Answer: Multiple carcinoid tumorlets

Histology: The histologic features of this lesion are relatively straight forward although there is an increase in lymphcytic infiltrate around the bronchioles which might cause confusion with follicular bronchiolitis, the predominant cell in the infiltrate is a small cuboidal or spindle cell with a very delicate “salt and pepper” nuclear chromatin and no mitotic figures. Inspection of the airways reveals that the same proliferation of cells involves the submucosa, whereas in other airways the actual lumen is obliterated by a combination of this cellular proliferation and fibroplasias. By light microscopy and especially with immunocytochemical studies (synaptophysin, CD56, chromogranin) one can see hyperplasia of these cells in the associated adjacent airspace walls.

Discussion: This patient has an unusual form of “obliterative bronchiolitis” caused by idiopathic neuroendocrine cell hyperplasia (multiple pulmonary carcinoid tumors). The process represents a spectrum of diseases. Probably the most common situation in which multiple tumorlets are found is in the lung adjacent to a clinically diagnosed carcinoid tumor (Am J Surg Pathol 1995;19:653-8). The other end of the spectrum is idiopathic diffuse hyperplasia of pulmonary neuroendocrine cells causing actual interstitial lung disease (Am J Surg Pathol 1995;19:963-970). A number of case reports (Thorax 1995;50:207-209 and Am J Rontgenol; 1997, 168: 1561-1562) have been reported. The clinical details of this entity have been presented by Cohen et al. (Am J Respir Crit Care Med 1998;158:1593-1599). One patient (Thorax 1995;50: 207-209) had been treated successfully by lung transplantation.

Other situations in which multiple carcinoid tumorlets can be found include bronchiectasis (and perhaps by association intralobar pulmonary “sequestrations”) multiple carcinoid tumors have been reported in the apparent absence of other multiple endocrine neoplasia (Cancer 2001;91:2104-2108). I have seen one familial example of multiple pulmonary carcinoid tumorlets causing obstructive lung disease.

The differential diagnosis is relatively limited. Neuroendocrine cell hyperplasia is not a feature of follicular or inflammatory bronchiolitis. Pulmonary meningothelial-like nodules (so-called “minute chemodectomas”) do not occur in airways; they are found predominantly in the interlobular septa accompanying veins. The endocrine cell proliferation here is bland and lacks mitotic figures or necrosis excluding the possibility of atypical carcinoid or small cell carcinoma.