[46] Recurrent Respiratory Papillomatosis with Malignant Transformation in Lungs: A Retrospective Longitudinal HPV Study

M Tretiakova, J Taxy. University of Chicago, Chicago

Background: Recurrent respiratory papillomatosis (RRP) is etiologically associated with vertical transmission during vaginal delivery from an HPV infected mother. Even though cervicovaginal HPV infection is extremely common, RRP occurs in only 4.3 per 100,000 children. Approximately 1-2% of the patients with an early onset of RRP eventually develop laryngeal squamous cell carcinoma (SCC); pulmonary SCC is even rarer. The malignant transformation of RRP to SCC has been linked to various HPV strains and may result from the spontaneous loss of HPV expression. Here we study HPV presence in the early, intermediate and terminal stages of RRP with extensive pulmonary involvement and development of SCC.
Design: Four laryngeal biopsies, obtained at early, intermediate and late stages of disease, as well as autopsy sections were studied by in-situ hybridization with low-risk (types 6/11) and high-risk (types 16/18) HPV DNA probes using Ventana kit on BenchMark XT autostainer with appropriate positive and negative controls. Autopsy was restricted to the chest.
Results: A 13-year-old male underwent 14 excisions of laryngeal papillomas since the age of 2. The lesions caused airway obstruction, frequently complicated by pneumonias and exacerbations of asthma. The patient died from respiratory failure and suppurative bronchopneumonia. Autopsy findings were remarkable for multiple squamous papillomas with viral change and dysplasia in the trachea and both main-stem bronchi. Some papillomas showed in-situ and invasive, focally necrotizing squamous cell carcinoma with vascular invasion and hilar lymph node metastasis. Lung parenchyma uninvolved with tumor demonstrated severe acute bronchopneumonia with microabscess formation. HPV assay showed consistent diffuse strong reaction (>400 viral copies) with low-risk HPV probes in all 4 RRP biopsies, as well as the in-situ and invasive SCC. Low-copy numbers (10-50) of high-risk HPV were detected only in 2 biopsies at the intermediate stage of RRP.
Conclusions: This is a rare instance of early onset RRP with documented progression to dysplastic papillomas, pulmonary SCC in situ and invasive SCC with local metastases. The rarity of RRP, presumed to be acquired during vaginal delivery, is not congruent with the common occurrence of low-risk HPV in the female genital tract, where these viruses are seldom associated with malignant transformation. The HPV typing in this case supports earlier similar reports and suggests an important role of low-risk HPV strains (6/11) in the malignant transformation of RRP in the lower respiratory tract.
Category: Autopsy

Wednesday, March 24, 2010 9:30 AM

Poster Session V # 8, Wednesday Morning


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