"Ghosts in my body": Seizure-like presentation of hypocalcemic tetany secondary to hypomagnesemia in a patient receiving cetuximab therapy for metastatic medulloblastoma.

Cetuximab, a monoclonal antibody specific for epidermal growth factor receptor, is increasingly used off-label and in early-phase trials for pediatric malignancies. Here, we report a patient with metastatic medulloblastoma receiving therapy with cyclophosphamide, vinblastine, and cetuximab. During evaluation for possible seizures, he was noted to be severely hypocalcemic, hypokalemic, and hypomagnesemic, a consequence of the blockade of renal epidermal growth factor receptor expression. His symptoms rapidly abated with intravenous electrolyte repletion. This case highlights the clinical heterogeneity of tetany and the importance of careful laboratory screening for known adverse effects of chemotherapy, particularly when newer biological agents are used off-study in combination chemotherapeutic regimens.

Primary high-grade B-cell lymphoma of the breast with concurrent IGH-BCL2 and MYC-IGL translocations in an adolescent patient.

BCL2 and MYC are oncogenes often deregulated in lymphomas. Concurrent IGH-BCL2 and MYC translocations result in a highly aggressive behavior of these tumors. Both primary breast lymphoma and lymphoma with concurrent BCL2-IGH and MYC translocations are rare and are primarily seen in adult patients. As a result of limited clinician experience and the condition's rarity, it poses a great challenge to pediatric pathologists and oncologists in terms of making an accurate diagnosis and choosing better treatment regimens. In this article, we report a case of an adolescent patient who presented with high-grade breast lymphoma with concurrent BCL2-IGH and MYC-IGL translocations, and we review the clinical, pathological, and genetic features; management strategies; and outcomes associated with this unusual neoplasm.

Metastatic alveolar rhabdomyosarcoma in multiple endocrine neoplasia type 2A.

Rhabdomyosarcoma (RMS), the most common pediatric soft tissue sarcoma, accounts for 3% of childhood malignancies. Multiple Endocrine Neoplasia (MEN) type 2A is an autosomal dominant syndrome associated with near universal development of medullary thyroid carcinoma. We describe a previously unreported association of MEN-2A with metastatic alveolar RMS and review the literature on associated hereditary cancer predisposition syndromes and current therapeutic options. The high penetrance of malignancy in patients with MEN warrants a heightened suspicion for the development of nonendocrine malignancies. The diagnosis of RMS should prompt consideration of screening for familial genetic syndromes in certain patients.

Thymoma in children: report of 2 cases and review of the literature.

Thymoma is an uncommon and slow-growing neoplasm. It is derived from thymic epithelial cells and comprises about 20% to 30% of mediastinal masses in adults, but only about 1% in pediatric patients. Patients usually present with mass-associated respiratory symptoms, superior vena cava syndrome, or paraneoplastic syndrome including myasthenia gravis, pure red cell aplasia, or acquired hypogammaglobulinemia, and connective tissue disorders. Due to the limited number of cases, knowledge, and experience with thymoma in pediatric patients, the diagnosis and treatment are very challenging for this age group. In this article, we report 2 cases of thymoma in childhood and provide a comprehensive review and analysis of the reported pediatric cases in the past 30 years (total of 32 cases). We found that patients younger than age 10 years were predominantly male (M:F = 6:1) and had advanced tumor stage more frequent than patients older than age 10 (P = .03). There were also significant associations of male sex with more advanced tumor stage and less favorable outcome (P = .03). These findings suggest that age and sex may be additional potential prognostic contributors in pediatric patients with thymoma. The clinicopathologic features, differential diagnosis, and current therapeutic recommendations of this uncommon tumor in pediatric patients are also addressed.

Vincristine induced peripheral neuropathy potentiated by voriconazole in a patient with previously undiagnosed CMT1X.

Peripheral neuropathy is a well-known side effect of vincristine, a micro-tubule inhibitor commonly used to treat malignancies. Severe neurologic adverse events can occur in patients with Charcot-Marie-Tooth disease (CMT) treated with vincristine. Voriconazole is an antifungal agent used increasingly in children with malignancy. Because of its metabolism by hepatic p450 enzymes, voriconazole may inhibit the clearance of many medications, including vincristine. We report a case of vincristine related neuropathy that was exacerbated by voriconazole in a patient with previously undiagnosed, X-linked CMT.

BCL6 expression correlates with monomorphic histology in children with posttransplantation lymphoproliferative disease.

Posttransplantation lymphoproliferative disease (PTLD) is a complication of organ transplantation with high mortality. Predicting response to first-line therapy, reduction of immune suppression, is difficult because of the heterogeneity of lesions and disease behavior. We sought to determine if BCL6 protein expression in PTLD cells is associated with poor outcome. In a cohort of 25 children with PTLD, 9 of the patients' tumor specimens were positive for BCL6 protein expression. Eight of 13 monomorphic lesions were BCL6 positive, compared with 1 of 11 evaluable polymorphic lesions (P=0.01). Only 1 of the patients with BCL6 expression responded to reduced immune suppression (P=0.19). Recipients of heart transplants who developed PTLD had reduced overall survival rates compared with recipients of other organ transplants who developed PTLD (P=0.04).

Renal medullary carcinoma: ultrastructural studies may benefit diagnosis.

Renal medullary carcinoma is a recently described highly aggressive malignancy that in most instances exhibits a constellation of clinical and light microscopic features sufficiently distinctive to enable a quick and confident diagnosis. Presented are three examples where, because of unusual elements in the clinical presentation, electron microscopic examination proved beneficial in establishing the diagnosis.

Posttransplant Hodgkin lymphoma preceded by polymorphic posttransplant lymphoproliferative disorder: report of a pediatric case and review of the literature.

Epstein-Barr virus-mediated posttransplant lymphoproliferative disorder (PTLD) is a well-recognized complication of immunosuppression in transplant patients and has broad clinical manifestations and pathologic features ranging from reactive lymphoid proliferation to malignant lymphoma. The category of Hodgkin lymphoma and Hodgkin lymphomalike PTLD is an uncommon variant of PTLD. Development of Hodgkin lymphoma subsequent to other subtypes of PTLD in the same patient is even more unusual, especially in pediatric patients. In this report, we describe a pediatric case of Epstein-Barr virus-associated posttransplant Hodgkin lymphoma developing several years after the patient was diagnosed with polymorphic PTLD and review the literature of the previously reported cases in children to further help characterize the clinical features, histopathologic appearances, biology, and treatment strategies of this uncommon entity.

Resection of neurogenic tumors in children: is thoracoscopy superior to thoracotomy?

BACKGROUND: Minimally invasive resection of solid tumors is controversial because of concerns of inadequate resection and local recurrence. Thoracoscopy has been used in the diagnosis of mediastinal tumors in children, but its role in resection is unproved. The purpose of this study was to compare thoracoscopic and open approaches to the resection of thoracic neurogenic tumors in children. STUDY DESIGN: The tumor registry of a regional children's hospital was queried to identify patients who underwent resection of neurogenic tumors over a 6-year period. Thoracoscopic and open groups were compared for demographic, operative, oncologic, and outcomes characteristics. RESULTS: Seventeen children underwent resection of mediastinal neurogenic tumors (10 thoracoscopic resections, 7 open resections). Mean age was 4.7 years (range 6 months to 12 years). The thoracoscopic and open groups showed no difference in operative time or blood loss. Tumors in the two groups were comparable in size (5.2+/-2.2 cm versus 5.7+/-2.6 cm), histology, surgical margin, and stage. Hospital stay was shorter after thoracoscopic resection (1.9+/-0.7 days versus 4.1+/-2.5 days, p<0.05). There were no regional recurrences. Distant metastases developed in one patient in each group. Eight of 10 children with malignant tumors remain disease-free at an average of 25 months of followup (range 3 to 80 months). CONCLUSIONS: Thoracoscopic resection of neurogenic tumors achieved similar local control and disease-free survival when compared with open resection in this preliminary series. These results were accompanied by a shorter hospital stay. These findings suggest that thoracoscopic resection of neurogenic tumors in children may offer advantages to open resection and should be studied in the context of a large, cooperative trial.

Primary ocular adnexal lymphoma in pediatric patients: report of two cases and review of the literature.

Primary ocular adnexal lymphoma (POAL) is a rare extranodal lymphoma. The mucosa-associated lymphoid tissue (MALT) subtype predominates and primarily occurs after the sixth decade of life. Most studies of ocular adnexal lymphoma are from the adult population. The data and experience in pediatric patients with POAL are limited to a few cases reported in the literature. Here we describe two pediatric cases of POAL and review the literature to further help characterize the clinical features and histopathologic appearance of this uncommon lymphoma.