An immunohistochemical survey for neuroendocrine cells in regional pancreatic lymph nodes: A plausible explanation for primary nodal gastrinomas?

Background. The existence of primary gastrinomas in lymph nodes continues to be controversial, because distinction from metastases from occult or regressed primary tumors may be difficult to exclude with certainty. If primary nodal gastrinomas do indeed occur, precursor neuroendocrine cells should be identifiable within lymph nodes. In an effort to detect these cells we undertook an immunohistochemical survey of regional pancreatic lymph nodes by using antibody against chromogranin, a highly specific marker for mature neuroendocrine cells. Methods. We retrospectively identified consecutive cases from five surgeons in which Whipple resections had been performed for nonendocrine pathologic conditions. All formalin-fixed, paraffin-embedded lymph nodes were identified from these 106 cases, excluding lymph nodes with metastases. Immunoperoxidase staining with monoclonal antibody against chromogranin A was performed on single tissue sections. All slides were reviewed by a single pathologist; chromogranin-positive cells were identified and, when possible, further evaluated immunohistochemically with additional neuroendocrine markers, including sequential synaptophysin staining. Results. A total of 1026 lymph nodes were available for review. Although well-formed intranodal chromogranin-positive nests were not identified, six nodes from three patients contained 13 strongly chromogranin-positive cells representing pulative neuroendocrine cells. Mast cells showed weak nonspecific staining with chromogranin but were morphologically distinct. Perinodal adipose tissue contained a single paraganglion and several small neuroendocrine clusters. Conclusions. Putative neuroendocrine cells are rarely (less than 1%) found in regional pancreatic lymph nodes. Although these may be embryonic rests and might represent precursors of primary nodal gastrinomas, specific hormones have yet to be identified in these cells. Although these data provide support for the concept of primary nodal gastrinomas, this remains a diagnosis of exclusion.