IgA nephropathy (IgAN) is characterized by a variable clinical course and multifaceted pathophysiology. There is substantial evidence to suggest that complement activation plays a pivotal role in the pathogenesis of the disease. Therefore, complement inhibition using the humanized anti-C5 monoclonal antibody eculizumab could be a rational treatment. We report here a 16-year-old male with the vasculitic form of IgAN who failed to respond to aggressive conventional therapy including high-dose steroids, cyclophosphamide and plasma exchange and who was treated with four weekly doses of 900 mg eculizumab followed by a single dose of 1200 mg. He responded rapidly to this treatment and has had a stable creatinine around 150 µmol/L (1.67 mg/dL) for >6 months. However, proteinuria was unabated on maximal conventional anti-proteinuric treatment, and a repeat renal biopsy 11 months after presentation revealed severe chronic changes. We believe this case provides proof of principle that complement inhibition may be beneficial in IgAN but also that development of chronicity may be independent of complement.

The demonstration of impaired C regulation in the thrombotic microangiopathy (TMA) atypical hemolytic uremic syndrome (aHUS) resulted in the successful introduction of the C inhibitor eculizumab into clinical practice. C abnormalities account for approximately 50% of aHUS cases; however, mutations in the non-C gene diacylglycerol kinase-« have been described recently in individuals not responsive to eculizumab. We report here a family in which the proposita presented with aHUS but did not respond to eculizumab. Her mother had previously presented with a post-renal transplant TMA. Both the proposita and her mother also had CharcotMarie-Tooth disease. Using whole-exome sequencing, we identified a mutation in the inverted formin 2 gene (INF2) in the mutational hotspot for FSGS. Subsequent analysis of the Newcastle aHUS cohort identified another family with a functionallysignificant mutation in INF2. In this family, renal transplantation was associated with post-transplant TMA. All individuals with INF2 mutations presenting with a TMA also had aHUS risk haplotypes, potentially accounting for the genetic pleiotropy. Identifying individuals with TMAs who may not respond to eculizumab will avoid prolonged exposure of such individuals to the infectious complications of terminal pathway C blockade.

Mazabraud's syndrome is a rare disorder characterized by the association of single or multiple intramuscular myxomas with fibrous dysplasia. Here, we present the first case of Mazabraud's syndrome visualized on 18F-FDG PET/CT with histopathological confirmation of the myxoma. Our case demonstrates a slightly increased FDG uptake (SUVmax 2.1) within the myxomas and a moderately to highly increased tracer uptake (SUVmax 7.0) within the fibrous dysplastic lesions. The typical histological appearance of the intramuscular myxoma confirmed the radiological diagnosis. Further, we discuss the imaging findings and the histopathological features of this rare case with a review of the related literature.

AimsEven though extensive melanoma sentinel node (SN) pathology protocols increase metastasis detection, there is a need for balancing high detection rates with reasonable workload. A newly tested Danish protocol recommended examining nodes at six levels 150 µm apart (six-level model) and using SOX10 and Melan-A immunohistochemistry (IHC). We explored if a protocol examining 3 levels 300 µm apart (three-level model) combined with IHC would compromise metastasis detection. The study aim was to optimise the protocol to reduce workload without compromising detection rate.Methods8 months after protocol implementation, we reviewed the pathology reports of SNs from 507 melanoma patients nationwide, including 117 SN-positive patients. Each report was reviewed to determine histopathological features, including detection of metastasis, exact levels with metastasis, exact levels with metastasis >1 mm in diameter and IHC results.ResultsThe six-level model detected metastases in 23% of patients, whereas the three-level model would have detected metastases in 22% of patients. The three-level model would have missed a few small metastases (n=4), measuring <0.1 mm, 0.1 mm, 0.4 mm and 0.1 mm, respectively. The six-level model detected metastases >1 mm in 7% of patients. One of these metastases (measuring 1.1 mm) would have been detected by the three-level model, but not as >1 mm. SOX10 and Melan-A had equal sensitivity.ConclusionsReducing the number of levels examined to three levels 300 µm apart combined with IHC does not have significant impact on metastasis detection rate, and we will therefore recommend that the future melanoma SN guideline takes this into consideration to reduce overall workload.