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Papillary adenoma of the lung: A case report and literature review

  • Authors:
    • Li-Qian Chen
    • Mai-Qing Yang
    • Su-Mei Gao
    • Zheng-Jiang Wang
    • Hong-Tao Xu
  • View Affiliations

  • Published online on: July 16, 2024     https://doi.org/10.3892/etm.2024.12658
  • Article Number: 369
  • Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Papillary adenoma of the lung, a rare and benign tumor, is easily confused with other primary benign or malignant lung tumors and especially with lung adenocarcinoma that has a papillary growth pattern. Enhanced understanding and an accurate diagnosis of papillary adenomas of the lung are crucial for clinical treatment and prognostic assessment. A 61‑year‑old man who presented with an opportunistic finding in relation to a left lower lobe lung nodule during an examination was admitted to The First Hospital of China Medical University (Shenyang, China) for further treatment. Computed tomography (CT) revealed a well‑circumscribed left lower lobe nodule (diameter, ~1 cm), comprising branched papillae with a fibrovascular core and no other structural components. The tumor cells appeared relatively uniform in shape and well arranged with round or oval nuclei. No nucleoli or mitotic figures were observed. Immunohistochemically, the papillary structures of the tumor cells were strongly and diffusely positive for cytokeratin (CK), CK7, Napsin‑A and thyroid transcription factor 1. The Ki‑67 index was ~1%. A pathological diagnosis of primary papillary adenoma of the lung was made based on these findings. A left lower‑lobe wedge resection was performed and the patient's postoperative course was uneventful. Surgical resection is the preferred treatment. Papillary adenoma of the lung is very rare, and its clinical manifestations and CT images are non‑specific. It is important to avoid misdiagnosing of papillary adenoma of the lung as another type of lung tumor, especially adenocarcinoma. A clear understanding of the morphological and immunohistochemical features of papillary adenomas is important for the diagnosis of this rare lung tumor.

Introduction

Primary papillary adenoma of the lung is a rare tumor first described by Spencer et al (1) in 1980. To date, only 44 cases of pulmonary papillary adenoma have been reported, predominantly involving peripheral lung tissue. Owing to its rarity, current understanding of papillary adenoma of the lung is limited, which makes it easily misdiagnosed as other types of primary benign or malignant lung tumors in clinical practice, especially lung adenocarcinoma with a papillary growth pattern. Typically, clinical symptoms of primary lung papillary adenoma are non-specific, and can manifest as cough, shortness of breath, asthma and chest pain; patients are often asymptomatic and are diagnosed accidentally by physical examination. Most of the patients are male and range in age from 2 months to 78 years-old. Most reported cases have predominantly involved peripheral lung tissue, and also in the hilar region, mainly appearing as a solitary pulmonary nodule on chest computed tomography (CT) images. Under imaging examination, pulmonary papillary adenomas were mostly solitary round or spherical nodules with smooth margins. The most common location was the lower lobe of the left lung, followed by the upper and lower lobes of the right lung. Pathologic examination revealed that the diameter of the tumors ranged from 0.2 to 9 cm, most of them had no capsule and were clearly demarcated from surrounding lung tissues (1-26). Most reported patients underwent only surgical treatment, with no recurrence or metastasis generally observed during follow-up; papillary adenomas of the lung are classified as benign tumors (1-26). Pulmonary papillary adenomas were extremely rare; pathologists do not have sufficient knowledge of the histological morphology of the tumor. In the present study, a rare case of papillary adenoma of the lung was reported and the relevant literature was reviewed.

Case report

Ethical approval. The present study was approved [approval no: LS (2021)009] by the Institutional Review Board of The First Hospital of China Medical University (Shenyang, China). Written informed consent was obtained from the patient for the participation in the present study and for the publication of the associated images. The study was conducted in accordance with the principles of the Declaration of Helsinki (2013 version).

Clinical history

A 61-year-old man with no history of smoking presented with a nodule in the lower lobe of the left lung during an examination and was admitted to the First Hospital of China Medical University (Shenyang, China) in December 2022 for further treatment. The patient had no relevant medical, personal, or family history. The male patient had no chest pain or any other relevant symptoms and was afebrile on presentation. A CT scan revealed a well-defined solid mass nodule in the left lower lobe measuring ~1 cm in diameter. The tracheobronchial and subcarinal lymph nodes were not enlarged (Fig. 1). The preoperative diagnosis was a lung mass, and a wedge resection of the lower lobe of the left lung was performed. Intraoperatively, the nodule was located in the left lower lobe and was ~1 cm in diameter. The surface of the tumor was rough and uneven. The edge of the mass was located 2 cm from the incisal margin. The resected lung specimen was sent for rapid intraoperative frozen tissue pathological examination, with a suggested diagnosis provided as follows: ‘Consider sclerosing pneumocytoma or papillary adenoma, to be determined and excluded from malignancy by paraffin section and immunohistochemical examination’. No lymph node sampling or lymphadenectomy was performed. The male patient did not receive postoperative radiotherapy or chemotherapy and had a favorable postoperative recovery. Follow-up at 15 months (to March 2024) revealed no evidence of recurrence or other metastatic occurrences. The follow-up result aligns with previous studies. Based on the available data, excluding two special cases and seven patients for whom follow-up information was unavailable, the remaining patients (36/45) did not experience any recurrence and exhibited positive outcomes (1-26).

Immunohistochemical staining

The resected specimens were fixed with 10% neutral-buffered formalin for 24 h at room temperature, embedded in paraffin blocks, and cut into 4-µm thick serial sections. Sections were stained for 5 min with hematoxylin and eosin (H&E; (cat. no. G1120; Beijing Solarbio Science & Technology Co., Ltd.) at room temperature for histological assessment under a light microscope (Nikon Corporation). For immunohistochemical analysis, after washing three times in 0.01 M phosphate buffered saline (pH 7.4) for 5 min each time at room temperature, the sections were incubated with 3% hydrogen peroxide at room temperature for 10 min. Antigen retrieval was performed with ethylene diamine tetra-acetic acid at 100˚C for 2.5 min. The sections were then incubated with undiluted primary antibodies at 37˚C for 60 min and ready-to-use secondary antibody at 37˚C for 20 min. The following primary antibodies were used: Broad-spectrum cytokeratin (CK, cat. no. MAB-0671), CK7 (cat. no. MAB-0828), CK5/6 (cat. no. MAB-0744), P40 (cat. no. RMA-0815), thyroid transcription factor 1 (TTF-1, cat. no. MAB-0677), Napsin-A (cat. no. MAB-0704) and Ki-67 (cat. no. MAB-0672; all Fuzhou Maixin Biotech Co., Ltd.). Ready-to-use biotinylated goat anti-mouse and rabbit secondary antibodies (cat. no. KIT-9710; Fuzhou Maixin Biotech Co., Ltd.) . Elastic fiber staining at room temperature according to the manufacturer's protocol (cat. no. BA4083B; Zhuhai Beso Biotechnology Co., Ltd.).

Morphological and immunohistochemical findings

Morphologically, the well-circumscribed tumor (maximum diameter, ~0.7 cm) had no surrounding fibrous capsule, revealed expansive growth and was pressed against healthy lung tissue. The tumor comprised branched papillae with a fibrovascular core and no other structural components. The papillary structures were covered with a single layer of cuboidal epithelial cells. The tumor cells were relatively uniform in shape and well arranged with round or oval nuclei (Fig. 2). No nucleoli or mitotic figures were observed. Lymphocyte infiltration was observed in the stroma of the tumor; however no significant edematous change was noted. No healthy lung tissue infiltration or vascular or neural invasion were observed in relation to the tumor.

Immunohistochemically, the papillary structures of the tumor cells were strongly and diffusely positive for CK, CK7, Napsin A and TTF-1. The stroma of the papillary structures was negative for CK, CK7 and TTF-1. The tumor was negative for CK5/6 and P40. The Ki-67 index was ~1% (Figs. 3 and S1). Positive staining for CK, CK7, and Napsin-A in the papillary structures of the tumor cells, along with a diffusely lower Ki67 index, aided in the diagnosis of pulmonary papillary adenoma. Elastic fiber staining was performed and discontinuous or fractured elastic fibers in papillary adenoma tissue were observed (Fig. S1); therefore, elastic fiber staining could not be used to differentiate between papillary adenoma and papillary adenocarcinoma.

Discussion

Based on the aforementioned clinical information, morphological features and immunohistochemical results, the tumor was diagnosed as a primary papillary adenoma of the lung. Papillary adenoma is a rare tumor that occurs mainly in the peripheral lung. In 1980, Spencer et al (1) first reported two cases of primary papillary adenoma of the lung (1). Only 45 patients with primary papillary adenoma of the lung have been reported to date. The clinicopathological features of the 45 reported cases (women, n=19; men, n=26) (1-26) are summarized in Table I, with most patients being asymptomatic, and the tumor being an incidental finding in 27 of the 45 cases. Patient ages varied widely between 2 months and 78 years (mean age, 50.5 years). The diameter of the tumors ranged from 0.2 to 9 cm (mean diameter, 2.5 cm), with the exception of 11 cases where tumor size was not reported. Tumor locations were as follows: Right lung, 20 cases; left lung, 18 cases; main airway, one case; both lungs, one case; and location not mentioned, four cases (1-26).

Table I

Clinicopathological characteristics of patients with primary pulmonary papillary adenoma.

Table I

Clinicopathological characteristics of patients with primary pulmonary papillary adenoma.

CaseSymptomsYearSexAge, yearsSize, cmSiteTherapyOutcome(Refs.)
12-month history of cough1980F264.0LSNM(1)
2None1980M7NMLSNM(1)
3None1982F252.1RS10 years FD(2)
4None1986M571.5RS8 years FD(3)
5None1992M231.8RS10 years FD(4)
6None1992M561.8RS2 years FD(4)
7None1992F521.2RS11 months FD(5)
8None1993M130.2R,LS6 years FD(6)
9None1994F<12RS2 years FD(7)
10None1996M352LS3 years FD(8)
11None2000M152.5LS9 years FD(9)
12None2000M272.4RS2 years FD(9)
13With osteosarcoma lung metastases2002M90.4LS,C6 years and 9 months FD(10)
14None2009M611.5LS7 years FD(11)
15None2010M701.1LS3 years FD(12)
16Shortness of breath2011M751.5LSNM(13)
17None2011M751.8LS38 months FD(14)
18History of asthma2013M246.0LS6 months FD(15)
19History of renal cancer2014F682.5LSNM(16)
20None2015F173.1RS12 months FD(17)
21None2016F783.8LS26 months FD(18)
22None2017F641.7RS6 months FD(19)
23None2017F412.0LSNM(19)
24None2019M591.5RSNM(20)
25Dizziness for 1 week2020M654.2RNMBrain metastasis(21)
26History of asthma2020M561.5LSDeveloped adenocarcinoma after 2 years(22)
27Cough2020M599RS6 years FD(23)
28None2020F62NMLNoFavorable(24)
29Cough2020M601.1LSFavorable(24)
30Chest pain2020F65ECHRSFavorable(24)
31Cough2020M64ECHRNoFavorable(24)
32None2020F621RSFavorable(24)
33None2020F721RSFavorable(24)
34Cough2020M47ECNMNoFavorable(24)
35None2020F783.4RNoFavorable(24)
36Cough2020F68BE exudationNMNoFavorable(24)
37Cough2020M48exudationRNoFavorable(24)
38Cough2020F63BE exudationNMNoFavorable(24)
39Cough2020F39ECNMNoFavorable(24)
40Cough2020F76ECNMNoFavorable(24)
41Chest pain2020M704LSFavorable(24)
42Cough2020M45BERNoFavorable(24)
43None2021M694Left main airwayS1 year FD(25)
44None2022F665.5RSNM(26)
45 present caseNone2023M611LS15 months FD 

[i] F, female; L, left lung; S, surgery; NM, not mentioned; M, male; R, right lung; Mo, months; FD, free of disease; C, chemotherapy; ECH, exudation consolidation hollow; EC, exudation consolidation; BE, bronchiectasis.

Owing to its rarity, pathologists may have insufficient knowledge of the histological morphology of this type of tumor. At present, papillary adenomas are considered to originate from the primitive multipotential respiratory epithelium, which shows bidirectional differentiation into type II alveolar epithelium and club cells (7,8,21). Primary papillary adenomas of the lung may be confused with other primary malignant or benign lung tumors such as adenocarcinoma with papillary growth patterns, metastatic papillary thyroid carcinoma, sclerosing pneumocytomas and bronchiolar adenomas. Papillary adenomas should be distinguished from adenocarcinomas with papillary growth patterns. Adenocarcinomas generally exhibit a high degree of cellular proliferation, nuclear atypia and a complex branching architecture. Lung adenocarcinoma may occasionally present with relatively mild papillary structures, showing infiltrative growth without a clear boundary. In addition, owing to the heterogeneity of lung adenocarcinomas, the papillary structure is usually not the only growth pattern and is accompanied by other structures, such as lepidic or glandular patterns. EGFR and KRAS gene mutations may play a role in the development of pulmonary adenocarcinoma (17). The diagnosis of metastatic papillary thyroid carcinoma relies primarily on nuclear morphology and immunohistochemical staining. Papillary thyroid carcinoma is characterized by the presence of cells with ground glass nuclei and colloid within thyroid follicles. Thyroglobulin and PAX8 are antibodies specifically expressed in thyroid carcinoma, while Napsin A is a marker for lung adenocarcinomas (27). Sclerosing pneumocytomas originate from the primitive respiratory epithelium (28). The histological morphology of sclerosing pneumocytomas varies. Four growth patterns are typically observed, namely, papillary, sclerotic, hemorrhagic and solid. Sclerosing pneumocytomas are comprised of two cell types. Tumor cells are arranged not only on the papillary surface and in the stroma, with papillary structures comprising TTF-1-positive stromal cells instead of fibrovascular cores (28). Bronchiolar adenomas (including proximal and distal types) are derived from bronchiolar epithelium and not from the alveolar epithelial cells. Therefore, the tumor cells on the surface of the papillary structures display differentiation of the ciliated columnar epithelium and mucus cells with basal cells at the bottom layer. CK5/6, P40, or P63 immunostaining helps to identify the basal cells of bronchiolar adenoma (29).

Owing to the rarity of papillary adenomas of the lung, definitive histopathological prognostic factors have not been elucidated. With the exception of 10 patients who did not receive therapy, most reported patients underwent only surgical treatment (excluding one with osteosarcoma lung metastases who received chemotherapy). All patients had a favorable prognosis with no tumor recurrence after surgery. Thus, papillary adenomas of the lung are classified as benign tumors, implying that patient sex and tumor characteristics, such as size and location, typically do not associate with prognosis or recurrence. Moreover, apart from a low Ki67 index, these adenomas lack specific biological markers. One patient with pulmonary papillary adenoma developed acinar adenocarcinoma and micropapillary adenocarcinoma components in the same tumor after 2 years of follow-up (22). Another case report indicated that a pulmonary papillary adenoma underwent malignant transformation. In that case, a CT scan taken prior to biopsy had already identified a lung tumor of diameter 4 cm and brain metastasis; therefore, the diagnosis of pulmonary papillary adenoma in that case remains contentious (21). Two reported cases of papillary adenoma exhibited invasive growth behavior (9). The prognostic factors and long-term outcomes for papillary adenomas of the lung remain unclear, and further longer-term follow-up studies are needed. A small number of pulmonary papillary adenomas may have malignant or transformation potential and should be treated early after detection or through close follow-up. Complete surgical resection of papillary lung adenomas is curative and feasible. After diagnosis and treatment, excluding the aforementioned two cases and seven patients with no follow-up information, the remaining patients (36/45) had no recurrence and favorable prognosis. Based on these findings, regular CT examinations can be employed for preventive and follow-up monitoring.

In summary, a case of primary pulmonary papillary adenoma was reported. Surgical resection is the primary treatment option for such tumors. Careful examination of histological features and immunohistochemistry is essential for accurate diagnosis and prognostic evaluation. Additional studies on primary pulmonary papillary adenoma are necessary to validate previously reported findings.

Supplementary Material

(A) Tumor cells were positive for cytokeratin 7 (magnification, x100). (B) Elastic fiber staining demonstrated discontinuous or fractured elastic fibers in papillary adenoma tissue (magnification, x100).

Acknowledgements

Not applicable.

Funding

Funding: No funding was received.

Availability of data and materials

The data generated in the present study are included in the figures and/or tables of this article.

Authors' contributions

HTX and MQY conceived the study and confirm the authenticity of all the raw data. HTX conceptualized the present study. LQC, SMG and ZJW developed the methodology. LQC, MQY and HTX wrote the original manuscript, and reviewed and edited the manuscript. All authors read and approved the final manuscript.

Ethics approval and consent to participate

The research protocol was approved [approval no. LS (2021) 009] by the Institutional Review Board of The First Hospital of China Medical University (Shenyang, China). The patient provided written informed consent to participate in the present study.

Patient consent for publication

Written informed consent was obtained from the patient for the publication of the present case report and the accompanying associated images.

Competing interests

The authors declare that they have no competing interests.

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Chen L, Yang M, Gao S, Wang Z and Xu H: Papillary adenoma of the lung: A case report and literature review. Exp Ther Med 28: 369, 2024.
APA
Chen, L., Yang, M., Gao, S., Wang, Z., & Xu, H. (2024). Papillary adenoma of the lung: A case report and literature review. Experimental and Therapeutic Medicine, 28, 369. https://doi.org/10.3892/etm.2024.12658
MLA
Chen, L., Yang, M., Gao, S., Wang, Z., Xu, H."Papillary adenoma of the lung: A case report and literature review". Experimental and Therapeutic Medicine 28.3 (2024): 369.
Chicago
Chen, L., Yang, M., Gao, S., Wang, Z., Xu, H."Papillary adenoma of the lung: A case report and literature review". Experimental and Therapeutic Medicine 28, no. 3 (2024): 369. https://doi.org/10.3892/etm.2024.12658