Acta Otorrinolaringol Esp. 2017;68(5):251---261
www.elsevier.es/otorrino
ORIGINAL ARTICLE
Sinonasal Papillomas in a Private Referral Otorhinolaryngology Centre: Review of 22 Years Experience夽 Aderito de Sousa Fontes,a,∗ Minaret Sandrea Jiménez,b Nelson Urdaneta Lafée,c Perfecto A. Abreu Durán,d Liwven E. Quintana Páez,e Andreina Carmina de Sousa de Abreuf a
Unidad de Otorrinolaringoendoscopia, Instituto Médico La Floresta, Unidad Interdisciplinaria de Cirugía Endoscópica de base de cráneo, Post-grado de Neurocirugía, Hospital Militar Dr. Carlos Arvelo, Caracas, Venezuela b Instituto Médico La Floresta, Cátedra de Histología y Embriología, Escuela de Medicina Luis Razetti, Universidad Central de Venezuela, Caracas, Venezuela c Unidad de Radioterapia Oncológica y Medicina Nuclear, Instituto Médico La Floresta, Smilow Cancer Hospital y Yale Cancer Center, Yale University, USA, Cátedra de Radioterapia y Medicina Nuclear, Hospital Universitario UCV, Universidad Central de Venezuela, Caracas, Venezuela d Unidad de Radioterapia Oncológica, Instituto Médico La Floresta, Caracas, Venezuela e Equipo Interdisciplinario de Cirugía Endoscópica de base de cráneo, Instituto Médico La Floresta, Postgrado de Neurocirugía, Hospital Militar Dr. Carlos Arvel, Caracas, Venezuela f Pasantía dirigida en Otorrinolaringología, Unidad de Otorrinolaringoendoscopia, Instituto Médico La Floresta, Caracas, Venezuela Received 5 June 2016; accepted 9 September 2016
KEYWORDS Sinonasal neoplasm; Sinonasal papilloma; Inverted papilloma; Fungiform papilloma; Oncocytic papilloma
Abstract Objectives: To evaluate the clinical presentation, treatment outcome and follow-up of all patients managed with sinonasal papillomas (SP), at a tertiary private otorhinolaryngology centre in Caracas (Venezuela). Material and methods: We reviewed 94 patients with SP that were treated at our otolaryngology centre, from July 1st 1993 to June 31st 2015. The demographic data, clinical features, radiological findings, anatomical origin, disease extension into the adjacent structures, surgical approaches performed, histopathology outcomes, recurrent risk, malignant transformation rate and coadjuvant therapies were assessed. Results: Sixty-five patients (69.1%) were male and 29 (30.9%) female with an average age of 44.5 years (range 9---80 years). All patients underwent endoscopic sinus surgery. The most
夽 Please cite this article as: de Sousa Fontes A, Sandrea Jiménez M, Urdaneta Lafée N, Abreu Durán PA, Quintana Páez LE, de Sousa nos de experiencia. Acta de Abreu AC. Papilomas rinosinusales en un centro de referencia otorrinolaringológico privado: revisión de 22 a˜ Otorrinolaringol Esp. 2017;68:251---261. ∗ Corresponding author. E-mail address:
[email protected] (A. de Sousa Fontes).
2173-5735/© 2016 Elsevier Espa˜ na, S.L.U. and Sociedad Espa˜ nola de Otorrinolaringolog´ıa y Cirug´ıa de Cabeza y Cuello. All rights reserved.
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A. de Sousa Fontes et al. commont histologic subtypes of SP were inverted papilloma (58 patients; 61.7%), fungiform papilloma (35 patients; 37.2%) and oncocytic papilloma (one patient; 1.1%). SP was associated in 2 patients with undifferentiated squamous cell carcinoma. Twelve patients (12.8%) had disease with extension beyond the sinus without associated malignancy. All these patients received adjuvant treatment with advanced techniques of radiotherapy. The mean duration of the followup period was 9 years and 2 months. Eighteen patients (19.1%) had recurrent disease during the entire course of follow-up. Conclusions: Complete endoscopic surgical removal of SP is the treatment of choice. In less endoscopically accessible tumours, with peripheral extension or incompletely resected, Intensity Modulated Radiotherapy and Volumetric Modulated Arc Therapy may be indicated. Timely post-operative endoscopic follow-up with biopsy of suspected lesions is important for early detection of recurrences and associated malignancy. © 2016 Elsevier Espa˜ na, S.L.U. and Sociedad Espa˜ nola de Otorrinolaringolog´ıa y Cirug´ıa de Cabeza y Cuello. All rights reserved.
PALABRAS CLAVE Tumour nasosinusal; Papiloma rinosinusal; Papiloma invertido; Papiloma fungiforme; Papiloma oncocítico
Papilomas rinosinusales en un centro de referencia otorrinolaringológico privado: revisión de 22 a˜ nos de experiencia Resumen Objetivos: Evaluar la presentación clínica, los resultados al tratamiento y el seguimiento de los pacientes con papilomas rinosinusales (PRS), en un centro de atención terciaria otorrinolaringológica en Caracas (Venezuela). Material y métodos: Se realizó una revisión de 94 pacientes con PRS que fueron diagnosticados en nuestro centro otorrinolaringológico desde el 1de julio de 1993 hasta el 31 de junio de 2015. Se evaluaron los datos demográficos, las características clínicas, los hallazgos radiológicos, el origen anatómico, la extensión de la enfermedad hacia estructuras adyacentes, los procedimientos quirúrgicos realizados, la histopatología, el riesgo de recurrencia y la tasa de transformación maligna, y las terapias coadyuvantes. Resultados: Sesenta y cinco pacientes (69,1%) eran varones y 29 (30,9%) mujeres, con una edad promedio de 44,5 a˜ nos (rango 9-80 a˜ nos). Todos los pacientes fueron sometidos a cirugía endoscópica de senos paranasales. Los subtipos histológicos más comunes de PRS fueron el papiloma invertido (58 pacientes; 61,7%), el papiloma fungiforme o exofítico (35 pacientes; 37,2%) y el papiloma oncocítico (un paciente; 1,1%). El papiloma invertido se asoció en 2 pacientes con carcinoma indiferenciado de células escamosas. Doce pacientes (12,8%) presentaron enfermedad de extensión extrasinusal. Todos estos pacientes recibieron tratamiento adyuvante con técnicas avanzadas de radioterapia. El promedio de duración del seguimiento fue de 9 a˜ nos y 2 meses. Dieciocho pacientes (19,1%) presentaron enfermedad recurrente durante todo ese periodo de seguimiento. Conclusiones: La resección endoscópica completa de los PRS es el tratamiento de elección. En lesiones menos accesibles endoscópicamente, con extensión periférica o tumores resecados de forma incompleta, las técnicas de radioterapia avanzadas como la radioterapia de intensidad modulada y la radioterapia en arcos de volumen modulado pueden estar indicadas con éxito. El control endoscópico postoperatorio oportuno con biopsias de lesiones sospechosas son importantes para la detección precoz de recidivas y malignización asociada. © 2016 Elsevier Espa˜ na, S.L.U. y Sociedad Espa˜ nola de Otorrinolaringolog´ıa y Cirug´ıa de Cabeza y Cuello. Todos los derechos reservados.
Introduction Sinonasal papillomas (SNP) are benign tumours with an epithelial origin. They arouse strong interest due to their aggressive behaviour, with a propensity to relapse and the risk of becoming malignant.
Although they are considered to be benign neoplasias because they are unable to cause metastasis, their worrying biological behaviour means they have certain ‘‘subtle characteristics of malignity’’ due to their predisposition to invade structures adjacent to the nose and the paranasal sinuses (PNS), even in the absence of associated malignancy.
Sinonasal Papillomas in a Private Referral Otorhinolaryngology Centre In histopathological terms SNP are classified as inverted or Schneiderian papillomas (IP), fungiform papillomas (FP), inverted or exophytic, and oncocytic papillomas (OP) or cylindrical cell. The treatment of neoplasias of this type currently involves the complete surgical endoscopic resection of the lesion and postoperative follow-up over the long term to identify any relapse at any early stage. The accumulated knowledge about the origin, characteristics, behaviour and evolution of this neoplasia has influenced recent developments in the management and treatment of SNP. This is especially so for tumours at an advanced stage, in cases of multiple recurrence, in incompletely resected lesions, in biologically aggressive tumours extending into the eye socket and and/or intracranially, and in neoplasias associated with malignity, improving results and patient quality of life. The aim of this study is to evaluate the clinical characteristics, distribution according to age and sex, radiological findings, location, extension, histopathology, therapeutic management and results in patients with SNP treated in our private tertiary referral hospital by rhinonasal and cranial base endoscopic surgery during a 22 year period.
Materials and Methods A longitudinal retrospective descriptive study was performed of all the clinical histories of SNP patients diagnosed and treated during the period from 1 June 1993 to 31 July 2015 (22 years). The study was carried out in a national referral hospital for rhinonasal endoscopic surgery. The patients visited or were referred to the surgery of the Otorhinolaryngeal endoscopy Unit of the La Floresta Medical Institute, located in Caracas (Venezuela). Data were gathered from the clinical histories of each one of the patients, on sex, age, symptoms, location and anatomical extension of the disease (correlation between endoscopy and radiological data), surgical treatment performed, postoperative follow-up, histopathological results, frequency of recurrence and time until this occurred, extrarhinosinusal involvement (cranium, eye socket or subcutaneous cellular tissue) with or without associated malignisation, association with malignity and interdisciplinary management (Neurosurgery, Ophthalmology, Radiotherapy and Chemotherapy). The patients included in this review consented to take part in the study. The resulting data were summarised and analysed using the Excel 2010 program to obtain measurements of frequency and the central tendency. The study was undertaken according to the principles set out in the Helsinki Declaration, and it was approved by the institutional review board of La Floresta Medical Institute.
Results A total of 94 patients with SNP were studied, of whom 69.1% (n=65) were male and 30.9% (n=29) were female. Their ages ranged from 9 to 80 years old (with an average age of 44.5 years old). The group of patients who were treated contains only one patient of paediatric age, who was female.
Table 1
253 Frequency of Clinical Manifestations.
Symptom
% (n)
Nasal obstruction Rhinorrea Cephaleas and/or facial algias Hypoacusia Epiphora Epistaxis Anosmia Nasofacial deformity
100 67 36.2 36.2 24.5 10.6 9.6 2.1
(94) (63) (34) (34) (22) (10) (9) (2)
Nasal obstruction was the most frequent clinical manifestation, and it was present in 100% of cases. 77.7% of the patients (n=73) presented unilateral obstruction of the side corresponding to the lesion. Nasal obstruction was bilateral in 22.3% of cases (n=21), and it was caused in 21.3% of cases (n=20) by contralateral deviation of the nasal septum, while in 1.1% of cases (n=1) it was caused by bilateral neoplastic disease. Rhinorrea was present in 67% (n=63) of cases, while cephalea and craniofacial algia were present in 36.2% (n=34). Hypoacusia and epiphora were present in 36.2% (n=34) and 24.5% (n=22) of cases, respectively. Epistaxis was present in 10.6% (n=10) of the patients studied. Anosmia was present in 9.6% (n=9) of the patients evaluated. Nasofacial deformation due to neoplastic growth or extension was reported in 2.1% (n=2) of cases. In one patient it took the form of broadening of the nasal pyramid caused by bone destruction and neoplastic extension in the soft tissues of the nasofacial region. In another patient deformation of the middle third of the face was evident, including deformity of the osseous nasal pyramid, hypertelorism, combined hypotropy and exotropy caused by the expansion and growth of the neoplasia to both eye sockets, to the anterior base of the cranium and the soft parts of the nasofacial region, due to osseous destruction of the anteroinferior wall of the frontal sinus1 (Table 1). 98.9% of the patients (n=93) presented unilateral endoscopic evidence of a vegetative polypoid lesion with a papillomatous appearance in a nasal fossa, while in 1.1% of cases (n=1) endoscopic and radiological evidence was found of disease in both nasal fossae.1 Computerised tomographic imaging studies of the paranasal sinuses (CTPNS) performed in all cases showed opaque or cloudy areas caused by the presence of this neoplasia. In 86.2% of the patients (n=81) clear tomographic signs were observed of focal thickening of the bone (hyperostosis) associated with the opaque or cloudy image caused by the neoplastic disease (Fig. 1). A magnetic resonance imaging study (MRI) was only requested for 38 patients (17%) in this study, as they presented indicative or evident tomographic signs of remodelling or erosion of the orbital or cranial bone walls, and in patients with clear signs of extrasinusal tumour extension. MRI documented different degrees of intraorbital or intracranial invasion. This was due to tumour extension in 14.9% of cases (n=15). In all cases extrasinusal involvement was of the expansive type (the mass effect) rather than infiltration (Figs. 2---4).
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A. de Sousa Fontes et al.
Figure 1 Coronal CT images (A) and axial images (B) of PNS showing complete clouding of the ethmoidal sinuses and the left maxillary sinus with a focal image of calcification or hyperostosis (arrowed), located at the level of the nasal side wall. This sign may be indicative of the point of origin of the SNP and may also indicate associated malignisation.
All of the MRI studies with and without contrast in all of these patients revealed an outlined pattern with alternating hypointense and hyperintense striations inside the neoplasias, with a cerebriform appearance (Figs. 2---4). The location of the neoplastic lesion in the patients was determined endoscopically and tomographically. In 60.6% of patients (n=57) the neoplastic lesion was located in
the left side, while in 38.3% of cases (n=36) it was in the right side, and in 1.1% (n=1) the lesion was bilateral. Recurring disease was present in 38.3% (n=36) of all the SNP subtypes treated. 35.1% of the patients (n=33) with active tumoural disease referred at least one incident of previous rhinonasal surgery.
Figure 2 Coronal CT images (A and B) showing significant opacity in the sphenoid sinus with clear signs of bone erosion (arrowed). MRI in T1 without contrast (C) and in T1 with contrast (C) determines that the lesion, which corresponds to a recurring IP without associated malignity, and in spite of the fact that it has attacked the bone wall, does not extend into the mid-cranial fossa. In this case endoscopic surgical resection could not be performed completely due to the critical risk of causing a severe intraoperative complication (lesion of the internal carotid and/or optic nerves), so that the patient was given coadjuvant treatment with intensity modulated radiotherapy, achieving control of the disease during the 12 years of follow-up after surgery.
Sinonasal Papillomas in a Private Referral Otorhinolaryngology Centre
255
Figure 3 CT and MRI studies with and without contrast in a patient who presented an IP with extension into the eye socket and soft tissues of the nasofacial region. Coronal and axial CT of the PNS (A and B) showing a significant opacity of all the PNS, with erosion of the right orbital wall and lateral and anterior displacement of the intraorbital content and subcutaneous cellular tissue in the nasofacial region. Coronal MRI (C and D) with contrast in T1 and sagittal MRI in T2 without contrast, respectively, showing a striking pattern of changes in the signal inside the lesion, with alternating markedly hyperintense bands separated by low density striations (a pattern with a cerebriform outline), usually observed in IP.
No patient was subjected to a previous biopsy of the lesion in the surgery, and the presumed diagnosis of SNP was made on the basis of endoscopic and imaging study findings (TC and MRI) for each patient. The size and extension of the neoplasias were determined in each one of the cases studied, according to the findings of endoscopy and the imaging studies (TC and MRI). Krouse’s classification was used to establish the stage of the neoplastic disease. 36.2% (n=31) of the patients were in stage I, 28.7% (n=26) were in stage II, 22.3% (n=21) were in stage III and 17% (n=16) were in stage IV (Table 2). 98.9% of the patients were treated using endonasal endoscopic resection and only in 1.1% of cases (n=1) was a combined endoscopic approach used (endonasal and external by minitrepanning both frontal sinuses) due to advanced bilateral disease with intracranial and orbital extensions on both sides.
Table 2
Histopathological studies of the resected lesions in all of the patients were consistent with the diagnosis of IP in 69.1% (n=65) of cases, with FP in 29.8% (n=28) of patients and OP in a single patient (1.1%). Associated malignisation (undifferentiated epidermoid carcinomas) were present in 5.9% (n=2) of the cases and correspond to individuals in the oldest age group (78---80 years old), one of whom presented recurring disease. Our study analysed the distribution of the different subtypes of SNP according to age, sex, anatomical origin of the tumour, recurrence and association with concurrent malignity (Table 3). The average age at which the neoplasias appeared was 44.5 years old (from 9 to 80 years) for IP and 27 years old (from 18 to 36 years old) for FP, while for OP it was 66 years old. IP presented predominantly in males, at a ratio of 3:1 (44 men and 14 women), FP also presented more in males, at
Distribution of the Patients According to Krouse’s Classification Neoplasia Stage.
Stage
Tumour extension
% (n)
I II III
Tumour confined to the nasal cavity Tumour limited to the ethmoidal sinus and the medial and/or upper part of the maxillary sinus Tumour involving the lower and/or lateral part of the maxillary sinus, or involving the frontal or sphenoid sinuses Tumour extending beyond the nasal cavities and/or sinuses, or associated with malignity
36.2 (31) 28.7 (26) 22.3 (21)
IV
17 (16)
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A. de Sousa Fontes et al.
Figure 4 CT and MRI of the PNS in a patient with bilateral recurring IP, without associated malignisation and with intracranial, orbital and soft tissue extension in the nasofacial region. (A) Coronal CT showing major clouding in all of the PNS caused by a mass that expands from the base of the cranium and orbital walls, causing serious alteration of the rhinosinusal architecture, with lateral displacement of the medial walls of both eye sockets. Areas of bone erasure and focal thickening are visible (hyperostosis) in both sides of the orbital walls and in the anterior base of the cranium. Clear invasion is also observed of the lesion from the left frontal sinus towards the orbital cavity, causing a notable displacement of the corresponding eyeball outwards and downwards. (B) Coronal CT showing significant clouding of the sphenoid sinus with erasure of the laterosuperior wall. (C) Sagittal CT showing complete opacity of the frontal sinus, the ethmoidal sinuses and the sphenoid sinus, with a clear and extensive defect in the posterior wall of the frontal sinus, with marked distortion and areas of thickening of the bone wall (focal hyperostosis) in the nasofrontal area. (D) Axial T2 MRI showing a solid mass in the frontal sinus, with intracranial extension and exercising a mass effect in both frontal cerebral lobe without infiltrating them. Changes in the signal with an outlined appearance can be seen inside the said mass (hypointense and hyperintense striations).
Table 3 Distribution of the Patients According to Lesion Histopathology, According to Average Age, Anatomical Origin and Associated Malignisation. Type of the papilloma
Histology, % (n)
Age at commencement in years, average (range)
Sex (M:F)
Anatomical origin
Recurrence, % (n)
Associated malignity, % (n)
Inverted papilloma
61.7 (58)
44.5 (9---80)
3:1
30.9 (29)
5.9 (2)
Fungiform papilloma (exophytic papilloma) Oncocytic papilloma (cylindrical cell papilloma)
37.2 (35)
27 (18---36)
5:1
11.4 (4)
No
66
M
Nasal side wall, sphenoethmoidal recess and PNS Anterior nasal septum Nasal side wall
No
No
1.1 (1)
Sinonasal Papillomas in a Private Referral Otorhinolaryngology Centre a ratio of approximately 5:1 (29 men and 6 women). The only case recorded as OP was in a male. The apparent anatomical origin of the lesions was determined during the operation; for IP, in 87.9% (n=51) of the patients the origin of the neoplasia was in the nasal side wall, and in 12.1% (n=7) the lesion started in the sphenoethmoidal recess. In all cases the anatomical origin of FP was in the anterior portion of the nasal septum, while the only OP treated seemed to have an origin in the nasal side wall. 30.9% of the patients (n=29) in this study mentioned previous surgery with resection of a lesion with reported histology diagnosed IP. 20.7% of the patients (n=6) in this subgroup of recurring disease mentioned the previous surgical resection of a lesion reported histologically as ‘‘polyposis’’. One of the patients in this last group consulted due to bilateral disease with intracranial and orbital extension, as well as into the soft tissues of the nasofacial region. This was the most aggressive case, without associated malignisation, of the series of cases presented in this study (Fig. 4). When reviewing the paraffin blocks of the specimen resected in the primary surgery of this patient it was found that the original histological diagnosis was incorrect, and that it corresponded to an IP. In the other 5 cases it was not possible to locate the paraffin blocks for re-evaluation. In the patients with a histological diagnosis of FP, 11.4% (n=4) referred to the precedent of a previous resection. In all cases this had taken place in the surgery under local anaesthetic. Associated malignisation was present in this study in 5.9% (n=2) of the patients, and in both cases the histological diagnosis of the first neoplasia was IP. Sixteen patients (17.2%) presented tumoural disease with clear signs of bone wall erosion, with extension of the neoplasia to the orbital region and/or the base of the cranium. 62.5% (n=10) of this subgroup had a history of previous surgery and were therefore considered to be recurring cases. 37.5% of these patients (n=6) presented primary neoplastic disease. In 50% (n=8) of the patients the radiological signs of bone erosion affected the eye socket wall, and in 37.5% (n=6) the signs of erosion affected the bone wall of the base of the cranium. In one patient (6.25%) both osseous walls were affected (cranial and orbital) and the extrasinusal extension of the disease towards both compartments and the subcutaneous facial tissue was considerable1 (Fig. 4). In another case (6.25%) with erosion of the anterior orbital wall and involvement of the lacrimal bone, extension of the tumour into the eye socket was evident in imaging studies (CT and MRI), as well as to the subcutaneous cellular tissue and nearby skin. In both cases the histopathological studies agreed with the diagnosis of IP without associated malignisation. In 93.8% of the patients (n=15) with tomographic signs of bone erosion, the histopathological reports corresponded to IP, while in 6.25% of cases (n=1) they corresponded to OP histology. All of the patients in this group with disease involving osseous walls were subjected to endoscopic resection of most of the tumour volume (debulking), avoiding the risk of causing major intraoperative complications, postoperative morbidity and the extransinusal spread of the neoplasia. All of these cases were treated using intensity modulated radiotherapy (IMRT).
257
The average postoperative follow-up for all SNP subtypes was 11 years 3 months (from 6 months to 22 years). In the particular case of the patients with IP and OP subjected to coadjuvant treatment with IMRT the average postoperative follow-up was 4 years and 8 months (from 8 months to 9 years) after radiotherapy ended. During this follow-up period none of the patients treated using IMRT presented recurring disease. Both patients with malignity-associated disease individually rejected postoperative oncological treatment (radiation and/or chemotherapy) and they died due to causes other than the diagnosed tumours.
Discussion SNP represent from 0.4 to 5% of all primary nasal tumours, with an incidence of 0.2---0.6 cases per 100,000 patients per year.2,3 In 1971 Hyams4 classified papillomas according to their histological growth pattern as: IP due to its endophytic growth pattern, FP due to its exophytic papillary growth pattern (column or mushroom-shaped) and OP or cylindrical cell papilloma due to the cylindrical exophytic growth pattern combined with areas of endophytic growth. The latter type is considered to be a key reference in the classification described by Shanmugaratnam and Sobin5 on the different histological types of upper respiratory tract and ear tumours. Since 1991 this has been used by the World Health Organisation as the classification of head and neck tumours. Although some authors4---7 clearly establish that each one of the 3 histological subtypes of SNP are completely different entities, some hybrid lesions exist that combine the histological characteristics, with a mixed endophytic and exophytic growth pattern in the same lesion.7---9 Three subtypes of SNP are currently recognised: IP, FP and OP or cylindrical cell type.4 IP is the most frequent and represents from 47% to 73% of SNP; FP represent from 19% to 50%, and OP represent from 3% to 8%. IP and OP originate in the nasal side wall or inside the PN. They have similar biological behaviour with locally aggressive growth, high recurrence rate and the risk of malignisation.10 On the contrary, FP originates especially in the nasal septum, has a low recurrence rate and very rarely becomes malignant. To date the aetiology of SNP is still highly controversial and is actively being researched. Several factors have been described as involved in its etiopathogenesis, including certain human papilloma virus serotypes, allergy, chronic rhinosinusitis, environmental agents, exposure to tobacco, hepatocyte growth factors and over-exposure to its receptor (c-Met), as well as several enzymes such as metalloproteinase 2 and 9.11---17 SNP are usually unilateral neoplasias which in the early stages of growth are small and generally asymptomatic lesions. When they grow larger they cause nasal obstruction and rhinorrea (anterior and/or posterior). When they grow very large they may cause epistaxis, cephaleas, olfactory alterations and ophthalmological manifestations.15,18,19 SNP and especially IP and OP tend to relapse because the histologically abnormal neoplastic tissue spreads laterally and gradually replaces the adjacent healthy respiratory
258 epithelium. This lateral extension probably explains the high rate of local recurrence after resection of the lesion.20 Kraft et al.21 reported that the most common SNP subtype was IP (79%), followed by FP (12%) and OP (9%). Associated malignisation occurred in 9% of cases and recurrence occurred in 19% of the patients. 4.7% of these recurrences occurred in patients who had been subjected to endoscopic resection. Kadapa et al.22 state that the recurrence rate was 21% for IP and that this occurred most particularly in the first 2 years after surgery. Some authors23,24 have stated that the average time to relapse in IP is 41 months after resection (3---79 months), and there are even reports of recurrences observed after 11 years.25 Endoscopically SNP are lesions with a polypoid vegetative appearance with multiple digitations and which bleed easily. The radiological appearance of SNP produces an opaque or cloudy image of the nasal fossa or affected PNS, similar to that corresponding to an important rhinonasal inflammatory disease. As the neoplasia grows it becomes more opaque and involves the nasal fossa or one or more PNS. The expansion of the neoplasia may displace adjacent structures and lead to erasure of the bone walls, extending to adjacent areas such as the walls of the eye sockets and the base of the cranium. CTPNS is the gold standard for the radiological study of chronic inflammatory disease and neoplastic disease of the nose and the PNS, as it makes it possible to create anatomical reconstructions using bone and soft tissue algorithms. As SNP grows and spreads beyond the limits of the sinonasal anatomy, CTPNS studies may reveal alterations such as: cortical erosion, destruction, remodelling, sclerosis and thickening of the underlying bone. The presence of calcification foci within the SNP may indicate associated malignisation, and focal hyperostosis of the bone adjacent to the neoplasia periphery may indicate the point of origin of the tumour26,27 (Figs. 2 and 3). In some cases CTPNS is unable to delimit the volume of a neoplasia and cannot distinguish the density of the tumour tissue when secretions retained within the PNS are present concomitantly, when the tumour obstructs the drainage of the PNS. This is why some authors28,29 states that MRI should also be considered to be a study with diagnostic value that is complementary to CT. They also state that diagnostic strategy and surgical planning should be considered in SNP, especially when the disease is extensive and has involved or spread extrasinusally. On the other hand, MRI may reveal characteristics sign of this type of neoplasias, especially in IP and OP, which are characterised by the presence of a typical pattern of alternating hypointense or hyperintense striations or bands inside these tumours. Some authors have denominated this an outlined cerebriform pattern, and they consider it to be a radiological sign that is characteristic of these types of PRS30 (Figs. 3 and 4). The presence of clear signs of bone destruction and tumour infiltration into adjacent sinonasal structures may be a distinctive sign for the suspicion of malignisation in coexistence with SNP (Fig. 4). Several authors31---34 state that in spite of the fact that CT is of key importance in the diagnosis and planning of surgical treatment for SNP, MRI offer better information than CT in the pre-treatment evaluation of these tumours,
A. de Sousa Fontes et al. especially in lesions with aggressive behaviour and in cases with associated malignity. Given the need to have a means of evaluating the efficacy of the different approaches and the prognosis for SNP, Krouse35 established a staging system based on the location, extension and malignity of lesions as set by diagnostic nasal endoscopy and CT (Table 3). Although other classification systems have been described,36---38 Krouse’s system is the most widely used.35 From the histopathological viewpoint, the 3 SNP subtypes have histological characteristics that differentiate them very clearly. IP has a hyperplasic endophytic or inverted growth pattern of the squamous or transitional cells of the respiratory epithelium. In this neoplasia the growth pattern of the squamous cell layers progresses towards the underlying stroma, without causing alterations in the basal membrane or connective tissue. Numerous intraepithelial microcysts containing cell remnants, macrophages and mucin are present among the squamous cells of the respiratory epithelium, without keratinisation. When areas of moderate to severe dysplasia are found, or atypical and/or focal keratinisation on the epithelial surfaces of the tumour, microscopic evaluation of all the tissue sent for study must be performed to investigate foci of malign transformation associated with PI.39 Histologically FP has a cellular composition similar to that of IP, but with a squamous or transitional respiratory epithelial cell growth pattern towards the epithelial surface (exophytic). Unlike IP, keratin formation may be present in the epithelial surface and observed as hyper- or parakeratosis. Chronic inflammatory cells may sometimes be observed (macrophages, lymphocytes and plasmatic cells) together with koilocytosis in the surface cells.39 Histological evaluation of OP shows an exophytic and endophytic growth pattern, with several layers of cylindrical cells arranged in a pseudostratified pattern, with small uniform dark rounded nuclei and eosinophilic cytoplasm. Likewise, it is possible to observe numerous microcysts among the squamous cells that contain cell remnants and mucin. OP must be distinguished from adenocarcinoma by the presence of stratified epithelium, intact basal membranes, the absence of nuclear pleomorphism, mitotic activity and bone destruction.39,40 The treatment of choice for SNP is complete surgical resection. Different surgical procedures have been proposed for this purpose. With the development of nasal and PNS endoscopic surgery and progress in this field, endoscopic approach and resection is currently the gold standard in the treatment of the vast majority of SNP, permitting complete resection of the tumour with fewer complications and lower postoperative morbidity than external approaches. Illumination is improved endoscopically, and this technique also broadens the angle of the operative field in areas that are hard to access in rhinosinusal anatomy that is characterised by confined spaces, cavities and incisions, as well as by critical adjacent structures. Other relevant advantages of an approach of this type are that it shortens the duration of operations, can be performed on an out-patient basis and has advantages in terms of patient comfort and the cost of medical treatment.41---43 Postoperative followup of SNP must be over the long term, especially for IP and OP as they behave more aggressively and have a major
Sinonasal Papillomas in a Private Referral Otorhinolaryngology Centre risk of recurrence and malignisation.1,44---48 Intracranial or intraorbital extension of SNP in the absence of associated malignity, especially for IP and OP, generally occurs in cases with advanced neoplasias and in patients with recurring disease, especially when the lesion affects the lamina cribosa, the frontal sinus, the ethmoidal roof and the orbital wall, and when the neoplasia was resected using an unsuitable surgical procedure that is aggressive and incompletely monitored.1,48,49 Radiotherapy was at first only indicated for SNP with associated malignisation. Its indication in SNP without concomitant malignity was reported to be exceptional, leading to major controversies.50---54 Some authors50,51 separately reported cases of malignity in papillomatosis and SNP which had previously been benign, stating that radiation was a factor in the anaplasic transformation of SNP and that it was not effective in preventing recurrences. Both of these arguments were subsequently considered to be irrelevant in the light of successive studies which were unable to confirm them in the majority of SNP cases with associated malignity.54,55 The efficacy of radiotherapy as an adjuvant treatment for biologically aggressive IP without associated malignity has been studied and reported by several authors.53---56 Nevertheless, conventional radiotherapy is associated with a high risk of treatment-related toxicity.57,58 Using modern radiotherapy techniques such as IMRT and volume modulated arc therapy, it is possible to increase the dose of radiation delivered to the tumour while reducing the dose at the lesion edges and avoiding radiating adjacent organs and structures at risk (the eyes, the optic nerve and chiasm, important vessels, the brain stem and the rest of the CNS), preserving the function of the organ and improving quality of life.1,59---61
Conclusions Based on our experience we are able to state that SNP, although they are considered to be benign neoplasias as they are unable to cause metastasis, are lesions with a biological behaviour that may be worrying. This is because they tend to be locally aggressive, may relapse and may also be associated with histological malignisation. Of the 3 histological SNP subtypes, IP and OP arouse the most clinical interest due to their aggressive growth and predisposition to invade extrasinonasal structures, even in the absence of concomitant malignity, and the risk of association with carcinoma. Endoscopic diagnosis with SNP patients must be supported by imaging studies (CT and MRI with contrast), especially in cases with major or advanced disease. We agree with the reports which state that the management of neoplasias of this type includes the complete endoscopic resection of the lesion and an exhaustive longterm follow-up. However, in our experience with patients who present advanced disease without associated malignisation and with extrasinonasal extension, endoscopic resection was combined with adjuvant radiotherapy using modern treatment procedures such as IMRT and volume modulated arc radiotherapy, with highly successful and safe results. In these cases which are hard to manage, the
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neoplasia cannot be broadly and completely resected due to the involvement of critical extrasinonasal anatomical structures and the high risk of undesirable intraoperative complications due to extensive resection of the lesion. Modern techniques of radiotherapy such as IMRT and volume modulated arc radiotherapy have opened up a new horizon in management, most particularly for biologically aggressive advanced IP and OP without associated malignity, especially in incompletely resected patients and in those with proven associated histological malignisation.
Conflict of Interests The authors have no conflict of interest to declare. This work was revised and approved by the Ethics Committee of La Floresta Medical Institute, Caracas (Venezuela).
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