Solitary glandular papilloma of the lung with molecular analysis: A case report and literature review.

BACKGROUND: Solitary papillomas of the lung are rare. One of their subtypes is glandular papilloma with only a very few cases described in the literature. We describe a case of pulmonary glandular papilloma with emphasis in its differential diagnosis and its molecular analysis. CASE DESCRIPTION: A 64-years old former smoker was incidentally found to have an endobronchial tumor of the right main bronchus. Microscopic and immunohistochemical findings revealed a glandular papilloma. EGFR, KRAS and BRAF V600E mutation analysis, as well as HPV detection analysis revealed no mutation or HPV infection. Detailed differential diagnosis and literature review are presented. CONCLUSION: Glandular papillomas of the lung are usually central, affecting older patients than squamous or mixed squamous cell and glandular papillomas. In previously reported cases, one glandular papilloma with KRAS mutation and another one with BRAF mutation have been reported. The present case harbored no mutation or HPV infection.

Systemic bevacizumab for recurrent respiratory papillomatosis: A national survey.

OBJECTIVES/HYPOTHESIS: Aggressive laryngeal, tracheal, and pulmonary papilloma is an extremely challenging clinical problem without proven treatment options. A recent German report documented promising results with systemic bevacizumab. The objective of this study is to report the initial experience of this novel treatment in the United States for recurrent respiratory papillomatosis (RRP). STUDY DESIGN: Cases series. METHODS: Electronic survey of the RRP Task Force of the American Society of Pediatric Otolaryngology, American Broncho-Esophagological Association, and physicians known to the authors to have used systemic bevacizumab for RRP. RESULTS: Eleven completed surveys were obtained. In three cases, systemic bevacizumab was considered clinically but not administered. Eight patients were treated with systemic bevacizumab, all for aggressive papillomatosis uncontrolled by surgical and adjuvant therapy, including seven of eight with pulmonary disease. Treatment dosing ranged from 5 to 10 mg/kg every 2 to 4 weeks, with all patients responding (7/8 partial response, 1/8 complete response). In four patients who had postbevacizumab chest imaging, three demonstrated improvement of disease and one stabilization. Treatment interval could be lengthened in seven patients and clinical response maintained. One patient with long-standing pulmonary disease (>10 years) was diagnosed with malignant transformation while on treatment, and bevacizumab was discontinued in lieu of other chemotherapeutic agents. All other patients continue on systemic bevacizumab with minimal complications (hemoptysis n = 1, proteinuria n = 1). CONCLUSIONS: Systemic bevacizumab appears to have significant promise in the most treatment-resistant and aggressive forms of papillomatosis with a low complication profile. These results suggest bevacizumab should be studied in a formal clinical trial for RRP. LEVEL OF EVIDENCE: 4. Laryngoscope, 127:2225-2229, 2017.

Glandular papilloma of the lung with malignant transformation / 영남의대학술지

Glandular papilloma of the lung is one of three histologic types of solitary endobronchial papillomas. It is known as an uncommon benign neoplasm. No malignant glandular papillomas have been reported. Herein, the first case of granular papilloma with malignant transformation is reported. A 74-year-old man with huge right lung mass extended upper and lower lobe was admitted to the hospital complaining of progressive cough and dyspnea. An open lung biopsy was performed. Microscopically, the tumor showed papillary growth pattern with thick fibrovascular cores. The stroma of the fibrovascular cores shown the infiltration of lymphoplasmacytic cells and proliferation of capillaries. The epithelial cells surrounding the papillary fronds were cilliated columnar cells with focal cellar atypia, and frequent mitoses. Suspicious pleural invasion foci were identified. The Ki-67 labeling index was about 24.3% and p53 labeling index was about 31.7%. Glandular papilloma is known as a benign neoplasm, which is lack of atypia and mitosis. In present case, there were several indications of malignant transformation, such as cellular atypia, frequent mitosis, architectural distortion, and pleural invasion. Pathologists must be aware that glandular papilloma can have a changes of malignant transformation. Further studies about disease behavior and molecular characteristics are needed.

Glandular papilloma of the lung with malignant transformation / 영남의대학술지

Glandular papilloma of the lung is one of three histologic types of solitary endobronchial papillomas. It is known as an uncommon benign neoplasm. No malignant glandular papillomas have been reported. Herein, the first case of granular papilloma with malignant transformation is reported. A 74-year-old man with huge right lung mass extended upper and lower lobe was admitted to the hospital complaining of progressive cough and dyspnea. An open lung biopsy was performed. Microscopically, the tumor showed papillary growth pattern with thick fibrovascular cores. The stroma of the fibrovascular cores shown the infiltration of lymphoplasmacytic cells and proliferation of capillaries. The epithelial cells surrounding the papillary fronds were cilliated columnar cells with focal cellar atypia, and frequent mitoses. Suspicious pleural invasion foci were identified. The Ki-67 labeling index was about 24.3% and p53 labeling index was about 31.7%. Glandular papilloma is known as a benign neoplasm, which is lack of atypia and mitosis. In present case, there were several indications of malignant transformation, such as cellular atypia, frequent mitosis, architectural distortion, and pleural invasion. Pathologists must be aware that glandular papilloma can have a changes of malignant transformation. Further studies about disease behavior and molecular characteristics are needed.

Mixed squamous cell and glandular papilloma of the lung resembling early adenocarcinoma: A case report.

INTRODUCTION: An extremely rare case of mixed squamous cell and glandular papilloma of the lung is reported. The correlation between the radiological and the pathological features as well as the clinical pitfall in making a diagnosis is discussed. PRESENTATION OF CASE: An asymptomatic 68-year-old female with a cigarette smoking habit presented with a small nodule in her peripheral lung. A wedge resection was performed though it failed on-site diagnosis which was instead obtained following pathological scrutiny. The postsurgical course was excellent with no recurrence of disease. DISCUSSION: A small ground glass nodule gradually enlarged and transformed to a partially solid nodule a year and a half later. This transformation falsely made us suspect an early adenocarcinoma development. Eventually, the extremely rare subtype of pulmonary papilloma, with biphasic glandular and squamous cells, had been demonstrated to obstruct the peripheral bronchiole; and the adjoining alveoli had filled with a large volume of mucus. These pathological features seemed to have constituted the inner solid portion and the marginal ground glass portion respectively in the CT images, mimicking invasive lepidic adenocarcinoma. CONCLUSION: Both pre- and intra-operative diagnoses are difficult mainly because of the rareness of the disease, however, mixed squamous cell and glandular papilloma may be considered in case the presence of primary adenocarcinoma is not validated.

Xenograft model for therapeutic drug testing in recurrent respiratory papillomatosis.

OBJECTIVE: Identifying effective treatment for papillomatosis is limited by a lack of animal models, and there is currently no preclinical model for testing potential therapeutic agents. We hypothesized that xenografting of papilloma may facilitate in vivo drug testing to identify novel treatment options. METHODS: A biopsy of fresh tracheal papilloma was xenografted into a NOD-scid-IL2Rgamma(null) (NSG) mouse. RESULTS: The xenograft began growing after 5 weeks and was serially passaged over multiple generations. Each generation showed a consistent log-growth pattern, and in all xenografts, the presence of the human papillomavirus (HPV) genome was confirmed by polymerase chain reaction (PCR). Histopathologic analysis demonstrated that the squamous architecture of the original papilloma was maintained in each generation. In vivo drug testing with bevacizumab (5 mg/kg i.p. twice weekly for 3 weeks) showed a dramatic therapeutic response compared to saline control. CONCLUSION: We report here the first successful case of serial xenografting of a tracheal papilloma in vivo with a therapeutic response observed with drug testing. In severely immunocompromised mice, the HPV genome and squamous differentiation of the papilloma can be maintained for multiple generations. This is a feasible approach to identify therapeutic agents in the treatment of recurrent respiratory papillomatosis.