Langerhans Cell Histiocytosis Research Articles

Targeted Therapy With Vemurafenib in Brazilian Children With Refractory Langerhans Cell Histiocytosis: Two Case Reports and Review of Literature.

Langerhans cell histiocytosis (LCH) is a clonal myeloid neoplasm with inflammatory component. Refractory disease is a challenge, but vemurafenib has emerged as a therapeutic option. We will delineate the cases of two Brazilian children suffering from refractory LCH with a positive response to vemurafenib. Both cases had a diagnosis of multisystem disease with involvement of organs at risk and had not responded to standard and second-line treatment. After refractoriness to classic treatment regimens, the BRAF mutation was investigated and found to be positive in both patients, and target therapy with vemurafenib was sought. The first case has been using vemurafenib for about 2 years and the second case has been using it for about 3 years, having had an attempt to suspend the medication after concomitant use with maintenance therapy. However, the disease returned 4 months after stopping the medication. Fortunately, the disease returned to remission status after the medication was reintroduced. These cases represent the first reported instances of off-label vemurafenib use in Brazil for the treatment of LCH and both patients have demonstrated excellent responses to the medication. However, the long-term side effects are unknown in children, and prospective studies are needed. In addition, there is a lack of epidemiological data on histiocytosis in Brazil and studies evaluating the budgetary impact of incorporating BRAF mutation research and the use of vemurafenib into the public health system. These reports could be a starting point.

Etiological Spectrum of Lymphadenopathy Among Children on Lymph Node Biopsy.

Background Pediatric peripheral lymphadenopathy is commonly a benign condition and most cases resolve spontaneously; however, it can be a manifestation of a serious underlying disease. This study aimed to determine the etiological spectrum of persistent pediatric lymphadenopathy on excisional biopsy in a tertiary care children's hospital in a low-middle-income country and to make recommendations regarding evaluation, diagnostic testing, and surgical interventions best suited to the population. Methodology A prospective cross-sectionalstudy was conducted on 243 pediatric patients between the ages of one to 12 years undergoing excisional biopsy for persistent lymphadenopathy (more than four weeks duration) from April 1, 2021, to March 31, 2024. Patient demographic data along with signs, symptoms, and results of investigations including histopathological diagnosis were documented on a structured proforma. Results Patients' age range was two to 12 years (mean = 7.29 ± 2.30 years). The male-to-female ratio was 1:53. The Mean duration of lymphadenopathy was 35.89 ± 6.95 days (range = 25 to 57 days). The average size of lymph nodes ranged from 1 cm to a complex nodal mass of 7 cm. Histopathology showed reactive hyperplasia (40.32%, n = 98), tuberculosis (TB) (33.7%, n = 82), lymphoma (10.3%, n = 25), atypical mycobacterial adenitis (6.99%, n = 17), chronic granulomatous inflammation-histiocytosis (6.2%, n = 15), and Langerhans cell histiocytosis (2.5%, n = 6). The most common site was cervical. Sputum GeneXpert for TB had a true-positive rate of 78.84% while PPD was positive in only 13 TB patients. Atypical mycobacterial adenitis was successfully treated with excision and antibiotics. Supraclavicular nodes were strongly associated with lymphoma (p = 0.008). Conclusions Persistent pediatric lymphadenopathy is most commonly caused by TB followed by lymphoma. Positive sputum GeneXpert for TB with a suggestive clinical picture in endemic regions may be sufficient to start empiric therapy without the need for excisional biopsy in mycobacterial TB adenitis with negative PPD results and normal chest X-ray. In all other cases, excisional biopsy remains the gold standard for diagnosis. However, further studies should be conducted to formulate less invasive management algorithms.

Clinical Outcomes of Langerhans Cell Histiocytosis: A Single-Center Experience

Objective: To evaluate the clinical outcome of Langerhans cell histiocytosis (LCH) in countries with limited resources.Material and Methods: A retrospective chart review of patients <15 years old, diagnosed with LCH and treated at Siriraj Hospital; from January 1, 2002 until December 31, 2016, was performed. The patients’ demographic data, treatment protocol, and efficacy of treatment were collected and analyzed.Results: LCH was diagnosed in 38 patients, with a median age of 1.9 years old; of whom, 24 had multisystem disease (MS) and 14 had single system disease (SS). In the MS group, 16 patients had risk of organ (RO) involvement, with hepatic involvement being most common. The prevalence of central diabetes insipidus was 21.0%. Reactivation was observed in 11 patients (28.9%). RO involvement of the hematopoietic system (p-value=0.016), spleen (p-value=0.031), and MS (p-value=0.001) were significantly associated with a poor response to induction therapy. RO involvement of the hematopoietic system (p-value=0.016), liver (p-value=0.0), and spleen (p-value=0.005), as well as MS (p-value=0.013) were significantly associated with reactivation risk. The 5-year event-free survival rate of patients with and without RO involvement were 9.2% and 88.3%, respectively. The 5-year overall survival rate of patients with and without RO involvement were 82.5% and 96.4%, respectively.Conclusion: The prevalence of MS and RO involvement seemed high in this cohort; however, the outcomes were comparable to other Asian studies. Novel treatment for RO involvement may improve clinical outcomes.

Mechanism of neurodegeneration mediated by clonal inflammatory microglia.

Langerhans cell Histiocytosis (LCH) and Erdheim-Chester disease (ECD) are clonal myeloid disorders, associated with MAP-Kinase activating mutations and an increased risk of neurodegeneration. Surprisingly, we found pervasive PU.1+ microglia mutant clones across the brain of LCH and ECD patients with and without neurological symptoms, associated with microgliosis, reactive astrocytosis, and neuronal loss. The disease predominated in the grey nuclei of the rhombencephalon, a topography attributable to a local proliferative advantage of mutant microglia. Presence of clinical symptoms was associated with a longer evolution of the disease and a larger size of PU.1+ clones (p= 0.0003). Genetic lineage tracing of PU.1+ clones suggest a resident macrophage lineage or a bone marrow precursor origin depending on patients. Finally, a CSF1R-inhibitor depleted mutant microglia and limited neuronal loss in mice suggesting an alternative to MAPK inhibitors. These studies characterize a progressive neurodegenerative disease, caused by clonal proliferation of inflammatory microglia (CPIM), with a decade(s)-long preclinical stage of incipient disease that represent a therapeutic window for prevention of neuronal death.

Liver involvement with Langerhans cell histiocytosis in adults.

Liver involvement portends poor prognosis in adults. We aimed to characterize the clinical features, liver function tests, radiologic findings, molecular profiles, therapeutic approaches and outcomes of adults patients with Langerhans cell histiocytosis (LCH) with liver involvement. We conducted a retrospective analysis of all adults with LCH (≥ 18 years) seen at Peking Union Medical College Hospital (Beijing, China) between January 2001 and December 2022. Among the 445 newly diagnosed adults with LCH, 90 patients had liver involvement at diagnosis and 22 patients at relapse. The median age was 32 years (range, 18-66 years). Of 112 evaluable patients, 108 had full liver function testing, including alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase (ALP), γ-glutamyl transpeptidase (GGT), and total bilirubin and albumin. Elevated ALP was seen in 63.0% and GGT in 86.1%; 14.8% had elevated bilirubin. Next-generation sequencing of 54 patients revealed frequent BRAFN486_P490 (29.6%), BRAFV600E (18.5%), and MAP2K1 (14.8%). After a median 40 months' follow-up (range 1-168 months), 3-year progression-free survival (PFS) and overall survival were 49.7% and 86.6% respectively. In multivariable analyses, ≥3 abnormal liver function tests (HR 3.384, 95% CI 1.550-7.388, P = .002) associated with inferior PFS; immunomodulatory drug therapy (HR 0.073, 95% CI, 0.010-0.541, P = .010) correlated with superior PFS versus chemotherapy. In summary, elevated GGT and ALP were common in adults with LCH liver involvement. Greater than equal to 3 abnormal liver function tests predicted poor outcomes. Immunomodulatory drug therapy was associated with favorable progression-free survival compared to chemotherapy.

Chronic recurrent multifocal osteomyelitis: Case report and review of the literature.

Chronic recurrent multifocal osteomyelitis (CRMO) is a rare inflammatory disease. This report aims to analyze the clinical characteristics of CRMO and enhance clinicians' comprehension. We present 3 atypical cases, highlighting their unique clinical features, diagnostic challenges, and effective treatment strategies. We retrieved 3 CRMO cases in our hospital from September 2019 to August 2022. The clinical features were analyzed retrospectively, and relevant literatures were reviewed. All 3 cases initially presented with bone pain, normal leucocyte counts, negative rheumatoid factors and no signs of sclerotic or hyperostotic lesions. Case 1, a 12-year-old girl, exhibited concurrent acne on the forehead and historic necrotizing lymphadenitis, a previously unreported association with CRMO. Case 2, a 14-year-old boy, tested positive for human leukocyte antigen-B27 and displayed scoliosis along with multifocal osteomyelitis. Case 3, a 9-year-old girl, presented with scoliosis, and chest computed tomography revealed changes in the T8 vertebral body, initially suggesting Langerhans cell histiocytosis. Bone biopsy was conducted in case 1 and case 3, revealing chronic inflammation. All 3 cases affected long bones, pelvis, and vertebra, involving 8, 6 and 5 bones, respectively, identified by magnetic resonance imaging. Genetic analysis was undertaken in cases 1 and 2 but no pathogenic mutations were identified. Upon the confirmation of a CRMO diagnosis, all patients were initiated on a treatment regimen comprising nonsteroidal anti-inflammatory drugs and tumor necrosis factor-α inhibitors. In cases 1 and 2, due to the severity of their bone pain, they were also administered to disease-modifying anti-rheumatic drugs, specifically methotrexate. All 3 patients achieved remission of bone pain. To gain a more comprehensive understanding of CRMO, we conducted a thorough review of relevant literature. CRMO is a rare autoinflammatory bone disorder with diverse clinical presentations and a lack of specific laboratory tests, which leads to potency to misdiagnosis or delayed diagnosis. By raising awareness and improving diagnostic criteria, physicians are now better equipped to identify CRMO. We contribute to share our understanding of CRMO by presenting 3 cases with untypical clinical features, highlighting the importance of recognizing this rare condition for timely and effective management.

A case report of primary Kaposiform hemangioendothelioma of the humerus.

To examine the clinicopathological and immunohistochemical features of Kaposiform hemangioendothelioma (KHE) and discuss its differential diagnosis and prognosis. A patient with KHE was examined; the patient's clinical and histopathological features were observed, and the expression levels of CD31, CD34, ERG, D2-40, SMA, GLUT-1, and LANA-1 were assessed. The patient was a four-year-old child with primary KHE of the humerus. She was admitted to the hospital because of pain in the right elbow joint and limited movement for more than 2years. Imaging revealed Langerhans cell histiocytosis. The child was not diagnosed with Kasabach-Merritt phenomenon (KMP). The tumor consists of multiple hemangiomatous nodules with infiltrative growth separated by fibrous connective tissue. The proliferating hemangiomatoid nodules consisted of crisscrossing short spindle-shaped cell bundles and erythrocyte-containing lacunar or crescentic vessels. Immunohistochemical staining showed that the tumor cells diffusely expressed CD31, CD34, ERG, and other vascular endothelium-derived markers; further, the tumor cells expressed neither GLUT-1 nor LANA-1. The patient's general condition improved after surgical resection. There was no tumor recurrence after more than 8months of follow-up. Primary KHE of the humerus is a rare vasculogenic tumor. It presents with morphological features that require an accurate differential diagnosis.

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.

Solitary Langerhans Cell Histiocytosis of the Palpebral Conjunctiva Presenting as Leukoplakia: Case and Review of Literature.

A 69-year-old male presented with a superior palpebral conjunctival white leukoplakic lesion. Excisional biopsy showed Langerhans cell histiocytosis. Positron emission tomography scanning revealed no lesions beyond this site. Native Langerhans cells are known to exist in the conjunctiva, yet only a few cases in the literature have described Langerhans cell histiocytosis of the conjunctiva, mostly in children. Conjunctival Langerhans cell histiocytosis has rarely been reported in an adult as leukoplakia. The authors advocate excisional biopsy for palpebral conjunctival Langerhans cell histiocytosis in older patients if the morbidity of closure is minimal, in addition to surveillance for multifocal disease.

Preoperative planning of craniectomy and reconstruction using three-dimension-printed cranioplasty for treatment of calvarial lesion.

Common calvarial lesions include fibrous dysplasia (FD), intraosseous meningioma, osteoma, Langerhans cell histiocytosis (LCH), intraosseous hemangioma, dermoid and epidermoid cyst, and malignancy. Surgical removal with removal of the involved skull is the choice of treatment for these lesions. Previously, the skull defect was repaired using allograft, and alloplastic materials have been replaced with newer polyetheretherketone (PEEK) material, which is more resistant, biocompatible, and can be 3-dimension (3D)--printed. High-resolution 3D printing uses very fine extruders to put materials in fine layers to recreate patients' anatomy authentically, which gives superior cosmetic outcomes. Our objectives were preoperative planning of craniectomy and reconstruction for calvarial lesions and reconstruction of skull defects using 3D-printed cranioplasty with PEEK materials. In this series, we describe 11 cases in which skull lesions were removed and reconstructed in the same sitting using a 3D-printed PEEK implant designed preoperatively using high-resolution computer tomography. All the cases were done in the neurosurgery department of Bangabandhu Sheikh Mujib Medical University from 2021 to 2023. Patients were followed up for 6 months after surgery. Regarding 11 cases, six cases were FD, three cases were intraosseous meningioma, one case was intraosseous hemangioma, and one case was LCH. Average lesion size were 12.73-5.77 cm. Cranioplasty was done with PEEK material. Minor complications were treated conservatively. Seroma, postoperative fever, and nausea were among these. The human bone-like biocompatibility and resistance to physical forces leads to more frequent use of PEEK, which enables to repair of complex craniofacial defects with better cosmesis. Despite some limitations, the PEEK cranioplasty implant continued to thrive and showed its promise to be an excellent material. Further, research and investment should be put into developing the technique.

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.

Pulmonary involvement in children with Langerhans cell histiocytosis

Background. Pulmonary Langerhans cell histiocytosis (pLCH) is a rare disease, mostly a component of multisystemic LCH. We aimed to investigate the clinical features and treatment results in children with pLCH. Methods. We retrospectively reviewed the clinical, radiological, and treatment data of 37 patients with pLCH, diagnosed from 1974 to 2022. Results. 10% (n=37) of 367 patients with LCH had lung involvement. The median age was 1.8 years (range: 0.4 & 17.7) with a male-to-female ratio of 2.3. At admission 29.7% (n=11) presented with respiratory symptoms. Imaging showed a spectrum from nodular opacities to multiple cysts. All but one patient had multisystem disease. Twenty-nine received vinblastine-containing therapy. Ten-year event-free (EFS) and overall survival (OS) rates were 47.8% and 63.3%, respectively. In children younger and older than two years of age, the 10-year EFS was 53.3% vs. 40.2% and the 10-year OS was 58.7% vs. 68.8%, respectively. In children with and without risk organ involvement, 10-year EFS was 51.9% vs. 46.3% and 10-year OS was 51.9% vs. 73.7%. Conclusions. Lung and multisystem involvement are significant concerns in LCH, highlighting the need for careful management to reduce morbidity and mortality.

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.

Cutaneous Langerhans cell histiocytosis and other systemic inflammatory or autoimmune disease manifestations in the setting of clonal hematopoiesis

AbstractThe clinical manifestations and pathophysiology of clonal hematopoiesis (CH)‐associated immunological dysfunction are poorly understood. We describe an elderly woman with CH who developed various systemic inflammatory or autoimmune diseases (SIADs), including cutaneous Langerhans cell histiocytosis (LCH) and temporal arteritis. Sequencing of the LCH revealed somatic oncogenic mutations in MAP2K1, IDH2, and SRSF2, with enrichment of the latter two in her peripheral blood at high allele frequencies. These findings raise concern for the future development of a myeloid malignancy. Given the mounting evidence for adult‐onset autoinflammatory conditions caused by somatic blood mutations, we suspect CH‐mediated immune dysregulation is contributing to her multi‐organ involvement by a combination of SIADs.

Cladribine in the Treatment of Multifocal Multisystem Langerhans Cell Histiocytosis in a Patient with a Poor Prognosis. A Case Report

Langerhans cell histiocytosis is a hematologic clonal disease. The treatment of localized histiocytosis includes local methods such as radiotherapy or surgery. In cases of disseminated lesions with multiple system damage, chemotherapy is administered, which provides recovery in some patients. The present paper is a case report of multifocal multisystem Langerhans cell histiocytosis with bone, liver, spleen, abdominal lymph node and pituitary lesions in a 40-year-old patient. The diagnosis was verified by histology and immunohistochemistry of bone biopsy specimens. Polymerase chain reaction revealed no V600E mutation in the BRAF gene in tumor tissue. Persistent antitumor response was achieved after 6 chemotherapy cycles with cladribine monoregimen. This drug was well tolerated by the patient. By the time of this publication, the patient had preserved the persistent response for 38 months.

Multisystemic recurrent Langerhans cell histiocytosis misdiagnosed with chronic inflammation at the first diagnosis: A case report

BACKGROUND Langerhans cell histiocytosis (LCH) is characterized by diabetes insipidus and is an uncommon occurrence. Pathological biopsies still have a certain degree of diagnostic probability. We present a case in which LCH initially affected the pituitary gland. This resulted in a misdiagnosis of chronic inflammation upon pathological examination. CASE SUMMARY A 25-year-old female exhibited symptoms of diabetes insipidus. Magnetic resonance imaging revealed an enhanced foci in the pituitary gland. After surgical resection of the pituitary lesion, the pathological diagnosis was chronic inflammation. However, the patient later experienced bone destruction in the skull and lower limb bones. After the lower limb bone lesion was compared with the initial pituitary lesion, the final diagnosis was modified to LCH. The patient was treated with multiple chemotherapy courses. However, the patient’s condition gradually worsened, and she eventually passed away at home. CONCLUSION LCH should be considered when patients exhibit diabetes insipidus and absence of high signal intensity in the pituitary gland on sagittal T1-weighted image and abnormal enhancement in the pituitary region.

A rare case report of Langerhans cell histiocytosis exclusive to the colon in adults

A rare case report of Langerhans cell histiocytosis exclusive to the colon in adults

Chronic recurrent multifocal osteomyelitis masquerading as multifocal bone Langerhans cell histiocytosis in children: A case series from a tertiary cancer center

Chronic recurrent multifocal osteomyelitis (CRMO), also known as chronic non-bacterial osteomyelitis (CNO), is an autoimmune inflammatory bone disorder mainly affecting children and adolescents. The clinical presentation varies from mild, self-limiting unifocal bone inflammation, which is more common, to multifocal recurrent disease. CRMO can be misdiagnosed as multifocal bone Langerhans cell histiocytosis (LCH), infections, lymphoma, or metabolic bone disease. Clinical features are highly variable and not very specific. Most children experience vague aches and pains over prolonged periods but remain generally well and do not exhibit growth failure. In this article, we describe a case series of three children who presented with multifocal bone disease and were initially referred for LCH; however, detailed investigations confirmed the diagnosis of CRMO. The treatment options included non-steroidal anti-inflammatory drugs, corticosteroids, and disease-modifying anti-rheumatic drugs. Other treatment options included anti-tumor necrosis factor agents and bisphosphonates, similar to those used for autoimmune bone diseases. CRMO should be considered a differential diagnosis in children presenting with chronic, vague, and recurrent bony symptoms with or without systemic symptoms.

OTHR-24. CLINICAL COURSE OF ISOLATED PITUITARY STALK THICKENING IN PEDIATRIC PATIENTS AND RISK FACTOR FOR NEOPLASTIC ETIOLOGY: A SINGLE INSTITUTIONAL EXPERIENCE

Abstract BACKGROUND The incidence of pituitary stalk thickening (PST) has increased in recent years due to the increased utilization of diagnostic MRI of the brain. The etiology of PST includes germ cell tumors, Langerhans cell histiocytosis (LCH), and lymphocytic hypophysitis, among others. The clinical significance of PST, appropriate diagnostic workup, and clinical course for these patients is not well documented. We report our institutional experience with patients presenting with PST. METHODS After IRB approval, we reviewed lists of patients discussed in pediatric tumor boards from 2003-2023 to identify patients with PST. We excluded patients with other significant intracranial masses from our analysis. We followed the clinical course of these patients to collect applicable data. RESULTS A total of 20 patients were identified with PST, five patients were excluded due to additional MRI findings. The median age of diagnosis with PST was 14 years; 60% of cases were female. Seven patients had diabetes insipidus (DI), and five patients had other endocrinological abnormalities. Initial diagnostic workup included serum and CSF tumor markers (AFP, B-HCG), skeletal survey, CBC, and CMP. With this initial workup, no patients were diagnosed with neoplasm. All patients were followed with serial MRIs. Four patients (26.6%) displayed progression of PST, warranting biopsy. The median time from diagnosis to biopsy was seven months (range 4-26 months). Among four patients with biopsy, two had LCH, one had germinoma, and one inconclusive result. Among those diagnosed with neoplasm, 100% of them had DI. Three patients had complete resolution of PST during the follow-up period. Eight patients had stable PST during the median follow-up period of 19.5 months (Range 3-59 months). CONCLUSIONS Most isolated PST among pediatric patients remained stable during the follow-up period. The risk for neoplastic process was high among patients with increasing thickening of pituitary stalk and DI.

GCT-24. ISOLATED PITUITARY STALK THICKENING

Abstract BACKGROUND Few studies have examined predictive factors and outcome of isolated pituitary stalk thickening (iPST) in children. We aim to describe our institutional cohort to determine predictors of future proliferative disease. METHODS A search of the radiology, endocrinology and neuro-oncology databases was performed to identify patients with iPST diagnosed between January 2000 and June 2019. Clinical data was collected along with detailed radiology review of MRIs in a blinded fashion. RESULTS Forty-seven patients were identified, with 40 meeting criteria for inclusion. Median age of baseline MRI was 9.6 years (range 0.9-17.5). Twenty-five (63%) were female. Median follow up time was 5.2 years (range 0.3-18.6). Indication for MRI was symptoms of diabetes insipidus (DI) in 29 patients followed by concerns for anterior endocrine disturbance (6), headache (1) or visual impairment (1). Thirty-four (85%) subjects had pituitary dysfunction, including 31 with DI however DI was not predictive of future development of proliferative disease (69% with presumed hypophysitis vs 93% with proliferative disease, p=0.12). Fourteen (35%) patients developed proliferative disease, with germinoma (8), Langerhans cell histiocytosis (5) and lymphoma (1) at median of 1.3 years (range 0.3-4.0), 2.2 years (range 0.3-9.4) and 1.1 years after initial MRI respectively. Lumbar puncture was performed in 24 patients with elevated white blood cell count (>5 x 106/L) found in 6 (75%) patients with germinoma, 1 (100%) patient with lymphoma, 0 patients with LCH and 3 of 11 (27%) patients with presumed hypophysitis (p=0.015). Thickening of the entire stalk at time of diagnosis and radiographic progression were more likely to be seen in those that developed proliferative disease. CONCLUSION In this cohort 35% of children with PST were eventually diagnosed with a proliferative disease. Importantly, central DI was not associated with risk of proliferative disease. Several radiographic features and elevated CSF WBC were predictive of this outcome.