Appropriate and inappropriate neuroendocrine products in pulmonary tumourlets.

Abstract

Pulmonary tumourlets are focal aggregates of neuroendocrine cells that occur in the periphery of the lung and may be associated with chronic inflammation and scarring. Six such lesions were seen in five lungs from a series of 35 pairs of lungs studied at necropsy. MethodsTumourlets were sought in the lungs of 35 patients coming to necropsy, the only criterion for selection being that the necropsy was performed within 48 hours of death. In each case the left lung was distended with Bouin's solution, allowed to fix for 48 hours, and cut into 1 cm sagittal slices. At least 12 random blocks were then taken from each, a numbered perspex grid being placed over each slice, and a table of random numbers being used to select the blocks, with the proviso that large airways and vessels were avoided. Multiple blocks were taken from the non-distended right lungs at the time of the necropsy and these were also fixed in Bouin's solution for 48 hours. After being embedded in paraffin wax sections were stained with haematoxylin and eosin and the elastic van Gieson method and examined by light microscopy.When a tumourlet was discovered, serial sections of the block in which it was contained were cut and immunochemically labelled for neurone specific enolase and protein gene product 9 5, markers of pulmonary neuroendocrine cells,67 and a series of products of neuroendocrine cells (table 1) by the peroxidase-antiperoxidase technique.8 These substances were chosen for study because either they are found in the neuroendocrine cells of the normal human lung (gastrin releasing peptide, calcitonin, leucineenkephalin, and 5-hydroxytryptamine)9"' or

Morphology and antigen expression profile of pulmonary neuroendocrine cells in reactive proliferations and diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH)

“…For all other antigens sought, expression, when present, appeared to neither increase nor decrease notably as proliferation progressed. This uniform pattern of expression is broadly consistent with the few previous studies that have examined some of these antigens in normal and proliferating PNECs 10,14,15,22 . In the cases of DIPNECH, there was no difference in antigen expression between carcinoids and the proliferative lesions that appear to precede them.…”

“…This uniform pattern of expression is broadly consistent with the few previous studies that have examined some of these antigens in normal and proliferating PNECs. 10,14,15,22 In the cases of DIPNECH, there was no difference in antigen expression between carcinoids and the proliferative lesions that appear to precede them. Tumourlets and carcinoids have been shown to be genotypically different even when contiguous, 24 but we know little of any other genotypic or phenotypic features that might distinguish them.…”

“…Of those antigens that have been sought previously in proliferating PNECs, TTF‐1 has been described as both absent from or expressed strongly by them, 20,21 neuroendocrine markers and peptide products as consistently demonstrable in them, 10,22 34βE12 15 and c‐kit 14 as absent from them and Ki67 as being occasionally expressed by some tumourlets 23 …”

Pulmonary neuroendocrine cell system in pediatric and adult long disease

“…The most frequently demonstrable is ACTH, but beta-endorphin, ST, vasoactive intestinal polypeptide (VIP), human growth hormone (HGH) and subunits of HCG have all been described (Fukayama et al, 1990;Gould et al, 1983;Sheard and Gosney, 1996;Tsutsumi et al, 1983). Such substances have also been demonstrated in tumourlets (Fukayama et al, 1990;Gosney et al, 1990;Tsutsumi, 1989;Tsutsumi et al, 1983). Not surprisingly, elevated serum levels of ACTH have been described in subjects with inflammatory pulmonary conditions such as tuberculosis, chronic bronchitis and emphysema and pulmonary abscess (Ayvazian et al, 1975;Dupont et al, 1984;Gewirtz and Yalow, 1974;Wolfsen and Odell, 1979), in whom its high molecular weight form and non-suppressibility are against its being of pituitary origin, supporting its source as the neuroendocrine cells in the diseased lung.…”