Small Cell Carcinoma of the Ovary, Hypercalcemic Type, in a 12-Month-Old Girl.

Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is a highly aggressive malignant tumor affecting predominantly young adults and adolescents with an average age of 23.9 at time of diagnosis. Up to two thirds of patients have paraneoplastic hypercalcemia. The molecular signature of these tumors is SMARCA4 mutations, with somatic and germline pathogenic variants previously described. We report a case of a previously healthy one-year-old girl who was noticed to have mild anemia and an abdominal mass during a well-child visit. Further laboratory testing revealed hypercalcemia. A computerized tomography scan showed a left-sided ovarian mass (9.3 x 7.3 x 7 cm). The resection specimen showed a large ovarian tumor with solid tan-yellow cut surfaces and small foci of necrosis. Microscopically, the tumor was composed of sheets of small, hyperchromatic epithelioid cells with focal rhabdoid large cell morphology. The tumor cells were strongly and diffusely positive for WT1 (N-terminal antibodies) with focal EMA and Pan-keratin positivity. Absent SMARCA4 (BRG1) protein expression by immunohistochemistry ultimately established the diagnosis of small cell carcinoma of the ovary, hypercalcemic type. To our knowledge, this is the youngest patient reported in the literature.

A novel homozygous VPS45 p.P468L mutation leading to severe congenital neutropenia with myelofibrosis.

VPS45-associated severe congenital neutropenia (SCN) is a rare disorder characterized by life-threating infections, neutropenia, neutrophil and platelet dysfunction, poor response to filgrastim, and myelofibrosis with extramedullary hematopoiesis. We present a patient with SCN due to a homozygous c.1403C>T (p.P468L) mutation in VPS45, critical regulator of SNARE-dependent membrane fusion. Structural modeling indicates that P468, like the T224 and E238 residues affected by previously reported mutations, cluster in a VPS45 "hinge" region, indicating its critical role in membrane fusion and VPS45-associated SCN. Bone marrow transplantation, complicated by early graft failure rescued with stem cell boost, led to resolution of the hematopoietic phenotype.

Application of a standardized screening protocol for diagnosis of invasive mold infections in children with hematologic malignancies.

PURPOSE: This study describes a standardized screening protocol for diagnosis of invasive mold infections in pediatric oncology patients with neutropenia and prolonged or recurrent fever. METHODS: A retrospective chart review was performed of children receiving intensive chemotherapy for hematologic malignancies who developed invasive mold infections from 2004 to 2011. Characteristics and outcomes were compared before and after implementation of the screening protocol in November 2006. The screen includes direct nasal endoscopy performed at the bedside by an otorhinolaryngologist, noncontrast computed tomography (CT) of the chest, and abdominal ultrasound in patients with neutropenia and prolonged or recurrent fever. RESULTS: Fifty patients had proven, probable, or possible invasive mold infections. Before routine use of direct nasal endoscopy, invasive nasosinal disease was detected in 5 of 19 patients (26 %) and all had a compatible clinical presentation. Thirteen of 31 patients (42 %) in the post-screen group had nasosinal disease, and fever was the only sign for 8 patients (62 %). Twenty-four patients with nasosinal disease had a sinus CT, and radiologic findings of bony erosion or peri-sinus invasion were never detected. Eight of 19 patients in the pre-screen group died from mold infection (42.1 %) versus 4 of 31 (12.9 %) in the post-screen group (p = 0.04). CONCLUSIONS: A screening protocol including direct nasal endoscopy, noncontrast chest CT, and abdominal ultrasound was effective in detecting invasive mold infections in at-risk patients. Nasosinal involvement often occurs before specific symptoms develop, and sinus CTs are insensitive and nonspecific. Bedside nasal endoscopy precludes radiation exposure associated with sinus CT and was associated with decrease in mold-related mortality, likely due to earlier diagnosis and initiation of appropriate antifungal therapy.

Association of hospital construction with the development of healthcare associated environmental mold infections (HAEMI) in pediatric patients with leukemia.

BACKGROUND: Healthcare associated mold infections (HAEMI) increase morbidity and mortality in children with leukemia. Excavation adjacent to Children's Medical Center Dallas (CMCD) April 2006-February 2007 provided an opportunity to determine if excavation adjacent to a hospital building is associated with increased risk of developing HAEMI in children receiving intensive chemotherapy for acute leukemia. METHODS: Children who began receiving intensive chemotherapy for acute leukemia at CMCD from 2004 to 2008 were identified (n = 275). Exposures to the CMCD campus during intensive chemotherapy and duration of neutropenia per exposure were recorded. Proven, probable, or possible invasive fungal disease (IFD) was classified using EORTC/MSG guidelines. Institutional guidelines categorized mold infections as definite or possible HAEMI. A bivariate time-to-event model compared the association of excavation with HAEMI and yeast infections, controlling for neutropenia. RESULTS: There were 7,454 CMCD exposures, 1,007 (13.5%) during excavation. Of 50 cases of IFD, 31 were HAEMI. By time-to-event analysis exposure to the CMCD campus during the excavation period was significantly associated with HAEMI (HR = 2.8, P = 0.01) but not yeast infections (HR = 0.75, P = 0.75). Neutropenia was significantly associated with both HAEMI and yeast infections (P < 0.001). Voriconazole prophylaxis did not prevent HAEMI in 42% of the 14 patients with AML who had been receiving this agent. CONCLUSION: This study is the first to demonstrate an association between exposure to hospital construction that includes excavation and HAEMI in pediatric oncology patients. Since neutropenic patients need protection from aerosolized fungal spores during visits to expanding medical centers, preventive strategies with adherence monitoring need additional study.

Measuring disparities in event-free survival among children with acute lymphoblastic leukemia in an academic institute in Oklahoma, 2005-2019.

BACKGROUND: Acute lymphoblastic leukemia (ALL) is the most common type of childhood cancer. While there have been successes in the treatment of leukemia, less information is available on reasons for disparities in event-free survival (EFS) among underserved populations. METHODS: We partnered with a children's hospital at an academic institution to abstract data from the institution's cancer registry, the state cancer registry, and electronic medical records on cancer diagnosis, treatment, and outcomes for children with ALL (n = 275) diagnosed from 2005 to 2019 prior to age 20. We evaluated the relation between 1) race/ethnicity, 2) distance to the children's hospital, and 3) area deprivation with EFS, defined as time from diagnosis to relapse, death, or the end of the study period. We evaluated differences in EFS using Kaplan-Meier analysis with the log-rank test. We used the Cox Proportional Hazards Model for multivariable survival analyses. RESULTS: Most children were diagnosed with ALL under five years of age (45%) and with Pre-B ALL (87%). Twelve percent of children experienced a relapse and 5% died during induction or remission. EFS at 5 years was 82%. Non-Hispanic (NH) Black children had worse, though imprecise, EFS compared to NH White children (Adjusted Hazard Ratio: 2.07, 95% CI: 0.80, 5.38). Children residing in areas with higher deprivation had a higher adjusted hazard of poor outcomes compared to the least deprived areas, though estimates were imprecise (2nd quartile HR: 1.51, 3rd quartile: 1.85, 4th quartile: 1.62). We observed no association between distance to the children's hospital and EFS. CONCLUSION: We observed poorer EFS for NH Black children and children residing in areas with high deprivation, though the estimates were not statistically significant. Our next steps include further evaluating socioeconomic factors in both rural and urban children to identify disparities in outcomes for children with ALL and other childhood cancers.