Pulmonary involvement in a case of juvenile-onset recurrent respiratory papillomatosis. (Original Article).

Abstract

Juvenile-onset recurrent respiratory papillomatosis is primarily a disease of children and adolescents. Although most patients experience spontaneous regression at a later age, some patients continue to be affected throughout their lives. We report the case of a 35-year-old woman with a 33-year history of juvenile-onset recurrent respiratory papillomatosis who developed pulmonary dissemination with malignant transformation. Malignant transformation is the most feared sequela of pulmonary dissemination, and it should be addressed aggressively. If treated promptly, the patient can enjoy prolonged survival. Computed tomography is superior to plain radiography for detecting and evaluating the extent of disease.

Introduction

Juvenile-onset recurrent respiratory papillomatosis is caused by human papillomavirus (HPV) subtypes 6 and 11; HPV-11 papillomatosis has a more aggressive course. (1,2) This disease, which has been reported to be the most common benign neoplasm of the larynx in children, is characterized by the presence of exophytic lesions of the airway. (3) It is usually diagnosed when patients reach the age of 3 years, and it is correlated with the epidemiologic triad of the firstborn, vaginally delivered child of a teenage mother. (4) Although it is usually benign, distal tracheal and pulmonary spread has been reported in 5% of patients. (5) Spread to the tracheobronchial tree has been associated with a previous tracheotomy in more than 95% of cases. (6) When pulmonary spread occurs, the disease becomes highly morbid and life-threatening, and there is a possibility of malignant transformation. (3) Treatments for respiratory papillomatosis include carbon dioxide ([CO.sub.2]) laser laryngoscopy, photodynamic therapy, alpha- interferon, indole-3-carbinol, and more recently, cidofovir. (3,7)

In this article, we describe the clinical and radiologic features of a patient with a 33-year history of juvenile-onset recurrent respiratory papillomatosis who developed pulmonary dissemination with malignant transformation.

Case report

A 35-year-old black woman came to us with a long history of juvenile-onset recurrent respiratory papillomatosis, which was first discovered on her larynx when she was 2 years of age. She was her mother's third child; her mother was 27 years old at the time. None of the patient's siblings had any history of papillomatosis.

After being diagnosed with papillomatosis, the patient underwent multiple surgical debridements every 1 to 3 months. When she was roughly 10 years old, she began undergoing [CO.sub.2] laser ablation via direct laryngoscopy. Despite treatment, the papillomas spread to the tracheobronchial tree (figure 1). At the age of 19 years, the patient took part in a yearlong trial of interferon (she had been in the active-treatment group rather than the placebo-control group). Her papillomatosis had regressed while she was taking interferon, but it quickly worsened once she stopped. She had discontinued interferon primarily because it had elevated her liver transaminase levels. Thereafter, she continued to undergo serial laser ablations approximately once a month (figure 1). On several occasions, her papillomas were noted to extend as far superiorly as the nasopharynx.

At the age of 30 years, the patient developed cystic changes in the right upper lobe of her lung. She underwent a right upper lobectomy. Pathology revealed the presence of small foci of squamous cell carcinoma, which were found to represent malignant transformation of the papillomas.

At the age of 32 years, the patient gave birth to a girl who thus far has not developed papillomatosis. Throughout her pregnancy, the patient continued to undergo regular CO2 laser ablations via direct laryngoscopy and bronchoscopy while under general anesthesia. Her airway was not noted to be a troublesome factor during her pregnancy or delivery.

During the 3 years since then, the patient underwent serial computed tomography (CT) scans, which showed that her multiple bilateral nodular lesions and cystic changes had worsened (figure 2). The papillomas in her larynx were biopsied several times, and they revealed the presence of mild-to-moderate dysplasia. The patient is currently undergoing [CO.sub.2] laser ablation of the larynx and trachea every 2 weeks. For several years, she has not been able to speak above a breathy whisper. At each ablation procedure, the patient receives 20 mg of intravenous dexamethasone. Yet despite multiple steroid injections, her adrenocorticotrophic hormone (ACTH) and cortisol levels have been found to be normal. Overall, the patient has undergone upwards of 1,000 surgical procedures. She has never undergone a tracheotomy.

Discussion

Juvenile-onset recurrent respiratory papillomatosis is primarily a disease of children and adolescents. Although most patients experience spontaneous regression at a later age, some patients continue to be affected throughout their lives. The case of our patient represents a dramatic and severe example of lifelong disease. She has experienced most the possible sequelae of papillomatosis in its most aggressive form.

A small subset of patients with juvenile-onset recurrent respiratory papillomatosis develops tracheobronchial spread. Although most who manifest this ominous finding have previously undergone a tracheotomy, our patient demonstrates that such is not the absolute rule. The disseminated disease in our patient might have been a result of the formation of embolic papillomatous particles secondary to the multitude of surgical interventions she underwent, or they might have been caused by a biologically more aggressive infection.

Radiology has a role in the detection and surveillance of pulmonary disease in patients with recurrent respiratory papillomatosis. In patients who have undergone a tracheotomy or who have required multiple surgeries, the clinical suspicion for pulmonary spread should be high, and it is reasonable to obtain routine chest x-rays. CT is superior to radiography for detecting and evaluating the extent of disease, and therefore it should be ordered whenever x-rays detect possible lesions or when they are equivocal in light of clinical evidence. Characteristic CT findings include nodular lesions and cystic changes.

Although tracheobronchial spread in patients with recurrent respiratory papillomatosis is associated with increased morbidity, it is possible for patients to enjoy a certain amount of normalcy when the disease is aggressively monitored and controlled. The most feared sequela of pulmonary dissemination is malignant transformation, and it should be addressed aggressively. Patients who are treated promptly can enjoy prolonged survival. It has been 4 years since our patient underwent her lobectomy.

Although our patient has been treated for 33 years and had tracheobronchial spread diagnosed 5 years ago, she continues to have a voice, she is able to effectively communicate and hold a job, and she has given birth to a healthy child. She has never experienced acute airway distress or required a tracheotomy, and she has arguably enjoyed a reasonable quality of life. Future considerations for her care include the administration of cidofovir, either intralesionally or systemically, but for the foreseeable future, she will continue to undergo periodic laser ablations.

References

(1.) Rimell F, Maisel R, Dayton V. In situ hybridization and laryngeal papillomas. Ann Otol Rhinol Laryngol 1992;101(Pt 1):119-26.

(2.) Rabah R, Lancaster WD, Thomas R, Gregoire L. Human papillomavirus- 11-associated recurrent respiratory papillomatosis is more aggressive than human papillomavirus-6-associated disease. Pediatr Dev Pathol 2001;4:68-72.

(3.) Derkay CS, Darrow DH. Recurrent respiratory papillomatosis of the larynx: Current diagnosis and treatment. Otolaryngol Clin North Am 2000;33: 1127-42.

(4.) Kashima HK, Shah F, Lyles A, et al. A comparison of risk factors in juvenile-onset and adult-onset recurrent respiratory papillomatosis. Laryngoscope 1992;102:9-13.

(5.) Derkay CS. Task force on recurrent respiratory papillomas. A preliminary report. Arch Otolaryngol Head Neck Surg 1995;121:1386-91.

(6.) Cole RR, Meyer CM III, Cotton RT. Tracheotomy in children with recurrent respiratory papillomatosis. Head Neck 1989;11: 226-30.

(7.) Dancey DR, Chamberlain DW, Krajden M, et al. Successful treatment of juvenile laryngeal papillomatosis-related multicystic lung disease with cidofovir: A case report and review of the literature. Chest 2000; 118:1210-14.

From the Department of Otolaryngology, Children's Hospital of Michigan, Wayne State University, Detroit.

Reprint requests: Shawn P. McKay, MD, Department of Otolaryngology, Wayne State University, 5E UHC, 4201 St. Antoine, Detroit, MI 48201. Phone: [phone]; fax: [phone]; e-mail:[e-mail]