Treatment strategies for inverted papillomas with intracranial or intraorbital involvement

Objective Sinonasal inverted papillomas are challenging benign tumours of the nasal cavity because of their high recurrence rates and the lifetime malignant transformation risk of 10 per cent as well as their locally aggressive behaviour. This study aimed to describe treatment strategies for inverted papillomas with intracranial or intraorbital involvement. Method This was a prospective case series study of 18 patients with inverted papilloma with intracranial or intraorbital involvement. Patient demographic data, imaging, pathology, surgical technique and recurrences were recorded prospectively over a period of seven years. Results A total of 83 per cent of the patients in this study had been previously operated on, consisting of 8 cases with intracranial involvement, 1 case with intraorbital involvement and 9 with both. During follow up with a medium of 37 months (range, 13–115 months) there were two recurrences. Conclusion It was postulated that intracranial or intraorbital involvement observed in this series was the result of multiple revisions. However, using accurate imaging protocols and the pedicle-oriented approach for tumour excision, complete tumour removal was achieved in most cases with minimal post-operative complications.

Establishment and genetic characterization of cell lines derived from proliferating nasal polyps and sinonasal inverted papillomas

To better understand the pathogenesis of nasal polyps (NPs) and sinonasal inverted papillomas (SIPs), we aimed to establish cell lines from fresh tissues of NPs and SIPs and characterize them. Primary cell cultures were obtained from two NP tissues (NP2 and NP3) and one SIP tissue (IP4). All the cells were polygonal in shape, expressed cytokeratin 14, and had normal diploid chromosome status. HPV58 DNA was detected in NP3. To obtain immortal primary cells, NP2 and IP4 cells were transduced with a combination of mutant CDK4, cyclinD1 and TERT. These cells were thereafter named NP2/K4DT and IP4/K4DT, respectively. HPV58-positive NP3 cells were transduced with TERT alone, the resulting cells named NP3/T. Phenotypic and genotypic identity of original tissues and derived cells was investigated. All the cell cultures with transgenes were confirmed to be derived from their parental cells and primary tumor tissues by analysis of short tandem repeats (STR) and maintained in vitro growth, genetic profiles and gene expression characteristics of the primary cells. These virtually immortalized cells, as well as the primary cells, have potential as in vitro models for studying the pathogenesis of NPs and SIPs and for preclinical study to develop new therapeutic agents.

A Short-Term Efficacy of Anlotinib in the Treatment of Refractory Nasopharyngeal Inverted Papilloma: A Case Report

To our knowledge, no studies have reported the use of anlotinib in the treatment of locally cancerous nasopharyngeal inverted papillomas that cannot be operated on or treated with radiotherapy. Here, we report a case of a 53-year-old woman diagnosed with recurrent local canceration of nasopharynx papilloma. Magnetic resonance imaging (MRI) showed that the right parapharyngeal space, nasopharynx, and ethmoid sinus were changed, and recurrence was considered. There was no indication for surgery or radiotherapy. Imaging showed that the tumor had obvious enhancement and abundant blood vessels. Immunohistochemistry showed that vascular endothelial growth factor receptor (VEGFR) 2 expression was positive in papilloma tissue and in local canceration tissue of the papilloma. After the patient’s consent was obtained, anlotinib treatment was started in May and ended in November 2019. Then, the patient was treated with intensity-modulated radiotherapy (IMRT) with planning gross tumor volume (PGTV) 66 Gy, planning clinical tumor volume 1 (PCTV1) 60 Gy, and planning clinical tumor volume 2 (PCTV2) 54 Gy in 33 fractions. No disease recurrence was reported at 4 months after radiotherapy.

HPV-Associated Benign Squamous Cell Papillomas in the Upper Aero-Digestive Tract and Their Malignant Potential

Squamous cell papilloma (SCP) in the upper aero-digestive tract is a rare disease entity with bimodal age presentation both at childhood and in adults. It originates from stratified squamous and/or respiratory epithelium. Traditionally, SCPs have been linked to chemical or mechanical irritation but, since the 1980s, they have also been associated with human papillomavirus (HPV) infection. Approximately 30% of the head and neck SCPs are associated with HPV infection, with this association being highest for laryngeal papillomas (76–94%), followed by oral (27–48%), sinonasal (25–40%), and oropharyngeal papillomas (6–7%). There is, however, a wide variation in HPV prevalence, the highest being in esophageal SCPs (11–57%). HPV6 and HPV11 are the two main HPV genotypes present, but these are also high-risk HPVs as they are infrequently detected. Some 20% of the oral and oropharyngeal papillomas also contain cutaneous HPV genotypes. Despite their benign morphology, some SCPs tend to recur and even undergo malignant transformation. The highest malignant potential is associated with sinonasal inverted papillomas (7–11%). This review discusses the evidence regarding HPV etiology of benign SCPs in the upper aero-digestive tract and their HPV-related malignant transformation. In addition, studies on HPV exposure at an early age are discussed, as are the animal models shedding light on HPV transmission, viral latency, and its reactivation.

Localization and genotyping of canine papillomavirus in canine inverted papillomas

Numerous canine papillomaviruses (CPVs) have been identified (CPV1–23). CPV1, 2, and 6 have been associated with inverted papillomas (IPs). We retrieved 19 IPs from 3 histopathology archives, and evaluated and scored koilocytes, inclusion bodies, giant keratohyalin granules, cytoplasmic pallor, ballooning degeneration, and parakeratosis. IHC targeting major capsid proteins of PV was performed, and CPV genotyping was achieved by PCR testing. Tissue localization of CPV DNA and RNA was studied by chromogenic and RNAscope in situ hybridization (DNA-CISH, RNA-ISH, respectively). IPs were localized to the limbs (50%), trunk (30%), and head (20%), mainly as single nodules (16 of 19). In 15 of 19 cases, immunopositivity was detected within the nuclei in corneal and subcorneal epidermal layers. PCR revealed CPV1 in 11 IPs and CPV2 DNA in 3 IPs. Overall, 14 of 17 cases were positive by both DNA-CISH and RNA-ISH, in accord with PCR results. A histologic score >5 was always obtained in cases in which the viral etiology was demonstrated by IHC, DNA-CISH, and RNA-ISH. IHC and molecular approaches were useful to ascertain the viral etiology of IPs. Although IHC is the first choice for diagnostic purposes, ISH testing allows identification of PV type and the infection phase. RNA-ISH seems a promising tool to deepen our understanding of the pathogenesis of different PV types in animal species.

Nestin Expression Is Associated with Relapses in Head and Neck Lesions

Background: The aim was to investigate the clinical significance of nestin immunohistochemical expression in head and neck area lesions and to study its role in patient survival and recurrence. Methods: 39 (44.3%) nasosinus, 37 (42%) major salivary gland (6 submandibular and 31 parotid) and 12 (13.6%) oral cavity lesions of paraffin-embedded samples were retrospectively included. Results: The expression was categorized into grades, negative for 55 (62.5%) cases, grade 1 in 10 cases (11.4%), grade 2 in 12 cases (13.6%), and grade 3 in 11 cases (12.5%); 100% of pleomorphic adenomas were positive for nestin with grade 3 intensity, 100% of polyps and inverted papillomas were negative (p < 0.001). The lowest estimate of disease-free-survival (DFS) was for grade 1 expression, with 50 months, confidence interval (CI): 95% 13.3–23.9 months and the highest for grade 3 expression, 167.9 months (CI: 95% 32.1–105 months; Log-Rank = 14.846, p = 0.002). ROC (receiver operating characteristic) curves revealed that the positivity for nestin (+/−) in relation to malignancy, presented a sensitivity of 50.98%, a specificity of 81.08%, with an area under the curve of 0.667 (p = 0.009). Conclusions: Nestin could be a useful marker to detect the presence of stem cells in head and neck tumors that have a role in tumor initiation and progression.