INTRODUCTION: Recurrent respiratory papillomatosis (RRP) is a disease caused by the human papilloma virus (HPV). It is characterized by exophytic lesions in the respiratory tract, most often involving the larynx. Extralaryngeal spread occurs in 30% of children and 16% of adults, with distal pulmonary involvement in less than 5%. The following case describes a novel method of diagnosing pulmonary involvement of RRP by using a specific HPV ribonucleic acid (RNA) probe.
CASE PRESENTATION: A 24-year-old male with a history of laryngeal papillomatosis was referred by otolaryngology for fatigue, increasing sputum production, and worsening infiltrates on chest computed tomography (CT) (Fig 1). Patient was healthy aside from laryngeal papillomatosis, diagnosed at age one via tissue biopsy. Treatment history included intralesional cidofovir and intravenous interferon. Past surgical history was significant for over 60 procedures, including multiple laser surgeries of the larynx and trachea, reconstructive surgery of the oropharynx, and multiple tracheostomies. Bronchoscopy was performed to confirm parenchymal involvement with HPV and to consider therapy with intravenous cidofovir. Bronchoscopy revealed two tracheal lesions and yellow mucus in the left lower lobe (LLL). The family declined biopsy of the trachea and distal pulmonary tree, fearing increased spread of HPV. Bronchoalveolar lavage in the LLL revealed an alveolitis consisting of 81% neutrophils. An RNA probe performed on lavage fluid was positive for HPV. The test is a signal amplified hybridization microplate assay using chemiluminescence detection. An RNA probe cocktail forms a hybrid with HPV DNA, an antibody to the DNA/RNA hybrid extracts them, and the enzyme based chemiluminescence detects the specific type of HPV. Respiratory cultures were positive for streptococcus pneumonia and haemophilus influenza. Antibiotic treatment cleared the large infiltrate on chest CT and only a smaller lesion, the suspected HPV, remains (Fig 2). Treatment of pulmonary HPV is rarely curative but clearly slows the progression of disease.
DISCUSSIONS: RRP is a benign laryngeal tumor that occurs in 4.3 per 100,000 children. It has a bimodal distribution, occurring between ages 2-4 years and 20-40 years. It is caused by HPV types 6 and 11. Pulmonary parenchymal involvement of HPV occurs in less than 5% of patients. Type 11 is more virulent, and is associated with a greater risk of distal spread. RRP occurs at the junction between the ciliated (respiratory) and squamous epithelium. Trauma causes squamous metaplasia of the respiratory epithelium, and this explains recurrence in injured areas such as biopsy sites. Pulmonary involvement results in pneumatoceles, cavitary empyema, atelectasis and recurrent pneumonias. Malignant transformation may occur in 3% of cases. Pulmonary parenchymal HPV should be suspected in symptomatic patients with known RRP who have radiographic evidence of pulmonary lesions. Diagnosis of pulmonary HPV includes tissue culture, PCR, or an RNA probe. The RNA probe is FDA approved for cervical specimens, and use on other specimens, while technically accurate, remains experimental.
CONCLUSION: To our knowledge, use of an RNA probe assay to diagnose pulmonary involvement in RRP has not been previously described in the literature. Less tissue injury is caused by lavage, as compared to a biopsy or cytobrush, and this may limit further spread of the virus. We contend this test is a less invasive and non-traumatic diagnostic tool. This assay can be a valuable aid in confirming the diagnosis of pulmonary HPV.
DISCLOSURE: Erik Osborn, None.