Unique case of inverted papilloma of septum with nasopharyngeal carcinoma:Is it a metachronous tumour?

Inverted papilloma is a rare and benign tumour. It affects the nasal cavity and paranasal sinuses, has a high rate of recurrence and is associated with malignant transformation. Only few cases of a poorly differentiated carcinoma arising from inverted papilloma have been reported, none of which in the nasopharynx. We report a case of a 37-year-old female, who presented originally in 2012 with inverted papilloma of the nasal septum which was surgically resected. Nasopharyngeal biopsy from 2014 was reported as carcinoma in situ and treated with local endoscopic resection. Three years later she presented with a solitary lesion of the right Eustachian tube opening, confirmed as invasive poorly differentiated carcinoma. Imaging revealed T4 N2b M0 malignancy with skull base and prevertebral space invasion, likely extension into right temporal lobe and malignant adenopathy. Although rare, malignant transformation of inverted papilloma in unusual places should be considered during workup and monitoring of patients

Optimum imaging for inverted papilloma

Inverted papilloma is the most common benign tumour of the nose and paranasal sinuses, and usually arises in the lateral wall of the nasal cavity and the middle meatus. The diagnosis is suggested on computed tomography (CT) when there is a mass continuous from the middle meatus into the adjacent maxillary antrum, through an expanded maxillary ostium. The mass may contain areas of high density or calcification, and there may be sclerosis of the wall of the affected sinus. The main advantage of magnetic resonance imaging (MRI) is in defining the extent of the tumour, and in differentiating it from adjacent inflammatory tissue, but there are no certain signal intensity or enhancement characteristics to help differentiate inverted papilloma from sinus malignancy. In the differential diagnosis, antro-choanal polyp, malignant sinus tumours and chronic rhinosinusitis and fungal disease need to be excluded. The combination of bone deformity and sclerosis with the typical antro-meatal mass suggests a slow-growing tumour such as inverted papilloma

Optimum management of inverted papilloma

Surgery offers the optimum modality of treatment for inverted papilloma although a considerable range of operative approaches have been described. The results are presented in a cohort of 37 cases treated by both endoscopic and combined endoscopic and external approaches with a recurrence rate of eight and 21 per cent respectively. This series is compared with those in the literature and demonstrates that it is extent of disease which primarily determines the choice of surgical approach, with previous treatment, individual patient factors and surgical expertise as secondary determinants

Management and treatment of sinonasal inverted papilloma

Aims: The aim of this paper is to describe the surgical experience of 35 patients with Inverted Papilloma (IP) of paranasal sinuses and its recurrence rate after a year of follow-up. Materials: A retrospective chart review was performed on patients presenting with IP of paranasal sinuses. Thirty-five patients comprised the focus of this study. For all patients was performed a pre-surgery TC, and for more 5 patients it was necessary to perform a Magnetic Resonance (MR) with gadolinium. Results: Among 35 patients selected, 18 patients underwent to open surgery, 4 patients had a combined approach with endoscopy and open surgery, while 13 patients were managed only with an endoscopic approach, with a minimum of 1 year of follow-up. Our results highlighted that the global percentage of success 12 months after the treatment was 93% and it not vary according to the tipology of the approach used if a radical excision of the lesion is achieved. More in depth, among 35 cases, only 2 patients were found to have recurrences and were treated with coronal and endoscopic approach. Conclusion: It is fundamental to underline that surgery must be carried on in a radical manner to treat these tend to recur. A complete removal of the lesion and bone peripheral border filing are essential to perform a correct and definitive treatment. Also, endoscopic approach can be taken into account when tumors are localized median to a sagittal plan crossing the orbit median wall and when they did not massively compromised paranasal sinus walls

Downregulation of major histocompatibility complex class I in bovine papillomas

Bovine papillomavirus (BPV) induces papillomas in cattle; in the great majority of cases, these regress due to the host immune response, but they can persist and progress to malignancy. Even in the absence of malignant transformation, BPV infection persists for a significant period of time before activation of the host immune system, suggesting that the host immune system is unaware of, or disabled by, BPV. E5 is the major oncoprotein of BPV, which, in addition to its transforming properties, downregulates the expression and transport to the cell surface of major histocompatibility complex class I (MHC I). Here, it is shown that co-expression of MHC I and E5 in papillomas caused by BPV-4 infection is mutually exclusive, in agreement with the inhibition of surface MHC I expression by E5 that is observed in vitro. The inhibition of MHC expression in E5-expressing papilloma cells could explain the long period that is required for activation of the immune response and has implications for the progression of papillomas to the malignant stage; absence of peptide presentation by MHC I to cytotoxic T lymphocytes would allow the infected cells to evade the host cellular immune response and allow the lesions to persist

Sinonasal inverted papilloma; recurrence, malignant transformation and risk factors

Sinonasal inverted papilloma is a rare benign epithelial tumor. Its three main clinical characteristics are the tendency of recurrence, the destructive ability of nearby structures and malignant transformation. The primary manifestations of this tumor include nasal obstruction, headaches, runny nose, hemorrhage and impaired sense of smell. The diagnosis is based on the clinical and endoscopic examination completed by CT or MRI scans and biopsy of the lesion. Allergies, chronic inflammation, nicotinism and viral infections such as HPV infection are considered possible causes of pathogenesis and potential risk factors for relapse and malignancy. The treatment for this condition is the complete removal of the tumor with disease-free margins. Postoperative follow-up is essential for the early detection of recurrence or malignant transformation. One of the most basic and important steps in managing these patients is to acknowledge the presence of the mentioned risk factors and avoid exposure. Due to the high risk of relapse, the follow-up must be aggressive and thorough and always include the endoscopic examination. In our article, we wish to highlight the importance of the proper surgical intervention, but also the difference in the overall outcome of the patient ensured by the correct management of the risk factors, allowing us to prevent recurrence and malignant transformation

Therapeutic evaluation of homeopathic treatment for canine oral papillomatosis

Aim: A study was conducted to evaluate the ameliorative potential of homeopathic drugs in combination (Sulfur 30C, Thuja 30C, Graphites 30C, and Psorinum 30C) in 16 dogs affected with oral papillomatosis which was not undergone any previous treatment. Materials and Methods: Dogs affected with oral papillomatosis, which have not undergone any initial treatment and fed with a regular diet. Dogs (total=16) were randomly divided into two groups, namely, homeopathic treatment group (n=8) and placebo control group (n=8). Random number table was used for allocation. Homeopathic combination of drugs and placebo drug (distilled water) was administered orally twice daily for 15 days. Clinical evaluation in both groups of dogs was performed by the same investigator throughout the period of study (12 months). Dogs were clinically scored for oral lesions on days 0, 5, 7, 10, 15, 20, 25, 30, 45, 60, 90, 120, and 150 after initiation of treatment. Results: The homeopathic treatment group showed early recovery with a significant reduction in oral lesions reflected by clinical score (p<0.001) in comparison to placebo-treated group. Oral papillomatous lesions regressed in the homeopathic group between 7 and 15 days, whereas regression of papilloma in the placebo group occurred between 90 and 150 days. The homeopathic treated group was observed for 12 months post-treatment period and no recurrence of oral papilloma was observed. Conclusion: The current study proves that the combination of homeopathy drugs aids in fastening the regression of canine oral papilloma and proved to be safe and cost-effective

ROCK2/rasHa cooperation induce malignant conversion via p53 loss, elevated NF-κβ and tenascin C-associated rigidity but p21 inhibits ROCK2/NF-κβ-mediated progression

To study ROCK2 activation in carcinogenesis, mice expressing 4-hydroxytamoxifen (4HT)- activated ROCK2 [K14.ROCKer] were crossed to mice expressing epidermal activated ras Ha [HK1.ras1205]. At 8 weeks, 4HT-treated K14.ROCKer-HK1.ras1205 cohorts exhibited papillomas similar to HK1.ras1205 controls; however, K14.ROCKer-HK1.ras1205 histotypes comprised a mixed papilloma/well-differentiated squamous cell carcinoma [wdSCC], exhibiting p53 loss, increased proliferation, and novel NF-κβ expression. By 12 weeks, K14.ROCKer-HK1.ras1205 wdSCCs exhibited increased NF-κβ and novel tenascin C, indicative of elevated rigidity; yet despite continued ROCK2 activities /p-Mypt1 inactivation, progression to SCC required loss of compensatory p21 expression. K14.ROCKer -HK1.ras1205 papillomatogenesis also required a wound-promotion stimulus, confirmed by breeding K14.ROCKer into promotion-insensitive HK1.ras1276 mice, suggesting a permissive K14.ROCKer-HK1.ras1205 papilloma context [wound-promoted/NF-κβ+ve/p53-ve/p21+ve] preceded K14.ROCKer-mediated [p-Mypt1/tenascin C/rigidity] malignant conversion. Malignancy depended on ROCKer/p-Mypt1 expression, as cessation of 4HT-treatment induced disorganised tissue architecture and p21-associated differentiation in wdSCCs; yet tenascin C retention in connective tissue ECM suggests the rigidity laid down for conversion persists. Novel papilloma outgrowths appeared expressing intense, basal-layer p21 which confined endogenous ROCK2/p-Mypt1/NF-κβ to supra-basal layers, and was paralleled by restored basal-layer p53. In later SCCs, 4HT-cessation became irrelevant as endogenous ROCK2 expression increased, driving progression via p21 loss, elevated NF-κβ expression and tenascin C-associated rigidity; with p-Mypt1 inactivation/actinomyosin-mediated contractility to facilitate invasion. However, p21-associated inhibition of early-stage malignant progression and the intense expression in papilloma outgrowths, identifies a novel, significant antagonism between p21 and ras Ha/ROCK2/NF-κβ signalling in skin 3 carcinogenesis. Collectively these data show that ROCK2 activation induces malignancy in rasHa-initiated/promoted papillomas in the context of p53 loss and novel NF-κβ expression;whilst increased tissue rigidity and cell motility/contractility help mediate tumour progression

K-Ras and β-catenin mutations cooperate with Fgfr3 mutations in mice to promote tumorigenesis in the skin and lung, but not in the bladder

The human fibroblast growth factor receptor 3 (FGFR3) gene is frequently mutated in superficial urothelial cell carcinoma (UCC). To test the functional significance of FGFR3 activating mutations as a ‘driver’ of UCC, we targeted the expression of mutated Fgfr3 to the murine urothelium using Cre-loxP recombination driven by the uroplakin II promoter. The introduction of the Fgfr3 mutations resulted in no obvious effect on tumorigenesis up to 18 months of age. Furthermore, even when the Fgfr3 mutations were introduced together with K-Ras or β-catenin (Ctnnb1) activating mutations, no urothelial dysplasia or UCC was observed. Interestingly, however, owing to a sporadic ectopic Cre recombinase expression in the skin and lung of these mice, Fgfr3 mutation caused papilloma and promoted lung tumorigenesis in cooperation with K-Ras and β-catenin activation, respectively. These results indicate that activation of FGFR3 can cooperate with other mutations to drive tumorigenesis in a context-dependent manner, and support the hypothesis that activation of FGFR3 signaling contributes to human cancer

The role of midfacial degloving in modern rhinological practice

The midfacial degloving approach has been available for twenty five years and is slowly increasing in popularity in the management of extensive benign lesions of the sinonasal region, for selected malignancy in this area and to afford access to the nasopharynx and infra-temporal fossa. The advantages, applications and low complication rate are presented in a cohort of 86 patients, ranging from three to 79 years of age with a mean follow-up of 5.5 years. Seventy-seven per cent of the group had benign pathology of which juvenile angiofibroma was the commonest (40 cases). The 20 cases of malignant disease were a heterogeneous group histopathologically including adenoid cystic carcinoma (four cases), malignant schwannoma (two cases), rhabdomyosarcoma (two cases) and squamous cell carcinoma (two cases). Five underwent bilateral radical maxillectomies combined with orbital clearance in one patient. Complications include ore-antral fistula (three cases) and epiphora (three cases) all of which were successfully treated