Leiomyosarcoma Arising in the Pancreatic Duct: A Case Report and Review of the Current Literature

Context. Leiomyosarcomas are rare malignant smooth muscle tumors that may arise in any organ or tissue that contains smooth muscle, commonly within the gastrointestinal tract. They are most often found in the stomach, large and small intestines, and retroperitoneum. Primary pancreatic leiomyosarcoma is extremely rare, and to the best of our knowledge only 30 cases have been reported in the world literature since 1951. Our case represents the first to have a clear origin from the main pancreatic duct. Case Report. This case was diagnosed in a large, tertiary care center in Tampa, Florida. Pertinent information was obtained from chart review and interdepartmental collaboration. A mass in the tail of the pancreas was identified with large pleomorphic and spindle-shaped cells. Immunohistochemistry for vimentin, smooth muscle actin, and desmin was positive. All remaining immunohistochemical markers performed were negative. The tumor clearly originated from the pancreatic duct wall, filled and expanded the duct lumen, and was covered with a layer of benign biliary epithelium. Conclusion. Leiomyosarcoma of the pancreas is an extremely rare malignancy with few reported cases in the literature. The prognosis is poor, and treatment consists of alleviating symptoms and pain management. To our knowledge, this represents the first reported case demonstrating clear origin of a leiomyosarcoma from the pancreatic duct

Primary Colorectal Adenocarcinoma Metastatic to the Breast: Case Report and Review of Nineteen Cases

Metastases to the breast from extramammary primaries are uncommon and account for 0.5–6% of all breast malignancies (Georgiannos et al., 2001, and Vizcaíno et al., 2001). Malignant melanoma, lymphoma, and lung and gastric carcinomas are the most frequently encountered nonmammary metastases to the breast in adults (Georgiannos et al., 2001, and Chaignaud et al., 1994). Primary colorectal adenocarcinoma (CRC) metastatic to the breast is extremely rare, with the medical literature having only 19 recorded cases. Typically CRC metastatic to the breast is indicative of widely disseminated disease and a poor prognosis. Here we present a case of poorly differentiated colon cancer metastatic to the breast and review the current literature on this rare event

Lipogenesis mediated by OGR1 regulates metabolic adaptation to acid stress in cancer cells via autophagy

Malignant tumors exhibit altered metabolism resulting in a highly acidic extracellular microenvironment. Here, we show that cytoplasmic lipid droplet (LD) accumulation, indicative of a lipogenic phenotype, is a cellular adaption to extracellular acidity. LD marker PLIN2 is strongly associated with poor overall survival in breast cancer patients. Acid-induced LD accumulation is triggered by activation of the acid-sensing G-protein-coupled receptor (GPCR) OGR1, which is expressed highly in breast tumors. OGR1 depletion inhibits acid-induced lipid accumulation, while activation by a synthetic agonist triggers LD formation. Inhibition of OGR1 downstream signaling abrogates the lipogenic phenotype, which can be rescued with OGR1 ectopic expression. OGR1-depleted cells show growth inhibition under acidic growth conditions in vitro and tumor formation in vivo. Isotope tracing shows that the source of lipid precursors is primarily autophagy-derived ketogenic amino acids. OGR1-depleted cells are defective in endoplasmic reticulum stress response and autophagy and hence fail to accumulate LDs affecting survival under acidic stress

Genomic patterns of malignant peripheral nerve sheath tumor (MPNST) evolution correlate with clinical outcome and are detectable in cell-free DNA

Malignant peripheral nerve sheath tumor (MPNST), an aggressive soft-tissue sarcoma, occurs in people with neurofibromatosis type 1 (NF1) and sporadically. Whole-genome and multiregional exome sequencing, transcriptomic, and methylation profiling of 95 tumor samples revealed the order of genomic events in tumor evolution. Following biallelic inactivation of NF1, loss of CDKN2A or TP53 with or without inactivation of polycomb repressive complex 2 (PRC2) leads to extensive somatic copy-number aberrations (SCNA). Distinct pathways of tumor evolution are associated with inactivation of PRC2 genes and H3K27 trimethylation (H3K27me3) status. Tumors with H3K27me3 loss evolve through extensive chromosomal losses followed by whole-genome doubling and chromosome 8 amplification, and show lower levels of immune cell infiltration. Retention of H3K27me3 leads to extensive genomic instability, but an immune cell-rich phenotype. Specific SCNAs detected in both tumor samples and cell-free DNA (cfDNA) act as a surrogate for H3K27me3 loss and immune infiltration, and predict prognosis