Harlequin syndrome associated with ganglioneuroblastoma-induced Horner syndrome.

A 1-year-old boy presented with a 4-month history of hypertension, ptosis of the right upper eyelid, left hemifacial sweating, and flushing. He was diagnosed with Harlequin syndrome associated with Horner syndrome. Computed tomography revealed a mass lesion in the right superior mediastinum. Therefore, the patient underwent total tumor resection. Histological examination demonstrated ganglioneuroblastoma. The MYCN oncogene was not amplified, and the mitosis-karyorrhexis index was low. Accordingly, radiation and chemotherapy were not performed. No recurrence was observed within 8 months after surgery, and the patient's blood pressure was normalized. However, the ptosis, hemifacial sweating, and flushing persisted.

Lymphnode tuberculosis in a 4-year-old boy with relapsed ganglioneuroblastoma: a case report.

BACKGROUND: Mycobacterium tuberculosis (M. tuberculosis) disease is a generally well-known problem among immunocompromised adults and children. In pediatric oncology, only few cases of M. tuberculosis disease are reported so far. CASE PRESENTATION: We report a case of concomitant lymphnode tuberculosis in a 4-year-old German boy with relapsed ganglioneuroblastoma. 18 months after the initial diagnosis, relapse with new paravertebral lesions and new lesions in the left lower lobe of the lung and in the perihilar lymphnodes suspicious of metastases of the ganglioneuroblastoma were detected. While relapse in the tumor was confirmed, unexpectedly, pathologic examination revealed morphological diagnosis of lymphnode tuberculosis. The boy was of German background without previous history of tuberculosis exposure. Both, antituberculostatic and relapse treatment were immediately initiated. Three months on, MRI revealed regressive findings in the lung and lymphnodes and partial response in the tumor. The patient underwent second MiBG therapy and haploidentical stem cell transplantation. CONCLUSION: The diagnosis of lymphnode tuberculosis in a 4-year-old German boy with relapsed ganglioneuroblastoma was only made by chance, but most likely saved his life. Pediatric oncologist should be aware of tuberculosis as the incidence might increase over time and the timely diagnosis of a potentially preventable M. tuberculosis disease is irreplaceable. Further studies are needed to explore the incidence of M. tuberculosis infections and the value of IGRA, testing for latent tuberculosis infection prior to chemotherapy in children with underlying malignancies.

Resolution of Elevated Urine Glycosaminoglycans and Clinical Features of Mucopolysaccharidosis After Successful Treatment of Neuroblastoma.

We report a patient with stage 3 ganglioneuroblastoma who initially presented with clinical and laboratory features consistent with mucopolysaccharidosis including coarse facial features, developmental delay, and an elevated quantitative urine glycosaminoglycan (GAG) level. All mucopolysaccharidosis features resolved following successful treatment of neuroblastoma. High GAG levels have been documented in the pediatric oncology literature, yet not as a potential marker of malignancy or other target for clinical utility. This patient prompts further investigation into the relationship between neuroblastoma and elevated GAG levels.

Ganglioneuroblastoma during pregnancy--A rare case report.

PURPOSE: To report a rare case of ganglioneuroblastoma encountered rarely in adults, especially during pregnancy. Materials and METHODS: The authors present a case of ganglioneuroblastoma relapse during the third trimester of pregnancy in a patient previously treated for ganglioneuroblastoma who had a eight-year disease-free interval. Late manifestation of neurological symptoms (vestibular syndrome, nystagmus, slightly right motor deficit) was perhaps influenced by the hormonal pregnancy effects. In this case the option was for caesarean section under general anesthesia at 36 weeks. RESULTS: Based on MRI result, the neurosurgical consultation stated the need of postpartum brain tumor excision. Recovery of the mother was complication-free with persistent, constant postoperative neurological symptoms. It resulted in a healthy newborn, not requiring special follow-up. CONCLUSIONS: Pregnancy and brain tumor have mutual negative effect on the patient. Therapeutic management in this case was a medical dilemma regarding mode setting and timing of delivery, taking into account the maternal-fetal risk-benefit.

Anti-Hu antibody associated paraneoplastic neurological syndrome in a child with ganglioneuroblastoma: A rare case report and literature review.

RATIONALE: Paraneoplastic neurological syndrome with anti-Hu antibody (Hu-PNS) is a neurological disorder that occur in patients with malignancy. The syndrome has a wide range of presentations and can present before diagnosis of primary malignancy. Familiarity with these paraneoplastic neurological syndromes can help early recognition and take appropriate regimens. PATIENTS CONCERNS: Diagnosis and treatment of Hu-PNS. DIAGNOSES: This is retrospective study that analyzed the clinical data of this case. Through retrospective analysis and targeted antibody screening, serum anti-Hu antibody was detected. Subsequent spinal imaging revealed a mass in the paraspinal region, which was confirmed as ganglioneuroblastoma by pathologic examination. INTERVENTIONS: The child was treated with a course of intravenous immunoglobulin and radical surgical operation without chemotherapy. OUTCOMES: The neurological symptoms were gradually improved and no signs indicate disease progression or tumor recurrence. LESSONS: Hu-PNS has rarely been reported in children with ganglioneuroblastomas. They can mimic non-neoplastic processes, making detection and diagnosis difficult. Serum and/or cerebrospinal fluid onconeural antibody can strongly indicate occult cancers. Early detection of paraneoplastic neurological syndromes can help take appropriate regimens and improve prognosis.

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.

Outcomes and Histological Variations of Neuroblastoma and Ganglioneuroblastoma with Paraneoplastic Syndromes.

BACKGROUND: Neuroblastomas are the most common extracranial solid malignancy in children with variable manifestations and complications depending on the presence of paraneoplastic syndromes. MATERIALS AND METHODS: We performed a single institution retrospective cohort study of all patients less than 18 years old diagnosed with neuroblastoma or ganglioneuroblastoma between January 2002 and July 2022. Patients were identified through the pathology and cancer registry and cross-referenced with pediatric records. Patient demographics, clinical presentation, treatment, and outcomes were collected. A univariate descriptive analysis of the collected data was conducted. RESULTS: In our study period, 130 children were diagnosed with neuroblastoma, and 15 were diagnosed with ganglioneuroblastoma. There were 12 children with a paraneoplastic syndrome identified, 8 with NBL and 4 with ganglioneuroblastoma (GNBL). The average age at diagnosis was 22 months. All but 1 underwent resection prior to treatment of paraneoplastic syndrome, and 4 children required neoadjuvant therapy. Neurological complications were the most common with 10 children (83%). The average time from symptom onset to diagnosis was 0.7 months. Eight children had complete resolution of their symptoms after treatment and resection, 2 children recently started treatment within a year, 1 had partial resolution, and 1 died during treatment. The presence of tumor-infiltrating lymphocytes occurred in 4 children with neurologic paraneoplastic syndromes. Six children had neuropil rich tumors. CONCLUSION: The histological profile of paraneoplastic syndromes of neuroblastoma and ganglioneuroblastoma and their treatment across a single institution can be highly variable. The presence of tumor-infiltrating lymphocytes and neuropil may have an impact on paraneoplastic pathology.

Cervical Ganglioneuroblastoma Diagnosed by 68Ga-DOTATOC PET/CT in a Child with Opsoclonus Myoclonus Syndrome.

We performed a 68Ga-DOTATOC PET/CT scan on a 25-mo-old female patient who presented with opsoclonus myoclonus ataxia syndrome and had negative initial anatomic imaging. The scan showed a somatostatin receptor-overexpressing cervical tumor in favor of a cervical neuroendocrine tumor, with subsequent histopathologic findings of ganglioneuroblastoma.

Ofatumumab for a rituximab-allergic child with chronic-relapsing paraneoplastic opsoclonus-myoclonus.

Ofatumumab is a fully human anti-CD20 monoclonal antibody in phase II-III trials for various autoimmune and lymphoreticular diseases. We used it to treat a rituximab-allergic child with severe, chronic-relapsing, opsoclonus-myoclonus syndrome (OMS), characterized by persistent cerebrospinal fluid (CSF) B-cell expansion and T-cell dysregulation. He had relapsed despite chemotherapy, plasma exchange with immunoadsorption, and resection of ganglioneuroblastoma, detected 3 years after OMS onset. The four ofatumumab infusions (1,195 mg/m(2) total dose) were well tolerated, and CSF B-cell expansion was eliminated. No further relapses have occurred in 3 years, but he remains on low-dose ACTH with neuropsychiatric residuals of OMS.

Ganglioneuroblastoma in a young child with Turner syndrome.

X chromosome aneuploidy has been identified as a potential risk factor for the development of neuroblastic tumors. We report a case of a 4-year-old girl with a 45,X karyotype incidentally discovered to have a large ganglioneuroblastoma on initial screening ultrasound. The incidence of these tumors in girls with Turner syndrome as well as their possible relationship to recombinant human growth hormone treatment is discussed.

ROHHAD(NET) Syndrome: Systematic Review of the Clinical Timeline and Recommendations for Diagnosis and Prognosis.

CONTEXT: Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, autonomic dysregulation and neural crest tumor (ROHHHAD[NET]) is a rare and potentially fatal disease. No specific diagnostic biomarker is currently available, making prompt diagnosis challenging. Since its first definition in 2007, a complete clinical analysis leading to specific diagnosis and follow-up recommendations is still missing. OBJECTIVE: The purpose of this work is to describe the clinical timeline of symptoms of ROHHAD(NET) and propose recommendations for diagnosis and follow-up. DESIGN: We conducted a systematic review of all ROHHAD(NET) case studies and report a new ROHHAD patient with early diagnosis and multidisciplinary care. METHODS: All the articles that meet the definition of ROHHAD(NET) and provide chronological clinical data were reviewed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis individual patient data guidelines. The data were grouped into 7 categories: hypothalamic dysfunction, autonomic dysregulation, hypoventilation, NET, psychiatric symptoms, other clinical manifestations, and outcome. RESULTS: Forty-three individual patient data descriptions were analyzed. The timeline of the disease shows rapid-onset obesity followed shortly by hypothalamic dysfunction. Dysautonomia was reported at a median age of 4.95 years and hypoventilation at 5.33 years, or 2.2 years after the initial obesity. A NET was reported in 56% of the patients, and 70% of these tumors were diagnosed within 2 years after initial weight gain. CONCLUSION: Because early diagnosis improves the clinical management and the prognosis in ROHHAD(NET), this diagnosis should be considered for any child with rapid and early obesity. We propose guidance for systematic follow-up and advise multidisciplinary management with the aim of improving prognosis and life expectancy.

Ganglioneuroblastoma-associated vitamin D deficiency rickets.

Vitamin D deficiency is the most common cause of rickets mainly in breast-fed dark-skinned, African or Asian children receiving inadequate sunlight exposure. We report a case of a 1.5 year-old Afro-Italian male infant living in South Italy who came to our observation with the typical clinical picture of vitamin D deficiency rickets. The child was exclusively breast-fed for 8 months without vitamin D supplements. Owing to the rarity of vitamin D deficiency rickets in the South of Italy he underwent several investigations, which demonstrated the association with an abdominal ganglioneuroblastoma. To our knowledge, ganglioneuroblastoma has never been reported in association with vitamin D deficiency rickets. Although the association between these 2 rare conditions may be coincidental, the protective action of vitamin D against cancer suggests that vitamin D deficiency might have contributed to the development of ganglioneuroblastoma in our patient.

Rituximab for treatment of opsoclonus-myoclonus syndrome in neuroblastoma.

Opsoclonus-myoclonus syndrome (OMS) is a rare paraneoplastic syndrome that occurs in 2%-3% of patients with neuroblastoma. The cause of this syndrome is believed to be immune mediated, but the exact mechanism still remains unclear. There is an urgent need to improve our current strategies for treating patients with OMS, as many patients have significant long-term neurologic deficits and behavior disorders with current treatment approaches. Therapies that have shown to improve symptoms in these patients have ranged from ACTH and corticosteroids, to intravenous gammaglobulin and plasmapheresis. We report our experience with Rituximab in a patient with neuroblastoma and OMS.

Response to rituximab and prednisolone for opsoclonus-myoclonus-ataxia syndrome in a child with ganglioneuroblastoma.

Opsoclonus-myoclonus-ataxia (OMA) syndrome is a rare neurobehavioral paraneoplastic disorder in children with neuroblastic tumors. The neurologic symptoms are generally treated with a number of immunosupressive and immunomodulating agents. A 4-year-old previously healthy male patient was admitted to the authors' center with progressive ataxia, gait disturbance, difficulty of speech, and opsoclonus. He had a diagnosis of ganglionueroblastoma at the thoracal paraspinal region. Following surgery, the patient received IVIG and prednisolone but his cerebellar symptoms progressed. Rituximab therapy was started and continued for total 8 weeks without any side effect. The authors observed excellent neurologic response in the patient at the 4th week of treatment. Rituximab is a new, promising, and safe therapy for OMA syndrome in children with neuroblastoma.