Red blood cell distribution width as a potential inflammatory marker in pediatric osteomyelitis.

Background: Red cell distribution width (RDW) has been used in the differential diagnosis of anemia and revealed to be a potential marker of inflammation. Method: We conducted a retrospective study of acute-phase reactant changes in correlation with RDW among pediatric patients with osteomyelitis. Results: We identified 82 patients whose mean RDW increased on average by 1% during antibiotic therapy (mean 13.9% on admission, 95% CI 13.4-14.3, and 14.9% at the end of antibiotic therapy, 95% CI 14.5-15.4). Overall, the RDW was weakly correlated with absolute neutrophil count (r = -0.21, P = 0.001), erythrocyte sedimentation rate (r = -0.17, P = 0.007), and C-reactive protein (r = -0.21, P = 0.001). The generalized estimating equation model showed a weak negative correlation between RDW and C-reactive protein during the therapy duration (B= -0.03, P = 0.008). Conclusions: The mild increase in RDW, and its weak negative correlation with other acute-phase reactants during the study course, limits its utility as a therapy response marker in pediatric osteomyelitis.

Sarcoma as Second Cancer in a Childhood Cancer Survivor: Case Report, Large Population Analysis and Literature Review.

The majority of pediatric patients are cured of their primary cancer with current advanced developments in pediatric cancer therapy. However, survivors often experience long-term complications from therapies for primary cancer. The delayed mortality rate has been decreasing with the effort to reduce the therapeutic exposure of patients with pediatric cancers. Our study investigates the incidence of sarcoma as second cancer in pediatric cancer survivors. We present a 9-year-old male who survived embryonal hepatoblastoma diagnosed at 22 months of age. At 4.5 years of age, he presented with a non-metastatic primitive neuroectodermal tumor (PNET) of the left submandibular area. He has no evidence of recurrence of either cancer for 51 months after finishing all chemotherapy and radiotherapy. We used the Surveillance, Epidemiology, and End Results (SEER) database to identify the current rate of second sarcomas in pediatric cancer survivors. Our literature review and large population analysis emphasize the impact of sarcoma as a second malignancy and provide help to physicians caring for pediatric cancer survivors.

How to Treat Cytomegalovirus-induced Hemophagocytic Lymphohistiocytosis in a Child With Leukemia.

Hemophagocytic lymphohistiocytosis (HLH) is a syndrome characterized by a hyperinflammatory state due to an aberrant activation of the immune cells. It can be familial or secondary to malignancy, autoimmune or metabolic diseases. Most HLH cases are triggered by infection. Histiocyte society suggested HLH-2004 protocol for diagnosis and treatment of both forms. Here, we present a three-year-old girl with B-cell acute lymphoblastic leukemia who developed HLH secondary to cytomegalovirus infection during maintenance therapy. She was successfully treated without needing full HLH protocol therapy. We discuss modified therapy for this specific group of HLH, summarizing 5 other similar cases in the literature.

Von Hippel-Lindau with early onset of hemangioblastoma and multiple drop-metastases like spinal lesions: A case report.

RATIONALE: Hemangioblastoma is a rare tumor of the central nervous system (CNS). It is usually observed in patients with von-Hippel Lindau (VHL). The peak age for hemangioblastoma is between 20 and 50 years of age with very few cases over 65 or below 18 years of age. PATIENT CONCERNS: We report a female with a rare VHL mutation (c.337C>T) who was diagnosed with multifocal CNS hemangioblastoma at a very young age. DIAGNOSIS: At 17-years of age, she presented with obstructive hydrocephalus due to large cystic cerebellar mass. Imaging showed multiple lesions resembling drop metastases throughout her spinal cord. Immunohistochemistry of the resected tumor confirmed the pathological diagnosis of hemangioblastoma (World Health Organization Grade 1). INTERVENTIONS AND OUTCOME: She was treated with multi-stage resection of her primary and drop- metastasis like disease. She presented six months later with retinal hemangioblastoma while her other lesions were stable. She presented with multiple CNS and eye hemangioblastomas after failing to follow up for 2 years. Subsequently, Everolimus was started to treat her systemic disease. LESSONS: The unique feature of our case is the presence of multiple drop-metastases like spinal lesions, which has not been reported in the literature to be associated with hemangioblastoma.

Medulloblastoma in a toddler with Gorlin syndrome.

Gorlin syndrome (GS) is a rare hereditary multisystem disorder caused by mutations in PTCH1, PTCH2, or SUFU. It is characterized by multiple anomalies and an increased risk of developing various tumors. Basal cell carcinoma is most common, and medulloblastoma (MB) is especially frequent in patients with SUFU mutations. MB treatment often includes radiation therapy in patients older than 3 years; however, such treatment is very toxic to patients with GS. Most reported cases of MB in patients with GS present after GS is diagnosed. We report a male toddler with multicentric posterior fossa tumor and calcifications along the falx cerebri, suggesting MB and GS. Pathology revealed nodular MB. His testing confirmed a germline SUFU mutation. His tumor resolved with three induction cycles of chemotherapy, but he died of respiratory failure due to infection at 20 months of age. Overlooking calcifications along the falx cerebri in children with MB can induce significant morbidity.

The use of haematopoietic stem cell transplantation in Fanconi anaemia patients: a survey of decision making among families in the US and Canada.

BACKGROUND: Fanconi anaemia (FA) is a rare genetic disorder associated with bone marrow failure (BMF), congenital anomalies and cancer susceptibility. Stem cell transplantation (SCT) offers a potential cure for BMF or leukaemia, but incurs substantial risks. Little is known about factors influencing SCT decision making. OBJECTIVE: The study objective was to explore factors influencing patients' with FA and family members' decision making about SCT. DESIGN: Using a mixed-methods exploratory design, we surveyed US and Canadian patients with FA and family members who were offered SCT. MAIN VARIABLES STUDIED: Closed-ended survey items measured respondents' beliefs about the necessity, risks and concerns regarding SCT; multivariable logistic regression was used to examine the association between these factors and the decision to undergo SCT. Open-ended survey items measured respondents' perceptions of factors important to the SCT decision; qualitative analysis was used to identify emergent themes. RESULTS: The decision to undergo SCT was significantly associated with greater perceived necessity (OR = 2.81, P = 0.004) and lower concern about harms of SCT (OR = 0.31, P = 0.03). Qualitative analysis revealed a perceived lack of choice among respondents regarding the use of SCT, which was related to physician influence and respondent concerns about patients' quality of life. CONCLUSIONS: Overall, study results emphasize the importance of the delicate interplay between provider recommendation of a medical procedure and patient/parental perceptions and decision making. Findings can help providers understand the need to acknowledge family members' perceptions of SCT decision making and offer a comprehensive discussion of the necessity, risks, benefits and potential outcomes.

Thoracic vertebral osteomyelitis with paraspinous mass and intraspinal extension: an atypical presentation of cat-scratch disease.

Children with cat-scratch disease (CSD) commonly present with fever and tender lymphadenopathy. The disease is mild and manifestations of infection resolve spontaneously within several weeks. However, some children with CSD have unusual features that present diagnostic challenges. Children with atypical CSD may present with prolonged fever, hepatosplenic disease or ocular disease. We performed an MRI on a child who presented with persistent back pain. The MRI demonstrated a paravertebral mass with intraspinous extension and the collapse of T7 vertebral body. A biopsy was reported to show a small round blue cell tumor. An evaluation for malignancy was negative, but Bartonella henselae DNA was detected by polymerase chain reaction on the biopsy specimen. We present this case because it is a rare but important radiological presentation of CSD.

Durable complete response to chemotherapy in an infant with a clival chordoma.

Chordomas are rare bone tumors of notochord remnants that may occur anywhere within the axial skeleton. The standard of care is complete surgical removal. Proton beam irradiation is commonly used when the tumor is inaccessible or has recurred. Chemotherapy has been used in the treatment of patients at relapse but it has been generally proven ineffective. We report a 7-month-old infant with a clival chordoma who responded to combination chemotherapy consisting of cycles of vincristine/cyclophosphamide/doxorubicin alternating with etoposide/ifosfamide. She has been off chemotherapy for 2 years and is well at age 5.

Bone marrow cell cycle markers in inherited bone marrow failure syndromes.

Patients with inherited bone marrow failure syndromes (IBMFS) are at increased risk of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), possibly related to cell cycle dysregulation. In a cross-sectional analysis of bone marrow from 77 IBMFS, 71 sporadic conditions (AML, MDS, acquired aplastic anemia) and 22 normal controls we found overexpression of p53 in IBMFS, AML, and MDS; of Ki-67 in IBMFS and AML; and of survivin in IBMFS compared with all other groups. The patterns of expression of cell cycle markers in IBMFS are thus distinct. Longitudinal studies will determine the diagnostic and prognostic significance of these findings.

Hepatoblastoma and heart transplantation in a patient with cardio-facio-cutaneous syndrome.

Cardio-facio-cutaneous syndrome (CFC) and Costello syndrome (CS) are disorders with an overlapping spectrum of congenital anomalies. Mutations in the RAS-MAPK pathway have recently been reported in both of these syndromes, with HRAS mutations characteristic for CS and BRAF and MEK1/2 mutations for CFC. We report on a 3-year-old boy who underwent a cardiac transplant at age 8 months for hypertrophic cardiomyopathy; he was subsequently suspected to have CS. At age 35 months he presented with an intra-cardiac mass that was diagnosed as metastatic hepatoblastoma. Although hepatoblastoma is not known to have an increased frequency in immunocompromised patients, questions were raised as whether the post-transplant immuno-suppressive therapy played a role in tumor development. The patient died shortly thereafter and his post-mortem DNA analysis revealed a MEK1 mutation (Y130C) previously reported in CFC. While CS is associated with increased cancer risk, only a single case of leukemia has been reported in a patient with CFC, making this the first case of a solid tumor reported in a patient with CFC.

Further delineation of the phenotype resulting from BRAF or MEK1 germline mutations helps differentiate cardio-facio-cutaneous syndrome from Costello syndrome.

Because Cardio-facio-cutaneous (CFC) syndrome has significant phenotypic overlap with Costello syndrome, it may be difficult to establish the diagnosis on a clinical basis. The recent discoveries of germline HRAS mutations in patients with Costello syndrome and mutations in BRAF, MEK1, and MEK2 in CFC syndrome uncovered the biologic mechanism for the shared phenotypic findings based on the close interaction of the affected gene products within the MAP kinase pathway. We evaluated a series of patients who were either clinically diagnosed with Costello syndrome, or in whom the diagnoses of both Costello and CFC syndromes were considered. After excluding mutations in HRAS, we identified eight changes in BRAF and five in MEK1. Five mutations are novel, and all changes occurred de novo among those triads tested. A review of the clinical abnormalities showed important differences between patients with either a BRAF or MEK1 mutation, and those previously reported with an HRAS mutation. Statistical significance was achieved, despite the relatively small number of patients with BRAF and MEK1 mutations reported here, for polyhydramnios, growth hormone deficiency and the presence of more than one papilloma, which were less common in CFC compared to HRAS mutation positive patients. Although both CFC and Costello syndrome are characterized by cardiac abnormalities in about three-fourths of patients, the pattern of congenital heart defects (CHD), hypertrophic cardiomyopathy (HCM), and tachycardia differs somewhat. CHD, especially pulmonic stenosis associated with a secundum-type atrial septal defect, are more common in CFC than Costello syndrome (P = 0.02). Atrial tachycardia is less frequent in CFC patients with BRAF or MEK1 mutations, compared to Costello syndrome patients with HRAS mutation (P = 0.04). Chaotic atrial rhythm or multifocal atrial tachycardia was observed only in Costello syndrome. Malignant tumors have been viewed as characteristic for Costello syndrome due to HRAS mutations, however, we report here on a MEK1 mutation in a patient with a malignant tumor, a hepatoblastoma. Although this indicates that the presence of a tumor is not specific for Costello syndrome with HRAS mutation, it is noteworthy that the tumor histology differs from those commonly seen in Costello syndrome. Based on these clinical differences we suggest that patients with BRAF and MEK mutations should be diagnosed with CFC syndrome, and the diagnosis of Costello syndrome be reserved for patients with HRAS mutations.