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Mod Pathol. 2019 Aug 5. doi: 10.1038/s41379-019-0334-5. [Epub ahead of print]

Sclerosing epithelioid mesenchymal neoplasm of the pancreas - a proposed new entity.

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Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Department of Pathology, Koç University, Istanbul, Turkey.
St. Jude Children's Research Hospital, Memphis, TN, USA.
Department of Pathology, University of Verona and IRCCS Sacro Cuore Don Calabria Hospital, Negrar, Verona, Italy.
Department of Pathology, Jichi Medical University, Shimotsuke, Japan.
Department of Pathology, Washington University, St. Louis, MO, USA.
Department of Pathology, St. Francis Hospital and Medical Center, Hartford, CT, USA.
Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Department of Pathology, Azienda Ospedaliera-Universitaria di Bologna, Bologna, Italy.
Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA.
Department of Pathology, SRH Poliklinik Gera GmbH, Gera, Germany.
Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands.
Department of Pathology, University Hospital Heidelberg, Heidelberg, Germany.
Department of Pathology, University of New Mexico, Albuquerque, NM, USA.
Department of Neuropathology, University Hospital Heidelberg and CCU Neuropathology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.


We have encountered pancreatic tumors with unique histologic features, which do not conform to any of the known tumors of the pancreas or other anatomical sites. We aimed to define their clinicopathologic features and whether they are characterized by recurrent molecular signatures. Eight cases were identified; studied histologically and by immunohistochemistry. Selected cases were also subjected to whole-exome sequencing (WES; n = 4), RNA-sequencing (n = 6), Archer FusionPlex assay (n = 5), methylation profiling using the Illumina MethylationEPIC (850k) array platform (n = 6), and TERT promoter sequencing (n = 5). Six neoplasms occurred in females. The mean age was 43 years (range: 26-75). Five occurred in the head/neck of the pancreas. All patients were treated surgically; none received neoadjuvant/adjuvant therapy. All patients are free of disease after 53 months of median follow-up (range: 8-94). The tumors were well-circumscribed, and the median size was 1.8 cm (range: 1.3-5.8). Microscopically, the unencapsulated tumors had a geographic pattern of epithelioid cell nests alternating with spindle cell fascicles. Some areas showed dense fibrosis, in which enmeshed tumor cells imparted a slit-like pattern. The predominant epithelioid cells had scant cytoplasm and round-oval nuclei with open chromatin. The spindle cells displayed irregular, hyperchromatic nuclei. Mitoses were rare. No lymph node metastases were identified. All tumors were positive for vimentin, CD99 and cytokeratin (patchy), while negative for markers of solid pseudopapillary neoplasm, neuroendocrine, acinar, myogenic/rhabdoid, vascular, melanocytic, or lymphoid differentiation, gastrointestinal stromal tumor as well as MUC4. Whole-exome sequencing revealed no recurrent somatic mutations or amplifications/homozygous deletions in any known oncogenes or tumor suppressor genes. RNA-sequencing and the Archer FusionPlex assay did not detect any recurrent likely pathogenic gene fusions. Single sample gene set enrichment analysis revealed that these tumors display a likely mesenchymal transcriptomic program. Unsupervised analysis (t-SNE) of their methylation profiles against a set of different mesenchymal neoplasms demonstrated a distinct methylation pattern. Here, we describe pancreatic neoplasms with unique morphologic/immunophenotypic features and a distinct methylation pattern, along with a lack of abnormalities in any of key genetic drivers, supporting that these neoplasms represent a novel entity with an indolent clinical course. Given their mesenchymal transcriptomic features, we propose the designation of "sclerosing epithelioid mesenchymal neoplasm" of the pancreas.


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