The classification of acute myeloid leukemia (AML) has evolved to the most recent World Health Organization (WHO) schema, which integrates genetic, morphologic, and prognostic data into a single system. However, this system was devised using adult data and how this system applies to a pediatric cohort is unknown. Performing a retrospective chart review, we examined our single-center experience with AML in 115 children and classified their leukemia using the WHO 2008 schema. We examined patient samples for mutations of FLT3, NPM1, and CEBPA. Overall survival was calculated within categories. In our pediatric population, most cases of AML had recurrent genetic abnormalities of favorable prognosis. More than 10% of patients in our series were categorized as AML, with myelodysplasia-related changes, an entity not well-described in pediatric patients. In addition, a large proportion of patients were categorized with secondary, therapy-related AML. To our knowledge, this is the first application of the WHO 2008 classification to a pediatric cohort. In comparison to adult studies, AML in the pediatric population shows a distinct distribution within the WHO 2008 classification.

Globally, adult intensive care units routinely use the International Society on Thrombosis and Haemostasis (ISTH) scoring system for identifying overt disseminated intravascular coagulation (DIC). However, in our pediatric intensive care unit, a modified diagnostic criterion (Texas Children's Hospital [TCH] criteria) that requires serial monitoring of the coagulation variables is employed. A retrospective analysis of 2,136 DIC panels from 130 patients who had at least 4 DIC panels during 1 admission to a pediatric intensive care unit was done to compare the diagnostic utility of the TCH criteria with the ISTH scoring method in children. Both scoring systems were evaluated against the gold standard diagnostic method of autopsy confirmation of DIC in the subset of children who died. Receiver operating characteristic analysis indicates that TCH diagnostic criteria are comparable to the ISTH scoring method (area under the curve of 0.878 for TCH and 0.950 for ISTH). On the contrary, TCH diagnostic criteria perform better, with a sensitivity significantly higher than the ISTH scoring method when tested against the gold standard (P < .05). Fibrinogen is not a significant predictor of overt DIC in both models. Sequential testing of coagulation parameters is recommended for improved sensitivity when applying ISTH criteria to pediatric populations.

Patients with the most common weak D types 1, 2, and 3 can be safely considered D positive. We evaluated 1,113 Rh-negative Egyptian samples for weak D expression to propose a cost-effective strategy related to D variant testing. D variants were tested using polymerase chain reaction with sequence-specific priming. Fifty samples were D variants (4.5%): weak D type 4.2 (32%), weak D type 4.0/4.1 (16%), and weak D type 15 (2%). Fifteen (62.5%) of 24 samples were identified serologically as partial D. We also studied the probability of the development of anti-D in 52 Rh-negative children with thalassemia who were receiving units for which weak D was not tested. Anti-D alloimmunization was observed in 63.5% of patients with thalassemia. It is prudent to implement weak D typing in Egyptian donors. Weak D variants of Egyptians are significantly different compared with Caucasians. Ethnicity must be taken into consideration when developing clinical and prenatal strategies related to D variants.

Storing packed red blood cells (pRBCs) increases the potassium concentration. This effect is characterized in citrate phosphate dextrose/citrate phosphate dextrose adenine units but not published for Adsol (AS-5) units. The change in whole-blood potassium concentration in pediatric patients during routine transfusion is also poorly characterized. In this study, pediatric patients undergoing transfusion had pre- and posttransfusion whole-blood potassium measurements. The pRBC unit transfused and the unit's segment were sampled, with potassium concentration measured. In addition, potassium concentration in AS-5 units was measured over 42 days of storage. Unit extracellular potassium increased in AS-5 units after day 7 at 0.83 mmol/L/d. The mean change in patient potassium concentration was 0.08 mmol/L (range, -0.5 to 0.5 mmol/L). No correlation with unit age or unit potassium concentration was identified with change in patient whole-blood potassium concentration. The lack of clinical effect on patient potassium does not support the use of "fresh" pRBC units with routine pediatric transfusion.

Screening for monoclonal gammopathies is usually done by serum protein electrophoresis (SPEP) and serum free light chain tests. SPEP may be followed by immunofixation electrophoresis (IFE). IFE may be ordered by the treating physician or be at the discretion of the pathologist. We examined the appropriateness of IFE ordering by treating physicians and report on our findings, follow-up changes to the ordering process, and results of the change. We retrospectively analyzed the data from our laboratory from April 2009 through July 2012. In April 2009, 3 options for test ordering were available for the clinicians: SPEP with reflex IFE, SPEP only, and SPEP with IFE. This test ordering option was limited to SPEP with reflex IFE only in April 2010. We compared the rates of SPEP and IFE performed in the 2 periods (ie, April 2009 through April 2010 and May 2010 through July 2012). There was a substantial drop in the IFE/SPEP ratio from 0.47 to 0.21. Review of electronic medical records by the consultant pathologist was instrumental in improving the utilization and enhancing the value of pathology consultation. Possible impacts on laboratory costs, revenue, and overall health care are also presented.

FK506 (tacrolimus), a macrolide immunosuppressant, is widely used in pediatric transplant patients, but a relatively narrow therapeutic window in children vs adults requires close and accurate monitoring of whole blood FK506 levels. High-pressure liquid chromatography/tandem mass spectrometry (HPLC/MS/MS)-based assays have been viewed as the gold standard but are more time and labor intensive than cloned enzyme donor immunoassay (CEDIA). To analyze differences between the 2 assays, we assayed FK506 in 348 split samples simultaneously by both methods. A further 70 samples were stratified by organ transplantation type: cardiac (13%), renal (23%), small bowel (22%), or liver transplantation (42%). Results were analyzed using standard statistical techniques for method comparison. CEDIA overestimated the FK506 value relative to HPLC/MS/MS by more than 20% in 40% of cases (139/348), whereas CEDIA underestimated the FK506 value relative to HPLC/MS/MS by more than 20% in 13.5% of cases, for a total inaccuracy of 53% using a ±20% cutoff. Only 28% of samples (99/348) measured by CEDIA were within 10% of the value obtained by HPLC/MS/MS. Bland-Altman analysis showed a mean bias of 9.5% in favor of CEDIA over HPLC/MS/MS (95% confidence interval, 6.1%-12.9%). Positive bias was greatest for liver transplant and R(2) values were lowest for intestinal transplant patients, indicating that HPLC/MS/MS may be a better option for this pediatric transplant subgroup.

Adrenocortical carcinomas (ACCs) with myxoid features are rare neoplasms. We identified 7 cases of myxoid ACC and studied the clinicopathologic and immunohistochemical features of these neoplasms. The patients were 5 men and 2 women with a mean age of 45 years. Histologically, the tumors contained alcian blue-positive myxoid areas ranging from 10% to 50% of the tissue examined. One case showed lipomatous metaplasia. Areas of conventional ACC were present in all cases. Immunohistochemically, the tumors were positive for steroid receptor cofactor 1, inhibin, melan A, calretinin, and synaptophysin but negative for high-molecular-weight cytokeratin, CAM5.2, and Pax8. Clinical follow-up information for 4 patients demonstrated that all patients had died of their disease 11 to 69 months after diagnosis. Myxoid ACCs are rare tumors that expand the differential diagnosis of myxoid neoplasms involving the retroperitoneum. Contrary to previous reports proposing that the biologic behavior is similar to conventional ACC, our series seems to indicate that myxoid morphology is associated with more aggressive behavior.

Ewing family tumors (EFTs) and prostate carcinomas are characterized by rearrangement of ETS genes, most commonly FLI1 (EFTs) and ERG (prostate carcinomas). Previously, we characterized an antibody against ERG (EPR3864) for detecting ERG-rearranged prostate carcinoma. Because EPR3864 also cross-reacts with FLI1, we evaluated the usefulness of EPR3864 for discriminating EFTs from other small round blue cell tumors (SRBCTs) with immunohistochemistry. Of 57 evaluable EFTs, 47 (82%) demonstrated at least moderate, diffuse, nuclear ERG/FLI1 staining (including 89% and 100% of cases with confirmed EWSR1:FLI1 and EWSR1:ERG fusions, respectively), of which 1, 3, and 43 showed negative, cytoplasmic, or membranous CD99 staining, respectively. Among other SRBCTs (61 cases, 7 types), at least moderate, diffuse, nuclear EPR3864 staining was seen in all precursor B-lymphoblastic lymphomas/leukemias and subsets of Burkitt lymphomas (10%) and synovial sarcomas (45%). In summary, EPR3864 may be useful in detecting EWSR1:FLI1 and EWSR1:ERG rearranged EFTs in addition to prostate carcinomas.