Small neuroendocrine lesions in intrathoracic lymph nodes of patients with primary lung adenocarcinoma: real metastasis?

The presence of individual neuroendocrine cells in rare peripancreatic lymph nodes (LNs) suggests that neuroendocrine tumor or nested neuroendocrine cell proliferation can arise in situ from neuroendocrine cells native to any LN. However, it is very difficult to ascertain whether any neuroendocrine lesion in LNs is a primary tumor or a metastasis from adjacent organs. We encountered 4 cases of neuroendocrine proliferation in intrathoracic LNs (ILNs) of patients with primary lung adenocarcinoma. All patients had a single lung mass without mediastinal lymphadenopathy based on computed tomography and positron emission tomography imaging. Mediastinal staging was done by either mediastinoscopy or thoracotomy and none of them had metastasis from adenocarcinoma in any LN. One patient had three ILNs positive for neuroendocrine proliferation measuring 1.7, 1.8, and 4.0 mm, respectively and a minute tumorlet less than 1.0 mm in the lung. Three other patients had small areas of neuroendocrine proliferation no more than 1 mm in single ILN without any lung neuroendocrine lesion. Neuroendocrine cells in ILNs often formed nests of varying size with similar morphology to carcinoid tumorlet in the lung. Small clusters of neuroendocrine cells without any particular pattern were often seen together with these nests. These cells were positive for neuroendocrine markers: synaptophysin, chromogranin, and CD56. They were also positive for CK7 and TTF-1. It is interesting to note, single cells positive for neuroendocrine markers and TTF-1 were identified near or away from these neuroendocrine nests or clusters. These findings suggest that neuroendocrine lesion can be incidentally identified in ILNs. Close clinical follow-up is warranted as metastasis from or synchronous lesions in adjacent organs cannot be excluded.