April 2023 – Pulmonary Case 2

Bronchiolar adenoma/ciliated muconodular papillary tumor.

Bronchiolar adenoma/ciliated muconodular papillary tumor (BA/CMPT) is a benign pulmonary neoplasm. Clinically, BA/CMPT typically occurs in individuals 60 years of age and older and equally affects both sexes. This lesion is most often discovered incidentally on imaging and presents as either a solid nodule or ground-glass opacity in the peripheral lung. Most BA/CMPTs measure between 0.5-1.5 cm. Irregular borders and occasional central cavitation seen on imaging may raise concern for malignancy.

BA/CMPT can be further subdivided into either classic CMPT (demonstrated in this case) and non-classic CMPT. Classic CMPT was first described in 2002 and is characterized by a cellular bilayer consisting of papillary or glandular ciliated columnar epithelium with a continuous layer of basal cells underlying the epithelium. Epithelial cells appear bland and often contain mucin, though this is not required for diagnosis. Non-classic CMPT more closely resembles distal airways with a bilayer consisting of cuboidal, club-like epithelium without cilia or mucin and a continuous basal cell layer.

Molecularly, both classic and non-classic BA/CMPT are positive for BRAF V600E mutations in approximately 40% of cases. Studies have also shown alterations in EGFR, KRAS, HRAS, ALK, and AKT1 genes, though these mutations have not demonstrated as high a prevalence as BRAF V600E.

Key differential diagnoses in these cases include invasive mucinous adenocarcinoma, adenocarcinoma in situ, mucoepidermoid carcinoma, peribronchiolar metaplasia, and metastases. The most important distinguishing feature in BA/CMPT is the presence of a continuous basal cell layer, which stains positive for p40/p63. In adenocarcinoma and mucoepidermoid carcinoma, a continuous basal cell layer will be absent. Additionally, ciliated cells will not be seen in these malignancies but are apparent in classical BA/CMPT. Unlike BA/CMPT, peribronchiolar metaplasia will not form a discrete nodule or opacity, arises in the setting of inflammation or injury, and is often multifocal. Positive TTF-1 staining is useful in establishing pulmonary origin and targeted immunostains can be used to rule out possible metastatic disease (CDX2 was used in this case to rule out an intestinal primary).

References

1. WHO Classification of Tumours Editorial Board. Thoracic tumours [Internet]. Lyon (France): International Agency for Research on Cancer; 2021 [cited 2023 February 20]. (WHO classification of tumours series, 5th ed.; vol. 5). Available from: https://tumourclassification.iarc.who.int/chapters/35.
2. Yang Y, Xie X, Jiang G, Zhang L, Liu H. Clinicopathological characteristic of ciliated muconodular papillary tumour of the lung. J Clin Pathol. 2022;75(2):128-132.
3. Kao TH, Yeh YC. Ciliated muconodular papillary tumor/bronchiolar adenoma of the lung. Semin Diagn Pathol. 2021;38(5):62-71.
4. Shirsat H, Zhou F, Chang JC, et al. Bronchiolar adenoma/pulmonary ciliated muconodular papillary tumor. Am J Clin Pathol. 2021;155(6):832-844