Coexistence of Langerhans Cell Histiocytosis and Ganglioneuroblastoma Revealed by 18 F-FDG PET/CT in a Pediatric Patient.

ABSTRACT: Coexistence of Langerhans cell histiocytosis and ganglioneuroblastoma is rare and seldom reported in the literature. A 3-year-old girl with Langerhans cell histiocytosis underwent 18 F-FDG PET/CT imaging for staging, which demonstrated significant 18 F-FDG accumulation in the mandibles. Unexpectedly, a mild hypermetabolic soft mass was detected in the upper retroperitoneum. Results of surgical pathology of the abdominal mass were consistent with ganglioneuroblastoma.

Langerhans cell histiocytosis of the thyroid mimicking thyroiditis in a boy: a case report and literature review.

BACKGROUND: Langerhans cell histiocytosis affecting the thyroid commonly presents with nonspecific clinical and radiological manifestations. Thyroid Langerhans cell histiocytosis is typically characterized by non-enhancing hypodense lesions with an enlarged thyroid on computed tomography medical images. Thyroid involvement in LCH is uncommon and typically encountered in adults, as is salivary gland involvement. Therefore, we present a unique pediatric case featuring simultaneous salivary and thyroid involvement in LCH. CASE PRESENTATION: A 3-year-old boy with complaints of an anterior neck mass persisting for 1 to 2 months, accompanied by mild pain, dysphagia, and hoarseness. A physical examination revealed a 2.5 cm firm and tender mass in the left anterior neck. Laboratory examinations revealed normal thyroid function test levels. Ultrasonography revealed multiple heterogeneous hypoechoic nodules with unclear and irregular margins in both lobes of the thyroid. Contrast-enhanced neck computed tomography revealed an enlarged thyroid gland and bilateral submandibular glands with non-enhancing hypointense nodular lesions, and multiple confluent thin-walled small (< 1.5 cm) cysts scattered bilaterally in the lungs. Subsequently, a left thyroid excisional biopsy was performed, leading to a histopathological diagnosis of LCH. Immunohistochemical analysis of the specimen demonstrated diffuse positivity for S-100, CD1a, and Langerin and focal positivity for CD68. The patient received standard therapy with vinblastine and steroid, and showed disease regression during regular follow-up of neck ultrasonography. CONCLUSIONS: Involvement of the thyroid and submandibular gland as initial diagnosis of Langerhans cell histiocytosis is extremely rare. It is important to investigate the involvement of affected systems. A comprehensive survey and biopsy are required to establish a definitive diagnosis.

The value of 18F-FDG PET/CT in Langerhans cell histiocytosis.

OBJECTIVE: To investigate the value of 18F-FDG PET/CT in diagnosis and disease evaluation of Langerhans cell histiocytosis (LCH). METHODS: A retrospective analysis of 31 patients with LCH confirmed by histopathology was performed. A systematic analysis of the PET/CT imaging manifestations of LCH was performed, recording patients who were treated and receiving PET/CT for efficacy evaluation. In addition, clinical and laboratory data of LCH patients were collected, and the correlation between these data and PET/CT metabolic parameters was initially investigated. RESULTS: Of the 31 patients, thirty had at least 1 PET/CT positive lesions (96.7%), and one had only skin damage without abnormalities on PET/CT. Of 31 patients, fifteen (48.4%) had single system (SS) disease (9 cases with a single site and 6 cases with multiple sites) and 16 (51.6%) had multisystem (MS) disease (6 low risk and 10 high risk cases). The incidence of LCH lesions in the bone, lymphatic system, pituitary gland, liver, soft tissue, thyroid gland, thymus, and lungs was 20 cases (64.5%), 12 cases (38.7%), 3 cases (9.7%), 2 cases (6.5%), 2 cases (6.5%), 1 case (3.2%), 1 case (3.2%), and 8 cases (25.8%), respectively. A total of 21 PET/CT follow-up scanning were performed in 13 patients receiving chemotherapy, with 13 (61.9%) partial metabolic remission (PMR), 6 (28.6%) progressive metabolic disease (PMD), and 2 (9.5%) stable metabolic disease (SMD), according to PET Response Evaluation Criteria in Solid Tumors (PRECIST) 1.0. Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and Lactic Dehydrogenase (LDH) were positively correlated with TTLG (total TLG) (R2 = 0.3256, 0.2409, 0.4205, P < 0.05). The Re-examine SUVmax is positively correlated with re-examine LDH (R2 = 0.7285, P < 0.05). CONCLUSIONS: 18F-FDG PET/CT is an effective way to diagnose and evaluate LCH. PET metabolic parameters were associated with laboratory inflammatory markers, suggesting that 18F-FDG PET/CT may be helpful in evaluating disease activity of LCH.

Hepatobiliary involvement in Langerhans cell histiocytosis.

Langerhans cell histiocytosis (LCH) is a rare, proliferative disorder that occurs primarily in children. Periportal lesions were detected on ultrasound at different stages of evolution. In this article, we aim to discuss the sonographic findings in liver involvement of LCH.

The role of 18F-FDG PET/CT imaging in paediatric Langerhans disease: Case report.

Langerhans cell histiocytosis (LCH) is a haematological disorder, affecting single or multiple organs, characterized by abnormal proliferation of Langerhans cells in children. Accurate tumour delineation (number of lesions, organs involved) is crucial for staging/re-staging, and follow-up (response to therapy). Conventional imaging techniques (computed tomography (CT), magnetic resonance imaging (MRI)) have been employed for initial diagnosis, staging and assessment of response to therapy focusing on the healing effect therapeutic protocols have on the disease. In this case report, whole-body positron emission tomography/computed tomography (PET/CT) was shown either to provide information on the metabolic activity of histiocytes, or identify lesions otherwise asymptomatic. It is clear that PET/CT, combining anatomic and metabolic information, provides data for accurate staging, therapeutic protocol selection and assessment of response to therapy.

A rare imaging presentation with multisystemic clinicopathological features of Langerhans cell histiocytosis: Case report and literature review.

RATIONALE: Langerhans cell histiocytosis (LCH) is a kind of rare disease in which dendritic cells proliferate abnormally. It often occurs in children and can involve any tissue and organ. The affected sites usually include bone, skin, pituitary gland, and lungs, while the thyroid gland and external auditory canal are rarely observed. The perineal and labial involvement of this disease has not been reported yet. PATIENT CONCERNS: A 47-year-old female patient experienced a swelling of the anterior neck area without an obvious inducement. She noticed a quail egg-like mass on the left side, and the mass increased progressively within 3 months. The anterior neck area was found to be swollen, and some flaky red rashes were seen on the scalp and bilateral external auditory canals. DIAGNOSES: Imaging examination showed enlarged thyroid and cervical lymph nodes, multiple low-density nodules in the liver, and reduced signal in the posterior pituitary gland. The biopsy pathological result of the increased left cervical lymph node indicated that LCH was detected. INTERVENTIONS: VP regimen (vincristine, dexamethasone per os) and related supportive treatments were given as inducing chemotherapy for 6 weeks. OUTCOMES: After the second chemotherapy, the rash on the scalp and external auditory canal improved, and the neck mass was significantly reduced. After the third chemotherapy, the rash was mostly disappeared, while the neck lumps increased during chemotherapy. Thus, clatribine chemotherapy was recommended as the follow-up. LESSONS: Imaging examinations played an important role in the diagnosis and follow-up of the disease, especially 18F-FDG PET/CT, which could show multiple involving organs at the same time. When a patient suffering from diabetes insipidus, skin rash, or fever, has a high FDG uptake PET/CT result in multiple tissues and organs throughout the body, it is necessary to consider the possibility of LCH.

Langerhans Cell Histiocytosis Showed Intense Uptake of 68 Ga-FAPI.

ABSTRACT: A 23-year-old man was recently diagnosed with Langerhans cell histiocytosis (LCH). 68 Ga-FAPI PET/CT showed multiple lesions with intense FAPI uptake in the axial and appendicular skeleton with lytic or mixed bone destruction, consistent with osseous lesions of LCH. FAPI-avid foci around the right atrium and inferior vena cava, as well as micronodules and thin-walled cysts in the lungs, were also noted, possibly also involvement of LCH. This case suggested that 68 Ga-FAPI PET/CT may have the potential to be applied in evaluation of LCH.

Langerhans cell histiocytosis with aneurysmal bone cyst-like changes: a case-based literature review.

BACKGROUND: Langerhans cell histiocytosis (LCH) is a neoplastic transformation of myeloid precursors that commonly presents as an osteolytic lesion of the long or flat bones in children. Aneurysmal bone cysts (ABC) are benign neoplasms that frequently affect the metaphysis of long bones and the spine, often revealing a rapidly expansile lesion with fluid-fluid levels. LCH with secondary ABC-like changes is a rare condition that has only been reported five times, with two presentations in the cranium. The aim of this paper is to review the etiology, clinical and radiographic presentations, and treatment of this condition, as well as to present a novel case on the topic. CASE DESCRIPTION: We describe a 5-year-old boy with a rapidly growing head mass and eye pain resulting in a diagnosis of LCH with secondary ABC-like changes. Radiography demonstrated an expansile, lytic lesion of the left parietal bone with fluid-fluid levels. A confirmatory diagnosis was made through histopathology, demonstrating an inflammatory, histiocytic infiltrate staining positive for CD1a, CD68, CD207 (Langerin), and S-100. The lesion was surgically excised, and the patient recovered without any complications. CONCLUSION: We present a novel case of LCH with secondary ABC-like changes managed with surgical excision. While a radiographic workup with multiple imaging modalities is helpful for diagnosis, a thorough immunohistochemical analysis is essential as imaging characteristics are variable and nonspecific. Furthermore, surgical excision should be considered first-line treatment for lesions involving the skull in surgically accessible areas as it is curative, alleviates symptoms, and allows for histopathological diagnosis.

A case of neurodegenerative Langerhans cell histiocytosis exhibiting high osteopontin in cerebrospinal fluid without specific radiological abnormalities.

Neurodegenerative Langerhans cell histiocytosis (ND-LCH) manifests several years after onset of LCH, with progressive neurological symptoms and characteristic brain imaging features. Although ND-LCH has a dismal neurological prognosis, distinct treatment strategies are not available owing to the unknown pathophysiology. We describe the case of a 6-year-old boy who developed left convergent strabismus four years after onset of multisystem LCH (MS-LCH). Although radiological imaging showed no abnormalities, the osteopontin level in the cerebrospinal fluid (CSF-OPN) was highly elevated without other abnormal CSF findings, leading to a diagnosis of ND-LCH. The patient received monthly intravenous immunoglobulin therapy for four years, without symptoms worsening. To investigate the relevance of OPN levels in LCH, we retrospectively analyzed serum and CSF OPN levels in eight LCH patients. Serum OPN levels were markedly elevated in the two MS-LCH patients with macrophage activation (400 and 445 ng/mL) compared to the other six patients (mean: 59 ng/mL). CSF-OPN levels were elevated in the ND-LCH patient (620 ng/mL) compared to the two patients with pituitary involvement (160 and 182 ng/mL), suggesting that the pathophysiology of ND-LCH reflects its inflammatory status. Analysis of CSF-OPN levels would be a useful tool to detect and treat ND-LCH.

Langerhans Cell Histiocytosis in the Pediatric Spine Requiring Stabilization: A Literature Review and Report of 3 Cases.

CASE: This report describes 3 cases of Langerhans cell histiocytosis (LCH) of the cervical and thoracic spine in patients aged 4 to 10 years. Each patient had painful lytic spinal lesions with vertebral body collapse and posterior involvement suggesting instability requiring corpectomy, grafting, and fusion. All 3 patients were doing well at their most recent follow-up without pain or recurrence. CONCLUSION: Although LCH of the pediatric spine is usually successfully treated non-operatively, we recommend corpectomy and fusion when there is instability of the spinal column and/or severe stenosis. Posterior element involvement occurred in all 3 cases and may lead to instability.

99m Tc-MDP Bone Scan Findings of Recurrent Langerhans Cell Histiocytosis in an Adult Involving Femur After Joint Replacement.

ABSTRACT: Langerhans cell histiocytosis (LCH) is a rare proliferative histiocytic disorder. It mainly occurs in children and is rare in adults. We reported 99m Tc-MDP bone scan findings of recurrent LCH in an adult, which involved the right femur after right-side total hip arthroplasty. This case emphasizes that the possibility of LCH should be considered in osteolytic lesions in adults, especially after joint replacement. In addition, LCH should be included in the differential diagnosis of prosthetic joint pain and abnormal 3-phase bone scan after prosthesis arthroplasty.

Comparison of neuroimaging features of histiocytic neoplasms with central nervous system involvement: a retrospective study of 121 adult patients.

OBJECTIVES: To compare neuroimaging characteristics of three types of histiocytoses, namely Langerhans cell histiocytosis (LCH), Erdheim-Chester disease (ECD), and Rosai-Dorfman disease (RDD), with central nervous system (CNS) involvement. METHODS: A total of 121 adult patients with histiocytoses (77 LCH, 37 ECD, and 7 RDD) and CNS involvement were retrospectively included. Histiocytoses were diagnosed based on histopathological findings combined with suggestive clinical and imaging features. Brain and dedicated pituitary MRIs were systematically analyzed for tumorous, vascular, degenerative lesions, sinus, and orbital involvement and for hypothalamic pituitary axis involvement. RESULTS: Endocrine disorders, including diabetes insipidus and central hypogonadism, were more common in LCH patients than in ECD and RDD patients (p < 0.001). In LCH, tumorous lesions were mostly solitary (85.7%), located in the hypothalamic pituitary region (92.9%), and without peritumoral edema (92.9%), while in ECD and RDD, tumorous lesions were often multiple (ECD: 81.3%, RDD: 85.7%), their distribution was more widespread with meninges mostly involved (ECD: 75%, RDD: 71.4%), and they most likely presented with peritumoral edema (ECD: 50%, RDD: 57.1%; all p ≤ 0.020). Vascular involvement was an exclusive imaging characteristic of ECD (17.2%), which was not observed in LCH or RDD; this was also associated with a higher risk of death (p = 0.013, hazard ratio = 11.09). CONCLUSION: The typical characteristic of adult CNS-LCH was endocrine disorders with radiological findings limited to the hypothalamic pituitary axis. The pattern of multiple tumorous lesions with predominant involvement of meninges was the main manifestation of CNS-ECD and CNS-RDD, while vascular involvement was pathognomonic for ECD and associated with poor prognosis. CLINICAL RELEVANCE STATEMENT: Involvement of the hypothalamic-pituitary axis is the typical imaging characteristic of Langerhans cell histiocytosis. Multiple tumorous lesions, predominantly involving but not limited to meninges, occur in most Erdheim-Chester disease and Rosai-Dorfman disease patients. Vascular involvement occurs only in Erdheim-Chester disease patients. KEY POINTS: • The different distribution patterns of brain tumorous lesions can help differentiate among LCH, ECD, and RDD. • Vascular involvement was an exclusive imaging finding of ECD and was associated with high mortality. • Some cases with atypical imaging manifestations were reported to further expand the knowledge on these diseases.

Detection of BRAF V600E mutation in radiological Langerhans cell histiocytosis-associated neurodegenerative disease using droplet digital PCR analysis.

Langerhans cell histiocytosis-associated neurodegenerative disease (LCH-ND) is the most serious late complication secondary to LCH and is gradually progressive, destructive, and irreversible. Detection of the BRAF V600E mutation in peripheral blood mononuclear cells (PBMCs), even in the absence of active LCH lesions, is considered a sign of clinical LCH-ND, presenting with both abnormal imaging findings and neurological symptoms. However, the detection of the BRAF V600E mutation in PBMCs of patients with asymptomatic radiological LCH-ND (rLCH-ND) without active LCH lesions who present only with abnormal imaging findings is unknown. In this study, we analyzed the BRAF V600E mutations in PBMCs and cell-free DNA (cfDNA) of patients with rLCH-ND without active LCH lesions (n = 5) using a droplet digital polymerase chain reaction (ddPCR) assay. The BRAF V600E mutation in PBMCs was detected in three out of five (60%) cases. The mutant allele frequencies in the three positive cases were 0.049%, 0.027%, and 0.015%, respectively. However, the cfDNA BRAF V600E mutation remained undetected in all patients. Detection of the BRAF V600E mutant allele in PBMCs may be helpful in identifying asymptomatic rLCH-ND in patients at high risk for developing LCH-ND, including those with relapses at CNS risk sites or central diabetes insipidus.

Treatment of Langerhans cell histiocytosis with subcutaneous cytarabine.

Patients with Langerhans cell histiocytosis (LCH) have been effectively treated with intravenous cytarabine. Intravenous or subcutaneous cytarabine infusions have been effective for leukemia patients, and pharmacokinetic studies have shown very similar blood levels of the drug with either route. We present three LCH patients treated with subcutaneous cytarabine either because intravenous access could not be maintained or due to patient refusal. One patient with pulmonary and skin LCH had a complete response. Another patient had a partial response of pulmonary and cutaneous lesions, but progressive bone disease. The third patient was treated for LCH-related cerebellar changes eight years after the diagnosis of isolated diabetes insipidus, with stable brain MRI for 5 years post-treatment. Subcutaneous cytarabine administration provides an alternative for patients with LCH in whom vascular access is not possible or practical, such as in some resource-limited circumstances.

Comparison of whole-body DW-MRI with 2-[18F]FDG PET for staging and treatment monitoring of children with Langerhans cell histiocytosis.

PURPOSE: To assess and compare the diagnostic accuracy of whole-body (WB) DW-MRI with 2-[18F]FDG PET for staging and treatment monitoring of children with Langerhans cell histiocytosis (LCH). METHODS: Twenty-three children with LCH underwent 2-[18F]FDG PET and WB DW-MRI at baseline. Two nuclear medicine physicians and two radiologists independently assessed presence/absence of tumors in 8 anatomical areas. Sixteen children also performed 2-[18F]FDG PET and WB DW-MRI at follow-up. One radiologist and one nuclear medicine physician revised follow-up scans and collected changes in tumor apparent diffusion (ADC) and standardized uptake values (SUV) before and after therapy in all detectable lesions. 2-[18F]FDG PET results were considered the standard of reference for tumor detection and evaluation of treatment response according to Lugano criteria. Sensitivity, specificity, positive and negative predictive values, and diagnostic accuracy of WB DW-MRI at baseline were calculated, and the 95% confidence intervals were estimated by using the Clopper-Pearson (exact) method; changes in tumor SUVs and ADC were compared using a Mann-Whitney U test. Agreement between reviewers was assessed with a Cohen's weighted kappa coefficient. Analyses were conducted using SAS software version 9.4. RESULTS: Agreement between reviewers was perfect (kappa coefficient = 1) for all analyzed regions but spine and neck (kappa coefficient = 0.89 and 0.83, respectively) for 2-[18F]FDG PET images, and abdomen and pelvis (kappa coefficient = 0.65 and 0.88, respectively) for WB DW-MRI. Sensitivity and specificity were 95.5% and 100% for WB DW-MRI compared to 2-[18F]FDG PET. Pre to post-treatment changes in SUVratio and ADCmean were inversely correlated for all lesions (r: -0.27, p = 0·06) and significantly different between responders and non-responders to chemotherapy (p = 0.0006 and p = 0·003 for SUVratio and ADCmean, respectively). CONCLUSION: Our study showed that WB DW-MRI has similar accuracy to 2-[18F]FDG PET for staging and treatment monitoring of LCH in children. While 2-[18F]FDG PET remains an approved radiological examination for assessing metabolically active disease, WB DW-MRI could be considered as an alternative approach without radiation exposure. The combination of both modalities might have advantages over either approach alone.

Pulmonary Langerhans Cell Histiocytosis That Progressed from a Single-system to a Multisystem Form despite Smoking Cessation.

A 36-year-old Japanese man presented with cavities and nodular shadows in the lower lobes of his lungs and osteolytic lesions in the thoracic spine. He was diagnosed with multisystem Langerhans cell histiocytosis (LCH). Three years earlier, he had been noted to have small cavities and granular lesions noted in the upper lobes of his lungs, which later improved with smoking cessation. It was likely that his single-system pulmonary LCH (PLCH) progressed to multisystem LCH despite smoking cessation. Relapse or progression may occur in cases where PLCH lesions improve after smoking cessation. Thus, close follow-up is vital.