TY - JOUR
T1 - Ductuloinsular tumors of the pancreas
T2 - Endocrine tumors with entrapped nonneoplastic ductules
AU - Van Eeden, Susanne
AU - De Leng, Wendy W.J.
AU - Offerhaus, G. Johan A.
AU - Morsink, Folkert H.
AU - Weterman, Marian A.J.
AU - De Krijger, Ronald R.
AU - Klöppel, Günter
AU - Klimstra, David S.
PY - 2004/6
Y1 - 2004/6
N2 - Rare pancreatic neoplasms have been reported that show both endocrine and exocrine differentiation in the neoplastic components. In addition, pancreatic endocrine tumors may contain small, cytologically bland ductules intimately admixed with the endocrine component. It was recently suggested that these ductules represent an intrinsic part of the tumor, ie, that the ductules are neoplastic, and the term "ductulo-insular tumors of the pancreas" was proposed. In the present study, the nature of the ductular component of 16 cases of ductule-containing pancreatic endocrine tumors was investigated at the molecular level. Molecular genetic changes often present in ductal pancreatic neoplasms were not found by immunohistochemistry for DPC4, p53, and ERBB2 and by sequence analysis of KRAS codon 12. An X-chromosome inactivation clonality assay of one such tumor from a female patient indicated that the neuroendocrine component was monoclonal, contrasting with the ductular component that was polyclonal. The lymph node and liver metastases from three patients only contained the neuroendocrine component, and no ductules were observed. Although certain morphologic features of ductule-containing endocrine tumors are reminiscent of the embryonic development of the human pancreas, none of the tumors expressed PDX-1, a transcription factor essential in pancreatic organ development. Based on our results, it is suggested that the ductular component occasionally found in pancreatic endocrine tumors is the result of entrapment of preexisting nonneoplastic ductules and that the tumors are otherwise not distinctive from conventional pancreatic endocrine tumors. Although the phenomenon is rare, it is important to recognize and to distinguish these tumors from true mixed ductal-endocrine neoplasms, which are generally more clinically aggressive. "Pancreatic endocrine tumors with entrapped ductules" would be the preferred nomenclature since it better reflects the nonneoplastic nature of the ductules.
AB - Rare pancreatic neoplasms have been reported that show both endocrine and exocrine differentiation in the neoplastic components. In addition, pancreatic endocrine tumors may contain small, cytologically bland ductules intimately admixed with the endocrine component. It was recently suggested that these ductules represent an intrinsic part of the tumor, ie, that the ductules are neoplastic, and the term "ductulo-insular tumors of the pancreas" was proposed. In the present study, the nature of the ductular component of 16 cases of ductule-containing pancreatic endocrine tumors was investigated at the molecular level. Molecular genetic changes often present in ductal pancreatic neoplasms were not found by immunohistochemistry for DPC4, p53, and ERBB2 and by sequence analysis of KRAS codon 12. An X-chromosome inactivation clonality assay of one such tumor from a female patient indicated that the neuroendocrine component was monoclonal, contrasting with the ductular component that was polyclonal. The lymph node and liver metastases from three patients only contained the neuroendocrine component, and no ductules were observed. Although certain morphologic features of ductule-containing endocrine tumors are reminiscent of the embryonic development of the human pancreas, none of the tumors expressed PDX-1, a transcription factor essential in pancreatic organ development. Based on our results, it is suggested that the ductular component occasionally found in pancreatic endocrine tumors is the result of entrapment of preexisting nonneoplastic ductules and that the tumors are otherwise not distinctive from conventional pancreatic endocrine tumors. Although the phenomenon is rare, it is important to recognize and to distinguish these tumors from true mixed ductal-endocrine neoplasms, which are generally more clinically aggressive. "Pancreatic endocrine tumors with entrapped ductules" would be the preferred nomenclature since it better reflects the nonneoplastic nature of the ductules.
KW - Endocrine tumor
KW - KRAS
KW - Pancreas
KW - PDX-1
KW - X-chromosome inactivation
UR - http://www.scopus.com/inward/record.url?scp=2542435230&partnerID=8YFLogxK
U2 - 10.1097/01.pas.0000112546.57641.c7
DO - 10.1097/01.pas.0000112546.57641.c7
M3 - Article
C2 - 15166675
AN - SCOPUS:2542435230
SN - 0147-5185
VL - 28
SP - 813
EP - 820
JO - American Journal of Surgical Pathology
JF - American Journal of Surgical Pathology
IS - 6
ER -