Large cell neuroendocrine carcinoma (LCNEC)
is a high-grade non–small-cell lung carcinoma (NSCLC)
and is part of the neuroendocrine spectrum of pulmonary tumours.
Large cell neuroendocrine carcinoma (LCNEC) of the lung displays morphologic and
immunohistochemical characteristics common to neuroendocrine tumours and
morphologic features of large-cell carcinomas.
neuroendocrine carcinoma is composed of cells with moderate amounts of
cytoplasm and nuclei that show peripheral clumping of chromatin, a
Much mitotic activity and extensive
necrosis, as seen in any large cell carcinoma.
However, it is soon noticed that the tumour
cells are arranged in well demarcated groups or cords with peripheral
This feature is reminiscent of a carcinoid
pattern and the relationship to carcinoid is strengthened by shared
immunocytochemical and ultrastructural features of neuroendocrine
differentiation such as the presence neural cell adhesion molecule (CD56),
chromogranin, synaptophysin and scanty dense-core granules.
Certain squamous cell carcinomas also show
these neuroendocrine features - these have been termed non-small
cell carcinoma with neuroendocrine features.
Neuroendocrine differentiation can be
demonstrated by electron microscopy or immunohistochemistry in 10-15% of
non-small cell carcinomas of the lung despite an absence of morphological
of large cell neuroendocrine carcinoma includes atypical carcinoid tumour
but the organoid pattern of that tumour is not so well developed and the
degree of atypia, mitotic activity and necrosis all far exceed those seen
in an atypical carcinoid (which has between 2 and 10 mitoses per 2mm
square [=10 high power fields] .
In general, large
cell neuroendocrine carcinomas are tumours of middle-aged or elderly
cigarette smokers that arise in central bronchi.
Despite the morphological
evidence of neuroendocrine differentiation, ectopic hormone secretion is
not a feature.
Patients with large cell neuroendocrine carcinomas have a significantly
worse survival after resection than patients with large cell carcinomas,
even in stage I disease.
Accurate differentiation of large cell neuroendocrine carcinoma from large cell carcinoma is important because it
identifies those patients at highest risk for the development of recurrent
The clinical significance of these tumours has yet to be
fully evaluated but their recognition is of potential therapeutic
significance for their undoubted neuroendocrine nature links them to
classic small cell carcinoma and it would be important if their metastases
were similarly sensitive to chemotherapy.
However, reports available to
date regarding their chemosensitivity are contradictory and as yet there
have been no large scale, prospective, controlled trials of small cell
chemotherapy for this subgroup of large cell carcinomas or for other
non-small cell carcinomas showing neuroendocrine differentiation.
Furthermore, the clinical importance of neuroendocrine differentiation may
diminish if a current trend towards treating all inoperable lung
carcinomas with aggressive chemotherapy continues.