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pulmonary large cell neuroendocrine carcinoma

Wednesday 8 October 2014

large cell neuroendocrine carcinoma of the lung

Definition: Large cell neuroendocrine carcinoma of the lung, was described in 1991, as a high-grade large cell carcinoma with neuroendocrine morphology and immunohistochemical demonstration of at least one neuroendocrine marker.


- Pulmonary Large Cell Neuroendocrine Carcinoma

From a prognostic point of view, large cell neuroendocrine carcinoma was initially placed between atypical carcinoid and small cell carcinoma but subsequently found to be similar in behavior to small cell carcinoma.

It was included as a variant of "large cell carcinoma of the lung" in the 1999 WHO schema on the basis that all large cell carcinomas originate from a pluripotent stem cell and that neuroendocrine differentiation does not imply origin from a specific neuroendocrine cell.

However, since then there have been numerous publications advocating its inclusion in the neuroendocrine tumor group rather than the large cell category based on common clinical morphological, immunohistochemical, and molecular features that are shared by the spectrum of neuroendocrine carcinomas.

Another controversial issue related to this matter is how to categorize tumors that either show neuroendocrine differentiation by immunohistochemistry or electron microscopy but lack the morphological characteristics of endocrine tumors (large cell carcinoma with neuroendocrine differentiation) or vice versa (large cell carcinoma with neuroendocrine morphology).

The literature is still full of debate whether neuroendocrine morphology or differentiation in non-small cell carcinoma is associated with better or worse patient outcome, thereby still precluding firm categorization of such tumors.

For a diagnosis of large cell neuroendocrine carcinoma, certain criteria have to be met.

Firstly, the tumors need to show the typical growth pattern of neuroendocrine carcinomas, ie, tumor cells forming organoid nests, rosettes or trabecular structures, and peripheral palisading of tumor cells.

Tumor cells are large with vesicular nuclei, prominent nucleoli, and abundant cytoplasm. Per definition, more than 10 mitoses must be present in 10 high-power fields (HPF), and necrosis is commonly seen.

In addition to these morphological features, the tumors must show neuroendocrine differentiation either based on the presence of neurosecretory granules as identified by electron microscopy or positive staining for at least one neuroendocrine immunohistochemical stain.

Rarely, large cell neuroendocrine carcinomas can contain components of other non-small cell carcinomas and are then classified as combined large cell neuroendocrine carcinoma.