copies of the alternate alleles in the top 2 SNPs had BRAF V600E + lesions. In terms of the new GWAS, 31 novel loci were associated with LCH at P-value=5x10 -8, including 2 separate loci on Chr 9, with the top hit being intergenic between KCNV2 and VLDLR on Chr 9 and the second being intergenic between OLFM1 and LOC401557. Other identified top hits suggest putative biologic significance in terms of LCH pathogenesis. Conclusion: We identified additional support that inherited genetic variation impacts LCH risk. We are concurrently assessing the role of ancestry-specific loci on LCH risk and analyzing newly generated SMAD6 targeted sequence and GWAS data in an independent set of case-parent trios (n=185) to integrate with the findings reported here. Next steps include a meta-analysis of our discovery GWAS, the new GWAS reported here, and the recently genotyped new set of 185 case-parent trios. We also aim to determine the role of variants on clinical characteristics (e.g., ancestry, age at onset, BRAF V600E). Our work suggests an important and complex role of germline variants and ancestry in LCH pathogenesis.

A rare convergence: adult-onset Langerhans cell histiocytosis and HIV infection

While primarily described in children, adult-onset Langerhans cell histiocytosis (LCH) has been reported, albeit infrequently. In the present scenario, we unveil a unique case of adult-onset LCH in an HIV-infected individual. After the diagnosis was made, the patient was successfully treated and demonstrated total disease remission. This case illustrates the diagnostic challenge that rare clinical entities such as LCH pose, especially in the context of an untreated HIV infection. Furthermore, the complexity of treating adult-onset Langerhans cell histiocytosis in an HIV-positive patient is highlighted, with emphasis given on a multidisciplinary approach.

Langerhans Cell Histiocytosis in the Oral Cavity

Background: Langerhans cell histiocytosis (LCH) is a rare hematological malignancy. The incidence of this disease is only 1% of soft tissue and lymph node cancer. Clinical manifestations and organ involvement vary widely. Lesions in the oral cavity are rare. LCH occurs more often in children, 10 times more often than in young adults.
 Case presentation: A 20-year-old male came with the main complaint of a lump on the roof of the mouth and the right inner cheek. Physical examination of the face and oral cavity found a mass attached to the palate 1x1x1 cm with the same color as the surrounding tissue, flat surface, soft consistency, could be moved, and a mass was found in the left buccal 2x2x2 cm, with the same color as the surrounding tissue, flat surface, cystic consistency, not fixed and can be moved. Hematology laboratory examination was within normal limits, so no examination was carried out for bone marrow puncture (BMP). From the results of a CT scan of the head and neck, a solid mass was found with a hypodense part in it in the right buccal area attached to m. right masseter, and in the left hard palate area, which was suggestive of Langerhans cell histiocytosis. The results of histopathological examination of the lesion which underwent an incisional biopsy showed positive S100 and CD1a, this patient was diagnosed with Langerhans cell histiocytosis LCH. Next, this patient was treated with excision of the mass in the palate and buccal area. The patient was treated in the surgical inpatient department for 2 days, and the postoperative wound was in good condition.
 Conclusion: Cases of Langerhans cell histiocytosis (LCH) are very rare cases that have different clinical symptoms depending on the organs involved, so it is important to understand this disease better. In this case, it was unilocal LCH without the involvement of other organs, so only local therapy was carried out in the form of surgical excision and observation was carried out after 3 months after surgery with the results of the wound improving without any new lumps appearing.

Somatic ARAF mutations in pediatric Langerhans cell histiocytosis: clinicopathologic, genetic and functional profiling.

ARAF mutations have been identified in a limited subset of patients with Langerhans cell histiocytosis (LCH), a rare disorder characterized by abnormal proliferation of Langerhans cells. LCH is primarily instigated by mutations in the mitogen-activated protein kinase (MAPK) signaling pathway, with BRAFV600E and MAP2K1 mutations constituting most cases. ARAF mutations in LCH highlight the heterogeneity of the disease and provide insights into its underlying molecular mechanisms. However, the occurrence of ARAF-positive LCH cases is extremely rare, with only two reported globally. Although they may be linked to a more aggressive form of LCH and a more severe clinical progression, the clinical significance and functional consequences of these mutations remain uncertain. We performed next-generation sequencing (NGS) to explore driver mutations in 148 pediatric LCH patients and recognized a series of mutations, including an identical novel somatic ARAF mutation, c.1046_1051delAGGCTT (p.Q349_F351delinsL), in four pediatric LCH patients. It was considered an ARAF hotspot mutation. All reported ARAF-positive patients worldwide exhibited characteristic pathological features of LCH, albeit with involvement across multiple systems. In vitro functional studies showed that this mutation could trigger the MAPKinase pathway and phosphorylate its downstream effectors MEK1/2 and ERK1/2 (relatively weaker than BRAFV600E). Over-activation of mutant A-Raf kinase could be inhibited by the BRAF inhibitor vemurafenib. LCH is uncommon, and ARAF mutation is even rarer. In our study, we have identified a novel hotspot somatic ARAF mutation, which has been verified through functional analysis to be an activating mutation. LCH patients with ARAF mutation typically have an unfavorable prognosis due to limited treatment experiences, although they do not exhibit a high relapse rate. To aid in the development of personalized treatment approaches and prognostic markers for LCH patients, it is recommended to conduct typical pathological and immunohistochemical examinations, as well as genetic tests utilizing a targeted gene panel or whole exome sequencing (WES), for LCH diagnosis, thereby promoting the use of inhibitor treatment strategies.

An interesting case of Langerhans cell histiocytosis with manifestation in oral cavity

An interesting case of Langerhans cell histiocytosis with manifestation in oral cavity

The Placenta in Congenital Langerhans Cell Histiocytosis: A Case Report of Unusual Involvement of Chorionic Plate and Umbilical Vein.

The congenital presentation of Langerhans cell histiocytosis (LCH) is a rare presentation of an uncommon neoplastic process. Concurrent placental parenchymal involvement is even more rare, with just 2 cases of congenital multisystem LCH with placental involvement reported in English medical literature thus far. Here, we present a case of a liveborn male born at 37-weeks, 6-day gestation with congenital LCH focally involving the placenta. Langerhans cells were identified in an area of the placenta showing an unusual mononuclear cell infiltrate in the wall of the umbilical vein. Langerhans cells were also focally identified in areas of chronic villitis, as well as normal-appearing chorionic plate. The examination of the placenta in cases of clinical suspicion of LCH can be of paramount importance since it may provide the early diagnostic evidence of LCH. In this context, placental involvement by LCH should be considered even in the absence of abnormal histology.

Adult-onset Langerhans cell histiocytosis of bone: A case series highlighting a rare entity

Langerhans cell histiocytosis (LCH) is a neoplastic disorder derived from LCH precursor cells that can manifest as a single-system disease or a multisystem disorder. While extensively studied in children, LCH has received less attention in adult patients. We aimed to investigate the pathology and clinical course of LCH in adults presenting with a bone lesion. Cases of osseous LCH diagnosed in patients ≥18 in our center were analyzed. Histologic slides were reviewed, and clinical data were collated. Molecular analysis for BRAF mutation was performed in a subset. Twelve osseous LCH cases with classic morphology and CD1a+/S100+ immunophenotype were identified. Tumors occurred in six females and five males with a median age of 34 years (range: 18–77 years) and involved the craniofacial bones (4), pelvis (3), spine (2), appendicular skeleton (2), and rib (1). Radiographically, tumors appeared as ill-defined lytic lesions, often accompanied by cortical erosion and soft tissue extension, with pain being the most common presentation. On staging work-up with available data, two patients had multifocal bone lesions, two had multi-system disease, and four had solitary lesions. Two patients had prior or concurrent neoplasms, and 63 % of patients (5 out of 8) had a history of smoking. BRAF mutational analysis performed in six cases revealed a BRAFV600E mutation in one, negative result in one, and failed in four archived specimens. Our study highlights the importance of performing staging in patients with adult-onset LCH presenting as a bone lesion, as the clinical extent of the disease can vary widely among individuals.

Multiple Langerhans cell histiocytosis with spinal involvement.

The aim of this study was to report the long-term prognosis of patients with multiple Langerhans cell histiocytosis (LCH) involving the spine, and to analyze the risk factors for progression-free survival (PFS). We included 28 patients with multiple LCH involving the spine treated between January 2009 and August 2021. Kaplan-Meier methods were applied to estimate overall survival (OS) and PFS. Univariate Cox regression analysis was used to identify variables associated with PFS. Patients with multiple LCH involving the spine accounted for 15.4% (28/182 cases) of all cases of spinal LCH: their lesions primarily involved the thoracic and lumbar spines. The most common symptom was pain, followed by neurological dysfunction. All patients presented with osteolytic bone destruction, and 23 cases were accompanied by a paravertebral soft-tissue mass. The incidence of vertebra plana was low, whereas the oversleeve-like sign was a more common finding. The alkaline phosphatase was significantly higher in patients with single-system multifocal bone LCH than in patients with multisystem LCH. At final follow-up, one patient had been lost to follow-up, two patients had died, three patients had local recurrence, six patients had distant involvement, and 17 patients were alive with disease. The median PFS and OS were 50.5 months (interquartile range (IQR) 23.5 to 63.1) and 60.5 months (IQR 38.0 to 73.3), respectively. Stage (hazard ratio (HR) 4.324; p < 0.001) and chemotherapy (HR 0.203; p < 0.001) were prognostic factors for PFS. Pain is primarily due to segmental instability of the spine from its destruction by LCH. Chemotherapy can significantly improve PFS, and radiotherapy has achieved good results in local control. The LCH lesions in some patients will continue to progress. It may initially appear as an isolated or single-system LCH, but will gradually involve multiple sites or systems. Therefore, long-term follow-up and timely intervention are important for patients with spinal LCH.

NEUROHISTIOCYTOSIS: TWO CASES OF A RARE DISEASE

Histiocytosis is a rare systemic disease, with heterogeneous and diverse clinical and radiological presentations. Diagnosis can therefore be intriguing. Several consensus recommendations have emerged in recent years, particularly with the advent of targeted therapies, changing the management and prognosis. The authors present two cases of neurohistiocytosis. The case of Langerhans cell histiocytosis was about an adolescent with polyuria-polydipsic syndrome in whom a cerebellar biopsy was inconclusive. The patient was lost to follow-up for one year and then returned with a multisystemic neurological, bone, and dermatological presentation. The diagnosis was confirmed based on skin biopsy results. The patients condition rapidly deteriorated after chemotherapy with vinblastine and corticosteroids, leading to his death. The case of Erdheim-Chester disease was about a 53-year-old man who presented with cerebellar syndrome. His biological and radiological workup showed neurological, endocrine (diabetes insipidus) renal (hairy kidney), and bone (fibrosis) involvement. The diagnosis was confirmed by femoral biopsy and the patient was treated with Cladribine with an excellent evolution with an 18-month follow-up. This manuscript aims to report our personal experience and underline the entitys heterogeneity, non-specificity, and repercussions.

Palatal manifestations of Langerhan cell histicytosis in pediatric age: a case report with review of literature

Langerhans cell histiocytosis (LCH) is characterised by multisystem disorder with various entities grouped together under same name. Oral cavity manifestations of this disease is yet to be explored. In oral cavity it can present with ulceration, swelling or osteolysis of underlying bone. Oral cavity involvement due to LCH might confuse the examining doctor resulting in misdiagnosis of such dreadful disease. So here we are reporting a case of LCH in a 4 years old female presented to us with ulceration over hard palate mucosa. Biopsy was taken from the ulcer site which was positive for LCH. On further examination and evaluation of the patient multisystem involvement was found with involvement of skull bone.

A case of langerhans cell histiocytosis with cholangitis

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Resolution of blood eosinophilia and limited mouth opening after short-term follow-up in a pediatric Langerhans cell histiocytosis case.

Langerhans cell histiocytosis (LCH) is an inflammatory myeloid neoplasia that often affects children, presenting a broad clinical spectrum. Here, we report a 13-year-old male Salvadorian patient who was referred presenting a nodular swelling at the mandibular angle region, mildly symptomatic, few weeks ago, which relevantly was associated with limited mouth opening. Intraoral examination was unremarkable. Imaginological exams revealed an osteolytic lesion affecting the vestibular cortex at the right mandibular angle. The blood test results were normal, except for eosinophilia (21%; absolute eosinophil count 4 × 109/L). After an incisional biopsy, microscopical and immunohistochemical analyses were consistent with LCH diagnosis, which corresponded to a single system-single site category. After a few weeks, the mandibular movements were re-established, and complete resolution of blood eosinophilia was observed. LCH with blood eosinophilia is rarely reported. To our knowledge, 3 cases have been previously published.

Langerhans cell hystiocytosis mimicking necrotizing ulcerative periodontitis - A case report

Langerhans cell histiocytosis (LCH) is a rare disease characterized by abnormal proliferation of bone marrow derived histiocytes followed by their deposition in tissues elsewhere in the body causing damage. Oral manifestations of LCH can sometimes be the only presenting symptoms or the first sign of a disseminated disease. Ulcerated lesions of oral mucosa are one of the common clinical manifestations and can help in early diagnosis of the disease when presented. Since the clinical features mimics several other diseases of oral and maxillofacial region it can be misdiagnosed easily as other pathologies. This article highlights the clinicopathological features of a case of LCH in an elderly patient who has reported to our outpatient department.

Langerhans Cell Histiocytosis Evolving into Juvenile Xanthogranuloma: Two Linked Entities.

Langerhans cell histiocytosis (LCH) represents a myeloid clonal proliferation that involves the skin and other organs. Occasionally, cases of LCH evolve into juvenile xanthogranuloma (JXG). A 7-month-old boy presented with an itchy, flaky rash resembling seborrheic dermatitis affecting the scalp and eyebrows. The lesions started at 2 months old. On physical examination, there were reddish/brown lesions on the trunk, denuded areas on the groin and neck, and a large lesion behind his bottom teeth. In addition, there were thick white plaques in his mouth and thick whitish material in both ears. A skin biopsy showed features of LCH. Radiologic examination demonstrated several osteolytic lesions. Chemotherapy produced marked improvement. A few months later, the patient developed lesions with clinical and histologic features of XG. A possible association between LCH and XG is explained by lineage maturation development. Chemotherapy may play a role in modifying the production of cytokines that enhance the transformation or 'maturation' of Langerhans cells into multinucleated macrophages (Touton cells) characteristic of a more favorable proliferative inflammatory condition.