Likelihood of bone recurrence in prior sites of metastasis in patients with high-risk neuroblastoma.

PURPOSE/OBJECTIVES: Despite recent improvements in outcomes, 40% of children with high-risk neuroblastoma will experience relapse, facing a guarded prognosis for long-term cure. Whether recurrences are at new sites or sites of original disease may guide decision making during initial therapy. METHODS AND MATERIALS: Eligible patients were retrospectively identified from institutional databases at first metastatic relapse of high-risk neuroblastoma. Included patients had disease involving metaiodobenzylguanidine (MIBG)-avid metastatic sites at diagnosis and first relapse, achieved a complete or partial response with no more than one residual MIBG-avid site before first relapse, and received no total body irradiation or therapy with (131)I-MIBG before first relapse. Anatomically defined metastatic sites were tracked from diagnosis through first relapse to determine tendency of disease to recur at previously involved versus uninvolved sites and to assess whether this pattern was influenced by site irradiation. RESULTS: Of 159 MIBG-avid metastatic sites identified among 43 patients at first relapse, 131 (82.4%) overlapped anatomically with the set of 525 sites present at diagnosis. This distribution was similar for bone sites, but patterns of relapse were more varied for the smaller subset of soft tissue metastases. Among all metastatic sites at diagnosis in our subsequently relapsed patient cohort, only 3 of 19 irradiated sites (15.8%) recurred as compared with 128 of 506 (25.3%) unirradiated sites. CONCLUSIONS: Metastatic bone relapse in neuroblastoma usually occurs at anatomic sites of previous disease. Metastatic sites identified at diagnosis that did not receive radiation during frontline therapy appeared to have a higher risk of involvement at first relapse relative to previously irradiated metastatic sites. These observations support the current paradigm of irradiating metastases that persist after induction chemotherapy in high-risk patients. Furthermore, they raise the hypothesis that metastatic sites appearing to clear with induction chemotherapy may also benefit from radiotherapeutic treatment modalities (external beam radiation or (131)I-MIBG).

Hepatoblastoma in a 15-month-old female with trisomy 13.

Trisomy 13 (T13) is a rare autosomal aneuploidy. Greater than 90% of patients die during the first year of life. Malignancies reported in association with T13 include two cases of Wilms tumor and one case of pilocytic astrocytoma. There is no previous report of hepatoblastoma in patients with T13. We report a unique case of hepatoblastoma in a 15-month-old female with constitutional T13. Our patient was born at 38 weeks gestation and was noted to have phenotypic features consistent with T13. Genetic testing confirmed an abnormal karyotype of 47,XX,+13 in all cells. At fifteen months of age she was noted to have a right hepatic lobe mass on a routine follow-up renal ultrasound for hydronephrosis. Serum alpha-fetoprotein level was 55,300 ng/ml. Staging work-up revealed the absence of metastases. She underwent a complete surgical resection with right hepatic lobectomy. Histopathology was consistent with hepatoblastoma, mixed epithelial and mesenchymal type. She had a protracted postoperative course complicated by Enterobacter aerogenes urosepsis, a significant biloma, chronic pancreatitis, and apneic episodes of uncertain etiology. She received four courses of doxorubicin monotherapy without any severe or unexpected toxicity. She continues to be in remission 8 months following diagnosis. This is the first reported case of hepatoblastoma in a child with constitutional T13. This may represent a non-random association, as somatic trisomy of chromosome 13 in hepatoblastoma tumors has been previously described in the literature. Prolonged survival may have allowed for hepatoblastoma to present in our patient.

Extended spectrum of human glucose-6-phosphatase catalytic subunit 3 deficiency: novel genotypes and phenotypic variability in severe congenital neutropenia.

OBJECTIVE: To delineate the phenotypic and molecular spectrum of patients with a syndromic variant of severe congenital neutropenia (SCN) due to mutations in the gene encoding glucose-6-phosphatase catalytic subunit 3 (G6PC3). STUDY DESIGN: Patients with syndromic SCN were characterized for associated malformations and referred to us for G6PC3 mutational analysis. RESULTS: In a cohort of 31 patients with syndromic SCN, we identified 16 patients with G6PC3 deficiency including 11 patients with novel biallelic mutations. We show that nonhematologic features of G6PC3 deficiency are good predictive indicators for mutations in G6PC3. Additionally, we demonstrate genetic variability in this disease and define novel features such as growth hormone deficiency, genital malformations, disrupted bone remodeling, and abnormalities of the integument. G6PC3 mutations may be associated with hydronephrosis or facial dysmorphism. The risk of transition to myelodysplastic syndrome/acute myeloid leukemia may be lower than in other genetically defined SCN subgroups. CONCLUSIONS: The phenotypic and molecular spectrum in G6PC3 deficiency is wider than previously appreciated. The risk of transition to myelodysplastic syndrome or acute myeloid leukemia may be lower in G6PC3 deficiency compared with other subgroups of SCN.