Multiple bronchiolar adenomas/ciliated muconodular papillary tumors of the bilateral lung with tumor budding and potential malignant transformation into squamous cell carcinoma: a case report and literature review

Abstract

Background: Bronchiolar adenoma (BA)/ciliated muconodular papillary tumor (CMPT) is a rare lung tumor characterized by ciliated, mucous and basal cells. Recently, some cases of driver mutations or malignant transformations have been reported. However, the nature of BA/CMPT remains controversial. Here, we report a case of bilateral pulmonary multiple BAs with tumor budding and squamous metaplasia.

Case description: A 55-year-old man presented with multiple small nodules in the lower lobes of the bilateral lungs on physical examination 7 years prior. During the past 3 years of regular follow-up, some nodules had slightly enlarged. Because the nodules were mostly solid, the patient underwent video-assisted thoracoscopic segmentectomy of the left lower lung. A postoperative pathological diagnosis of BA was made. In all lesions, the fusion and mutation of major driver genes were not detected by next-generation sequencing (NGS). No recurrence or metastasis was observed after 37 months of follow-up. Notably, all five resected lesions were BA/CMPT, and one lesion was accompanied by squamous metaplasia and tumor budding.

Conclusions: Our report found that BA/CMPT with squamous metaplasia and tumor budding has the potential to transform into lung squamous cell carcinoma, expanding its connection with malignant transformation. Smoking may be one of the risk factors. We also found that BA/CMPT can be multiple lesions rather than a solitary lesion.

Keywords: Bronchiolar adenoma (BA); case report; ciliated muconodular papillary tumor (CMPT); malignant transformation; tumor budding.

Figure 1

HRCT images showed a 10 mm × 7 mm irregular nodule (arrow) in the S9 segment of the left lower lobe with small ridges and vacuoles at the edge (A: coronal plane, B: transverse plane). There were three subpleural solid nodules (C-E, arrows) in the remaining lung segments approximately 5–7 mm in diameter. HRCT, high-resolution chest computed tomography.

Figure 2

HRCT images showed multiple small nodules (arrows) around the right lower lung approximately 4–6 mm in diameter, with ground-glass opacity (A), solid (B), with small cavities (C), adjacent to the pleura (D). HRCT, high-resolution chest computed tomography.

Figure 3

H&E and IHC staining results. Frozen section of the S9+10 nodule in the left lower lung. (A) The bronchial epithelium was papillary hyperplasia with abundant mucinous cells and a monolayer-like structure (yellow arrow). Frozen section of S6 nodule in left lower lung lobe (H&E, 200×). (B) Bronchial epithelium consists of a dual-layer cells (basal cells and luminal cells), basal cells in a continuous beaded arrangement (yellow arrow) (H&E, 400×). (C) The luminal cells show abundant mucinous (black arrow) and ciliated cells (white arrow) (H&E, 400×). (D) The nodule showed severe and abnormal proliferation of the squamous epithelium (H&E, 400×). (E) The continuation and transition of squamous epithelium and ciliated columnar epithelium can be seen in the bronchus (yellow arrow) (H&E, 10×). (F) Tumor budding was found at the edge of the nodule, showing cells arranged in a bud-like manner, projecting into the alveolar stroma, with enlarged nuclei and irregular nuclear membranes (H&E, 400×). (G,H) The basal cells show strong positivity for CK5/6 and p40 (IHC, 100×). (I) The basal cells are positive for p53 with varying degrees of intensity (IHC, 10×). H&E, hematoxylin and eosin staining; IHC, immunohistochemistry.

Figure 4

H&E and IHC staining results. (A) Both bronchial bilayer epithelial cells show positivity for TTF-1 (IHC, 100×). (B) Squamous epithelium with severe dysplasia and tumor budding showed positivity for p40 (IHC, 100×). (C) Atypia squamous metaplastic epithelium is irregularly arranged, with enlarged nuclei and increased nuclear plasma ratio (yellow arrow) (H&E, 10×). TTF-1, thyroid transcription factor-1; H&E, hematoxylin and eosin staining; IHC, immunohistochemistry.