Case Of Langerhans Cell Histiocytosis Research Articles

Isolated Langerhans Cell Histiocytosis of the Thyroid: A very rare case report

Langerhans cell histiocytosis (LCH) is a group of diseases that cause damage by local or widespread accumulation of atypical histiocytes in various tissues such as skin, bone, lung, liver, lymph nodes, mucocutaneous tissues, and endocrine organs. LCH was detected as a result of a total thyroidectomy biopsy performed on a 43-year-old female patient with a solitary euthyroid nodule following weight loss and an increase in the size of the thyroid nodule during outpatient clinic checks. Patient's whole body positron emission tomography. The case of LCH with isolated thyroid involvement is very rare, and a limited number of cases have been presented on this subject. In addition, it will contribute to the literature since there are fewer than ten LCH cases with thyroid involvement.

Isolated Perianal Langerhans Cell Histiocytosis in a Human Immunodeficiency Virus-Positive Adult: A Rare Incidental finding

Abstract Introduction/Objective Langerhans cell histiocytosis (LCH) is a rare disorder characterized by abnormal proliferation of antigen-presenting cells, primarily Langerhans cells. Although it commonly affects bones, skin, and lungs, involvement of the gastrointestinal tract is rare. Specifically, isolated perianal LCH is exceptionally uncommon, with only a few documented cases reported in the literature. Here, we report a case of incidental perianal LCH in an adult HIV patient, highlighting the exceptional rarity and clinical importance of this occurrence. Methods/Case Report A 56-year-old Caucasian male with HIV underwent surgical resection of a 0.5 x 0.4 x 0.3 cm verrucous lesion on the posterior anal margin. His past medical history included granulomatous lymphadenitis, penile warts, and anal dysplasia. Microscopic examination of the excised tissue revealed Langerhans cells with characteristic features, including abundant eosinophilic cytoplasm and irregular nuclear membranes (resembling “coffee-bean” or “folded paper” appearance). Immunohistochemical analysis confirmed the diagnosis by demonstrating positivity for CD1a, S100, and CD68. The BRAF mutation was evaluated on the same paraffin-embedded block, which revealed the lack of the mutant BRAF V600E. PET-CT imaging showed no evidence of metastatic disease, emphasizing the isolated nature of the perianal LCH in this patient. Results (if a Case Study enter NA) NA Conclusion This case highlights the significance of recognizing and thoroughly evaluating rare and incidental conditions such as LCH in HIV patients. Our findings emphasize the importance of maintaining a high index of suspicion for LCH among healthcare providers and ensuring proper follow-up to rule out systemic involvement. Furthermore, there is a need for future studies to investigate the correlation between LCH and HIV. Given its rarity and diverse clinical presentation in immunocompromised individuals, a multidisciplinary approach, tailored treatment plans, and long-term surveillance with imaging modalities like PET/CT are essential for effectively managing adult-onset isolated LCH.

Manifestations and outcomes of digestive tract involvement in adult Langerhans cell histiocytosis.

Langerhans cell histiocytosis (LCH) is a heterogeneous histiocytosis characterized by proliferation of Langerhans cells. While less common, manifestations of digestive tract involvement in LCH remain largely unrevealed. We conducted a retrospective analysis of demographics, clinical, endoscopic, genetic and follow-up data from 13 adult patients with pathologically confirmed gastrointestinal involvement of LCH (LCH-GI), in a single-center cohort of 465 patients. Digestive tract involvement was observed in 2.80% of LCH patients. At LCH-GI diagnosis, 7 patients (53.8%) had unifocal lesions, and 6 patients (46.2%) had multisystem disease. 6 patients (46.2%) experienced no gastrointestinal symptoms at LCH-GI onset, while others were symptomatic. Stomach was most commonly affected (61.5%), followed by esophagus (23.1%), colon (7.7%) and anus (7.7%). Endoscopic findings varied among 12 patients, including submucosal bulge (8 patients, 66.7%) and non-bulging lesions (4 patients, 33.3%) such as erosions, coarse granular mucosa, and regional abnormal coloration. Among 8 patients with genetic analysis, BRAFV600E mutation was detected in 5 patients (62.5%). The estimated 1-year overall survival rate was 91.7%. Progression-free survival of patients with submucosal bulges under endoscopy was significantly better than those with non-bulging lesions. This study presents 13 cases of LCH with digestive tract involvement. We emphasize the importance of endoscopy and biopsy for pathological examination of lesions such as submucosal bulges and erosions under endoscopy to assist in early detection of LCH. Comprehensive systemic assessment and regular endoscopic monitoring are essential in patient management. Treatment should be individualized with dynamic adjustments during follow-up.

Langerhans cell histiocytosis of the orbit: pediatric case series

ObjectiveTo describe the clinical, imaging characteristics, and treatment of pediatric orbital Langerhans cell histiocytosis (LCH). DesignRetrospective case series. ParticipantsChildren with orbital LCH. MethodsChildren with orbital LCH who presented to 4 different centres over the past 10 years. Demographic details, presenting features, imaging, histopathology, immunohistochemistry, and management outcomes were analyzed. ResultsSixteen patients were reviewed. The mean age of presentation was 6.56 ± 4.38 years (range, 1−18 years). Eyelid swelling was the most common presenting feature (13, 81%), followed by proptosis (1, 5%), eyebrow swelling (1,5%), and temple swelling (1, 5%). Imaging revealed superior orbital lesions with osteolytic defects of the orbital roof in 13 (72.2%) patients. Frontal and zygomatic bones were the most commonly affected. All the orbital lesions were extraconal. All patients in the study were diagnosed with LCH from orbital tissue biopsy. Three patients also demonstrated extra-orbital involvement. Two patients (12.5%) had intraoperative steroid injection with curettage, and 1 patient (6.25%) underwent curettage only. The remainder of the patients (n = 13, 81.25%) received systemic steroids and chemotherapy after undergoing biopsy. All patients had complete remission of disease without any signs of recurrence, except for 1 case of refractory LCH. ConclusionsLCH is a rare disorder of the orbit and should be considered in the differential diagnosis for osteolytic lesions involving the superior orbit among the pediatric age group. Histopathologic confirmation is mandatory. Although optimal treatment remains controversial, complete removal of unifocal orbital LCH is recommended and may be achieved through excision and curettage.

Langerhans cell histiocytosis in children born after assisted reproductive technology

Research QuestionAre children born after Assisted reproductive technologies (ART), at higher risk of developing Langerhans cell histiocytosis (LCH)? DesignRecords of children conceived after ART recorded by the Human Fertilisation & Embryology Authority were linked to National Registry of Childhood Tumours records to determine numbers of children developing LCH. Calculated person years at risk were used in conjunction with LCH incidence in the general population, to determine expected cases if the cohort had the same incidence as the general population with similar age and sex, over the same calendar years. The standardised incidence ratio (SIR) was derived as the ratio of observed to expected cases. Exact 95% confidence intervals were calculated. Results118,155 children born after ART contributed 796,633 person years follow-up; 6.74 years average follow-up. Eight cases of LCH were identified compared to 3.75 expected (SIR 2.135, 95% Confidence Interval 0.92 to 4.21, p = 0.074). Significantly more cases were associated with being born after intra-cytoplasmic sperm injection (SIR 4.02; 95% CI 1.31-9.39) and with male factor parental infertility (SIR 5.41; 95% CI 1.47-13.84). Most children had single system disease (n=6). ConclusionsThis study found a non-statistically significant excess of cases of LCH in children born after assisted reproduction. Significantly more cases were identified in children born after ICSI and after male factor parental infertility. Absolute excess risks were small. Given the rarity of LCH and small numbers of cases included in this large cohort, further studies into the risk of LCH in children born after ART are indicated.

朗格汉斯细胞组织细胞增生症合并噬血细胞综合征1例

朗格汉斯细胞组织细胞增生症合并噬血细胞综合征1例

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

A case of multisystem Langerhans cell histiocytosis with risk organ (liver) and special site (craniofacial) involvement

Langerhans cell histiocytosis (LCH) is a rare clonal proliferative disorder of immature dendritic cells that expresses an immunophenotype positive for S100 protein, CD1a and langerin (CD207) and contains cytoplasmic Birbeck granules. We present a case of multisystem LCH with risk organ (liver) and special site (craniofacial) involvement in a 4-year-old boy who presented with hypopigmented papulopustular lesions with scales over his scalp, face and trunk, along with polydipsia, polyuria and pain in the abdomen. Histopathology reports showed diffuse infiltration of large cells with eccentric grooved coffee bean nuclei with epidermotropism and admixed with numerous eosinophils. The patient was started on desmopressin, prednisolone and chemotherapy with vinblastine. Our goal is to expand awareness regarding the entity through this report.

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.

Letterer–Siwe disease: a case of multisystem Langerhans cell histiocytosis

Langerhans cell histiocytosis (LCH), previously known as histiocytosis X, is an idiopathic uncommon haematological condition affecting infants and young children but can occur at any age group characterized by clonal proliferation of abnormal Langerhans cells. Langerhans cells express an immunophenotype positive for S100 protein, CD1a and Langerin (CD207). Here we present a case of 2-year-old male patient presented with a multiple raw area associated with oozing, bleeding and crusted lesions were present over scalp, trunk and post-auricular areas. Radiographic examination revealed multiple osteolytic bone involvement. Histopathological examination revealed Langerhans cell histiocytosis. Immunophenotyping was positive for vimentin, CD1a, and S100. Based on radiological, histological and immunophenotyping findings suggestive of multisystem LCH. The purpose of this report is to describe a rare case of LCH in the 2-year-old male child with multisystem LCH involving skin, soft tissue and bones and to discuss clinical, radiological and histopathological features of LCH.

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.

Гистиоцитоз из клеток Лангерганса у детей

Langerhans cell histiocytosis (LCH) is a pathology rarely encountered in clinical practice. This disease has a multifaceted clinical picture, multiorgan damage, a varied course and presents significant diagnostic difficulties due to the lack of generally accepted international algorithms. In the early stages of the disease, patients turn to pediatricians, traumatologists or dermatologists, which leads to frequent diagnostic errors and inadequate therapy. Doctors of various specialties should pay attention to patients with soft tissue swellings, recurrent otitis and dermatitis in the absence of effect from the therapy and promptly refer them to an oncologist. The article presents an analysis of cases of Langerhans cell histiocytosis in children of the Oncohematology Department of the Children’s Republican Clinical Hospital in Kazan over a ten-year period, indicating the characteristic initial features of the disease for early diagnosis at the outpatient stage.

Characteristics of long-term complications in Langerhans cell histiocytosis

About 100 cases of Langerhans cell histiocytosis (LCH) occur annually in Japan. It predominantly occurs in infants, presenting as multisystem disease or multifocal bone involvement. However, LCH can also occur in adults aged 20 to 40. Single-system skin involvement is rare, with most cases presenting with multisystem disease, including bone lesions, which respond to chemotherapy. In adults, lung lesions that improve with smoking cessation are well-known, although multisystem disease is more common and requires aggressive therapeutic intervention similar to that in children. In some infant cases, progression of liver, spleen, and bone marrow lesions can be difficult to control and can become severe. However, targeted molecular therapies are now available as a lifesaving option. More than 30% of cases of multisystem LCH recur at least once, often leading to long-term complications. In particular, the emergence of central diabetes insipidus, anterior pituitary dysfunction, and central nervous system neurodegenerative disorders several years after the diagnosis of LCH is a unique feature not observed in other diseases. New therapeutic strategies are needed to counter these problems.

A Case of Langerhans Cell Histiocytosis of the Thyroid Gland

A Case of Langerhans Cell Histiocytosis of the Thyroid Gland

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.

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.

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.

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.