In a 5-year survey of nonpromyelocytic/nonmonocytic acute myeloid leukemias (AMLs) diagnosed in the University of Washington Hematopathology Laboratory, we identified 19 cases containing distinctive, cup-like nuclear indentation in 10% or more of the blasts ('AML-cuplike'). Fourteen of these cases (74%) demonstrated near-complete loss of HLA-DR expression, while the other five cases showed partial loss of HLA-DR. A total of 16 of the cases (84%) demonstrated internal tandem duplication (ITD) of the Flt3 gene. When compared to a selected set of AMLs lacking this nuclear morphology, AMLcuplike was significantly more likely to lack HLA-DR and CD34 expression, to express CD123 without CD133, to have a normal karyotype, and to harbor the Flt3 ITD. To characterize AMLcuplike in an unselected series of AMLs, we analyzed 42 consecutive nonpromyelocytic/nonmonocytic AMLs diagnosed in our laboratory during a 6-month period in 2002. Strikingly, in this unselected series, there was a statistically significant coincidence of invaginated nuclear morphology, loss of HLA-DR, and presence of the Flt3 ITD beyond that expected if these three features were unrelated, suggesting that AMLs with these three features may represent a distinct AML subset.

SummaryInternal tandem duplications in FLT3 are the most common mutation in acute myeloid leukaemia (AML), with agarose gel electrophoresis of polymerase chain reaction products (PCR/agarose) being the screening method of choice for these mutations. As PCR/agarose screening does not detect small mutations, single-stranded conformational polymorphism analyses (PCR/SSCP) were used in an attempt to identify previously unrecognized point mutations in FLT3 exons 14 and 15 of 140 AML patients, using newly designed primers that anneal within intron sequences. Novel missense point mutations were found in exon 14, suggesting additional investigations should be performed in AML and other haematopoietic malignancies, using this sensitive technique.

Giving difficult news to patients represents a common dilemma for health care professionals. Based on three decades of research, various authors have proposed guidelines outlining the ideal setting, delivery, and timing. Existing publications focus on patients of European descent and may not be applicable in cross-cultural settings. We explored perceptions of Spanish-speaking mothers who have a child with Down syndrome and how they preferred to receive the news of their child's diagnosis. We conducted semi-structured qualitative interviews (n = 14), which were coded and analyzed by thematic networks to identify common themes. Six significant themes emerged: Cultural Belief System, Communication, Support/Lack of Support, Feelings Engendered, Medical Issues, and Medical System. One overarching theme of mother-child bonding encompassed all sub-themes. The mothers desired the news in a more positive, balanced light and with more complete explanations about the condition. Mothers felt excluded from the diagnostic process and wanted to be better informed about the need for diagnostic studies. Participants used religious beliefs to explain the reason for their child's condition. Many factors influenced Latina mothers' ability to bond initially with their children with Down syndrome. Ideally, these factors should be acknowledged during informing interviews to assist Latino families in adjustment.

In the fertility clinic setting, a negative DNA paternity test result usually suggests a sample mix-up likely occurred at the testing company or in the clinic. However, we report a case where, despite repeat negative paternity test results, the alleged father (referred to as “the proband”) was confirmed to be the baby’s father. The proband, a 34 year-old male, contacted our research group when routine blood testing revealed discrepant blood types between the parents and the baby, repeat paternity tests were negative (excluding the proband as the baby’s father), and the fertility clinic found no evidence of any wrongdoing. Microarray technology was utilized to confirm biological relatedness, which revealed an avuncular (uncle/nephew) relationship. Additional tissue samples were analyzed and family studies were conducted at paternity and forensic laboratories using STR-based DNA tests to elucidate the proband’s condition of congenital tetragametic chimerism. His paternity was subsequently affirmed and the fertility clinic exonerated of claims of a semen sample mix-up. This case underscores the possibility that some allegations of fertility clinic missteps may be explained by undiagnosed chimerism, a condition where an individual harbors two distinct genomes. We offer specific suggestions for improving laboratory reporting and creating clinical guidelines to aid in identifying and rectifying future cases of false exclusions of paternity due to chimerism.Electronic supplementary materialThe online version of this article (10.1007/s10815-017-1064-6) contains supplementary material, which is available to authorized users.