Journal of Clinical Pathology Short report

Extreme hyperferritinaemia; clinical causes

Crook, M. A., Walker, P. L. C. — 2013-04-21T21:40:37-07:00

There are many causes of raised serum ferritin concentrations including iron overload, inflammation and liver disease to name but a few examples. Cases of extreme hyperferritinaemia (serum ferritin concentration equal to or greater than 10 000 ug/l) are being reported in laboratories but the causes of this are unclear. We conducted an audit study to explore this further. Extreme hyperferritinaemia was rare with only 0.08% of ferritin requests displaying this. The main causes of extreme hyperferritinaemia included multiple blood transfusions, malignant disease, hepatic disease and suspected Still's disease.

The somatic affairs of BRAF: tailored therapies for advanced malignant melanoma and orphan non-V600E (V600R-M) mutations

2013-04-21T21:40:37-07:00

BRAF V600R-M-D are uncommon mutations, not included in the experimental protocols of BRAF selective inhibitors. We report the evaluation of correlations among different types of BRAF somatic mutations in melanoma and their management with BRAF inhibitors. 21 patients with BRAF mutated metastatic melanoma were enrolled in the protocol with BRAF inhibitors for compassionate use at the University of Modena. Hot spot V600E mutations were found in 19 patients. V600R mutation and double (V600E -V600M) mutation were identified in two melanomas. In one case, V600K mutation was found. Two screening failures were noted. Mean progression free survival at follow-up of to 8 weeks, was 7.6 months. Five patients had a very short follow-up and the experimental protocol is still ongoing, so we cannot provide complete follow-up data. However, all of them are still under treatment and disease progression free. An objective response with few side effects was observed in all patients. in vitro studies with the aim of testing drug sensitivity.

Amplification refractory mutation system-PCR is essential for the detection of chimaeras with a minor allele population: a case report

2013-04-21T21:40:37-07:00

Blood chimaera is a rare but important issue for immunohaematology laboratories. Several molecular approaches, such as ABO genotyping, human leucocyte antigen (HLA) typing and DNA short tandem repeat (STR) analysis, have been used to identify chimaerism. Unfortunately, the minor allele population can be overlooked by PCR-based methods, which preferentially amplify the major allele population. A case with A_weakB (A_wB), demonstrating a mixed-field pattern, was sent to our laboratory for further evaluation. Direct sequencing of ABO exons 6 and 7 revealed a B101/O02 genotype. Analysis of the 12 STR loci and HLA typing did not provide any evidence of chimaerism. However, amplification refractory mutation system (ARMS)-PCR identified the minor A102 allele in addition to B101/O02. Three alleles of the chimaera were confirmed by cloning and sequencing. Thus, ARMS-PCR is essential, especially in the case of a chimaera with a minor allele population.