Small exophytic proliferation arising as incidental finding within a bronchiolus of a 16-week-old female Wistar rat (strain: Chbb:Thom SPF) from the low dose group of an inhalation toxicity study. The lesion is composed of central polygonal cells with weakly eosinophilic cytoplasm and large round nuclei and covered by respiratory epithelium.

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Fig. 1: H&E, x20	Fig. 2: H&E, x63

The finding in question was incidentally observed in the bronchiolar epithelium of a 16-week-old female Wistar rat (strain: Chbb:Thom SPF) from the low dose group of an inhalation toxicity study. The lesion is composed of central polygonal cells with weakly eosinophilic cytoplasm and large round nuclei and covered by respiratory epithelium. It consists of an accumulation of neuroendocrine cells located on a stalk of fine fibrovascular tissue.

These neuroendocrine cells were first described as "helle Zellen" by Fröhlich (1949), their presence was later confirmed by Feyrter (1954). Neuroendocrine cells of the airways either occur singly or in clusters known as neuroepithelial bodies. The cells are functionally and structurally related to the cells of the APUD series and is has been postulated that groups of these cells may have sensory receptor sites. For a long time these cells were thought to arise only in the fetal organism but systematic investigations had shown that Feyrter cells occur frequently also in adult rat.

Synonym: Aggregation of neuroendocrine (Feyrter) cells

The neuroendocrine origin of the alteration was suggested by about half of the participants. Several colleagues proposed to prove the origin using special staining methods such as NSE, chromogranin, or synaptophysin. The lesion also was expected to be immunoreactive for calcitonin, calcitonin gene-related peptide (CGRP), markers which are described as being specific for neuroendocrine cells. Indeed, the latter staining method gave evidence of the neuroendocrine origin (Figures 3 and 4).

The lesion seems to be too small and too well organized to call it already a benign tumor of neuroendocrine cells. However, a pre-neoplastic lesion (hyperplasia) is not described in the current criteria available for the rat.

The other half of the participants had suggested rather a respiratory epithelial origin of the lesion and names like "bronchiolar polyp", "stromal polyp" or "papilloma composed of non-ciliated bronchial epithelial cells" were given. The neuroepithelial structure might have been overlooked, since in the H&E stain there is no clear tinctorial or morphological difference between respiratory epithelial bronchial cells and neuroendocrine cells. The epithelial stalk moreover gives evidence of a papillomatous appearance.

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Fig. 3: PCNA, x40	Fig. 4: Calcitonin, x63

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•   Friedrich Feyrter 1895 - 1973, Pathologist in Vienna, Gdansk, Bratislava, Graz, Vienna and Goettingen