Tumorlets

Tumorlets are small, benign neuroendocrine proliferations in the lungs. They are discrete nodules typically less than 5 millimeters in diameter and are composed of clusters of neuroendocrine cells (Kulchitsky-type) within peribronchiolar or alveolar walls. They arise in areas of chronic lung injury or scarring, including bronchiectasis, fibrosis, sarcoidosis, and COPD, and are part of the spectrum of pulmonary neuroendocrine proliferations that includes diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH).

Clinically, tumorlets are usually incidental findings and patients may be asymptomatic. When symptoms occur, they reflect the underlying lung disease rather than the tumorlets themselves. Radiographically, multiple tiny nodules may be seen; conventional imaging cannot reliably distinguish tumorlets from small carcinoid tumors, and histology is definitive.

Histology shows well-differentiated, nest-like or sheet-like arrangements of uniform neuroendocrine cells with scant cytoplasm, minimal to no mitotic activity, and no necrosis. Immunohistochemistry typically shows positivity for neuroendocrine markers such as chromogranin A and synaptophysin; Ki-67 is low.

Distinguishing tumorlets from carcinoid tumors relies on size (<5 mm for tumorlets vs larger tumors), and absence of invasion, necrosis, or significant mitotic activity. Carcinoid tumors may be classified as typical or atypical and have malignant potential; tumorlets do not metastasize.

Prognosis is excellent, and management focuses on treating underlying lung disease. If tumorlets are part of DIPNECH with symptoms, therapy may address chronic cough or airflow limitation; no specific targeted therapy for tumorlets is standard.