Histologically benign inverted papilloma metastatic to the lung in a human immunodeficiency virus positive male

Introduction: Inverted Schneiderian papilloma is a histologically benign lesion of the nasal cavity and paranasal sinuses characterized by aggressive local invasion, a high recurrence rate following surgical resection, and an association with squamous cell carcinoma (SCC). We present a case of inverted papilloma with lung metastases in a human immunodeficiency virus (HIV) positive male, a finding not previously described. Case Presentation: A 49 year old HIV positive male with recurrent inverted papilloma of the right maxillary sinus presented with a new right lower lobe (RLL) pulmonary nodule. The patient complained of intermittent epistaxis, but denied cough, sputum production, hemoptysis, fever, chills, dyspnea on exertion, or chest pain. Past medical history revealed HIV positivity known since 1991 with a CD4 count of 350, coronary artery disease, insulin requiring diabetes mellitus, hepatitis C, and treated syphilis. Surgical history was significant for primary resection of a right maxillary inverted papilloma in 1991. Additional resections were required secondary to recurrences in May 1996 and March 1997 with embolization of the right internal maxillary and facial arteries secondary to involvement of the maxilla. All pathologic specimens revealed inverted papilloma with no evidence of SCC. Social history revealed a sixty pack year history of cigarette smoking, heavy alcohol use, and multiple sexual partners, including same sex partners. Medications on admission were indinavir, stavudine, lamivudine, insulin, and trimethoprim-sulfamethoxazole. Physical examination revealed an afebrile male, alert and in no respiratory distress. No skin lesions were noted. Head and neck exam was remarkable only for facial asymmetry and post surgical changes. There was no lymphadenopathy. Lungs were clear to auscultation bilaterally. The remainder of the examination was normal. Arterial blood gas, complete blood count, and serum chemistries were all normal. Chest roentgenogram revealed a 1.3 cm nodular noncalcified density in the RLL. Computed tomography (CT) of the chest revealed no significant adenopathy and a 1.2X1.3 cm soft tissue nodule in the lateral aspect of the RLL as well as four less than one cm nodules in the right upper and middle lobes. A tuberculin skin test was nonreactive. Pulmonary function tests revealed a mild restrictive defect with a forced expiratory volume in one second of 2.29 liters. Bronchoscopy revealed normal airways with no endobronchial lesions. Brushings and bronchoalveolar lavage from the right lateral basilar segment were negative for acid fast bacilli, fungi, and malignant cells. A CT-guided fine needle aspiration of the RLL nodule revealed no infectious or malignant process. Thoracotomy was performed with wedge resection of the RLL mass. Gross examination revealed a firm two cm lesion with central cavitation and possible necrosis. The pathologic diagnosis was papillomatosis of probable sinonasal origin. The lesion was described as consisting of tightly cohesive papillary and ball-like masses of small cytologically benign epithelial cells filling alveoli without destroying alveolar septa. These masses were histologically identical to the papillary fronds and islands in the sinonasal papilloma. DNA typing by in situ hybridization revealed human papilloma virus (HPV) types 6 and 11 in both sinonasal and lung specimens. The patient subsequently underwent radiation therapy for advanced recurrent sinonasal inverted papilloma and was referred for palliative radiation of the enlarging pulmonary nodules. Discussion: To our knowledge, this is the first reported case of inverted papilloma of the paranasal sinuses with metastasis to the lung. Inverted papilloma comprises 0.5%-4% of all primary nasal tumors and occurs primarily in the fifth and sixth decades with a male to female ratio of 3-4:1. The incidence of associated SCC and inverted papilloma is reported to be between 5% and 15%. In inverted papilloma, the proliferation of squamous epithelium extends into the mucosa, rather than producing the exophytic growth pattern seen in other bronchial papillomas. Juvenile tracheobronchial papilloma is thought to be secondary to aspiration of HPV in utero or during parturition. HPV-induced cervical lesions are more frequently associated with local recurrence and progression to malignancy in immunocompromised women with HIV than in immunocompetent controls. Our patient had a highly invasive sinonasal tumor without malignant transformation that required multiple resections and palliative radiation therapy. The RLL distribution of the lesions and the growth pattern in the alveoli suggest that the sinonasal papillomas may have spread to the lung parenchyma by inhalation or aspiration. We hypothesize that immunocompromised individuals with inverted papilloma have a higher propensity for more locally aggressive disease and for spread to the lung through inhalation or aspiration. Conclusions: In immunocompromised individuals with pulmonary nodules and a history of sinonasal inverted papilloma, the differential diagnoses should include not only metastatic or bronchogenic carcinoma, fungi, tuberculosis, and other infectious etiologies, but also airborne metastases of the primary upper airway papilloma.