Demographics and additional haematologic cancers of patients with histiocytic/dendritic cell neoplasms.

AIMS: The discovery of somatic genetic alterations established many histiocytic disorders as haematologic neoplasms. We aimed to investigate the demographic characteristics and additional haematologic cancers of patients diagnosed with histiocytic disorders in The Netherlands. METHODS AND RESULTS: We retrieved data on histiocytosis patients from the Dutch Nationwide Pathology Databank (Palga). During 1993 to 2022, more than 4000 patients with a pathologist-assigned diagnosis of a histiocytic disorder were registered in Palga. Xanthogranulomas were the most common subtype, challenging the prevailing assumption that Langerhans cell histiocytosis (LCH) is the most common histiocytic disorder. LCH and juvenile xanthogranuloma (JXG) had a peak incidence in the first years of life; males were overrepresented among all histiocytosis subgroups. 118 patients had a histiocytic disorder and an additional haematologic malignancy, including 107 (91%) adults at the time of histiocytosis diagnosis. In 16/118 patients, both entities had been analysed for the same genetic alteration(s). In 11 of these 16 patients, identical genetic alterations had been detected in both haematologic neoplasms. This included two patients with PAX5 p.P80R mutated B cell acute lymphoblastic leukaemia and secondary histiocytic sarcoma, further supporting that PAX5 alterations may predispose (precursor) B cells to differentiate into the myeloid lineage. All 4/11 patients with myeloid neoplasms as their additional haematologic malignancy had shared N/KRAS mutations. CONCLUSIONS: This population-based study highlights the frequency of xanthogranulomas. Furthermore, our data add to the growing evidence supporting clonal relationships between histiocytic/dendritic cell neoplasms and additional myeloid or lymphoid malignancies. Particularly adult histiocytosis patients should be carefully evaluated for the development of these associated haematologic cancers.

Endocrine features of Langerhans cell histiocytosis in paediatric patients: A 30-year review.

Langerhans cell histiocytosis (LCH) is a rare proliferative disorder characterised as an inflammatory myeloid neoplasia. Endocrine manifestations of LCH, particularly central diabetes insipidus (CDI), have been described from the 1940s, through case studies and small cohort analyses. There are limited Australian paediatric data described in recent literature. AIM: To document the incidence of endocrine features in paediatric patients with LCH, treated at a tertiary paediatric centre in Victoria, Australia. METHODS: Retrospective chart review of electronic medical records and oncology database of patients with LCH managed at a tertiary paediatric centre. Patients were excluded if a biopsy did not suggest LCH or if records were incomplete. RESULTS: One hundred seventy-one patients were identified and 141 records of patients diagnosed with LCH over the last 30 years were assessed for endocrinopathies, from diagnosis to last documented follow-up. Mean age at diagnosis was 5 years 8 months. Of these, 15% (n = 21) had CDI, 7% had growth hormone deficiency (GHD) (n = 10) and 8% (n = 11) had more than one endocrinopathy noted during follow-up. Forty percent (n = 57) were pre-pubertal at the time of audit or upon discharge from tertiary services. CONCLUSIONS: Ongoing pituitary assessment, in addition to CDI, is required to detect evolving deficiencies of GHD and gonadotropins as these can be subtle, late or missed. Close follow-up of growth and progression through puberty, even if discharged from tertiary care, is essential.

Long-term outcomes among adults with Langerhans cell histiocytosis.

Advances in the treatment of Langerhans cell histiocytosis (LCH) have resulted in a growing survivor population. There is a lack of data on long-term outcomes among adults with LCH. We conducted a retrospective record review of 219 adults (aged ≥18 years) with LCH. Most common presentation was multisystem (34.2%), followed by single-system pulmonary (32%), unifocal (28.3%), and single-system multifocal (5.5%) LCH. Risk organ involvement (the liver, spleen, or bone marrow) was seen in 8.7% of cases, and 40 of 88 (45.5%) tested cases were BRAFV600E. At a median follow-up of 74 months, 5-year progression-free survival (PFS) was 58.3% and estimated median PFS was 83 months. Median overall survival (OS) was not reached; 5- and 10-year OS rates were 88.7% and 74.5%, respectively. Risk organ involvement was associated with worse PFS (hazard ratio [HR], 4.5) and OS (HR, 10.8). BRAFV600E was not associated with risk organ involvement or survival. When compared with matched unaffected US population, individuals with LCH had a significantly higher risk of overall mortality (standardized mortality ratio [SMR], 2.66), specifically among those aged <55 years at diagnosis (SMR, 5.94) and those with multisystem disease (SMR, 4.12). Second cancers occurred in 16.4% cases, including diverse hematologic and solid organ malignancies. LCH-associated deaths constituted 36.1% of deaths and occurred within 5 years of diagnosis. After 5 years, non-LCH causes of death, including second cancers, chronic obstructive pulmonary disease, and cardiovascular diseases, predominated. Our study highlights, to our knowledge, for the first time, that adults with LCH experience early and late mortality from non-LCH causes and the need for development of targeted survivorship programs to improve outcomes.

BRAF V600E is associated with higher incidence of second cancers in adults with Langerhans cell histiocytosis.

In this retrospective study, BRAF mutation status did not correlate with disease extent or (event-free) survival in 156 adults with Langerhans cell histiocytosis. BRAFV600E was associated with an increased incidence of second malignancies, often comprising hematological cancers, which may be clonally related.

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

Background: Langerhans 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. Methods: We retrospectively evaluated the clinical characteristics, diagnosis, and treatment of 27 children and adult patients with thyroid LCH in our center between 2010 and 2021. Results: The 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). Conclusion: Thyroid 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.

Incidence, prevalence and survival in patients with Langerhans cell histiocytosis: A national registry study from England, 2013-2019.

This analysis is the largest population-based study to date to provide contemporary and comprehensive epidemiological estimates of all third edition of the International Classification of Diseases for Oncology (ICD-O-3) coded Langerhans cell histiocytosis (LCH) from England. People of all ages were identified from the National Cancer Registration Dataset using ICD-O-3 morphologies 9751-9754 for neoplasms diagnosed in 2013-2019. A total of 658 patients were identified, of whom 324 (49%) were children aged <15 years. The age-standardised incidence rate was 4.46 (95% confidence interval [CI] 3.99-4.98) per million children and 1.06 (95% CI 0.94-1.18) per million adults aged ≥15 years. Prevalence of LCH was 9.95 (95% CI 9.14-10.81) per million persons at the end of 2019. The 1-year overall survival (OS) was 99% (95% CI 97%-100%) for children and 90% (95% CI 87%-93%) for adults. Those aged ≥60 years had poorer OS than those aged <15 years (hazard ratio [HR] 22.12, 95% CI 7.10-68.94; p < 0.001). People in deprived areas had lower OS than those in the least deprived areas (HR 5.36, 95% CI 1.16-24.87; p = 0.03). There will inevitably be other environmental factors and associations yet to be identified, and the continued standardised data collection will allow further evaluation of data over time. This will be increasingly important with developments in LCH management following the large collaborative international trials such as LCH IV.

Evaluation of the etiological and clinical characteristics of pediatric central diabetes insipidus.

OBJECTIVES: Central diabetes insipidus (CDI) is a rare but important disease of varying etiology that poses challenges in diagnosis and follow-up. Identifying diagnostic difficulties in patients with CDI will help ensure an optimal approach to their management and follow-up. This study aimed to characterize the clinical and etiological characteristics of CDI in pediatric patients. METHODS: We analyzed the admission and follow-up data of CDI patients aged 0-18 years who were followed in our center between 2010 and 2019. RESULTS: The study included 56 patients with a mean age at diagnosis of 7.92 ± 5.11 years and symptom duration of 8.65 ± 21.3 months. The patients were grouped by etiology into those with organic causes, such as structural anomalies, tumors, and trauma (group 1, n=41) and other causes (group 2, n=15). The prevalence of idiopathic CDI was 16%. At least one pituitary hormone deficiency was detected in 60.7%, the most common being thyroid stimulating hormone deficiency. Patients in group 1 had a higher mean age at diagnosis, shorter symptom duration, and higher frequency of other pituitary hormone deficiencies compared to group 2. Additionally, germinoma was detected 1 year subsequent to normal MRI findings at diagnosis and another patient was diagnosed with Langerhans cell histiocytosis (LCH) 5 years after diagnosis. All patients responded well to replacement therapies, but two patients with germinoma died during follow-up. CONCLUSIONS: In the pediatric age group, intracranial organic pathologies are an important etiology of CDI, and despite a short symptomatic period, determining the cause may be challenging and prolonged. Patients presenting at a young age with a long history of symptoms and no other pituitary hormone deficiency are unlikely to have organic CDI. However, organic causes such as LCH should be evaluated at all ages. Patients with idiopathic disease are candidates for further etiological studies, and repeated cranial imaging is important during follow-up.

Langerhans cell histiocytosis and associated malignancies: A retrospective analysis of 270 patients.

PURPOSE: The frequency of Langerhans cell histiocytosis (LCH) and associated malignancies (AM) is greater than statistically expected. Here, we analyze LCH-AM co-occurrence in both children and adults. METHODS: Between 1991 and 2015, data were collected by regular questionnaires to members of the Histiocyte Society and searches in PubMed and Abstract Books. Patients were grouped by age at LCH diagnosis (≤ and >18 years), and types and timing of AM occurrence were plotted with respect to the LCH diagnosis. For the statistical analysis, only the first AM were considered. RESULTS: A total of 285 LCH-AM in 270 patients were identified, 116 (43%) ≤ 18 years, and 154 (57%) >18 years. In childhood LCH-AM pairs, leukemias and myeloproliferative disorders (n = 58; 50.0%) prevailed over solid tumors (n = 43; 37.1%) and lymphoma (n = 15; 12.9%). In adults, solid tumors were reported in 61 patients (39.6%), lymphoma, and leukemias and myeloproliferative disorders in 56 (36.4%) and 37 (24.0%) patients, respectively. In most children, AM followed LCH (n = 69, 59.5%), whereas in adults, LCH and AM occurred concurrently in 69 patients (44.8%). In children, T-lineage acute lymphoblastic leukemia (ALL) and promyelocytic acute myeloid leukemia (AML) and retinoblastoma were over-represented and thyroid carcinoma in adults. CONCLUSIONS: The largest collection of data on LCH-AM to date clearly indicates inherent relationships between specific types of AM and LCH, which may be due to therapy effects, clonal evolution, and germ-line predisposition, respectively. Prospective thorough genetic analysis is warranted and will hopefully shed light on the association of LCH and second neoplasms.

Prevalence of the BRAF V600E mutation in Greek adults with Langerhans cell histiocytosis.

Langerhans cell histiocytosis (LCH) is a rare inflammatory myeloid neoplasia with a broad spectrum of clinical manifestations. The activation of the MAP kinase pathway plays an integral role in its pathogenesis with genetic alterations found in the majority of cases that most frequently involve a somatic mutation of the oncogenic BRAFV600E variant. In this study we investigated the prevalence of the BRAFV600E mutation and its clinical relevance in adult Greek patients with LCH. Among 37 patients studied, the BRAFV600E mutation was identified in 12 out of 31 (38.7%), whereas in six patients (19.3%) the results were in conclusive. The presence of the mutation did not correlate with age at diagnosis, organ involvement, disease extent, response to initial treatment, development of diabetes insipidus and relapse risk. In our series the prevalence of the BRAFV600E mutation is at the lower range of the relative percentage found in children, but in line to that obtained in previous studies of adult patients with LCH that have found an up to 50% prevalence of the BRAFV600E mutation in these patients. Further studies with a larger number of adults are needed to identify the exact prevalence of mutations in the RAS-RAF-MEK-ERK pathway and their role on clinical parameters and disease outcomes.Supplemental data for this article is available online at https://doi.org/10.1080/08880018.2022.2029988 .

Langerhans cell histiocytosis of the head and neck in the pediatric population in a tertiary center: Clinical presentation, classification and treatment.

INTRODUCTION: Langerhans cell histiocytosis (LCH) is a rare disease of unknown etiology with a heterogeneous and unspecific clinical presentation. Any organ or system may be involved but the most frequent is the skeleton. The diagnostic gold standard is done through histopathology combined with immunohistochemistry in the correct clinical setting. Treatment is still controversial. The objective of this study is to present a series of pediatric patients in order to contribute to the diagnosis and treatment of LCH. MATERIAL AND METHODS: A longitudinal, descriptive and retrospective study was done in 20 pediatric patients histologically diagnosed of LCH int the last 10 years, in a tertiary center. A review of the medical history was done and data collection included: epidemiological data, clinical manifestations and classification, lesion characteristics, treatment employed, follow-up and evolution. RESULTS: The mean age presentation was 6.5 years (2-12). The most frequent disease presentation was a palpable skull tumor followed by headache. Other otorhinolaryngologic presenting symptoms were bloody otorrhea and post auricular swelling. Single-systems LCH with skull tumors was the most frequent classification. Treatment options (surgery, chemotherapy and corticosteroid infiltration) were indicated according to disease classification. CONCLUSION: LCH should be suspected in pediatric patients with a palpable cranial vault tumor, as well as in patients with chronic otorrhea with granulation tissue at the external ear canal. Management of LCH fundamentally includes chemotherapy and surgery, or the combination of both. High-risk organs lesions, including temporal bone lesions, and multi-system LCH are predictors of recurrence and should have a long-term follow-up.

Incidence, Clinical Features, and Outcomes of Langerhans Cell Histiocytosis in the United States.

Langerhans cell histiocytosis (LCH) is a disorder with highly diverse clinical manifestations. We explored if age, sex, race, organ system involved, and therapy approaches determine patient survival in the era of modern treatments. LCH patient data reported to the Surveillance, Epidemiology, and End Results (SEER) program in 2010-2016 (n=1282; age: 0 to 100 y) was analyzed. Age-specific LCH incidence flattening to a low level suggests an age cutoff for pediatric patients of 20 years. The overall survival probability is lower for patients 21 to 100 years old ( P <0.0001), irrespective of sex and race. The commonest sites involved in the 0- to 20-year age group were bone, skin, and bone marrow; this shifted to lung, bone, and skin as the commonest disease sites in patients 21 to 100 years of age. The treatments applied differed between age groups, as younger versus older patients were more likely to receive chemotherapy-based treatment (48.4% vs. 17%; P <0.0001). There also was a trend toward nonwhite versus white patients being less likely to receive chemotherapy-based treatment (31.7% vs. 38.2%; P =0.067). Whereas there are treatment disparities related to LCH patient age and perhaps race, patient age is the strongest predictor of survival, with patients 21 to 100 years of age with lung, lymph node, skin, and bone marrow disease having the worst outcomes ( P <0.0001).

Langerhans cell histiocytosis with lung involvement in isolation and multisystem disease: Staging, natural history, and comparative survival.

Langerhans cell histiocytosis (LCH) is a histiocytic neoplasm that can involve the lungs as single system (LCH-SSL) or multisystem disease (LCH-MSL). The role of full-body radiographic staging to determine whether patients have LCH-SSL or LCH-MSL is unclear. Long-term outcomes of LCH-SSL versus LCH-MSL and multisystem without lung involvement (LCH-MSNL) are unknown. A retrospective study of adult LCH patients seen at our center from January 2000 to 2020 was performed. In Part 1, we addressed utility of whole-body staging imaging among those presenting with isolated pulmonary signs or symptoms. Staging was defined as fluorodeoxyglucose positron emission tomography-computed tomography (CT) or whole-body CT obtained within 3 months of diagnosis. In Part 2, we examined the frequency of developing extra-pulmonary disease over time and mortality in patients with LCH-SSL. In Part 3, we compared the overall survival of LCH-SSL, LCH-MSL, and LCH-MSNL. Part 1: 240 patients with LCH were identified. A total of 112 (47%) had pulmonary signs or symptoms at presentation. Thirty-four (30%) underwent radiographic staging and only one showed evidence of extra-pulmonary disease. Part 2: 108 (45%) were LCH-SSL. Median follow-up duration of 4.5 years (95% confidence interval [CI]: 2.9-6.0). None developed extra-pulmonary disease. Part 3: 5-year survival: 94% (95% CI: 84%-98%) for LCH-SSL, 78% (95% CI: 59%-90%) for LCH-MSL, and 75% (95% CI: 53%-89%) for LCH-MSNL. LCH patients presenting with isolated pulmonary signs or symptoms rarely have extra-pulmonary involvement at the time of diagnosis and generally do not develop extra-pulmonary progression. LCH-SSL has the best overall survival, while LCH-MSL and LCH-MSNL have similar clinical outcomes.

High prevalence of BRAFV600E in patients with cholestasis, sclerosing cholangitis or liver fibrosis secondary to Langerhans cell histiocytosis.

Targeted therapies with MAPK inhibitors have proven to modulate the clinical manifestations of patients with Langerhans cell histiocytosis (LCH). We explored the presence of BRAFV600E mutation in our cohort of patients with LCH and cholestasis, sclerosing cholangitis, or liver fibrosis that presented resistance to chemotherapy. The BRAFV600E mutation was detected either in the diagnosis (skin and bone) or liver biopsy in our cohort of 13 patients. Thus, we observed a high incidence of BRAFV600E mutation in 100% either in diagnostic biopsy (skin and bone) or liver biopsy in patients with progressive liver disease, sequela, or liver transplant requirement.

Psychological features of adult patients with langerhans cell histiocytosis.

BACKGROUND: The prevalence of psychological symptoms and the co-occurrence of substance abuse disorders in adult patients with Langerhans cell histiocytosis (LCH) has not been previously explored. We aimed to use validated scales to evaluate depression and anxiety symptoms experienced by adult LCH patients. METHODS: In this cross-sectional study, all consecutive adult LCH patients seen at our national reference center between January 2012 and January 2013 were asked to complete the following instruments: the Hospital Anxiety and Depression scale (HADS); Barratt Impulsiveness Scale, Version 10 (BIS-10); and Cannabis Use Disorders Identification Test (CUDIT). Self-reported scores on these scales were used to determine the point prevalence of clinically significant psychological symptoms and substance use disorders in LCH patients. Patient profiles in terms of psychological features were assessed by principal component analysis including the HADS and BIS-10 instruments values, followed by hierarchical clustering. Fisher exact tests and Wilcoxon tests were used to examine the associations between disease-related parameters and high levels of anxiety and impulsivity. RESULTS: Seventy-one adult LCH patients, mainly with pulmonary LCH (PLCH), completed the evaluations. Clinically significant anxiety and depression symptoms were reported by 22 (31%) and 4 (6%) subjects, respectively. Impulsivity was detected in 14% (10/71) of the patients. Seventeen percent (12/71) of the patients used cannabis on a regular basis, with 50% of these individuals (6/12) exhibiting scores consistent with cannabis use disorder. Three derived clusters of patients were identified in the principal component analysis; these patient clusters differed in successful weaning from tobacco at the time of evaluation (p = 0.03). In univariate analyses, isolated PLCH and the use of psychotropic treatments were statistically associated with clinically significant anxiety symptoms. CONCLUSIONS: High levels of anxiety and impulsivity are common in adult patients with LCH. The consequences of these symptoms for the management of LCH patients warrant further evaluation.

Liver Transplantation for Langerhans Cell Histiocytosis: A US Population-Based Analysis and Systematic Review of the Literature.

Langerhans cell histiocytosis (LCH) is the most common histiocytic disorder. Liver involvement is seen in 10.1% to 19.8% of patients with LCH and can lead to secondary sclerosing cholangitis requiring liver transplantation (LT). We describe the characteristics and outcomes of patients undergoing LT for LCH. All patients undergoing a first LT for LCH in the United States were identified in the Scientific Registry of Transplant Recipients (SRTR) database (1987-2018). The Kaplan-Meier curve method and log-rank tests evaluated post-LT survival. A systematic literature review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) statement. A total of 60 LCH LT recipients were identified in the SRTR, and 55 patients (91.7%) were children with median total bilirubin levels at LT of 5.8 mg/dL (interquartile range [IQR], 2.7-12.9). A total of 49 patients (81.7%) underwent deceased donor LT (DDLT). The 1-year, 3-year, and 5-year patient survival rates were 86.6%, 82.4%, and 82.4%, respectively. The systematic review yielded 26 articles reporting on 50 patients. Of the patients, 41 were children (82.0%), 90.0% had multisystem LCH, and most patients underwent DDLT (91.9%; n = 34/37). Pre-LT chemotherapy was administered in 74.0% and steroids in 71.7% (n = 33/46) of the patients, and a recurrence of LCH to the liver was reported in 8.0% of the patients. Of the 50 patients, 11 (22.0%) died during a median follow-up of 25.2 months (IQR, 9.0-51.6), and the 1-year patient survival rate was 79.4%. LT can be considered as a feasible life-saving option for the management of liver failure secondary to LCH in well-selected patients.

The triptych of mixed histiocytosis: a systematic review of 105 cases and proposed clinical classification.

Histiocytoses are one of the ultimate diagnostic challenges that every physician face at least once in his/her life. Giving their protean manifestation and differentiated therapeutic needs, histiocytosis requires extensive characterization and multidisciplinary management. Mixed histiocytosis is an emerging group of syndromes defined by the overlap of Langerhans cell histiocytosis and another histiocytic disorder of different type. Despite rare, it may account for up to a fifth of systemic histiocytosis patients in some series. In this work, we comprehensively review for the first time the clinical, radiological, histopathological and molecular features of mixed histiocytosis in children and adults. Moreover, we propose a clinical classification in three groups that differentiate patients with systemic involvement and worse overall survival to other groups with more localized manifestations and indolent behavior, wanting to ease their recognition and treatment. Interestingly we also found that mixed histiocytosis harbor BRAFV600E mutations with a higher frequency comparing to all other histiocytoses, and may therefore benefit of specific inhibitory drugs.

Clinical outcomes of childhood Langerhans cell histiocytosis in Taiwan: A single-center, 20-year experience.

BACKGROUND/PURPOSE: The Taiwan Pediatric Oncology Group (TPOG) initiated two consecutive protocols for treating pediatric patients with Langerhans cell histiocytosis (LCH) since 1994. However, the results have not been analyzed and reported. This study aimed to investigate the survival outcomes of childhood LCH at the National Taiwan University Hospital over the past 20 years. METHODS: Treatment of pediatric patients with LCH according to TPOG protocols at the National Taiwan University Hospital began in 1994. During 1994-2003, patients were treated using the TPOG LCH-94 protocol. After 2003, patients were treated using the TPOG LCH-2003 protocol. Clinical data of these patients were obtained retrospectively by reviewing electronic medical records. Patients were followed up until July 31, 2018. RESULTS: Fifty-three newly diagnosed pediatric patients with LCH were treated at National Taiwan University Hospital during 1994-2015. Twenty-nine (54.7%) were treated with the TPOG LCH-94 protocol, and 24 (45.3%) were treated with the TPOG LCH-2003 protocol. The 5-year event-free survival and overall survival rates were 96.2 ± 2.6% standard error (SE) and 98.1 ± 1.9% (SE), respectively. Overall survival and 5-year event-free survival between patients treated with the TPOG LCH-94 and TPOG LCH-2003 protocols showed no significant difference. Multisystem, liver, or spleen diseases were associated with significantly bad survival outcomes. Among at-risk-organ involvement in LCH, liver involvement was an independent factor for poor prognosis. CONCLUSION: Clinical outcomes of children with LCH in Taiwan was good. The results of this study may help in the better classification of risk grouping for protocol designs in the future.

Descriptive Analysis of Histiocytic and Dendritic Cell Neoplasms: A Single-Institution Experience.

PURPOSE: Histiocytic and dendritic cell neoplasms are rare hematologic tumors. This study aimed to describe the epidemiologic features of the entire spectrum of histiocytic and dendritic cell neoplasms, including clinicopathological variables and patient outcomes. MATERIALS AND METHODS: We comprehensively reviewed 274 patients who were diagnosed with histiocytic and dendritic neoplasms at Severance Hospital, Seoul, South Korea between 1995 and 2018. RESULTS: The most common neoplasm was Langerhans cell histiocytosis (LCH), followed by dermal xanthogranuloma. Among non-LCH sarcomas, histiocytic sarcoma (HS) showed a relatively high prevalence, followed by follicular dendritic cell sarcoma (FDCS). Disseminated juvenile xanthogranuloma (DJG), Erdheim-Chester disease (ECD), indeterminate dendritic cell tumor (IDCT), and interdigitating dendritic cell sarcoma (IDCS) rarely occurred. Generally, these tumors presented in childhood, although the non-LCH sarcoma (HS/FDCS/IDCS/IDCT) group of tumors and ECD occurred in late adulthood. Multiorgan involvement and advanced Ann-Arbor stage, as well as recurrence and death of disease, were not uncommon. The non-LCH sarcoma group had the worst overall survival, compared to the DJG, ECD, and LCH groups. CONCLUSION: Our findings indicate that histiocytic and dendritic cell neoplasms exhibit heterogeneous epidemiologic characteristics and that some patients may have unfavorable outcomes, especially those with non-LCH sarcoma.