Genetic, immunohistochemical, and clinical features of medullary carcinoma of the pancreas

A newly described and characterized entity

R. E. Wilentz, M. Goggins, M. Redston, V. A. Marcus, N. Volkan Adsay, T. A. Sohn, S. S. Kadkol, C. J. Yeo, M. Choti, M. Zahurak, K. Johnson, M. Tascilar, G. J A Offerhaus, R. H. Hruban, S. E. Kern

Research output: Contribution to journalArticle

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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
StatePublished - 2000
Externally publishedYes

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Medullary Carcinoma
Microsatellite Instability
Pancreas
Adenocarcinoma
Carcinoma
ras Genes
In Situ Hybridization
Neoplasms
Phenotype

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Wilentz, R. E., Goggins, M., Redston, M., Marcus, V. A., Volkan Adsay, N., Sohn, T. A., ... 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.

Genetic, immunohistochemical, and clinical features of medullary carcinoma of the pancreas : A newly described and characterized entity. / Wilentz, R. E.; Goggins, M.; Redston, M.; Marcus, V. A.; Volkan Adsay, N.; Sohn, T. A.; Kadkol, S. S.; Yeo, C. J.; Choti, M.; Zahurak, M.; Johnson, K.; Tascilar, M.; Offerhaus, G. J A; Hruban, R. H.; Kern, S. E.

In: American Journal of Pathology, Vol. 156, No. 5, 2000, p. 1641-1651.

Research output: Contribution to journalArticle

Wilentz, RE, Goggins, M, Redston, M, Marcus, VA, Volkan Adsay, N, Sohn, TA, Kadkol, SS, Yeo, CJ, Choti, M, Zahurak, M, Johnson, K, Tascilar, M, Offerhaus, GJA, Hruban, RH & Kern, SE 2000, 'Genetic, immunohistochemical, and clinical features of medullary carcinoma of the pancreas: A newly described and characterized entity', American Journal of Pathology, vol. 156, no. 5, pp. 1641-1651.
Wilentz, R. E. ; Goggins, M. ; Redston, M. ; Marcus, V. A. ; Volkan Adsay, N. ; Sohn, T. A. ; Kadkol, S. S. ; Yeo, C. J. ; Choti, M. ; Zahurak, M. ; Johnson, K. ; Tascilar, M. ; Offerhaus, G. J A ; Hruban, R. H. ; Kern, S. E. / Genetic, immunohistochemical, and clinical features of medullary carcinoma of the pancreas : A newly described and characterized entity. In: American Journal of Pathology. 2000 ; Vol. 156, No. 5. pp. 1641-1651.
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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.",
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T1 - Genetic, immunohistochemical, and clinical features of medullary carcinoma of the pancreas

T2 - A newly described and characterized entity

AU - Wilentz, R. E.

AU - Goggins, M.

AU - Redston, M.

AU - Marcus, V. A.

AU - Volkan Adsay, N.

AU - Sohn, T. A.

AU - Kadkol, S. S.

AU - Yeo, C. J.

AU - Choti, M.

AU - Zahurak, M.

AU - Johnson, K.

AU - Tascilar, M.

AU - Offerhaus, G. J A

AU - Hruban, R. H.

AU - Kern, S. E.

PY - 2000

Y1 - 2000

N2 - 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.

AB - 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.

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