Pseudomyxoma peritonei (PMP) is a clinical syndrome characterized by gross mucinous ascites originating from a disseminated intraperitoneal neoplasm. Although typically confined to the abdomen, mortality is high if untreated. Biomarkers, including genetic mutation profiles, may aid treatment selection and decision making. We applied whole-exome sequencing to five patients diagnosed with low-grade appendiceal mucinous neoplasms, using paired tumor and germline samples identify biomarkers. Multiple bioinformatic approaches were applied to these data to assess both somatic mutation profiles and loss of heterozygosity events. Mutation profiles of the tumors were consistent with deamination of methylcytosine being the prevailing mechanism. Pathogenic mutations were identified in both KRAS and GNAS in all samples, and further mutations in genes implicated in PMP, namely FGFR2, APC, SMAD2, and FAT4. No TP53 somatic mutations were identified, matching expectations for low-grade tumors. Four of five samples exhibited clonal loss of heterozygosity; these regions were further examined and found to contain genes harboring pathogenic somatic mutations in some samples. RNF43 was hereby implicated in the pathogenesis of PMP of appendiceal origin, having previously been found to increase sensitivity to Wnt signaling and to have involvement in similar mucinous tumors. In conclusion, we have investigated the mutation profile of PMP of appendiceal origin and provided the first report of RNF43 involvement in its progression.
Rhabdomyosarcoma (RMS), arising from mesenchymal cells, is the most common soft tissue tumour in children and accounts for up to half of all sarcomas. We present the case of a 33-year-old male presented to the urology department of the University College Hospital Galway (Ireland) in March 2009 with a 2-month history of a left scrotal swelling, increasing in size.
Aims
To research and identify how often complicated diverticular disease of the appendix [appendiceal diverticular disease (ADD)] shows histological mimicry of low‐grade appendiceal mucinous neoplasms (LAMNs) and to provide guidance on the useful histopathological features that allow the appropriate diagnosis to be made.
Methods and results
Seventy‐four cases of complicated appendiceal diverticular disease were identified from two specialist centres. Of the second opinion/consultation cases, 71% of the ADD cases had been diagnosed by referring pathologists as LAMNs. Salient pathological features were identified and agreed upon to reach the applicable diagnosis. For a diagnosis of complicated diverticulosis, particularly when associated with mucus cysts, the following morphological features were regarded as important: relative retention of the normal mucosal architecture with lamina propria and a maintained crypt architecture, crypts arranged in regular array, epithelial hyperplasia and a lack of nuclear abnormalities extending the length of the crypts. In a formal case–control study undertaken on 30 cases with each diagnosis, ADD and LAMN, loss of lamina propria, a filiform architecture and hypermucinosis were significantly associated with low‐grade appendiceal mucinous neoplasms. Mucosal neuromas were significantly associated with diverticular disease of the appendix.
Conclusions
To our knowledge, this study represents the largest series in the world literature and serves to highlight the important pathological features to distinguish complicated diverticular disease of the appendix from LAMNs, and emphasises the difficulties experienced by diagnostic pathologists in diagnosing complicated appendiceal diverticulosis. This is important, as LAMNs have a significant risk of transcoelomic spread, while complicated appendiceal diverticulosis has no such risk.
With adequate patient selection (guided by histological classification and Ki-67 proliferation index) and complete cytoreduction with HIPEC, satisfactory outcomes can be achieved in selected patients with peritoneal mesothelioma.
Rhabdomyosarcoma (RMS), arising from mesenchymal cells, is the most common soft tissue tumour in children and accounts for up to half of all sarcomas. We present the case of a 33-year-old male presented to the urology department of the University College Hospital Galway (Ireland) in March 2009 with a 2-month history of a left scrotal swelling, increasing in size.
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