Proliferation Of Langerhans Cells Research Articles

Challenges in Diagnosis and Management of Langerhans Cell Histiocytosis in a 13-Month-Old child: A Rare Case Report

Introduction: Langerhans Cell Histiocytosis is a rare condition characterized by the proliferation of abnormal Langerhans cells in the skin and mucosa. It is mostly seen in children between one and three years old. Although the skeleton accounts for 80% of infiltration and the skin accounts for 33%, it can affect other organs as well. Case Presentation: We report a case of a 13-month-old male with fever, rash, and non-tender swelling in the frontal, temporal, and infraorbital regions. Imaging showed diffusion restriction in the frontal, left parietal, right sphenoid, right temporal bones, and right maxillary antrum. Biopsy and immunohistochemistry from the right maxilla confirmed the diagnosis. The patient was treated with vinblastine and prednisolone for 3 months, resulting in reduced swelling and no fever on follow-up. Discussion: Langerhans Cell Histiocytosis (LCH), formerly Histiocytosis X, has diverse clinical manifestations and is classified as localized or disseminated based on organ involvement. It is associated with viral infections, communication defects, and cytokine processes, with BRAF mutations and the MAPK/ERK pathway implicated. Diagnosis involves clinical, radiological, histological, and immunophenotypic methods, including identifying Birbeck granules in Langerin-positive cells. Treatment varies by disease extent, with vinblastine and prednisolone for children with multisystem disease and tailored approaches for adults Conclusion: Despite atypical presentation, thorough evaluation confirmed Langerhans Cell Histiocytosis in a pediatric patient. This highlights the necessity of considering Langerhans Cell Histiocytosis in differential diagnoses for persistent cutaneous lesions and bony swellings. Prompt detection and timely action are essential for successful treatment and better results.

Living-donor lobar lung transplantation for pulmonary Langerhans cell histiocytosis complicated by extensive thrombi in central pulmonary arteries

BackgroundPulmonary Langerhans cell histiocytosis (PLCH) is a rare disorder characterized by the proliferation of Langerhans cells along the small airways, which causes nodular and cystic changes in the lung parenchyma. Lung transplantation can be a life-saving option for patients with severe respiratory failure or pulmonary hypertension. Herein, we present a case of successful lung transplantation in a patient with PLCH who developed unusually large thrombi in the central pulmonary artery.Case presentationA 47-year-old woman with 16-year history of PLCH with rapidly developing respiratory failure was admitted to our hospital for the evaluation of a lung transplant. Enhanced computed tomography revealed large thrombi in dilated central pulmonary arteries. Right heart catheterization revealed severe pulmonary hypertension, with a mean pulmonary artery pressure of 48 mmHg. The thrombi shrank markedly after 3 months of anticoagulation therapy. However, the respiratory status of the patient did not improve. We performed bilateral living-donor lobar lung transplantation with thrombectomy under extracorporeal membrane oxygenation for the remaining thrombi in the main pulmonary arteries. The dilated main pulmonary arteries of the recipient required direct plication for size mismatch. The patient survived in good condition for more than 2 years with no recurrence of thrombosis.ConclusionPreoperative anticoagulation therapy for massive thrombi in the pulmonary arteries was effective and led to safe lung transplantation.

Comprehensive considerations for dermatologists: the application of FDG-PET in evaluating cutaneous lesions in pediatric Langerhans cell histiocytosis.

Langerhans cell histiocytosis (LCH) is a complex disorder characterized by the clonal proliferation of Langerhans cells, primarily affecting children and adolescents. This condition exhibits a wide spectrum of clinical presentations, necessitating a multidisciplinary approach for diagnosis, treatment, and follow-up. Cutaneous manifestations of LCH are significant, mimicking common dermatoses and posing diagnostic challenges. [18F]Fluorodeoxyglucose-Positron Emission Tomography (FDG-PET) has emerged as an important tool in the evaluation of pediatric LCH, offering insights into disease activity, extent, and therapeutic response. Moreover, FDG-PET provides a non-invasive means to distinguish between active LCH skin lesions and other dermatological conditions with similar clinical appearances, enhancing diagnostic accuracy and aiding in disease monitoring. This educational review summarizes the utility of nuclear imaging techniques, with a focus on PET scans, in the diagnosis and management of cutaneous pediatric LCH. A comprehensive literature search identified seven relevant articles, including retrospective studies and case reports. These studies highlight the efficacy of FDG-PET in localizing active LCH skin lesions, monitoring disease activity, and guiding treatment decisions. FDG-PET represents a valuable imaging modality for dermatologists, oncologists, and pediatricians managing pediatric LCH patients with cutaneous involvement. This non-invasive technique contributes to improved diagnostic accuracy and facilitates early intervention, ultimately enhancing patient care and outcomes.

Clinical Characteristics and Outcomes in Patients With Localized Gastric Langerhans Cell Histiocytosis: A Case Series

Objectives: Localized gastric Langerhans cell histiocytosis (LCH) characterized by abnormal proliferation of Langerhans cells in the stomach without systemic involvement, is rare; therefore, the clinical characteristics and outcomes of LCH remain unclear. We investigated the clinical characteristics and outcomes in patients diagnosed with localized gastric LCH and have also discussed treatment strategies for this rare disease.Methods: The study included seven patients diagnosed with localized gastric LCH at our hospital between September 1997 and December 2023. We retrospectively reviewed medical records and analyzed the clinicopathological characteristics and patient outcomes.Results: Endoscopically, localized gastric LCH appeared as a small erosion in the distal part of the stomach. Positron emission tomography-computed tomography revealed normal findings in 100.0% (4/4) of patients during pre-treatment workup. Immunohistochemical analysis using S-100 and CD1a showed immunopositive cells in all tested patients. Of the six patients who underwent follow-up, two (33.3%) showed metachronous recurrence at a location distinct from the initial site. However, all patients eventually showed spontaneous regression of the disease, and no gastric LCH-induced mortality was observed during follow-up.Conclusions: Careful and regular surveillance may be sufficient for patients with localized gastric LCH without systemic involvement.

Rare yet Critical Manifestations: A Case of Langerhans Cell Histiocytosis in a Child Presenting with Belt-Like Dorsalgia: Diagnostic and Therapeutic Approach

Langerhans cell histiocytosis (LCH) is a rare disease characterized by abnormal proliferation of Langerhans cells. We present the case of a 9-year-old girl complaining of recent belt-like dorsalgia, whose imaging revealed dorso-lumbar scoliosis and a tumor mass at the posterior arch of T11 with posterior epidural infiltration. Surgical decompression and tumor resection were performed, histopathologically confirming the diagnosis of LCH. This abstract highlight the diagnostic and therapeutic challenges of LCH, emphasizing the importance of a multidisciplinary approach for effective management of this rare disease. Additionally, it underscores the relevance of early intervention and meticulous follow-up to ensure optimal outcomes for patients with LCH.

Langerhans Cell Histiocytosis in the Sphenoid Wing

Langerhans Cell Histiocytosis (LCH) is a rare and broad-spectrum of disease caused by uncontrolled proliferation of pathologic Langerhans cell resulting in localize and systemic organ infiltration. The clinical presentation can be unspecific and varies between individuals depending on the anatomical location and organ involvement. In view of bony infiltration is the most common in LCH, clinicians have to deal with the challenge of diagnosis dilemmas such as Giant Cell Tumour, Ewing’s sarcoma, osteogenic sarcoma, plasmacytoma, osteomyelitis or bony metastasis, particularly from neuroblastoma. Hence, it requires an excellent multidisciplinary team to establish the diagnosis and start targeted treatment early to prevent fatal complications. The treatment modalities include surgery, immunosuppressive therapy, chemotherapy or in combination. Recently, a seven months old boy presented to our centre with one-week duration of left cheek swelling and left eye proptosis. After detailed clinical evaluation together with imaging and biopsy, the lesion over the bilateral sphenoid and left zygoma were concluded to be Langerhans Cell Histiocytosis (LCH).

Langerhans Cell Histiocytosis With Unusual Hexagonal Crystals in Addition to Usual Charcot-Leyden Crystals. Report of a Patient With Possible Process of Crystal Formation and Clinical Significance of a "Necrotic" Change.

Langerhans cell histiocytosis is a rare neoplastic disorder characterized by the proliferation of Langerhans cells and often accompanied by eosinophil infiltration. Charcot-Leyden crystals, composed of galectin 10, are occasionally observed in Langerhans cell histiocytosis; however, histological images are rarely reported. We herein present a patient with Langerhans cell histiocytosis with Charcot-Leyden crystals and hexagonal crystals by describing the histologic and immunohistochemical features of a lymph node. A unique distribution of Charcot-Leyden crystals and hexagonal crystals was observed in this patient, shedding light on their possible formation process of the latter. We discuss the biological significance of eosinophilic abscesses in Langerhans cell histiocytosis and propose that these crystals may be linked to extracellular trap-cell death (ETosis). This example challenges the conventional characterization of "necrosis" in Langerhans cell histiocytosis and underscores the importance of recognizing ETosis as a potential mechanism involved in the pathogenesis of Langerhans cell histiocytosis. Further studies are underway to validate significance of these findings in a larger cohort of Langerhans cell histiocytosis patients.

Langerhans Cell Histiocytosis Following Hodgkin Lymphoma in Adult: A Case Report

Introduction: Langerhans cell histiocytosis (LCH) is a very rare disorder, and usually considered a disease of childhood. It is rarely observed in adults. Its etiopathogenesis remains to be elucidated. One possible etiological cause is a reactive proliferation of Langerhans cells following chemotherapy or radiotherapy for Hodgkin's disease (HD). Eosinophilic granuloma is the benign accumulation of histiocytes located primarily in the bones, but which also affects other organs, including the skin, lungs and lymph nodes. The time interval between LCH occurrence and previous lymphoma is variable. The occurrence of eosinophilic granuloma in a patient with Hodgkin disease has rarely been reported. Objective: This case report aimed to describe the clinic-pathological, histopathological, immunohistochemical and other features of LCH and to analyze LCH clinical features for improving diagnosis and decreasing misdiagnosis rate. Case report: In this report, a 38-year-old female presented with LCH twenty-two months after diagnosis and treatment of nodular sclerosing HD. The patient presented with generalized lymphadenopathy and general weakness. The Langerhans cells diffusely infiltrated in the inguinal lymph node and the tumor cells were positive for CD1a and S-100 expression. The patient received chemotherapy and show complete remission. Conclusion: LCH has a very rare occurrence following HD in adult. The definitive diagnosis depends on pathological biopsy and immunohistochemistry. Although specific therapeutic approach hasn't been well established, combined chemotherapy for multisystem lesions and surgical operation or radiotherapy for unifocal lesions may improve the therapy.

Langerhans Cell Histiocytosis Mimicking Otitis Media

Langerhans cell histiocytosis (LCH) is a spectrum of disease characterised by proliferation of Langerhans cells causing local or systemic manifestations. We report a two-year old boy who presented with a two-month history of progressive painless swelling over the right zygomatic region with ipsilateral otorrhea. Radiological investigation revealed an expansile hypodense lesion within the temporal bone with erosion of surrounding structures and meningeal enhancement. An ultrasound-guided biopsy of the lesion confirmed the diagnosis of LCH. LCH of the temporal bone may masquerade as otitis media with intra-temporal complications. A high index of suspicion is essential to avoid delay in diagnosis and management.

A rare case of high risk multisystem Langerhans Cell Histiocytosis in infant

Objective: Langerhans cell histiocytosis (LCH) stands as the most common histiocytic disorder. It is categorized into single-system single site, single-system multi-site, and multisystem types, with or without involvement of risk organs. Clinical presentation exhibits considerable variability, contingent upon the affected organ systems. Given its rarity, diverse locations, and varying severity, there are currently no established treatment guidelines for LCH. Case Presentation: We documented the case of a 5-month-old male diagnosed with Langerhans cell histiocytosis (LCH), presenting with high-risk multisystem organ involvement and concurrent unifocal bone involvement. Bone marrow aspiration revealed infiltration by multinucleated giant cells within the marrow. Skin biopsy demonstrated Langerhans cell proliferation with epidermotrophism and the characteristic reniform nucleus resembling a coffee bean. The patient was treated following the histiocytosis protocol, which included daily oral prednisone and 6-mercaptopurine, in addition to weekly intravenous vinblastine and methotrexate administered every two weeks. Unfortunately, the patient displayed limited response during the initial phase of treatment and, tragically, passed away during the eighth week of therapy. Conclusion: Langerhans cell histiocytosis (LCH) is a rare disease characterized by variable disease presentations and is associated with significant morbidity and mortality. Timely recognition of clinical manifestations and risk factors, coupled with appropriate treatment, is crucial to reduce mortality and long-term complications associated with the condition.

A rare case of high risk multisystem Langerhans Cell Histiocytosis in infant

Objective: Langerhans cell histiocytosis (LCH) stands as the most common histiocytic disorder. It is categorized into single-system single site, single-system multi-site, and multisystem types, with or without involvement of risk organs. Clinical presentation exhibits considerable variability, contingent upon the affected organ systems. Given its rarity, diverse locations, and varying severity, there are currently no established treatment guidelines for LCH. Case Presentation: We documented the case of a 5-month-old male diagnosed with Langerhans cell histiocytosis (LCH), presenting with high-risk multisystem organ involvement and concurrent unifocal bone involvement. Bone marrow aspiration revealed infiltration by multinucleated giant cells within the marrow. Skin biopsy demonstrated Langerhans cell proliferation with epidermotrophism and the characteristic reniform nucleus resembling a coffee bean. The patient was treated following the histiocytosis protocol, which included daily oral prednisone and 6-mercaptopurine, in addition to weekly intravenous vinblastine and methotrexate administered every two weeks. Unfortunately, the patient displayed limited response during the initial phase of treatment and, tragically, passed away during the eighth week of therapy. Conclusion: Langerhans cell histiocytosis (LCH) is a rare disease characterized by variable disease presentations and is associated with significant morbidity and mortality. Timely recognition of clinical manifestations and risk factors, coupled with appropriate treatment, is crucial to reduce mortality and long-term complications associated with the condition.

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.

P20 A mysterious case of recurrent malignant melanoma

Abstract A 74-year-old White man presented to community dermatology services in 2020 with one lesion on the right temple and one on the left forehead. These were investigated with punch biopsies and reported as benign intradermal melanocytic naevi. One year later, he was referred to our teledermatology clinic with a pink nodule on the right temple, which had never healed following the 2020 biopsy. The teledermatology photos were more in keeping with basal cell carcinoma (BCC) and he was booked in for an excision. Histology reported the lesion as ulcerated invasive malignant melanoma (Breslow thickness 3.1 mm and mitotic figures). At this stage, previous biopsies from 2020 were reviewed and invasive malignant melanoma (MM) was confirmed. He was reviewed in the clinic and, on skin examination, he had a 7-mm BCC on the right upper nasal bridge. We found a small scar, but no lesions, on the left temple. He had areas of psoriasis on his elbows and knees. No organomegaly or lymphadenopathy was identified on systemic examination. He underwent wide local excision (WLE) of the right temple MM scar with sentinel lymph node biopsies from the right neck, which were negative. Initial radiological imaging did not show any metastases. Three-month follow-up computed tomography showed colon thickening, and the patient was diagnosed with hepatic flexure tumour, which was treated with right hemicolectomy. Further imaging showed no evidence of metastases. In September 2022, a new 6-mm, light-brown indentation was identified on the medial edge of the melanoma scar on the right temple. Initially, the biopsy results reported recurrent melanoma. Further histological slide review and immunochemical analysis demonstrated langerin with multinucleated histiocyte-like cell infiltrates and lymphohistiocytic inflammatory cell infiltrates; Langerhans cell histiocytosis (LCH) was diagnosed. He underwent WLE of this lesion and positron emission tomography; we are still awaiting the results. He has been referred to a specialist haematology team and is awaiting further management. LCH is a rare, multisystem haematological disorder of the clonal proliferation of Langerhans cells. Existing case reports document LCH with concomitant presentations of myeloproliferative disorders, particularly myeloid leukaemias, or noncutaneous manifestations, including pulmonary presentations. To the best of our knowledge, there have been no reports of LCH presenting exclusively with cutaneous manifestations clinically mimicking recurrent MM. The rare incidence and misleading presentation of LCH often results in its lack of consideration as a differential diagnosis for recurrent solitary skin lesions in adults. This case also highlights the diagnostic challenges and thorough investigation required for this unique condition.

Successful treatment of orbital Langerhans cell histiocytosis with stereotactic radiosurgery: A case report and literature review

Key Clinical MessageLangerhans cell histiocytosis (LCH) is a rare inflammatory myeloid neoplasm arising from the proliferation of pathologic Langerhans cells. LCH has a spectrum of presentations predominantly affecting male pediatric patients. As LCH is a relatively uncommon diagnosis, there is no standard of care for treatment of the disease and treatment is based largely on clinical judgment, lesion characteristics, and symptoms at presentation. Here we present a case of unifocal, isolated orbital LCH in a 19‐year‐old young man treated initially with surgical resection. Follow‐up imaging 2 months later demonstrated significant regrowth of the mass and no other sites of disease. The recurrent orbital disease was treated with stereotactic radiosurgery (SRS) to 7 Gy in one fraction. Near complete resolution of the mass was achieved with no recurrence after 1.5 years of follow‐up. SRS for treatment of orbital LCH is a novel treatment not previously described in the literature which may provide benefit in select cases.

A rare cause of solitary rib lytic lesion in adult – A case report

Langerhans cell histiocytosis (LCH) is characterized by the proliferation of Langerhans cells, which can occur in single or multiple organ systems. The most common sites of involvement include skeletal system, central nervous system, lungs, skin, and lymph nodes. LCH involving the rib is one of the rarest site among adults. Herein, we report a case of a 40-year-old man with solitary LCH in posterior aspect of 4th rib.

Лангергансоклітинний гістіоцитоз у дитини з мультисистемним ураженням, інфікованої поліомієлітом та SARS-CoV-2: особливості діагностики та перебігу хвороби. Клінічний випадок

Langerhans cell histiocytosis (LCH) is an abnormal clonal proliferation of Langerhans cells. The prognosis varies depending on the form of the disease and organ damage. Any organs and systems can be involved in the pathological process in various combinations. A poor response to standard therapy and an unfavorable prognosis are characteristic of patients with a multisystem form of LCH and involvement of organs at risk. Skin lesions are a classic sign of LCH. Purpose - to describe the complexity and duration of diagnosis of LCH with multisystem damage in a boy aged 2 years and 2 months, infected with poliomyelitis and coronavirus. Clinical case. The first clinical manifestations of LCH in the child debuted with an eczematous-seborrheic rash on the scalp with spread to the limbs and trunk. The child was treated for toxicoderma, hemorrhagic vasculitis at the place of residence for 6 months. The boy lost 1.5 kg of body weight in 1 month. At the time of hospitalization, seborrheic-eczematous rashes on the skin with a hemorrhagic component, trophic-inflammatory changes in the nails of the hands, signs of protein-energy deficiency, stomatitis, gingivitis, hepatosplenomegaly, polyserositis, diabetes insipidus, osteolytic foci of the frontal bones were found. Results of the tests: anemia, thrombocytopenia, hypoproteinemia and hypoalbuminemia, coagulation disorders. The patient had the onset of lower flaccid paraparesis, muscle hypotonia. The boy was diagnosed with a number of infectious complications, including poliomyelitis (a derivative of vaccine poliovirus type 2), COVID-19. The child received LCH-III cytostatic therapy with a positive effect. The research was carried out in accordance with the principles of the Helsinki Declaration. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the authors.

Novel characterization of CXCR4 expressing cells in uninfected and herpes simplex virus-1 infected corneas

PurposeTo characterize CXCR4-expressing cells in uninfected and herpes simplex virus-1 (HSV-1) infected corneas. MethodsThe corneas of C57BL/6J mice were infected with HSV-1 McKrae. The RT-qPCR assay detected CXCR4 and CXCL12 transcripts in uninfected and HSV-1-infected corneas. Immunofluorescence staining for CXCR4 and CXCL12 protein was performed in the frozen sections of herpes stromal keratitis (HSK) corneas. Flow cytometry assay characterized the CXCR4-expressing cells in uninfected and HSV-1-infected corneas. ResultsFlow cytometry data showed CXCR4 expressing cells in the separated epithelium and stroma of uninfected corneas. In the uninfected stroma, CD11b + F4/80+ macrophages are the predominant CXCR4-expressing cells. In contrast, most CXCR4 expressing cells in the uninfected epithelium were CD207 (langerin)+, CD11c+, and expressed MHC class II molecule, documenting the Langerhans cells (LCs) phenotype. After corneal HSV-1 infection, CXCR4 and CXCL12 mRNA levels increased significantly in HSK corneas than in uninfected corneas. Immunofluorescence staining showed CXCR4 and CXCL12 protein localization in the newly formed blood vessels in the HSK cornea. Furthermore, the infection resulted in LCs proliferation, causing an increase in their numbers in the epithelium at 4 days post-infection (p.i.). However, by 9-day p.i., the LCs numbers declined to the counts observed in naïve corneal epithelium. Our results also showed neutrophils and vascular endothelial cells as the prominent CXCR4-expressing cell types in the stroma of HSK corneas. ConclusionsTogether, our data demonstrate the expression of CXCR4 on resident antigen presenting cells in the uninfected cornea and on infiltrating neutrophils and newly formed blood vessels in the HSK cornea.

Langerhans cell histiocytosis: a rare cause of exudative enteropathy in a young child

Exudative enteropathy is a clinical syndrome characterized by excessive loss of proteins through the gastrointestinal tract and is a rare complication of various gastrointestinal diseases. One of the rarest causes of protein malabsorption is Langerhans cell histiocytosis, which occurs as a result of inflammatory neoplasia of myeloid precursor cells caused by mutations in the mitogenactivated protein kinase pathway. Abnormal proliferation and accumulation of Langerhans cells in the intestinal wall leads to a violation of the outflow of lymph, and causes clinical manifestations characteristic of enteropathy. Given that the lesion of the gastrointestinal tract with histiocytosis from Langerhans cells occurs in 2–3% of cases, and the clinical signs are not highly specific, timely diagnosis is difficult. Delayed verification of the diagnosis and late initiation of adequate treatment are risk factors for multisystem lesions and lead to an unfavorable outcome. The literature describes a few observations of the onset or manifestation of the disease with symptoms of protein malabsorption. We present a rare clinical case of diagnosing histiocytosis from Langerhans cells in a young child with severe manifestations of exudative enteropathy at the onset. The patient's parents gave their consent to the use of their child's data, including photographs, for research purposes and in publications.Refractory gastrointestinal symptoms require mandatory endoscopic and histological examination to identify rare causes of malabsorption. Timely initiation of targeted therapy with vemurafenib in combination with subsequent chemotherapy provided the child with a favorable prognosis and stable remission of the disease.

"Coexistence of Classical Hodgkin Lymphoma and Langerhans Cell Proliferation Presenting as a Tumor in Tumor Pattern"

"Coexistence of Classical Hodgkin Lymphoma and Langerhans Cell Proliferation Presenting as a Tumor in Tumor Pattern"

Possible involvement of CXCR3-CXCR6 + CD4 + T cells in Langerhans cell histiocytosis.

Langerhans cell histiocytosis (LCH) is a condition characterized by proliferation of Langerhans cells and wide-range pathologies, ranging from single granulomatous lesions to multi-organ involvement, associated with tissue destruction. LCH pathogenesis remains obscure although association with interleukin (IL)-17A has been reported. We report here a case that illustrates the potential pathogenic role of helper T17 (Th17) cells in LCH-related bone destruction. The patient was a 66-year-old woman. The clinical course included craniectomy and bone mass excision in X-9, diagnosis of LCH confirmed by histopathology, followed by 26-month chemotherapy. In August X, the patient was diagnosed with complete central diabetes insipidus. Symptoms improved after treatment with desmopressin. Pituitary magnetic resonance imaging showed swelling extending from the suprasellar region to the pituitary stalk, suggestive of LCH recurrence. This was followed by chemotherapy combined with mercaptopurine hydrate. RESULTS: Subsequent peripheral blood lymphocyte analysis showed marked increase in activated Th17 cells (CXCR3-CXCR6+ CD4+ T cells). Double staining for CD4 and IL-17 by immunofluorescence of pathological tissue samples obtained during temporal bone mass excision, which confirmed the diagnosis of LCH in X-9, showed areas of combined presence of CD4-positive cells and IL-17-positive cells. Chemotherapy resulted in size reduction of the pituitary lesion and decrease in peripheral blood-activated Th17 cells. We found abundant peripheral blood-activated Th17 cells and high percentages of IL-17-producing cells in osteolytic bone lesions in LCH. This finding, together with the decrease in peripheral blood-activated Th17 cells following chemotherapy, suggests the potential involvement of activated Th17 cells in LCH-related osteolysis.