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.
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).
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.