Genetic, immunohistochemical, and clinical features of medullary carcinoma of the pancreas: A newly described and characterized entity

Robb E. Wilentz, Michael Goggins, Mark Redston, Victoria A. Marcus, N. Volkan Adsay, Taylor A. Sohn, Shri Hari S. Kadkol, Charles J. Yeo, Michael Choti, Marianna Zahurak, Karen Johnson, Metin Tascilar, G. Johan A. Offerhaus, Ralph H. Hruban, Scott E. Kern

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    193 Scopus citations

    Abstract

    Medullary carcinomas of the pancreas are a recently described, histologically distinct subset of poorly differentiated adenocarcinomas that may have a unique pathogenesis and clinical course. To further evaluate these neoplasms, we studied genetic, pathological, and clinical features of 13 newly identified medullary carcinomas of the pancreas. Nine (69%) of these had wild-type K-ras genes, and one had microsatellite instability (MSI). This MSI medullary carcinoma, along with three previously reported MSI medullary carcinomas, were examined immunohistochemically for Mlh1 and Msh2 expression, and all four expressed Msh2 but did not express Mlh1. In contrast, all of the medullary carcinomas without MSI expressed both Msh2 and Mlh1. Remarkably, the MSI medullary carcinoma of the pancreas in the present series arose in a patient with a synchronous but histologically distinct cecal carcinoma that also had MSI and did not express Mlh1. The synchronous occurrence of two MSI carcinomas suggests an inherited basis for the development of these carcinomas. Indeed, the medullary phenotype, irrespective of MSI, was highly associated with a family history of cancer in first-degree relatives (P < 0.001). Finally, one medullary carcinoma with lymphoepithelioma-like features contained Epstein-Barr virus-encoded RNA-1 by in situ hybridization. Therefore, because of medullary carcinoma's special genetic, immunohistochemical, and clinical features, recognition of the medullary variant of pancreatic adenocarcinoma is important. Only by classifying medullary carcinoma as special subset of adenocarcinoma can we hope to further elucidate its unique pathogenesis.

    Original languageEnglish (US)
    Pages (from-to)1641-1651
    Number of pages11
    JournalAmerican Journal of Pathology
    Volume156
    Issue number5
    DOIs
    StatePublished - Jan 1 2000

    ASJC Scopus subject areas

    • Pathology and Forensic Medicine

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    Wilentz, R. E., Goggins, M., Redston, M., Marcus, V. A., Adsay, N. V., Sohn, T. A., Kadkol, S. H. S., Yeo, C. J., Choti, M., Zahurak, M., Johnson, K., Tascilar, M., Offerhaus, G. J. A., Hruban, R. H., & Kern, S. E. (2000). Genetic, immunohistochemical, and clinical features of medullary carcinoma of the pancreas: A newly described and characterized entity. American Journal of Pathology, 156(5), 1641-1651. https://doi.org/10.1016/S0002-9440(10)65035-3