Pulmonary papillomas are benign papillary tumors characterized by a fibrovascular core covered by an epithelium. These tumors are usually unique and rarely multiple. They can be proximal or peripheral. Many mimickers may be suspected due to their radiologic appearance but microscopic examination is the basis of making a confirmed diagnosis. Pulmonary papillomas consist of mainly 3 subtypes:
These tumors have a good prognosis with no recurrences in case of complete resection. Malignant transformation is rare and can be only observed in squamous cell papilloma.
Some causes or conditions have been reported in connection with pulmonary papillomas in the literature:
Pulmonary papillomas are rare accounting for less than 1% of all lung neoplasms. Squamous papillomas are the most common subtype followed by glandular papillomas which represent less than 20% of all solitary papillomas. Mixed papillomas are rare with less than 20 reported cases in the English literature. These lesions are more common in men than in women and patients are in their sixth decade of life [4] .
Papillomatosis involving the bronchial tree or lung parenchyma is commonly related to laryngotracheal papillomatosis where involvement is typically in the region of the larynx and subglottic area.
Pulmonary papillomatosis occurs primarily in children. It is usually the result of a vaginal delivery of a woman infected with HPV type 6 or 11. However, only a small fraction of HPV exposed individuals develops pulmonary papillomatosis. Genetic factors likely play a role in susceptibility.
Gross features consist of polypoid, tan-white and friable lesions. They range from 0.7 to 9 cm with a median size of 1.5 cm. These lesions protrude into airway lumens. Distal and sometimes proximal airways may be bronchiectatic. The distal lung may show secondary obstructive changes. Most of the lesions are histologically benign epithelial proliferations that develop at junctions of ciliated and squamous epithelium.
Microscopic findings vary according to the papilloma's subtype:
Clinical symptoms are non-specific.[1] These tumors may be asymptomatic and discovered, incidentally in 25% of the cases.
In the other cases, the most frequent symptoms reported consist of obstructive symptoms such as a cough or wheezing. The lesions can also produce hoarseness, stridor, and airway compromise. Hemoptysis may also reveal papilloma lesions, but when facing Hemoptysis in a patient who smokes, the physician has to rule out lung cancer.[8]
High-resolution CT findings consist of mainly endobronchial plaques, nodules or airway thickening in addition to air-trapping and bronchiectasis. Lung involvement with papillomatosis may show diffuse, poorly defined parenchymal opacities.[9][10] Papillomas are usually central and endobronchial or in rare cases peripheral and endobronchial.
Endoscopy may show endobronchial protuberances or atelectasis. Care should be taken when performing biopsy of laryngeal and central endobronchial lesions because of risk of uncontrolled bleeding and airway obstruction.
Pulmonary papillomas are removed by surgical resection or endoscopic removal. Other techniques include laryngeal micro-debrider therapy, laser, lesion injection of the antiviral drug cidofovir, photodynamic therapy, and subcutaneous interferon-alpha therapy. Surgically removed solitary papillomas do not recur, but recurrences are observed in approximately 20% of patients treated with endoscopic removal. The prognosis of completely surgically removed lesions is good. Rare recurrences are observed in incompletely removed lesions. Malignant transformation is rarely observed in squamous cell papillomas.[1][11]
Precautions should be taken with laser therapy to prevent aerosolization of HPV DNA particles with potential inhalation by medical staff.
Based on the clinical findings, the major differential diagnoses consist in carcinoid tumor and squamous cell carcinoma. Microscopic diagnosis is mandatory to rule out both diagnoses. Based on the microscopic features, the major pitfalls of squamous cell papilloma are represented by inflammatory polyp and squamous cell carcinoma. Inflammatory polyp lacks a true papillary structure in spite of the possible presence of squamous metaplasia. Squamous cell carcinoma is a malignant epithelial tumor characterized by nests of tumor cells centered by squamous pearls. Some dyskeratotic cells are also noticed. When the keratinization is not obvious, the immunohistochemical studies, especially the P63 and P40 antibodies, are useful to keep the diagnosis.
The differential diagnoses of glandular papilloma include primary and metastatic adenocarcinoma and other adenomas. Carcinomas display malignant feature consisting of cytological atypia and the invasion of the basal lamina and lack basal, ciliated and mucinous cells which are characteristic in a glandular papilloma.[6][12] Besides, diagnostic features of adenocarcinomas consist of glandular structures and/or mucus secretion. Both characteristics are absent in pulmonary papillomas.
Pulmonary papillomas are benign lesions with a good prognosis when they are completely removed. They can rarely recur when they are incompletely removed. Rare malignant transformations are possible in squamous cell papillomas. HPV-associated papillomas (subtypes 16, 18, and 31) are recognized as having malignant potential. Laryngotracheal papillomatosis can spread into the lower respiratory tract in up to 5% of the cases. Bronchial and alveolar involvement may be related to prior treatments or reflux disease.
Pulmonary papillomas are rare lesions that are best managed by an interprofessional team including pulmonologist, surgeon, otolaryngologist and nurses. These lesions should be excised surgically to prevent a recurrence. There is a very small risk of malignancy and hence follow up with serial imaging studies is recommended.
Most patients have an excellent outcome.
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