Pancreatic Mucinous Cystic Neoplasms with Sarcomatous Stroma: Molecular Evidence for Monoclonal Origin with Subsequent Divergence of the Epithelial and Sarcomatous Components

Abstract

Neoplasms with mixed carcinomatous and sarcomatous growth patterns occur in many organs and tissues. The pathogenesis of these cancers is thought to be either the result of two independent neoplastic processes merging to form a single tumor, or a neoplasm of monoclonal origin that develops phenotypic diversity. To address this issue, we characterized molecular alterations in separately microdissected epithelial and sarcomatous areas in three cases of pancreatic mucinous cystic neoplasms with sarcomatous stroma. Using microsatellite markers for six chromosomal loci commonly deleted in infiltrating ductal adenocarcinomas of the pancreas, we found genetic alterations to be virtually identical between the sarcomatous and epithelial components of two of the three neoplasms. In the third neoplasm, we found allelic losses and retentions to be identical at five of the six chromosomal loci, but at a single locus, we noted allelic loss in the neoplastic epithelial component but not the sarcomatous component. The same neoplasms were also analyzed for activating point mutations in codon 12 of the K-ras gene by using mutant-enriched polymerase chain reaction and allele-specific oligonucleotide hybridization. A K-ras mutation was identified in the epithelial component of one of the three neoplasms (the same tumor with an additional allelic loss in the neoplastic epithelial cells), but the sarcomatous component of this tumor was wild-type at codon 12 of K-ras, as were both components of the other two neoplasms.Overall, these results suggest a monoclonal origin with subsequent divergence of the neoplastic epithelial and sarcomatous portions of these neoplasms.

Gliosarcoma with epithelial differentiation: immunohistochemical and molecular characterization. A case report and review of the literature

“…24 Carcinosarcomas are malignant tumors having a mixture of carcinoma and sarcoma containing differentiated mesenchymal elements such as malignant cartilage, bone and muscle. 25,26 Recent data confirm that most, but not all, carcinosarcomas are monoclonal, [27][28][29] and that the carcinomatous element is the driving force and the sarcomatous component is derived from the carcinoma or from a stem cell that undergoes divergent differentiation. It is however important to differentiate these cases from true collision tumors, since the prognosis will vary.…”

Anaplastic carcinoma associated with a mucinous cystic neoplasm of the pancreas during pregnancy: Report of a case and a review of the literature

“…Only several cases have been reported to date (Table 2) [3][4][5][6][7][8][9][10][11][12] . Some underwent C B A D Figure 4 Pathology of the recurrent tumor at the pancreatic side (as pointed by a in Figure 3) revealing a borderline-type mucinous cystic neoplasm (HE, A: x 100, B: × 400) and at the gastric side (as pointed by b in Figure 3) an anaplastic carcinoma with giant cells, atypical spindle cells and round cells (C: × 100, D: × 400).…”

“…Immunohistochemical study alone cannot determine the origin of anaplastic carcinoma in the mucinous cystic neoplasms. Van den Berg et al [11] analyzed genetically three cases of anaplastic carcinoma related to mucinous cystic neoplasms, and disclosed that the sarcomatous and carcinomatous components are different phenotypically but genetically uniclone.…”

“…Table 2 Reported cases of anaplastic carcinoma occuring in association with MCNs ND: Not described; MCN: Mucinous cystic neoplasm. 1 Later re-analyzed genetically and reported by van den Berg W [11] .…”

Cystic lesions of the pancreas

“…119 Pure colloid carcinoma, which is the predominant type of invasive carcinoma in IPMNs, is exceedingly uncommon in MCNs, 113 once the latter is defined by the presence of ovarian-stroma.…”