Anti-TIF-1γ dermatomyositis: Erythematous eruption with weakness and normal creatine kinase.

We describe a case of a previously well 76-year-old woman who presented with 9 months of a generalised pruritic rash alongside fatigue, weight-loss and a symmetrical weakness of the legs.

Disseminated Bisifusarium infection following toxic epidermal necrolysis in a child with B-cell acute lymphoblastic leukemia.

Fusarium is a polyphyletic genus of plant pathogens, members of which can cause opportunistic human infections with varying superficial and systemic presentations, including disseminated infections which typically occur in immunocompromised patients and have a poor prognosis. Treatment is challenging due to intrinsic resistance to many antifungal agents, and antifungal susceptibility testing is therefore essential. Early suspicion, isolation of the organism, and prompt initiation of management are crucial to improving survival. We present a case of disseminated Bisifusarium infection following toxic epidermal necrolysis in a child with B-cell acute lymphoblastic leukemia, successfully treated with liposomal amphotericin B, voriconazole, flucytosine, and terbinafine.

Solid pseudopapillary tumour of the pancreas: clinicopathological analysis.

BACKGROUND: We report on our experience of the surgical management and outcomes of 11 patients with solid pseudopapillary tumour of the pancreas (SPT). We sought to correlate the immunohistochemical staining of these tumours with that previously reported in the literature. METHODS: A retrospective analysis of the clinical presentation, radiological findings, surgical treatment, histopathological characteristics and outcomes for patients surgically managed with SPT at The Royal London Hospital. A literature search was performed to analyse the immunohistochemical stains commonly used to diagnose SPT. RESULTS: Between August 2006 and April 2016, 10 females and one male patient underwent surgery for SPT. The localization of the tumour was in the pancreatic head in two patients, one in the neck, three in the body and five in the tail. All 11 patients had localised disease. Six patients suffered post-surgical complications. Histopathology shows immunoreactivity for: ß-catenin, vimentin, CD-10, CD-56, α1-antitrypsin and negative staining for synaptophysin and chromogranin. At a median of 24 months of follow-up, the disease-free survival rate was 100% and no recurrence was noted. A literature review generated 38 suitable articles with 116 individual cases of SPT, with high expression of vimentin and neuron specific enolase throughout, and low rates of chromogranin and synatophysin positivity. CONCLUSION: SPT is rare and affects mostly young women. An accurate diagnosis is important as the relative indolent behaviour can be managed with surgical resection even when large in size, bringing excellent long-term outcomes.

S100P-binding protein, S100PBP, mediates adhesion through regulation of cathepsin Z in pancreatic cancer cells.

Several S100 proteins are up-regulated in pancreatic ductal adenocarcinoma (PDAC), the most significant being S100P. We previously reported on S100PBP, a binding partner of S100P, that shows no homology to any described protein and whose functions are completely unknown. To determine S100PBP expression across human tissues and organs, immunohistochemistry was performed using both multiorgan- and in-house-constructed pancreatic tissue microarrays. To establish S100PBP functions, cell lines with either stably overexpressed or silenced S100PBP were generated and investigated using Affymetrix gene expression arrays and complementary functional assays. We show that S100PBP is differentially expressed in various healthy and tumor specimens, which is both cancer- and tissue-type dependent. In healthy pancreas, S100PBP is expressed in the nuclear/perinuclear region of both exocrine and endocrine compartments. In early precancerous lesions, S100PBP is translocated to the cytoplasm, whereas in PDAC and metastatic lesions, its expression is significantly diminished. The most pronounced phenotypic change after manipulation of S100PBP expression was seen in adhesion; this was significantly reduced after S100PBP up-regulation and increased after S100PBP silencing. Up-regulation or silencing of S100PBP also led to a concomitant change in the levels of the protease cathepsin Z, the silencing of which significantly reduced PDAC cell adhesion. We further demonstrate that the interaction of cathepsin Z with arginine-glycine-aspartic acid-binding integrins, specifically αvß5, mediates the changes seen in adhesion of PDAC cells.

Proteome of formalin-fixed paraffin-embedded pancreatic ductal adenocarcinoma and lymph node metastases.

Pancreatic ductal adenocarcinoma (PDAC) is a major cause of cancer-related death, largely due to metastatic disease. To better understand PDAC metastatic spread and identify novel therapeutic targets, we analysed the proteome of primary tumours and matched lymph node (LN) metastases. As frozen specimens of metastatic lesions are scarce, we examined formalin-fixed paraffin-embedded (FFPE) tissues. This poses technical challenges because of the cross-linkages induced by fixation. Using laser capture microdissection (PALM system), we isolated malignant epithelia from seven FFPE primary PDAC tumours and matched LN metastases. Following dissection, samples were analysed in duplicate using Multidimensional Protein Identification Technology (MudPIT); this resulted in the identification of 1504 proteins, 854 of which were common to all samples analysed. Comparison of the obtained proteins with data from previous proteomics studies on pancreatic tissue, pancreatic juice, serum, and urine resulted in a less than 30% overlap, indicating that our study has substantially expanded the current database of proteins expressed in this malignancy. Statistical analysis further showed that 115/854 proteins (13.5%) were significantly differentially expressed (g-value ≥ 3.8). Two proteins, S100P and 14-3-3 sigma, with highly significant g-values were confirmed to be significantly differentially expressed (S100P: p = 0.05 and 14-3-3 sigma: p < 0.001) in a larger series of 55 cases of matched primary PDAC and LN metastases using immunohistochemistry. Thus, laser capture microdissection of FFPE tissue coupled with downstream proteomic analysis is a valid approach for the investigation of metastatic PDAC. This is the first study to establish and compare the protein composition of primary PDAC and matched LN metastases, and has resulted in the identification of several potential epithelial-specific therapeutic targets, including 14-3-3 sigma and S100P.