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Purpose: To report a unique case of orbital inflammatory disease which was ultimately diagnosed as granulomatosis with polyangitis (GPA) and thus successfully treated. Observation: A 47 year-old man presented with a rapidly progressive necrotic soft tissue mass within the medial antero-superior aspect of the right eyelid and orbit. He also had transient retinal vasculitis in the left. Serology, histology and imaging were atypical of, but consistent with, GPA. He was thus successfully treated with intravenous rituximab followed by reconstruction of the medial eyelid. Conclusion and importance: A high index of suspicion of GPA is required in orbital inflammatory disease, especially when typical diagnostic findings are absent. Keywords: Orbital inflammatory disease, Rituximab, Eyelid reconstruction, Granulomatosis with polyangiitis

We present the 15-year experience of a family colorectal cancer screening service in Ireland with emphasis on real life experience and outcomes.Questionnaires were used to assess family cancer history and assign patients to risk categories; 'Moderate Risk', HNPCC, (suspected) genetic syndrome (non-HNPCC), 'Low Risk'. Screening was by full colonoscopy. We report neoplastic yield, examining effect of risk category, age, gender, and index colonoscopy findings.Between 1998 and 2013, 2242 individuals were referred; 57.3% female, 42.7% male, median age 46 years (range9-85yrs). Median follow up time was 7.9yrs (range 0.5-15.3yrs). Follow up data after exclusion (non-compliance, known CRC) was available in 1496 (66.7%): 'Moderate risk' 785 (52.5%), HNPCC 256 (17.1%), (suspected) genetic syndrome (non-HNPCC) 85 (5.7%), 'Low Risk' 370 (24.7%). Screening was performed in 1025(68.5%) patients; colonoscopy data available for 993 (96.9%); total 1914 colonoscopies. At index colonoscopy, 178 (18.0%) patients had adenomas; 56 (5.5%) advanced adenoma. During the entire study period, 240 (24.2%) had an adenoma; 69 (7.0%) advanced adenoma. Cancers were diagnosed on screening in 2 patients. Older age and male gender were associated with higher adenoma detection rate; p0.001, p=0.01, respectively. Risk category did not affect adenoma yield. Adenoma and advanced adenoma detection at index colonoscopy were associated with detection of same at follow up screening; p0.001.Male gender and age (50) were the core identifiable risk factors for neoplasia at screening colonoscopy in this family screening setting. Our results would support less intensive surveillance in younger patients (50), particularly where index colonoscopy is normal.

Reflex immunohistochemistry (rIHC) for mismatch repair (MMR) protein expression can be used as a screening tool to detect Lynch Syndrome (LS). Increasingly the mismatch repair‐deficient (dMMR) phenotype has therapeutic implications. We investigated the pattern and consequence of testing for dMMR in three Irish Cancer Centres (CCs). CRC databases were analyzed from January 2005–December 2013. CC1 performs IHC upon physician request, CC2 implemented rIHC in November 2008, and CC3 has been performing rIHC since 2004. The number of eligible patients referred to clinical genetic services (CGS), and the number of LS patients per center was determined. 3906 patients were included over a 9‐year period. dMMR CRCs were found in 32/153 (21%) of patients at CC1 and 55/536 (10%) at CC2, accounting for 3% and 5% of the CRC population, respectively. At CC3, 182/1737 patients (10%) had dMMR CRCs (P

Objectives Treatment options for recurrent low grade serous ovarian carcinoma (LGSOC) are limited. Herein we describe the potential utility of next generation sequencing in identifying therapeutic targets for this rare tumour. Methods 3 patients were included in this study. DNA was extracted from ten FFPE tumour samples (5 from primary surgery and 5 from recurrences) and whole blood. Whole exomes sequencing (WES) was performed on Illumina’s NextSeq platform to a depth of at least 10X. Sequence data were trimmed, aligned and single nucleotide variants and copy number alterations were called. Results All samples were microstatellite stable, 2 of the 3 patients had an elevated tumour mutational burden(TMB) (defined as >10 mutations/Mb). In the patient with low TMB we identified a class 3 ‘kinase-dead’ BRAF variant, D594G with concordant near-whole chromosome 1 amplification, covering the NRAS proto-oncogene. Single gene testing confirmed wild type EGFR and KRAS. This lady did not respond to a trametinib. The second case identified a pathogenic NBN R43* mutation with associated non pathogenic mutations in other DNA damage response genes. This patient who had previously declined cytotoxic chemotherapy has had a partial response to platinum based chemotherapy. The third patient did not have a targetable mutation but is awaiting PD-L1 testing. Conclusions WES may be helpful in refractory LGSOC when standard treatment options have been exhausted. Two of our patients had an elevated TMB suggesting that the efficacy of immunotherapy in LGSOC should be investigated.

Elastosis perforans serpiginosa (EPS) is a rare skin disorder in which there is transepithelial elimination of elastin fibers. It belongs to a group of perforating disorders of which there are four classic types. The EPS type is extremely rare. There have been no previous reports of elastosis perforans serpiginosa occurring as a paraneoplastic phenomenon. We report a case of paraneoplastic elastosis perforans serpiginosa in the setting of stage 4 ovarian cancer.

Laparoscopic and endoscopic colorectal intervention and operations have their basis in real-time, image-based decision-making and step-by-step sequenced technical progress. The capacity to visualize accurately malignant disease wherever it may be including within the primary lesion and its draining lymph node basin as well as at potential sites of metastatic harbor (i.e. peritoneum, liver and lung) would allow more accurate surgery at the time of operation and enable personalized, stratified surgical intervention. In addition, such capacity could efficiently compress the diagnostic and therapeutic stages of a patient's progress from presentation, through work-up and onto appropriate treatment, important in this era of restricted resource and increased user demand. Near-infrared endolaparoscopic illumination enables broad spectral imaging of tissue in situ, most often, at present, in conjunction with the approved safe and low-cost fluorophore indocyanine green. While additional targeted agents are in development, here we detail how this developed and available technology may be used as a visual probe of neoplasia to inform surgeons regarding functional, tissue characterization through the direct observation of metabolic and metabolomic processes within the area under inspection perhaps helping in the distinction between invasive cancer and non-invasive dysplastic lesions. This understanding can inform and accelerate development of specific agents and techniques that can better advance surgical practice into the era of surgical data science and true precision surgery.

Bronchial neuroendocrine tumors (NET) are classified into well-differentiated typical carcinoids (TC), atypical carcinoids (AC), large cell neuroendocrine carcinomas (LCNEC), and small cell lung carcinomas (SCLC). We retrospectively reviewed and analyzed the diagnostic and therapeutic aspects, follow-up data, and outcomes of all patients diagnosed with a bronchial NET from 1995 to 2015 at our institution. Patients with LCNEC or SCLC were excluded due to the biological and clinical differences from the other bronchial NET. The clinical, laboratory, imaging, treatment, and follow-up data were collected and analyzed keeping in mind the recently published international recommendations. Forty-six patients were included in the study. Of these, 37 had a TC and 5 an AC. In 4 patients, the histological characterization was inadequate. Forty-four patients underwent surgery. Four patients developed metastatic disease. Interestingly, 14 patients had one or more other tumors diagnosed at some stage and 3 of them had three different tumors. A total of 7 patients died. The analysis of the laboratory and pathology assessment identified some inconsistencies when compared to the international recommendations. Although the treatment of bronchial NET at our institution was consistent with the successively published recommendations, it appears that the diagnostic process and the follow-up surveillance were not. We think that a systematic multidisciplinary approach might improve bronchial NET patient care. A relatively high rate of occurrence of a second, or also a third, non-NET tumor was observed, though the statistical value of such observation could not be exhaustively elucidated in this numerically limited patient population. In our opinion, the observed high rate of second malignancies in this patient cohort highlights the necessity of optimizing the follow-up of the bronchial NET patients, also considering the very good survival rate achieved with regard to the bronchial NET.

The relationship between dysplastic changes in the cervical epithelium and progression to in situ carcinoma and invasive carcinoma has been extensively studied. The removal of dysplastic epithelium through the long loop excision of the transformation zone (LLETZ) in 95% of the cases is curative. About 18% to 37% of LLETZ specimens with dysplasia at the margins have recurrent/residual disease. Earlier small studies suggest that the degree of dysplasia at the margins could predict for recurrence and allow a risk-based stratification of follow-up. We tested this hypothesis in a large group of women post-LLETZ for high-grade dysplasia with follow-up histology and cytology over a 12-year period. The cases were divided according to the excision margin status for dysplasia and if positive, low-grade or high-grade dysplasia. The groups were compared to assess whether the LLETZ specimens' margin status had an impact on the subsequent cytology or histology results. Positive follow-up results were defined as any grade of dysplasia in cytology or histology. Two thousand three hundred twenty-one women had LLETZs containing high-grade dysplasia over the 12-year period. One thousand five hundred thirty-four (66.1%) women had full histology and cytology follow-up available. Eight hundred twenty (53.4%) LLETZ specimens had positive margins and 714 (46.6%) had negative margins. The grade of dysplasia at the margins was available in 796 cases (97%) with 115 (15%) showing low-grade dysplasia and 680 (85%) high-grade dysplasia. One hundred seventy (20.7%) of the specimens with positive margins had positive follow-up results compared with 105 (14.7%) of the specimens with negative margins. The presence of dysplasia at an LLETZ margin is associated with dysplasia on follow-up cytology and histology (P=0.0021); however, the grade of dysplasia at the excision margin is not predictive of recurrent/residual dysplasia.

BACKGROUND The profound reduction in serum dihydrotestosterone (DHT) observed with the dual 5 α-reductase inhibitor (5ARI) dutasteride makes it an attractive agent for prostate cancer therapy. The objective of the current study was to determine whether dutasteride would induce apoptosis in a range of prostate epithelial cell lines and primary cultures. METHODS Both human prostate androgen-sensitive cell lines (PwR-1E, PNT-2, LNCaP, and PC3[AR2]) and an androgen-independent cell line (PC-3) were grown to confluence. Primary epithelial cells extracted from fresh prostate cancer radical prostatectomy specimens also were grown to confluence under optimal conditions. Total cellular protein was extracted to confirm cytokeratin 18 and antihuman α-methylacyl-CoA racemase (AMACR) expression of the primary cells. Apoptosis was assessed by propidium iodide DNA staining and flow cytometry after 24 hours of culture in from 0 μM to 10 μM of dutasteride. RESULTS Dutasteride induced a dose-dependent increase in apoptosis in the androgen-sensitive prostate cell lines PwR-1E, PNT-2, and LNCaP and in the androgen receptor-expressing PC3(AR2) cell line. However, there was no significant apoptosis noted in the parental PC-3 cells. Of 16 primary epithelial cultures that were treated, 7 cultures were induced to undergo apoptosis, and 9 cultures were unresponsive. All primary cultures were positive for cytokeratin 18 expression, confirming their epithelial phenotype. Responder epithelial cells were positive for AMACR expression. CONCLUSIONS The results of the current study confirmed that dutasteride differentially induced apoptosis in a subset of prostate cell lines and primary prostate epithelial cells. Understanding the cellular phenotype may indicate susceptible cells. Cancer 2006. © 2006 American Cancer Society.

Live animal studies using an inoculation model of breast cancer indicate that anaesthetic drugs and techniques differentially affect cancer metastasis, inversely related to Natural Killer (NK) cell and T lymphocyte levels. Clinical histological studies demonstrate that the distribution of these immune cells and macrophages in intra-tumoral cancer tissue can predict prognosis and response to therapy. No study has evaluated whether the anaesthetic technique influences human breast cancer immune cell infiltration.Excised breast cancer specimens from patients previously enrolled in an ongoing, prospective, randomised trial (NCT00418457) investigating the effect of anaesthetic technique on long-term breast cancer outcome were immunohistochemically stained to enable a colour deconvolution technique to summate marked immune cell infiltration: CD56 (NK cells), CD4 (T helper cells), CD8 (T suppressor cells) and CD68 (macrophages). Patients were randomised to receive either a propofol-paravertebral anaesthetic with continuing analgesia (PPA, n=12) or a balanced general anaesthesia with opioid analgesia (GA, n=16) for 24 h postoperatively. Investigators were masked to group allocation.Normalised positive intensity values, (median (interquartile range (IQR)), for CD56 were lower in GA121 (116-134) versus 136 (132-142), p=0.015. CD4 was also lower in GA10.9 (5.5-27.8) versus PPA 19.7 (14.4-83.5), p=0.03 but CD8 5.5 (4.0-9.75) versus 13.0 (5.0-14.5) respectively, p=0.24 and CD 68 infiltration 5.8 (3.25-8.75) versus 8.0 (3.0-8.75), p=0.74 were not significantly different.PPA induces increased levels of NK and T helper cell infiltration into breast cancer tissue compared with GA but not T suppressor cells or macro phages. This is consistent with the hypothesis that the anaesthetic technique may affect perioperative immune function conducive to resisting breast cancer recurrence and metastasis.

Catastrophic genomic alterations may drive aggressive cancer phenotypes. We describe a diagnostically challenging and rapidly fatal case of medullary thyroid carcinoma (MTC) occurring in a young, morbidly obese man presenting with diffuse bone marrow involvement and disseminated intravascular coagulation. Whole-exome (WES) and shallow whole-genome sequencing (sWGS) were carried out for the primary tumour, adjacent normal, bone marrow tissues, multiple metastases and blood samples derived from the patient. We identified three germline single nucleotide polymorphisms (SNPs) within the RET proto-oncogene that remained undetected using routine hospital genetic testing procedures. One variant (L769L) has been previously reported to be associated with aggressive MTC presentation yet remains untested for in the routine diagnosis of MTC. Supported by findings from both WES and sWGS, we report for the first time in thyroid cancer on the occurrence of a “chromothripsis-like pattern”, which involved shattering of chromosome 4 leading to complete abrogation of normal chromosomal function, along with dramatic widespread copy number aberrations across both primary tumour and bone marrow samples. Based on the somatic variants identified, we describe the evolutionary pathway of the case, showing that bone marrow metastasis occurred separately to other metastatic sites. The presence of disease-associated SNPs within the RET proto-oncogene supports their inclusion as part of routine genetic testing for MTC cases. The copy number aberrations and chromothripsis-like pattern affected a much broader range of genes than single mutations and may have led to the widespread chromosomal instability evident, possibly contributing to the rapid fatal course of the case. These results provide a rationale for the application of comprehensive genomic analysis of cancers presenting with unusual and aggressive phenotypes to facilitate more appropriate therapeutic options and diagnoses. Citation Format: Darran P. O'Connor, Sudipto Das, Deirdre Kelly, Bruce Moran, Kathleen Han, Niall Mulligan, Ciara Barrett, Patrick Buckley, Peter McMahon, J McCaffrey, Henrik van Essen, Kate Connor, Bauke Ylstra, Diether Lambrechts, William M. Gallagher, Catherine M. Kelly. Post-mortem examination of an aggressive case of medullary thyroid cancer characterised by catastrophic genomic abnormalities [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3397. doi:10.1158/1538-7445.AM2017-3397

Twenty-seven-year-old woman attended Accident and Emergency department complaining of right-sided pleuritic chest pain for the past 3 to 4 weeks. She had no significant medical or surgical history. Her chest x-ray examination showed bulky right-sided hilar mass, consolidation in the right lower lung zone with ipsilateral pleural effusion (Figures 1A, B). Her routine blood tests were normal except of mildly elevated inflammatory markers. She underwent bronchoscopy, which did not reveal intrabronchial lesions. Cytology from bronchioalveolar lavage sample showed abnormal cells with signet ring features (Figure 2A). Transbronchial biopsy of right hilar mass showed adenocarcinoma with signet ring features (Figure 2B) that was positive on immunohistochemistry for thyroid transcription factor 1 (3 ) (Figure 2C) and was consistent with primary lung adenocarcinoma. Signet ring variant of lung primary adenocarcinoma is rare and can be associated with a novel genetic translocation joining the echinoderm microtubule-associated protein-like 4 gene (EML4) and the anaplastic lymphoma kinase (ALK) gene, forming EML4-ALK fusion gene. As previously described, presence of EML4-ALK fusion gene is associated with expression of ALK protein (2 ), which was confirmed by immunohistochemistry using anti-ALK antibody (DAKO Company, Carpinteria, CA) (Figure 2D).1,2 ALK positivity was confirmed on fluorescence in situ hybridization (FISH) as described previously.3 Positron emission tomography/computed tomography scan showed extensive neck, mediastinal, and paraaortic lymphadenopathy with multiple necrotic, and metabolically active lesions in right hilum and right lung base, which was extending through diaphragm into the posterior segments of the liver (Figures 3A–D). She was commenced on systemic chemotherapy with carboplatin (area under the curve 6) and pemetrexed (500 mg/m) every 21 days for a total of six cycles. She tolerated chemotherapy very well, and restaging positron emission tomography/computed tomography scan showed remarkable radiological response with significant decrease both in size and activity within all metastatic sites (Figures 3A–J). She continued on maintenance pemetrexed chemotherapy (500 mg/m every 21 days) for six more cycles with no evidence of disease progression 10 months after diagnosis. Signet ring variant of primary lung adenocarcinoma is very rare and is associated with EML4-ALK gene fusion that comprises approximately 5% of unselected patients with non-small cell lung cancer (NSCLC).1 In selected population of patients who are younger than 40 years, never/light smokers, and have nonsquamous histology, incidence of EML4ALK gene fusion may be as high as 13%.1 EML4-ALK positivity is associated with lack of response to epidermal growth factor receptor tyrosine kinase inhibitors.1 Recently published results of phase I/II clinical trial with orally bioavailable inhibitor (PF-0341066; crizotinib) of the ALK and c-Met/Hepatocyte Growth Factor receptor (HGFR) tyrosine kinases in patients with metastatic NSCLC who harbor EML4-ALK fusion gene showed remarkable response rates with minimal toxicity.3 Currently, crizotinib is investigated in two phase III randomized trials as a second-line treatment in patients with advanced/metastatic NSCLC with EML4-ALK gene fusion. We report herein complete radiological response to systemic chemotherapy with carboplatin and pemetrexed in this rare variant of NSCLC.

Summary We describe two patients with newly diagnosed dermatoses localizing to the radiotherapy field following treatment for breast cancer. Patient 1 was a 53-year-old woman who developed bullous morphoea on her left breast two years after radiotherapy. Patient 2 was a 43-year-old woman who developed urticaria pigmentosa on her right breast eight months after radiotherapy and similar lesions gradually developed beyond the radiotherapy field. Both patients experienced a significant delay in diagnosis due to diagnostic confusion and concern over breast cancer recurrence. Irradiated skin demonstrates gradual and sustained alterations in fibrosis due to the production of long-lived cytokines and chemokines. These changes can induce a koebnerizing response in conditions such as morphoea and urticaria pigmentosa. We explore the mechanisms behind radiotherapy-induced skin changes, and highlight the potential for radiotherapy to exacerbate or unmask underlying dermatoses and systemic disease in the months and years following treatment.

Osteopontin is a novel cytokine that is expressed in pulmonary granulomatous disease such as sarcoidosis and tuberculosis. It can regulate macrophage and T cell migration, activation, and cytokine expression, yet its role in granuloma formation and evolution is unknown. We induced hypersensitivity pulmonary granulomas by embolizing Schistosoma mansoni eggs to the lungs of osteopontin-deficient (null mutant) mice and osteopontin-sufficient (wild-type control) mice. Granulomas from osteopontin-null animals were smaller at early time points and contained remarkably few macrophages and macrophage-derived epithelioid cells and giant cells. T cell accumulation was unaffected by osteopontin deficiency. These results demonstrate that osteopontin regulates macrophage accumulation during pulmonary granuloma formation, and may explain the impaired ability of osteopontin-deficient hosts to control mycobacterial disease.

K-ras mutations have been detected in both ductal cell carcinoma and intraductal papillary mucinous tumor (IPMT) of pancreas. The frequency of this mutation in ductal cell carcinoma is high, whereas in IPMT, it is variable. It has been suggested that the relatively high frequency of this mutation in ductal cell carcinomas compared with IPMT may account for the differences in biological behavior between these tumor types. More recently, the significance of K-ras mutations in pancreatic tissue has been questioned with the demonstration of this mutation in nonneoplastic pancreata. The current study aims to estimate the relative frequency and evaluate the biological significance of K-ras gene mutations in these neoplasms by performing polymerase chain reaction (PCR) assays of microdissected areas of IPMT, ductal cell carcinomas, and resected chronic pancreatitis. The study also investigates whether alterations of p21ras occur in K-ras mutation-negative cases by using immunohistochemical staining for K-, N- and H-ras. K-ras codon 12 mutations were found almost as frequently in IPMT (71%) as in ductal cell carcinomas (78%). They were also associated with the earliest morphological lesion, flat mucinous change. This mutation also was detected in 42% of cases of chronic pancreatitis. Expression of p21ras was found to correlate closely with K-ras mutation status in IPMT and ductal cell carcinoma. Negative staining for pan-ras, H-ras, and N-ras in cases with wild-type K-ras genes suggests that alternative routes of ras gene alteration are not operative in IPMT or ductal carcinoma. The findings suggest that K-ras activation is frequently associated with both IPMT and ductal cell carcinoma. Its high prevalence in nonneoplastic pancreata suggests that it is also associated with self-limited morphological lesions of the pancreas that do not progress to malignancy.

Sarcoidosis is a systemic disease characterized by the accumulation of activated T cells and widespread granuloma formation. In addition, individual genetic predisposition appears to be important in this disease. Osteopontin, a noncollagenous matrix protein produced by macrophages and T lymphocytes, is expressed in the granulomas of tuberculosis, and is associated with genetic susceptibility to intracellular infection. The function of osteopontin in these T cell-mediated responses is unknown. We sought to elucidate the role of osteopontin in granulomatous inflammation by characterizing its expression in different stages of sarcoidosis and its effector function on T cells in vitro. Lymphocyte-associated expression of osteopontin in sarcoidosis was demonstrated by immunohistochemistry, and its expression correlated with granuloma maturity. In addition, osteopontin induced T cell chemotaxis, supported T cell adhesion (an effect enhanced by thrombin cleavage of osteopontin), and costimulated T cell proliferation. These results suggest a novel mechanism by which osteopontin and thrombin modulate T cell recruitment and activation in granulomatous inflammation.

Background and Purpose— Although symptomatic carotid stenosis is associated with 3-fold increased risk of early stroke recurrence, the pathophysiologic mechanisms of high early stroke risk have not been established. We aimed to investigate the relationship between early stroke recurrence after initial symptoms and histological features of plaque inflammation and instability in resected carotid plaque. Methods— Carotid endarterectomy tissue from consecutive patients with ipsilateral stenosis ≥50% and recent symptoms were analyzed using a validated histopathologic algorithm (Oxford Plaque Study [OPS] system). Nonprocedural stroke recurrence before carotid endarterectomy was ascertained at 7, 28, and 90 days after initial symptoms. Results— Among 44 patients meeting eligibility criteria, 27.3% (12/44) had stroke recurrence after initial stroke/transient ischemic attack but before carotid endarterectomy. Compared with patients without recurrence, stroke recurrence was associated with dense macrophage infiltration (OPS grade ≥3; 91.7% versus 37.5%; P =0.002), extensive (>25%) fibrous cap disruption (90.9% versus 37%; P =0.004), neovascularization (OPS grade ≥2; 83.3% versus 43.8%; P =0.04), and low plaque fibrous content (OPS grade P =0.003). Early recurrence rates were 82.3% (confidence interval, 49.2%–98.8%) in patients with extensive plaque macrophage infiltration (OPS grade ≥3) compared with 22.2% (confidence interval, 3.5%–83.4%) in those with OPS grade P =0.009). On multivariable Cox regression, including OPS macrophage grade (≥3 or P =0.04). Conclusions— Plaque inflammation and other vulnerability features were associated with highest risk of stroke recurrence and may represent therapeutic targets for future stroke prevention trials.

Background Neuroepithelial transforming gene 1 (NET1) mediates tumour invasion and metastasis in a number of cancers, including gastric adenocarcinoma. It is an indicator of poor prognosis in breast cancer and glioma. This study examined NET1 expression and its prognostic significance in patients with adenocarcinoma of the oesophagogastric junction (AOG). Methods NET1 expression was measured by immunohistochemistry in a tissue microarray, constructed from biobanked tissue collected over a 10-year interval, and linked to a prospectively maintained clinical database. Results Using the Siewert classification for AOG, type I tumours expressed significantly higher levels of NET1, with lowest expression in type III and intermediate levels in type II (P = 0·001). In patients with AOG type III, NET1-positive patients were more likely to be female (P = 0·043), have advanced stage cancer (P = 0.035), had a higher number of transmural cancers (P = 0·006) and had a significantly higher median number of positive lymph nodes (P = 0·029). In this subgroup, NET1-positive patients had worse median overall (15 versus 23 months; P = 0·025) and disease-free (11 versus 36 per cent; P = 0·025) survival compared with NET1-negative patients. Conclusion Although existing data show differences in clinical and prognostic indices across AOG subtypes, there are no studies showing differences in tumour biology. These data suggest NET1, a known mediator of an aggressive tumour phenotype in a number of gastrointestinal cancers, is expressed differentially across AOG subtypes and may be of prognostic significance in the clinical management of this condition.

e23000Background: Exome sequencing was undertaken on a patient with a novel presentation of metastatic medullary thyroid cancer to bone marrow presenting with disseminated intravascular coagulation...

A 53-year-old woman presented to the emergency department with a 2-week history of dyspnoea and chest pain. Computed tomography pulmonary angiography was performed to exclude acute pulmonary embolism (PE). This demonstrated a large right atrial mass and no evidence of PE. Transthoracic echocardiography followed by cardiac magnetic resonance imaging confirmed a mobile right atrial mass. Surgical resection was then performed confirming a giant right atrial myxoma. We describe the typical clinical, radiologic, and pathologic features of right atrial myxoma.

Terbinafine, a systemic antifungal commonly prescribed for onychomycosis (fungal infection involving the nails) has been reported to cause various cutaneous adverse effects. We describe an overlap syndrome between cutaneous lupus and erythaema multiforme induced by this medication with a review of other reported cases.

3574 Background: Colorectal cancers that show evidence of microsatellite instability (MSI-H) are marked by a high tumour infiltrating lymphocyte population (TiL) which is thought to be prognostic. ...

3571 Background: Lynch Syndrome (LS) accounts for 2-4% of all colorectal cancers (CRC) and is caused by germline mutations in DNA mismatch repair (MMR) genes. Increasing literature supports routine...

A 55-year-old woman presented with an extensive warfarin-induced skin necrosis while an inpatient for treatment of a pulmonary embolism and thromboembolic stroke. She had a background of diabetes mellitus, hypertension and dyslipidaemia. Her warfarin was stopped and she was anticoagulated with low-molecular weight heparin. The wound was successfully treated with a combination of antibiotic, debridement and negative pressure wound therapy.