Pulmonary Papilloma

Continuing Education Activity

Pulmonary papillomas are benign papillary tumors characterized by a fibrovascular core covered by an epithelium. These tumors are rarely multiple. They can be proximal or peripheral. Many mimickers may be suspected as papillomas due to their radiologic appearance but microscopic examination is the basis for making a confirmed diagnosis. This activity describes the presentation of pulmonary papillomas and highlights the role of the interprofessional team in their diagnosis and management.


  • Identify the etiology of pulmonary papilloma.
  • Review the presentation of a pulmonary papilloma.
  • Outline the treatment and management options available for pulmonary papilloma.
  • Explain the importance of improving coordination of care among interprofessional team members to improve outcomes for patients diagnosed with a pulmonary papilloma.


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:

  • Squamous cell papillomas 
  • Glandular papillomas
  • Mixed papillomas[1]

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:

  • Human Papilloma Virus (HPV) has a key role in squamous cell papilloma. Serotypes 6 and 11 are frequently reported in simple papillomas while subtypes 16, 18 and 31 play a key role in the malignant transformation. Malignant transformation is very rare. It occurs in squamous cell papilloma, and TP53 mutations have been frequently implicated.
  • Smoking has been implicated in squamous cell papilloma without real proof of its etiological role.
  • Rare conditions have been described and consist of mainly abscesses and eventually bronchiectasis, which may enhance the development of squamous cell papillomas.[2][3]


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:

  • Squamous cell papillomas feature arborizing loose fibrovascular cores covered by stratified squamous epithelium. Exophytic tumors have orderly epithelial maturation and often keratinized cells. Acanthosis, parakeratosis are common. A degeneration into a squamous cell carcinoma is very rare but can occur in association with TP53 mutations. Less than 25% of solitary papillomas present typical features of HPV infection including binucleate forms, wrinkled nuclei, and perinuclear haloes. Occasional dyskeratotic cells, large atypical cells and mitotic figures above the basal layer can be seen. Dysplasia is graded according to the current World Health Organization  (WHO) classification into discrete, mild and severe dysplasia. Parenchymal involvement can feature either solid intra-alveolar nests of cytologically bland non-keratinizing cells or large cysts lined by similar cells.
  • Glandular papillomas are characterized by a fibrovascular core covered by a pseudostratified or stratified columnar epithelium. The latter can form micro-papillary tufts. Uniform columnar cells have eosinophilic cytoplasm and round regular nuclei. The cytoplasm can be clear but nuclear atypia, necrosis and abnormal mitoses are absent.
  • Mixed squamous cell and glandular papilloma is characterized by a mix of both features with a majority of glandular epithelium and interspersed squamous islands.[5][6][7][4]. Glandular atypia and necrosis are never present, but squamous atypia may be observed in some cases.

History and Physical

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.

Treatment / Management

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.

Differential Diagnosis

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.

Pearls and Other Issues

  • Pulmonary papillomas are very rare lesions of the lung that can mimic, when based on the radiologic features, a malignant disease. This makes the microscopic exam mandatory to rule out the multiple mimickers and to keep the final diagnosis.
  • Radiologic findings consist mainly is a proximal polypoid mass.
  • Based on the radiologic investigation, the most relevant mimickers consist of carcinoid tumor and squamous cell carcinoma.
  • Malignant transformation accounts for less than 2% of the cases and is possible only in squamous cell papillomas.
  • Papillomavirus plays a key role especially in squamous cell papilloma

Enhancing Healthcare Team Outcomes

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.

Article Details

Article Author

Mouna Mlika

Article Author

Fatima Anjum

Article Editor:

Faouzi El Mezni


12/4/2020 2:11:15 PM

PubMed Link:

Pulmonary Papilloma



Brady P,McCreary C,O'Halloran KD,Gallagher C, Squamous Papilloma Causing Airway Obstruction During Conscious Sedation. Anesthesia progress. Fall 2017     [PubMed PMID: 28858548]


Miyoshi R,Menju T,Yoshizawa A,Date H, Expression of p16{sup}Ink4a{/sup} in mixed squamous cell and glandular papilloma of the lung. Pathology international. 2017 Jun     [PubMed PMID: 28470939]


Kim Y,Pierce CM,Robinson LA, Impact of viral presence in tumor on gene expression in non-small cell lung cancer. BMC cancer. 2018 Aug 22     [PubMed PMID: 30134863]


Yabuki K,Matsuyama A,Obara K,Takenaka M,Tanaka F,Nakatani Y,Hisaoka M, A unique case of a huge mixed squamous cell and glandular papilloma of non-endobronchial origin with a peripheral growth. Respiratory medicine case reports. 2018     [PubMed PMID: 29977775]


Histological typing of lung tumours. Tumori. 1981 Aug     [PubMed PMID: 6274068]


Fortes HR,von Ranke FM,Escuissato DL,Araujo Neto CA,Zanetti G,Hochhegger B,Souza CA,Marchiori E, Recurrent respiratory papillomatosis: A state-of-the-art review. Respiratory medicine. 2017 May     [PubMed PMID: 28427542]


Miyai K,Takeo H,Nakayama T,Obara K,Aida S,Sato K,Matsukuma S, Invasive form of ciliated muconodular papillary tumor of the lung: A case report and review of the literature. Pathology international. 2018 Sep     [PubMed PMID: 30043539]


Mitsumoto GL,Bernardi FDC,Paes JF,Villa LL,Mello B,Pozzan G, Juvenile-onset recurrent respiratory papillomatosis with pulmonary involvement and carcinomatous transformation. Autopsy     [PubMed PMID: 30101139]


Li YL,Wu MZ,Chai XM,Xu J, [CT findings of juvenile laryngeal papilloma spreading in bronchia and lung]. Lin chuang er bi yan hou tou jing wai ke za zhi = Journal of clinical otorhinolaryngology, head, and neck surgery. 2018 May     [PubMed PMID: 29873215]


Kozu Y,Maniwa T,Ohde Y,Nakajima T, A solitary mixed squamous cell and glandular papilloma of the lung. Annals of thoracic and cardiovascular surgery : official journal of the Association of Thoracic and Cardiovascular Surgeons of Asia. 2014     [PubMed PMID: 23995347]


Feng AN,Wu HY,Zhou Q,Sun Q,Fan XS,Zhang YF,Meng FQ, Solitary endobronchial papillomas with false impression of malignant transformation: report of two cases and review of the literature. International journal of clinical and experimental pathology. 2015     [PubMed PMID: 26339442]


Chuang HW,Liao JB,Chang HC,Wang JS,Lin SL,Hsieh PP, Ciliated muconodular papillary tumor of the lung: a newly defined peripheral pulmonary tumor with conspicuous mucin pool mimicking colloid adenocarcinoma: a case report and review of literature. Pathology international. 2014 Jul     [PubMed PMID: 25047506]