Abstract
Glandular papillomas are the rarest type of solitary endobronchial papillomas of the lung, which are in themselves extremely uncommon, and are mainly described in the literature as case reports. These tumours generally arise from the epithelium of central lobar or segmental bronchi and are thought to be benign, with only a single documented case of malignant transformation to date. Diagnosis may be challenging, and there is no consensus on treatment; however, surgical resection with a parenchymal-sparing approach is an accepted treatment option. In this report, we present two cases of solitary endobronchial glandular papilloma in young females who underwent surgical resection. In one case, we also describe an associated diagnosis of a concurrent pulmonary adenocarcinoma. We aim to contribute to the growing body of literature on these rare neoplasms and highlight the importance of a considered approach to their treatment.
Introduction
Solitary endobronchial papillomas of the lung are exceedingly rare benign neoplasms arising from the bronchial epithelium [1]. They are subclassified into three categories: squamous, glandular and mixed squamous and glandular papillomas [2]. They account for 0.38% of all lung tumours [3] and 7% of benign lung tumours, of which less than a fifth are glandular in subtype [2]. Glandular papillomas generally arise centrally from the main lobar or segmental bronchi [4]. To the best of our knowledge, there has only been one reported case of glandular papilloma with malignant transformation to date [3].
Solitary endobronchial papillomas largely affect adult males, however glandular papillomas affect females and males almost equally in the sixth or seventh decade of life [2].
Here we describe two cases of solitary endobronchial glandular papilloma in young females, in one case associated with a subsequent diagnosis of pulmonary adenocarcinoma.
Case report
Case 1
A 40-year-old lady with a 1 pack-year smoking history was referred to the Thoracic Surgical Clinic in January 2023. She reported increasingly severe and frequent cough and wheezing from March 2022, and several consecutive lower respiratory tract infections culminating in hospitalisation in December 2022 when her chest X-ray demonstrated a new left lower lobe collapse. A chest computed tomography (CT) scan revealed a lesion arising from the left lower lobe bronchus, obstructing the lower lobe and extending into the junction of the left main bronchus and upper lobe bronchus, which was severely stenosed. Flexible bronchoscopy showed a polypoid heterogenous endobronchial lesion at the left main bronchus; biopsies were initially suggestive of hamartoma (Fig. 1).
A section from a chest CT in the transverse plane in December 2022 showing a lesion arising from the left lower lobe bronchus, extending into the junction of the left main and left upper lobe bronchi (with severe stenosis of the latter) and causing collapse of the left lower lobe.
In February 2023, she underwent left posterolateral thoracotomy with excision of the endobronchial lesion via the left main bronchus and bronchoplasty. The histological diagnosis however was that of benign solitary endobronchial glandular papilloma: a well-circumscribed neoplasm comprising complex papillary fronds with fibrovascular cores, lined by columnar mucinous epithelium exhibiting cytological atypia, and extensive foci of metaplastic ossification. The sampled lymph nodes (stations 6 and 10) were negative for metastatic malignancy (Fig. 2).
A photomicrograph at ×20 magnification, showing an endobronchial papilloma comprising complex papillary fronds with fibrovascular cores lined by columnar mucinous epithelium, with high-grade cytological atypia. The papilloma was negative for thyroid transcription factor-1 (TTF-1) and Napsin A. Some basal cells were highlight by p63, and Ki-67 proliferation was around 5%.
Her immediate post-operative course was unremarkable, but a surveillance chest CT in January 2024 showed recurrence with occlusion of the left lower lobe bronchus, and the morphological features on biopsies from flexible bronchoscopy were identical to those of the previous glandular papilloma (Fig. 3).
The plain chest X-ray in January 2024 showing collapse of the left lower lobe (sail sign) (A), and a section from the chest CT in the transverse plane in January 2024 showing recurrence of the lesion with collapse of the left lower lobe (B).
In February 2024, she underwent redo thoracotomy and left lower lobectomy. Histopathological examination identified a papillary lesion focally attached to the bronchial wall, occupying and distending the left lower lobe bronchus, again exhibiting villiform areas lined by epithelial cells with high-grade cytological atypia, and with extensive metaplastic ossification among the stalks of the papillary projections. However, deeper within the lung parenchyma, amongst extensive obstructive pneumonitis, there were areas of invasive mucinous adenocarcinoma (~50 mm) with satellite tumour nodules. The pleura was not involved, and the bronchial margin and sampled lymph nodes (stations 9, 10, and 11) were negative for malignancy (Figs 4 and 5).
A photomicrograph at ×10 magnification, showing an endobronchial papilloma with an area of complexity, together with invasive pulmonary adenocarcinoma with a mostly mucinous morphology and spread through airspaces. The adenocarcinoma was negative for TTF-1, was highlight by cytokeratin 7 (CK7) and showed patchy cytokeratin 20 (CK20) expression. Less than 1% of cells were positive for programmed death ligand 1 (PD-L1), and no relevant epidermal growth factor receptor (EGFR) mutations were identified.
A photomicrograph at ×10 magnification, showing the invasive mucinous pulmonary adenocarcinoma close to but not involving the pleura.
She was diagnosed with a concurrent solitary endobronchial glandular papilloma and a pT3pN0M0 (stage IIB) lung adenocarcinoma, and received 4 cycles of carboplatin and pemetrexed. A surveillance chest CT in August 2024 showed bilateral metastatic lung nodules, and she received 24 cycles of maintenance pembrolizumab. In December 2025, pemetrexed was added to her maintenance regimen, and she has since received a further 4 cycles.
Case 2
A 28-year-old never-smoker was referred to the Thoracic Surgical Clinic in January 2024 with a yearlong history of recurrent respiratory tract infections and a lesion in the distal right lower lobe bronchus on chest CT. Flexible bronchoscopy demonstrated a polypoid endobronchial lesion occluding the right lower lobe lateral segmental bronchus. Serial biopsies identified a fragment of a tumour with a papillary architecture lined by simple to pseudostratified columnar epithelium with micropapillary tufts. These features were suggestive of an endobronchial glandular papilloma (Fig. 6).
Sections from a chest CT in the transverse plane (A) and in the coronal plane (B) showing a lesion in the distal part of the right lower lobe bronchus.
In April 2024, she underwent right posterolateral thoracotomy and lower lobectomy. Histological examination described a 10 mm endobronchial papillary lesion with papillary and micropapillary morphology lined by epithelium with mitoses and mild atypia, and focal stromal inflammation. The findings confirmed a benign solitary endobronchial glandular papilloma, and the surrounding lung parenchyma and bronchus appeared otherwise normal (Fig. 7).
A photomicrograph at ×20 magnification showing an endobronchial papilloma, with a papillary architecture lined by epithelium which expressed CK7 strongly and TTF-1 weakly and focally, with a well-preserved basal layer positive for p40, and with focal inflammation of the stroma.
Her post-operative course was unremarkable, and her latest surveillance chest CT in October 2025 did not demonstrate any signs of recurrence.
Discussion
Solitary endobronchial papillomas are unusual epithelial tumours, and papillomas of the glandular subtype are exceptionally rare, with only 34 cases described in the literature as of 2022 [2].
Solitary endobronchial papillomas are classified by the World Health Organisation as benign. Malignant transformation has been previously infrequently described for squamous as well as mixed papillomas but has only been documented once in the literature for glandular papilloma [3].
There is no consensus on resection strategy, and endoscopic treatment (such as bronchoscopy and snare electrocautery [5] or application of neodymium-YAG laser) followed by stringent monitoring or surgical resection (ranging from subsegmental resection to pneumonectomy in a few cases [6]) are both considered to be acceptable options [7]. Surgical resection maintains the advantages of ensuring removal in entirety of any occult malignancy, and of preventing recurrence secondary to incomplete endoscopic resection, but parenchymal-sparing approaches to conserve pulmonary function as far as possible should be prioritized [5].
In our manuscript, findings of the histological examination of the lobectomy specimen in the first case were in keeping with a synchronous endobronchial glandular papilloma and lung adenocarcinoma, rather than with malignant transformation of the former. We hypothesise that the underlying mechanism for this is de novo development of lung cancer in a chronically collapsed and inflamed left lower lobe [8], rather than exfoliation of epithelial cells from the papilloma into more distal airspaces [9].
In both cases, the histological findings were unexpected, given their extreme rarity, and particularly the patients’ unusually young age, compared with the more typical patient population outlined in the literature to date.
We feel these cases are noteworthy in that they contribute to the small but growing body of data on solitary endobronchial glandular papillomas, and furthermore that they highlight the necessity of a carefully considered approach to their treatment and clinical follow-up.
Acknowledgements
The authors are grateful to Dr Ian Said Huntingford, Consultant Histopathologist at the Department of Pathology, Mater Dei Hospital, Malta, who kindly provided images of the histological sections for this manuscript.
Conflicts of interest
None declared.
Funding
None declared.
