Citations

The Rare Cancer Network (RCN) was formed in the early 1990's to create a global network that could pool knowledge and resources in the studies of rare malignancies whose infrequency prevented both their study with prospective clinical trials. To date, the RCN has initiated 74 studies resulting in 46 peer reviewed publications. The First International Symposium of the Rare Cancer Network took place in Nice in March of 2014. Status updates and proposals for new studies were heard for fifteen topics. Ongoing studies continue for cardiac sarcomas, thyroid cancers, glomus tumors, and adult medulloblastomas. New proposals were presented at the symposium for primary hepatic lymphoma, solitary fibrous tumors, Rosai-Dorfman disease, tumors of the ampulla of Vater, salivary gland tumors, anorectal melanoma, midline nuclear protein in testes carcinoma, pulmonary lymphoepithelioma-like carcinoma, adenoid cystic carcinoma of the trachea, osteosarcomas of the mandible, and extra-cranial hemangiopericytoma. This manuscript presents the abstracts of those proposals and updates on ongoing studies, as well a brief summary of the vision and future of the RCN.

Approximately, twenty years ago, the Rare Cancer Network (RCN) was formed in Lausanne, Switzerland, to support the study of rare malignancies. The RCN has grown over the years and now includes 130 investigators from twenty-four nations on six continents. The network held its first international symposium in Nice, France, on March 21-22, 2014. The proceedings of that meeting are presented in two companion papers. This manuscript reviews the history of the growth of the RCN and contains the abstracts of fourteen oral presentations made at the meeting of prior RCN studies. From 1993 to 2014, 74 RCN studies have been initiated, of which 54 were completed, 10 are in progress or under analysis, and 9 were stopped due to poor accrual. Forty-four peer reviewed publications have been written on behalf of the RCN.

Aim We studied ERG expression in a large series of chondrogenic bone and soft tissue tumours to assess the value of ERG as a possible marker of chondroid/cartilaginous differentiation. Methods Formalin-fixed, paraffin-embedded whole sections from 111 bone and soft tissue tumours with chondroid differentiation or a morphology that may mimic cartilaginous differentiation were retrieved. Immunohistochemistry was performed using anti-ERG monoclonal antibody directed against the N terminus. Nuclear staining was scored as negative (<5%), 1+ (5%–25%), 2+ (26%–50%), 3+ (>51%). Results Nuclear ERG expression was seen in all cases of soft tissue chondroma (8), chondromyxoid fibroma (7), chondroblastic osteosarcoma (6) and clear cell chondrosarcoma (1). 10/12 conventional chondrosarcomas were also positive for ERG. In cases of dedifferentiated chondrosarcoma, the well-differentiated component was positive in 7/9 cases, while all dedifferentiated foci were negative. In cases of mesenchymal chondrosarcoma, the hyaline cartilage component was positive in 2/4 cases, whereas the primitive component in all cases was negative. Variable positivity was identified in extraskeletal myxoid chondrosarcomas (4/9), chondroblastomas (3/8) and mixed tumours/myoepitheliomas (2/11). Only 1/12 chordoma was positive for ERG (1+). Interestingly, 15/17 enchondromas were negative for ERG. Conclusions In this study, we further characterise the expression of ERG in mesenchymal tumours and found relatively constant nuclear ERG expression in selected chondrogenic tumours including conventional chondrosarcoma, chondromyxoid fibroma, chondroblastic osteosarcoma and clear cell chondrosarcoma. We also show that ERG may be a helpful ancillary tool in certain select diagnostic scenarios and that awareness of ERG expression in tumours with cartilaginous differentiation is important.

AbstractBackgroundDysphagia is considered an alarm symptom but detailed population‐based data on dysphagia are lacking. We aimed to estimate in a representative USA Caucasian population, the prevalence of dysphagia and potential risk factors.MethodsA modified version of the previously validated Bowel Disease Questionnaire was mailed to a population‐based cohort (n = 7640) of Olmsted County, MN. Dysphagia was measured by one validated question ‘In the last year, how often have you had difficulty swallowing (a feeling that food sticks in your throat or chest)?’ The medical records were reviewed for organic causes of dysphagia. The associations of reported frequency of dysphagia with potential risk factors were assessed using logistic regression models.Key ResultsThe sex‐specific, age‐adjusted (US White 2000) prevalence for dysphagia experienced at least weekly was 3.0% (95% CI: 2.2, 3.7) in females and 3.0% (95% CI: 2.0, 4.0) in males. Those with frequent heartburn (OR = 5.9 [4.0, 8.6]) and acid regurgitation (OR = 10.6 [6.8, 16.6]) were significantly more likely to report frequent dysphagia. Proton pump inhibitor (PPI) use was significantly associated with frequent (3.1, 95% CI 2.2, 4.4) and infrequent dysphagia (1.5, 955 CI 1.3, 1.8). Gastro‐esophageal reflux disease (GERD) was the most common diagnosis in those reporting dysphagia on the medical record; other organic explanations were rare and only found in the frequent dysphagia group.Conclusions & InferencesFrequent dysphagia is not rare in the community (3%), occurs in both women and men across all adult age groups, and is most likely to indicate underlying GERD.

Background: Although newer generations of total ankle arthroplasty designs have better clinical outcomes, failure due to aseptic loosening remains a frequent major complication. Arthrodesis is the most common salvage procedure for a failed total ankle replacement. There are several arthrodesis techniques each with its advantages and disadvantages. We present a technique of ankle arthrodesis for failed total ankle replacements using tantalum Trabecular Metal™ (Zimmer, Warsaw, IN) with internal fixation, thus sparing the subtalar joint. Methods: Three patients who had undergone arthrodesis for a failed total ankle replacement using tantalum Trabecular Metal were retrospectively reviewed. The mean follow-up period was 57 (range, 31-86) months. The mean age at ankle arthroplasty was 57 (range, 33-72) years and at ankle arthrodesis was 63 (range, 44-74) years. The mean time from arthroplasty to arthrodesis was 7 (range, 2-11) years. Results: The American Orthopaedic Foot and Ankle Society (AOFAS) score improved from 30.7 (range, 20-39) preoperatively to 72.7 (range, 65-77) postoperatively at the time of last follow-up. Arthrodesis was achieved at a mean of 3 months, and there were no complications. Conclusion: The technique described has several advantages when compared to other methods of salvage ankle arthrodesis. The subtalar joint is not included in the fusion unless it is degenerative and symptomatic. Height of the ankle is maintained throughout the fusion process. Furthermore, Trabecular Metal is abundantly available; it avoids donor site morbidity and eliminates the risk of transmissible diseases. Level of Evidence: Level V, expert opinion.

Key Points Deep sequencing identifies a significant reservoir of subclonal mutations affecting key genes in CLL pathogenesis. Convergent evolution of genetic lesions in tumor subclonal populations is recurrently found in CLL.

AimsBile salt export pump (BSEP) is a transporter expressed exclusively at hepatic canaliculi and drives bile‐salt efflux. Minimal data exist about BSEP expression in tumours. We hypothesized that BSEP immunohistochemistry would be specific for hepatocellular carcinoma (HCC).Methods and resultsTissue microarrays, including 48 HCC, 41 cholangiocarcinomas and 24 metastatic tumours in liver, were immunostained for BSEP. Expression was compared with common markers of hepatocytic differentiation including CD10, hepatocyte paraffin‐1 antigen (HepPar‐1), carcinoembryonic antigen, arginase‐1 (ARG) and glypican‐3 (GPC‐3). BSEP expression was assessed in normal tissues. Special attention was given to adrenal gland (normal and neoplasia). BSEP was easy to interpret and showed no background staining. Canalicular expression was seen in all normal livers, but not in other normal tissue. BSEP was 90% sensitive and 100% specific for HCC (canalicular in 33 of 43 positive cases). The sensitivity of ARG was slightly higher, but specificity was slightly lower (94% for both). HepPar‐1 was 90% sensitive and 97% specific. CD10, polyclonal carcinoembryonic antigen (pCEA) and GPC‐3 all had lower sensitivity (74, 81 and 54%, respectively).ConclusionsIn malignant tumours in the liver, BSEP marking was 100% specific and 90% sensitive for HCC. The specificity of BSEP for HCC obviates the need to identify a ‘canalicular’ pattern, which can limit the utility of other canalicular markers.