In this real world setting, high uptake of EGFR testing was achieved and associated with major changes in EGFR-TKI prescribing and improved health outcomes. Modifiable factors determined testing uptake. Study registration ACTRN12615000998549.

We describe a new type of cardiomyopathy caused by a mutation in the glycogenin-1 gene (GYG1). Three unrelated male patients aged 34 to 52 years with cardiomyopathy and abnormal glycogen storage on endomyocardial biopsy were homozygous for the missense mutation p.Asp102His in GYG1. The mutated glycogenin-1 protein was expressed in cardiac tissue but had lost its ability to autoglucosylate as demonstrated by an in vitro assay and western blot analysis. It was therefore unable to form the primer for normal glycogen synthesis. Two of the patients showed similar patterns of heart dilatation, reduced ejection fraction and extensive late gadolinium enhancement on cardiac magnetic resonance imaging. These two patients were severely affected, necessitating cardiac transplantation. The cardiomyocyte storage material was characterized by large inclusions of periodic acid and Schiff positive material that was partly resistant to alpha-amylase treatment consistent with polyglucosan. The storage material had, unlike normal glycogen, a partly fibrillar structure by electron microscopy. None of the patients showed signs or symptoms of muscle weakness but a skeletal muscle biopsy in one case revealed muscle fibres with abnormal glycogen storage. Glycogenin-1 deficiency is known as a rare cause of skeletal muscle glycogen storage disease, usually without cardiomyopathy. We demonstrate that it may also be the cause of severe cardiomyopathy and cardiac failure without skeletal muscle weakness. GYG1 should be included in cardiomyopathy gene panels.Electronic supplementary materialThe online version of this article (doi:10.1007/s10545-016-9978-1) contains supplementary material, which is available to authorized users.

Multifocal melanoma and melanoma in situ of the vulva and vagina are uncommon lesions, and our understanding of their natural history is limited. Vulvovaginal melanoma appears to be biologically different from cutaneous melanoma and has more in common with mucosal melanoma. A 60-year-old woman presented in 1977 with a pigmented vulvar lesion. Histologic examination revealed melanoma in situ associated with focal invasive melanoma. She re-presented with recurrent primary melanomas arising in melanoma in situ in 1990 and 1998 and died of widespread metastatic melanoma in 2000. Melanoma in situ of the vulva and vagina is rare and appears to have a relatively slow but definite progression to invasive melanoma. All suspicious pigmented lesions in this region should be biopsied, and if multifocal in situ melanoma is identified, vulvo(vagin)ectomy should be considered.

To investigate the clinical validity and utility of tests for detecting Epidermal Growth Factor Receptor (EGFR) gene mutations in non-squamous non-small cell lung cancer patients, tumour DNA extracts from 532 patients previously tested by the cobas EGFR Mutation Test (RT-PCR test) were retested by the Sequenom/Agena Biosciences MassArray OncoFocus mass spectrometry test (MS test). Valid results from both tests were available from 470 patients (88%) for agreement analysis. Survival data were obtained for 513 patients (96%) and 77 patients (14%) were treated with EGFR tyrosine kinase inhibitors (TKIs). Agreement analysis revealed moderately high positive (79.8%), negative (96.9%) and overall percentage agreement (93.2%) for the detection of EGFR mutations. However, EGFR mutations were detected by one test and not by the other test in 32 patients (7%). Retesting of discordant samples revealed false-positive and false-negative results generated by both tests. Despite this, treatment and survival outcomes correlated with the results of the RT-PCR and MS tests. In conclusion, this study provides evidence of the clinical validity and utility of the RT-PCR and MS tests for detection of EGFR mutations that predict prognosis and benefit from EGFR-TKI treatment. However, their false-positive and false-negative test results may have important clinical consequences.

Throughout the last century, there has been a marked decline in obstetric maternal deaths, resulting in an increase in the proportion of nonobstetric deaths among pregnant women. Trauma, in particular, has become a leading cause of maternal death. We report the case of a 20-year-old primigravid woman who was involved in a motor vehicle crash at 36 weeks gestation. The woman developed abruptio placentae, followed by disseminated intravascular coagulation, adult respiratory distress syndrome, and shock, and died the day after the crash. Widespread pulmonary embolization by chorionic villi was identified at autopsy. This report discusses traumatic maternal deaths, with emphasis on the differences in injury pattern observed in pregnant trauma victims in comparison with other adults. It is important that the pathologist be aware of these problems so that an accurate cause of death can be identified in cases of maternal death after trauma. Also discussed is the relationship between trauma and placental abruption and the mechanism of death in the patient. To the authors' knowledge, this is the first reported case of extensive embolism of chorionic villi to the lungs after trauma.