Adult Langerhans Cell Histiocytosis Research Articles

Langerhans cell histiocytosis in adults: literature review

Langerhans cells histiocytosis is a variant of malignant histiocytosis. The course and symptoms vary. patients with localized forms have a better prognosis, because local therapy is effective. patients with multifocal forms of histiocytosis receive systemic drug therapy, which cures some of the patients. This review provides up-to-date data about typical presentation of the organ involvement, diagnosis, course and therapy of various forms of Langerhans cells histiocytosis.

Whole-body magnetic resonance imaging for staging Langerhans cell histiocytosis in children and young adults.

Radiographic skeletal survey (R-SS) is the standard imaging technique for the initial staging of Langerhans cell histiocytosis (LCH). Whole-body magnetic resonance imaging (WB-MRI) has been proposed as an effective, radiation-free alternative. We prospectively assessed patients with LCH followed at three tertiary centers in Italy and Austria. Two national study protocols were independently designed, and data were then pooled to increase the power of their findings. R-SS and WB-MRI were performed at diagnosis and repeated at the follow-up to confirm the nature of the identified lesions and to study their evolution. Data from 67 patients were analyzed (52 from Italy and 15 from Austria). Compared to R-SS, WB-MRI identified 29 additional skeletal lesions in 14 patients (including two false-positive lesions). Two skeletal lesions were detected at R-SS and missed at WB-MRI (false negative). Per-lesion sensitivity rates were 78.6% (95% CI: 71.0-85.9) for R-SS and 98.4% (95% CI: 94.4-99.8) for WB-MRI, respectively. Based on WB-MRI findings, six patients would have been upstaged to a higher risk class than staging with R-SS. WB-MRI had a significantly higher detection rate for skeletal lesions compared to R-SS. Clinical and radiology expertise is required to avoid upstaging and overtreatment.

Isolated Scapular Lesion of Langerhans Cell Histiocytosis Detected by 18F-FDG PET/CT.

Langerhans cell histiocytosis (LCH) is a rare disease that occurs mainly in pediatric patients and most adult LCH is considered a part of multisystem or multifocal disease. Only 7.3% of cases present as unifocal bone lesion. Herein, we present a case of an isolated scapular lesion of LCH in a 48-year-old man.

CAN WE STOP THE POP?

CAN WE STOP THE POP?

Analysis of thyroid involvement in children and adult Langerhans cell histiocytosis: An underestimated endocrine manifestation.

BackgroundLangerhans cell histiocytosis (LCH) is a rare disease caused by the clonal expansion of CD1a+/CD207+ LCH cells. The thyroid involvement in LCH has mostly been described in case reports.MethodsWe retrospectively evaluated the clinical characteristics, diagnosis, and treatment of 27 children and adult patients with thyroid LCH in our center between 2010 and 2021.ResultsThe incidence of thyroid LCH was 14.00% (7/50) in children and 10.10% (20/198) in adults, respectively. Among patients with thyroid involvement, 81.5% presented with diabetes insipidus (DI) as the first symptom, and 51.9% complained of neck swelling or mass. Children and adults with thyroid LCH had higher frequencies of the hypothalamic-pituitary axis (HPA) (children: 100% vs. 62.8%, P=0.05; adult: 95% vs. 42.1%, P<0.001), the lung (children: 85.7% vs. 25.6%, P=0.004; adult: 70% vs. 50.6%, P=0.099), and a lower frequency of bone (children: 14.3% vs. 55.8%, P=0.049; adult: 45% vs. 73.6%, P=0.008) involvement than patients without thyroid involvement. Patients with thyroid LCH had a higher frequency of primary hypothyroidism and a lower frequency of euthyroidism than patients without it. The two major types of ultrasound imaging were diffuse (55%) and nodular type (45%). The standardized uptake value of thyroid on 18-F-fluorodeoxyglucose positron emission tomography/computed tomography was 5.3–12.8. The diagnoses were confirmed using thyroid aspiration (54.5%) or surgery (45.5%). In addition, thyroid LCH combined with papillary thyroid carcinoma was not rare (2/27).ConclusionThyroid involvement in LCH is not rare. Furthermore, identifying thyroid involvement can facilitate the pathological diagnosis of LCH. Therefore, the possibility of thyroid LCH should be fully investigated in patients with DI, primary hypothyroidism, abnormal thyroid ultrasound results, and multi-system disease. In addition, thyroid aspiration can confirm suspected thyroid LCH. Finally, special attention should be paid to evaluating HPA and pulmonary involvement in thyroid LCH.

Adult Langerhans cell histiocytosis with thyroid gland involvement: clinical presentation, genomic analysis, and outcome.

The present study aims to evaluate the characteristics and treatment outcomes of adult Langerhans cell histiocytosis (LCH) patients with thyroid involvement. We retrospectively described the clinical, biological, and genomic characteristics of a series of 36 LCH patients with thyroid involvement in our center between January 2001 and December 2021. At the time of diagnosis, only one patient was classified as having single-system LCH, and 35 patients were classified as having multisystem (MS) LCH. Three patients had coexisting papillary thyroid carcinoma. Patients with thyroid gland involvement had higher frequencies of pituitary (88.6% vs. 53.4%, P < 0.001), liver (45.7% vs. 20.7%, P = 0.003), and lymph node (54.3% vs. 31.6%, P = 0.012) involvement and a lower frequency of bone (45.7% vs. 72.0%, P = 0.003) involvement than patients without thyroid gland involvement. Sixteen patients had abnormal thyroid function, including nine patients with primary hypothyroidism, one patient with central hypothyroidism, and six patients with subclinical hypothyroidism. BRAFV600E, BRAF N486_P490, and MAP2K1 mutations were detected in 14.3%, 57.1%, and 7.1% of patients, respectively. After a 43-month median follow-up, none of the patients died, and 15 patients experienced reactivation. The median event-free survival was 37.5months. Two of 6 patients with subclinical hypothyroidism had normal thyroid function, and 12 patients still had hypothyroidism after treatment. As the largest adult LCH cohort with thyroid gland involvement to date, we found that patients with thyroid gland involvement had different clinical characteristics, genetic profiles, and outcomes than patients without thyroid gland involvement.

Progress in the Treatment of Adult Langerhans Cell Histiocytosis --Review

Langerhans cell histiocytosis (LCH) is a rare proliferative disease dominated by the proliferation of Langerhans cells, which is inflammatory myeloid neoplasms. Its clinical manifestations are variable, occurring at any age and at any site, and it is rarer in adults than in children. The gold standard for diagnosis is histopathological biopsy. Due to the rarity of adult LCH and the heterogeneity of this disease, treatment of adult LCH should be developed according to the extent of the disease and risk stratification. With the discovery of MAPK, PI3K and c-KIT signaling pathway activation, especially BRAF V600E and MAP2K1 mutations, targeted therapy has become a hot spot for therapeutic research. Meanwhile, the discovery of high expression of M2-polarized macrophages and Foxp3+ regulatory T cells (Treg) in LCH has provided an important basis for the immunotherapy. In this article, we will focus on reviewing the latest research progress in the treatment of adult LCH in recent years, and provide a reference for clinical research on the treatment of adult LCH patients.

International expert consensus recommendations for the diagnosis and treatment of Langerhans cell histiocytosis in adults

AbstractLangerhans cell histiocytosis (LCH) can affect children and adults with a wide variety of clinical manifestations, including unifocal, single-system multifocal, single-system pulmonary (smoking-associated), or multisystem disease. The existing paradigms in the management of LCH in adults are mostly derived from the pediatric literature. Over the last decade, the discovery of clonality and MAPK-ERK pathway mutations in most cases led to the recognition of LCH as a hematopoietic neoplasm, opening the doors for treatment with targeted therapies. These advances have necessitated an update of the existing recommendations for the diagnosis and treatment of LCH in adults. This document presents consensus recommendations that resulted from the discussions at the annual Histiocyte Society meeting in 2019, encompassing clinical features, classification, diagnostic criteria, treatment algorithm, and response assessment for adults with LCH. The recommendations favor the use of 18F-Fluorodeoxyglucose positron emission tomography-based imaging for staging and response assessment in the majority of cases. Most adults with unifocal disease may be cured by local therapies, while the first-line treatment for single-system pulmonary LCH remains smoking cessation. Among patients not amenable or unresponsive to these treatments and/or have multifocal and multisystem disease, systemic treatments are recommended. Preferred systemic treatments in adults with LCH include cladribine or cytarabine, with the emerging role of targeted (BRAF and MEK inhibitor) therapies. Despite documented responses to treatments, many patients struggle with a high symptom burden from pain, fatigue, and mood disorders that should be acknowledged and managed appropriately.

Adult Langerhans Cell Histiocytosis Presenting as Sclerosing Cholangitis in a Liver Explant

Adult Langerhans Cell Histiocytosis Presenting as Sclerosing Cholangitis in a Liver Explant

Adult Langerhans cell histiocytosis involving adjacent vertebra on 18F-FDG PET/CT imaging.

Langerhans cell histiocytosis (LCH) of the spine involving the intervertebral disk and adjacent vertebra is rare in adults. We report a case of a 56-year-old woman with neck pain and right upper limbs numbness. Fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) showed an osteolytic bone lesion in the fourth cervical vertebra (C4) with soft-tissue mass, invading the adjacent intervertebral disc and posterior vertebral body of C3, compressing dural sac and cervical spinal cord. The lesion showed increased 18F-FDG uptake with a maximum standardized uptake value (SUVmax) of 6.75. Subsequently, the histopathologic examination confirmed the diagnosis of LCH.

Treatment outcomes and prognostic factors of patients with adult Langerhans cell histiocytosis.

Adult Langerhans cell histiocytosis (LCH) remains poorly defined. We retrospectively studied 266 newly diagnosed LCH patients to understand the clinical presentation, treatment, and prognosis of adult LCH. The median age at diagnosis was 32 years (range, 18-79 years). At the time of diagnosis, 40 patients had single lesions within a single system, 18 patients had single pulmonary LCH, 26 patients had multiple lesions within a single system (SS-m), and 182 patients had multisystem disease (MS). The most common organ involved in MS patients was the bone (69.8%), followed by the pituitary (61.5%) and lung (61.0%). BRAFV600E , BRAF deletion, and MAP2K1 mutation were detected in 38.8%, 25.4%, and 19.4% patients, respectively. BRAF deletion was found more common in patients with MS LCH compared to single-system LCH (38.5% vs 7.1%, p=.004), also in patients with liver involvement (69.2% vs 14.3%, p < .001). The estimated 3-year overall survival (OS) and event-free survival (EFS) rates were 94.4% and 54.7%, respectively, in SS-m and MS LCH. Multivariate Cox regression showed that involvement of the liver or spleen at baseline predicted poor EFS and receiving cytarabine-based therapy as a first-line treatment and age older than 30 years at diagnosis predicted favorable EFS. The involvement of risk organs and age older than 50 years predicted poor OS, and receiving cytarabine-based therapy predicted favorable OS. Therefore, BRAF deletion was correlated with MS LCH, particularly those with liver involvement. Liver or spleen involvement at baseline indicates a poor prognosis, and a cytarabine-based regimen could be considered as first-line treatment for adult LCH patients.

Promising Real World Survival Data in Adult-Onset Langerhans Cell Histiocytosis: An Australasian Lymphoma Alliance 20 Year Retrospective Study

▪Background: Langerhans Cell Histiocytosis (LCH) is a rare inflammatory neoplasm originating from bone marrow-derived CD207+/CD1+ clonal dendritic cells, with cells expressing BRAF V600E in around 50% of cases. Although more common in the paediatric setting, LCH is rare in adults, with an incidence of 1 to 2 cases per million. This combination of disease heterogeneity and infrequency means that data on treatment strategies and outcomes is limited, and a consensus on management is lacking. Data has historically been extrapolated from the larger paediatric cohort, with emerging phase II data on the efficacy and safety of upfront methotrexate and cytosine arabinoside (AraC) in adult LCH. Other agents used include cladribine (CdA), hydroxyurea, vinblastine, and prednisolone-based regimens, and more recently MEK/BRAF inhibitors, but none of these have been trialled prospectively. LCH can be an aggressive disease with a poor prognosis.Methods : We included patients aged ≥18 years diagnosed with LCH on histopathology between January 1, 2000 and August 1, 2021 from ten sites across Australia and New Zealand. Variables included demographic data, system and organ involvement, central nervous system (CNS) involvement, bone marrow involvement and BRAF V600E mutation status. Outcomes measured included overall survival (OS), progression-free survival (PFS) and total lines of therapy. Response to therapy was modified from the Scoring System of the HS LCH III trial: Complete response (CR) was defined by resolution of all signs of disease activity, including neuroendocrine dysfunction, skin and radiological lesions; and a partial response (PR) was defined as patients with “active disease better” and those with “mixed response”. Stable or worsening symptoms/radiology were classified as progressive disease (PD). Patients who were alive or lost to follow-up were censored on the date of last follow-up.Results : We identified 46 patients with a median age at diagnosis of 39 years (range 18-81) (Table 1). The sex ratio was 1. 41% of patients had MS-LCH at diagnosis, of which 24% had high risk organ (liver, bone marrow, or spleen) involvement. 37% had multifocal bone disease. 28% of patients had CNS involvement at diagnosis. BRAF V600E mutation status was assessed in only 43% of cases, with a mutation frequency of 40%. The median number of lines of therapy was 1.7 (range 0-9). Three patients (7%) underwent lung transplantation for isolated pulmonary LCH. 31% percent of patients were treated with chemotherapy upfront, with the majority receiving AraC (43%,) and the remainder receiving vinblastine, prednisolone and 6-mercaptopurine (6-MP) (21%), vinblastine/prednisolone (21%), CdA (14%) or methotrexate and 6-MP (2%). Of note, 67% (n=4) of patients who were treated with upfront AraC and 100% (n=2) of patients treated with upfront CdA had a CR, while those patients treated with upfront vincristine-based regimes had, at best, a PR (50%, n=3) or PD (50%).Of the 46 patients, with a median follow up of 34.6 months (range 0.63-250.2), there were 7 deaths (15%) with 6/7 due to progressive disease, and the remaining death due to complications of lung transplantation. Median OS was not reached (Figure 1), while OS at 5 years was 85%. Median PFS was 9 years (range 0.05-21) (Figure 2), with a non-significant trend towards reduced PFS in patients with MS-LCH (5 years) compared to SS-LCH (9 years) (Figure 3). There was also a trend towards reduced OS in patients who received AraC as systemic therapy versus other forms of systemic therapy.Conclusion: We report the largest multicentre Australasian cohort of patients diagnosed with adult-onset LCH. OS and PFS were longer than previously reported in the literature. There remains significant heterogeneity in diagnostic and treatment strategies. There was a trend towards improved response rate to upfront AraC or CdA when compared to the vinblastine-based regimens, and further prospective research with these agents is required in this setting. Progress in this disease is challenging due its rarity, highlighting the need for standardisation of diagnostic and treatment strategies as well as a national and/or international registry. [Display omitted] DisclosuresFong: Amgen: Research Funding; AbbVie, Amgen, Novartis, Pfizer, Astellas: Honoraria; Amgen, BMS: Speakers Bureau. Ku: Antegene: Consultancy; Roche: Consultancy; Genor Biopharma: Consultancy. Cunningham: Principia Biopharma: Research Funding; Rigel: Research Funding; Janssen: Research Funding; Novartis: Research Funding; AbbVie: Research Funding; Amgen: Research Funding; Astex: Research Funding; Celgene: Research Funding. Hamad: Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

Survivorship Issues in Adult Patients With Histiocytic Neoplasms.

Adult-onset histiocytoses (AOH), primarily Rosai-Dorfman disease (RDD), Erdheim-Chester Disease (ECD), and adult Langerhans cell histiocytosis (ALCH), are a group of related histiocytic neoplastic disorders featuring multisystemic manifestations. The disorders are largely incurable, and are essentially chronic neoplastic diseases with a variable prognosis. Prompt diagnosis and treatment is important to prevent debilitating and even life-threatening complications. Survivorship issues abound in AOH, due to their multisystemic manifestations and the sometimes recalcitrant chronic inflammation, which can lead to other debilitating complications such as fatigue, weakness, and pain. Because these disorders are rare, few healthcare professionals are proficient in their management; therefore the aim of these guidelines is to offer guidance on how to manage patients, and how to create survivorship care plans through the efforts of an interdisciplinary team.

Recommendations for Managing Adults With Histiocytic Neoplasms: New NCCN Guidelines

The histiocytoses, a group of clonal and reactive conditions, arise from monocytic macrophage or dendritic cell lineages. The current NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Histiocytic Neoplasms reflect the most up-to-date, evidence-based data relating to the evaluation and management of this disease. Specifically, the guidelines focus on adult Langerhans cell histiocytosis, Erdheim-Chester disease, and Rosai-Dorfman disease. Because these disorders are rare, challenges have arisen regarding clinical suspicion, histologic diagnosis, treatment, and molecular subtyping. Future versions of the NCCN Guidelines will address the diagnosis and management of pediatric patients, as well as malignant histiocytosis.

Diagnosis and treatment of adult Langerhans cell histiocytosis

Diagnosis and treatment of adult Langerhans cell histiocytosis

Langerhans cell histiocytosis in adults: a retrospective, single-center case series.

Langerhans cell histiocytosis is rare in adults, and most of what we know about its diagnosis and treatment comes from pediatric studies. We report clinical findings and results of treatment in a retrospective series of 63 consecutive adult patients (18-76years old), treated at our pediatric unit from 1990 to 2020 using the same approach as for children. Patients were classified as having single-system disease (SS-LCH) in 41 cases, which was unifocal in 34 of them and multifocal in 7, or multisystem disease (MS-LCH) in 17 and primary pulmonary (pLCH) in 5. Twenty patients also had diabetes insipidus. A "wait and see" strategy was recommended after biopsy/surgery for patients with unifocal SS-LCH. Systemic treatment was proposed for cases of SS-LCH involving "special sites" or with multifocal disease, and in cases of MS-LCH. EFS and OS for the cohort as a whole were 62.2% and 100%, respectively, at 5years and 52.5% and 97.6% at 10years. Three patients died due to the damage caused by the multiple therapies administered. The rate of disease reactivation was high (affecting 40% of cases), with several reactivations over the years despite multiple lines of treatment. Though clinical history of LCH may differ between adults and children, in the absence of specific, tailored protocols, clinical approach to adult cases may draw on pediatric experience. Patients with limited disease have a good prognosis without any need for systemic therapy. Potentially greater toxicity in adults of systemic treatments generally used in pediatric setting should be borne in mind.

Efficacy of Single-Agent Cytarabine in Adult Langerhans Cell Histiocytosis

Langerhans Cell Histiocytosis (LCH) in adults is rare and has little prospective data to guide therapy. We describe a 36 year old gentleman who presented with a three-month history of isolated cervical lymphadenopathy, from which excision biopsy revealed sheets of large, atypical cells 10-15 um in size, with indented nuclei and fine chromatin along with eosinophilic microabscesses. Immunohistochemistry was positive for CD3, CD20, CD68, CD1a, S100, CD4, Langerin (CD207) and CD45 with a Ki67 index of 10%. PET scan showed FDG-avid uptake in left mastoid air cells, which was confirmed by MRI to indicate bony involvement with disease. Bone marrow and CSF were normal. He was diagnosed as multisystem LCH without risk organ involvement and initiated on single agent cytarabine at 100 mg/m2 five days a month. A PET scan after three cycles showed near complete metabolic resolution. He has completed six cycles of the same and is asymptomatic. He is planned for continuation of Cytarabine for another of 12 to 14 months. Single agent cytarabine appears safe and effective for adult patients with LCH. We provide a short summary of available data: compilation of prospective data will further clarify the utility of this regimen in adult patients with LCH.

Cutaneous Langerhans cell histiocytosis in adults: A retrospective cohort study of adult patients presenting to a single academic cancer center between 2003 and 2017

To the Editor: Due to the rarity of adult-onset Langerhans cell histiocytosis (LCH), guidelines on surveillance, staging, and management of cutaneous LCH are lacking.1 We determined the incidence and time to development of systemic LCH for patients first presenting to dermatology with cutaneous involvement of LCH and skin-limited symptoms and evaluated clinical features, disease course, and management.

Phenotypes and prognostic factors in adults with Langerhans cell histiocytosis.

7049 Background: Langerhans cell histiocytosis (LCH) can manifest as single system (SS) disease, multisystem (MS) disease, or pulmonary LCH (smoking-related). There is a paucity of data on prognostic factors including risk organ (RO) involvement (liver, spleen, and bone marrow) in adult LCH, which we sought to address in this study. Methods: Single-center retrospective study of patients ≥18y diagnosed with LCH from 1998 to 2020. Univariate and multivariate analyses for progression free survival (PFS) and overall survival (OS) were conducted using age, sex, organ involvement, LCH subtype, year of diagnosis, BRAF V600E status, and treatments. Results: We included 219 patients with LCH; median age 43y (range 19-88), females 51%, SS unifocal (23%), SS multifocal (6%), pulmonary (31%) and MS (40%). Commonly involved organs included lung (53%), bone (42%), skin (24%), pituitary (16%), and CNS (12%). BRAF V600E was positive in 40/88 (46%). Median follow-up duration was 6.1y (95% CI, 5.1- 7.1). On univariate analysis, factors associated with worse PFS were bone LCH, RO involvement, multifocal/MS LCH, and radiation therapy alone; those with worse OS included RO involvement, MS disease, BRAF V600E+, and age ≥45y at diagnosis. In multivariate analysis, BRAF V600E and age ≥45y at diagnosis were associated with worse mortality (Table). Median PFS was not reached (NR-NR) for SS unifocal LCH, 5mo (0-12.7) for SS multifocal LCH, 110mo (84.7-135.3) for pulmonary LCH, and 27mo (17.2-36.8) for MS LCH. 5-year OS was 97.4% for SS unifocal LCH, 100% for SS multifocal LCH, 96.1% for pulmonary LCH, and 79.9% for MS LCH. 41 (18.7%) developed a second primary malignancy (SPM), of which 11 were hematologic neoplasms. There was a trend towards a higher prevalence of SPMs in patients with BRAF V600E (28% vs. 17%; p = 0.22). Conclusions: In our large single-center study, PFS for multifocal and MS LCH was worse than SS unifocal or pulmonary LCH. RO involvement was not associated with outcomes in multivariate analysis. Overall prognosis was excellent for all subtypes except MS LCH. BRAF V600E and older age were associated with worse OS. The prevalence of SPMs was very high and needs to be explored further.[Table: see text]

Multifocal Multisystem Langerhans Cell Histiocytosis in an Adult Female Atypically Presenting With Multiple Abdominopelvic Abscesses

Introduction: Langerhans Cell Histiocytosis (LCH) is a condition of malignant clonal proliferation of myeloid bone marrow cells that more commonly affects children than adults. Furthermore, its presentation remains variable ranging from single organ to multisystem involvement including bone, skin, lymph, liver, spleen, lung, and central nervous system. We report an unusual case of multisystem LCH in an adult female presenting with multiple soft tissue abscesses. Case: We report a case of a 38-year-old female with a past medical history of polysubstance abuse, type 2 diabetes, polycystic ovarian syndrome, and isolated central diabetes insipidus who had multiple hospitalizations for recurrent soft tissue abscesses treated with incision and drainage and antibiotics. Imaging studies revealed multiple osteolytic lesions involving the bilateral iliac crests, acetabulum and femur, as well as an iliopsoas abscess. Given her prior history of isolated central diabetes insipidus, the possibility of LCH as the cause was entertained. Histological evaluation performed on an inguinal soft tissue sample stained positive for CD1a and S100, and a formal diagnosis of Langerhans Cell Histiocytosis (LCH) was made. The patient was treated with chemotherapy with good results. Conclusion: This report presents a rare and unusual case of adult onset multisystem LCH involving bone, skin, lymph, and central nervous system presenting with recurrent large abdominopelvic abscesses. These abscesses may represent a rare and unrecognized form of soft tissue involvement of LCH.