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Treatment of pediatric esthesioneuroblastoma with smell preservation
G Model
ANL-2419; No. of Pages 6 Auris Nasus Larynx xxx (2018) xxx–xxx Contents lists available at ScienceDirect
Auris Nasus Larynx journal homepage: www.elsevier.com/locate/anl
Case report
Treatment of pediatric esthesioneuroblastoma with smell preservation Giandomenico Maggiore, Maria Silvia Lazio *, Oreste Gallo Clinic of Otolaryngology, Head and Neck Surgery, Department of Translational Surgery and Medicine, University of Florence, Italy
A R T I C L E I N F O
A B S T R A C T
Article history: Received 31 October 2017 Accepted 6 February 2018 Available online xxx
Olfactory neuroblastoma is a rare malignant tumor of neuroectodermal origin and represents the most common cancer of the nasal cavity in pediatric age. The gold standard of treatment consists of en bloc resection, numerous studies have shown as the endoscopic approaches permit good control of the disease improving the quality of life after the treatment. Herein we describe the case of a 13year-old patient referred to our outpatient clinic with a polypoid multi-lobed lesion occupying the left nasal cavity and imaging that confirmed a left-sided nasal mass without cribriform plate involvement (Kadish B). We performed an unilateral endoscopic resection with transnasal craniectomy and anterior skull base reconstruction with a flap from the contralateral nasal septum based on the septal branches of the anterior and posterior ethmoidal arteries (Septal Flip Flap, SFF), that provided a faster healing process with reduction of nasal crusting, improvement in the quality of life of patient in the postoperative period and the preservation of the contralateral olfactory bulb that has allowed to save the smell. This treatment strategy of pediatric esthesioneuroblastoma was analyzed in the context of the current literature. © 2018 Elsevier B.V. All rights reserved.
Keywords: Paranasal tumors Olfactory neuroblastoma Esthesioneuroblastoma Smell preservation Sinonasal malignances
1. Introduction Olfactory neuroblastoma (ON), also known as esthesioneuroblastoma (ENB) was described by Berger in 1924, who described an “esthesioneuroepitheliome olfactif” [1]. Since the first description about 1000 cases have been reported in the world literature [2]. It represents about 3%–5% of all malignant nasal tumors [3] and has a bimodal age distribution, between 10 and 20 years and between 50 and 60 years. In pediatric age, the estimated incidence of ON is 0.1/100.000 children up to 15 years of age, but it is the most common cancer of the nasal cavity [4,5]. Tumor etiopathogenesis of ON is not yet clear, there are no known etiologic agent(s) for human olfactory neuroblastoma demonstrated. The main presenting symptoms * Corresponding author at: Clinic of Otolaryngology, Head and Neck Surgery, University of Florence, via Largo Brambilla, 3-50134 Firenze, Italy. E-mail address: [email protected] (M.S. Lazio).
are unilateral nasal obstruction (70%) and epistaxis (46%); less common manifestations include anosmia, headache, pain, excessive lacrimation and ocular disturbances, these symptoms are related to the site and local invasion of the tumor. Diagnosis is often made late because they are asymptomatic or produce nonspecific symptoms in their early stages, the mean delay between the appearance of the first symptom and the diagnosis being 6 months [6]. ON does not have any specific radiologic appearance and when seen, it is a homogenous soft-tissue mass in the nasal vault, with uniform and moderate contrast enhancement. Computed tomography (CT) images are essential for correct staging and they should be carefully examined for erosion of the lamina papyracea, cribriform plate, and fovea ethmoidalis. Magnetic resonance imaging (MRI) enables a better estimate of tumor spread into surrounding soft-tissue areas and can differentiate mucus from tumor, also showing any possible intraorbital or intracerebral extension. Regional and metastatic dissemination occurs, with 8–20% of patients having
https://doi.org/10.1016/j.anl.2018.02.003 0385-8146/© 2018 Elsevier B.V. All rights reserved.
Please cite this article in press as: Maggiore G, et al. Treatment of pediatric esthesioneuroblastoma with smell preservation. Auris Nasus Larynx (2018), https://doi.org/10.1016/j.anl.2018.02.003
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clinical or occult cervical nodal involvement at presentation [7]. Kadish et al. [8] were the first to propose a staging classification, of 3 stages (A–C) for ON, which was later modified by Morita [9], who added stage D indicating metastatic disease. Optimal treatment is still discussed controversially. In adults, Kadish Stage and Hyam’s histological grade have been shown to predict prognosis [10–12]. This has not been validated in children that generally present with more advanced stage disease than in adults, however, their prognosis is better. Most children are treated based on reviews of adult cases and series and based on the findings of a limited number of studies, the gold standard for treatment of ON is craniofacial resection (CFR) followed by adjuvant radiotherapy and/or chemotherapy [13]. Most recently, with the advent of endoscopic technologies, use of a transnasal surgical approach has achieved comparable outcomes to traditional open craniofacial resection [14–16]. Although combined surgery and radiation therapy has produced the best outcomes in adults, in children it can lead to significant long-term morbidity. Herein we describe the pediatric case of a patient with ON treated by radical endoscopic surgery alone with preservation of the contralateral olfactory bulb in order to preserve olfaction. 2. Case report A 13-year-old male referred to our outpatient clinic with a 3 months history of recurrent epistaxis from the right nostril, unilateral nasal obstruction and congestion symptoms without pain or ocular disturbances. Parents referred a normal psychophysical growth, no prior cranio-facial trauma, surgery or hospitalizations and a non-significant family medical history. Antibiotics, systemic anti-inflammatory and topical therapy were before prescribed without benefit. The University of Pennsylvania Smell Identification Test (UPSIT) [17] was administered to assess olfactory function that resulted normal with a score of 35. The video-endoscopic examination with 0 rigid telescope showed a polypoid multi-lobed lesion occupying the right nasal cavity, of dark red color and easily bloody with mechanical stimulation. The base of implant of the lesion was impossible to identify. It was required a MRI plus gadolinium that revealed a lesion with marked enhancement occupying the right nasal cavity and involved the medial wall of the maxillary sinus, extending backwards to the posterior ethmoid and the frontal recess. There was no evidence of orbital, meningeal and cerebral invasion (Fig. 1). CT scan confirmed the presence of the mass occupying the right nasal cavity with ipsilateral involvement of maxillary and ethmoid sinuses, the mass was in contact with the medial orbital wall without evidence of cribriform plate erosion. Because the mass showed a marked enhancement both on CT and MRI, the patient underwent a video endoscopic assisted biopsy under general anesthesia in order to avoid an important bleeding in outpatient setting, in the suspect of a vascular mass. Intraoperative biopsy showed malignant features of the lesion. After fixation, histopathological and immunohistochemical examination were diagnostic for ON with Hyams grade II differentiation. Positron Emission Tomography (PET-CT) scan was performed, with evidence of high metabolisms areas in the right nasal cavity and in a single
right retro-angolo- mandibular lymph node. This latter was examined with a neck ultrasonography that showed a reactive morphologic features of the lymph node. The ON was stage B, according to Kadish classification and T2 according to Dulguerov TNM staging [18]. Treatment management was discussed in our Pediatric Tumor Board with indication to surgical endoscopic resection. The patient underwent an endoscopic sinuses surgery, as first step we realized a debulking of the sinonasal tumour in order to assess the extent of disease and its origin and exclude any involvement of the nasal septum. Then the base of implant of the tumor was removed using a subperiosteal dissection plane, with the centripetal technique obtaining a clean macroscopic surgical field. Intraoperative frozen sections of the contralateral nasal septum mucosa were negative for malignancy. Once the bony of the anterior skull base was exposed, the skull base was drilled out using a diamond burr and last, after resection of the ethmoidal roof and the fovea ethmoidalis, we removed the dura mater of the olfactory cleft and the olfactory bulb (Fig. 2a). The dura was then circumferentially incised with angled scissors and resected at a safe distance from the suspected area of tumour invasion. We verified the surgical field with 11 frozen sections to minimize the risk of recurrence, resulting all free of disease. In our patient, it was possible to anatomically spare the contralateral olfactory cleft. The resulting skull base defect was reconstructed transnasal in a multilayer fashion using free grafts of iliotibial tract. in detail, the first layer was placed in the intradural gap and the second in the epidural one. The duraplasty was then resurfaced using the septal flip flap (SFF), a pedicled flap based on the septal branches of the contralateral ethmoidal arteries. After the preparation of the flap according to the technique described by Battaglia et al. [19] was made a superiorly hinged and freely rotated to cover the anterior skull base defect as a third layer (Fig. 2b). The flap is then properly fixed with fibrin glue and absorbable hemostat and the nasal cavities are packed bilaterally with polyvinyl alcohol sponge for about 48 h. The operation was free of complications, the subsequent pathology report confirmed that all margins were free from disease, in particular we obtained 22 margins to valuate for the definitive examination. Immediate Postoperative MRI and a CT scan revealed no evidence of residual tumor and the preservation of the left olfactory bulb (Fig. 3), and after a new discussion in our Pediatric Tumor Board no adjuvant radiation therapy was prescribed. During clinical follow up olfactory function was investigated by an interview (preserved or loss) and during the last clinical control a new UPSIT test was assessed and shows a normal smell function with a score of 38 at 24 months after surgical treatment. The patient remained disease free at last follow-up of 24 months. 3. Discussion Pediatric ON is a rare disease that usually affects the adolescent age group and due to its rarity, there are no randomized, controlled studies investigating optimal treatment guidelines. First-line treatment for ON is CFR with postoperative radiation therapy, combining a bifrontal craniotomy and transfacial approach to achieve true en bloc resection performed
Please cite this article in press as: Maggiore G, et al. Treatment of pediatric esthesioneuroblastoma with smell preservation. Auris Nasus Larynx (2018), https://doi.org/10.1016/j.anl.2018.02.003
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Fig. 1. Preoperative CT scan and MRI images.
Fig. 2. a and b.
with removal of the sinonasal component of the tumor in conjunction with the cribriform plate, olfactory bulbs, and any involved extracranial and intracranial structures [19]. It still remains an invasive procedure with serious complications (intracranial hemorrhage, CSF leakage, pneumocephalus, and infection) and morbidity [20]. In recent times, the endoscopic endonasal approach has been used in order to decrease treatment-related morbidity to the maximum extent possible and to achieve positive esthetic and functional outcomes [21– 23]. Stammberger et al. [24] first have published in the English literature their experience with endoscopic treatment of nasal malignancies, including esthesioneuroblastomas. In english literature we found numerous other authors that described endoscopic ON resection, with oncologic results comparable
with that of traditional CFR [25,26]. Castelnuovo demonstrated that a purely endoscopic approach can achieve histologically negative surgical margins [27]. With the improvements in endoscopy and instrumentation, complete endoscopic resection of ON has now gained wider acceptance. Numerous studies from multiple tertiary care centers have shown comparable long-term survival between endoscopic and open approaches [10,18,28–33]. Komotar et al. performed a thorough literature review comparing endoscopic approach with CFR and combined open/endonasal (CN) ON resection. The study revealed a greater rate of gross total resection for endoscopic approach cases (98.1%) compared with CFR (81.3%). Negative surgical margins were achieved in 93.8%, 95.8%, and 77.3% of endoscopic approach, CN, and CFR cases, respectively
Please cite this article in press as: Maggiore G, et al. Treatment of pediatric esthesioneuroblastoma with smell preservation. Auris Nasus Larynx (2018), https://doi.org/10.1016/j.anl.2018.02.003
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Fig. 3. Postoperative CT scan and MRI images.
[34]. Rimmer et al. reported local recurrence in 25.3% of their patients overall, with a higher rate in the CFR group compared to the endoscopic group. In the CFR group, 5-year survival was 76.5% and 10-year 67.8%, compared to 100% at both time points in the endoscopic group. DFS for those who underwent CFR was 73.5% at 5 years and 57.1% at 10 years, compared to 96% and 75.6%, respectively, for those treated endoscopically [7]. Olfactory sensory loss is an often-undervalued morbidity for patients after endoscopic procedures at the skull base as highlighted by a recent review by Patel et al. [35] and it is due of the removal of the cribriform plate and bilateral olfactory bulbs because ON is considered to arise from the olfactory neuroepithelium, and thus this approach would remove all potential malignant progenitor cells. Several studies showed that smell preservation is possible with the sparing of the contralateral cribriform and olfactory bulb in early-stage tumors and select patients with unilateral disease without affecting long-term survival or compromising oncologic principles [36– 38]. For our patient we adopted an endoscopic unilateral ON resection, in fact he had a mono lateral disease, without invasion of the contralateral cribriform mucosa at the frozen section and at the definitive pathological examination. We were able to perform a complete and radical resection of the lesion with an endoscopic approach and a brief hospitalization. In the postoperative period, our patient, confirmed the maintenance of his sense of smell. This case provides further support that olfactory preservation should be considered as an end objective, above all in patients with low-grade tumors (Kadish stages A and B) and unilateral disease with a meticulous preoperative planning and respecting oncologic margins. Radiation therapy is generally administered in the postoperative setting, it is very effective for local control of ENB but is associated with the
development of late effects such as craniofacial abnormality, endocrine dysfunction and secondary malignancy. In some instances, radiation therapy was not given due to the patient’s age and due to the rarity of the disease, there is no established standard of care for pediatric ENB. In a pediatric series by El Kababri et al., a 10 month old was treated with surgery and chemotherapy alone due to age and was a long-term survivor [39]. Venkatramani et al. [40] reported three patients treated without radiation therapy; in two patients there was no local relapse while the third patient experienced local relapse one year after diagnosis. In our case after discussion with our Pediatric Tumor Board, due to the negative margins taken with sufficient distant from the tumor, the early stage of the cancer and the age of the patient no adjuvant radiation therapy was prescribed. A radiation therapy could be used also as a salvaged therapy if it is necessary. The use of the septal flip flap for the external layer rather then other autologous free grafts such as fascia lata or iliotibial tract ensured a faster healing process with reduction of nasal crusting and improvement in the quality of life of patients in the postoperative period. Our patient returned to practices a completely normal life with high intensity sport activities, such as soccer. Thorough evaluation of ON resection techniques requires long-term follow-up because recurrence and metastases have been reported up to 10 years after initial treatment [41] and for this reason the follow-up has to be extended over the entire life of the patient. 4. Conclusion ON is the most common cancer of the nasal cavity affected adolescents. An unilateral endoscopic resection in our selected case was possible and it allowed smell preservation with
Please cite this article in press as: Maggiore G, et al. Treatment of pediatric esthesioneuroblastoma with smell preservation. Auris Nasus Larynx (2018), https://doi.org/10.1016/j.anl.2018.02.003
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sparing of the contralateral cribriform and olfactory bulb. Endoscopic endonasal approach and negative margins demonstrated similar oncologic control, reducing postoperative morbidity, mortality and time of hospitalization over traditional transcranial approaches. The use of the septal flip flap ensured greater speed in the healing process, with a reduction of nasal crusting and corresponding patient discomfort. Because the complete resection of the tumour and the age of the patient, the adjuvant radiation therapy was not suggested by our Tumor Pediatric Board. But it remains an option of salvage treatment in case of necessity. Regarding the rarity of this tumor entity in children and adolescents futures studies must incorporate longterm follow up to adequately assess the rate of oncologic cure compared with traditional approaches and to personalize the way of reconstruction most suitable for the necessity of the patients. Ethical statement Our study was approved by the Institutional Review Board, and before submitting it we obtained written informed consent from our patient. The patient’s anonymity was preserved. References [1] Berger L, Luc R, Richard D. Olfactory neuroblastoma [in French]. Bull Assoc Fr Etude Cancer 1924;13:410–21. [2] Broich G, Pagliari A, Ottaviani F. Esthesioneuroblastomas: a general review of the cases published since the discovery of the tumor in 1924. Anticancer Res 1997;17:2683–706. [3] Bradley PJ, Jones NS, Robertson I. Diagnosis and management of esthesioneuroblastoma. Curr Opin Otolaryngol Head Neck Surg 2003;11:112–8. [4] Benoit MM, Bhattacharyya N, Faquin W, Cunningham M. Cancer of the nasal cavity in the pediatric population. Pediatrics 2008;121:141–5. [5] Eich HT, Hero B, Staar S, Micke O, Seegenschmiedt H, Mattke A, et al. Multimodality therapy including radiotherapy and chemotherapy improves event-free survival in stage C esthesioneuroblastoma. Strahlenther Onkol 2003;179:233–40. [6] Dulguerov P, Calcaterra T. Esthesioneuroblastoma: the UCLA experience 1970–1990. Laryngoscope 1992;102:843–9. [7] Rimmer J, Lund VJ, Beale T, Wei WI, Howard D. Olfactory neuroblastoma: a 35-year experience and suggested follow-up protocol. Laryngoscope 2014;124:1542–9. [8] Kadish S, Goodman M, Wang CC. Olfactory neuroblastoma. A clinical analysis of 17 cases. Cancer 1977;37:1571–6. [9] Morita A, Ebersold MJ, Olsen KD, Foote RL, Lewis JE, Quast LM. Esthesioneuroblastoma: prognosis and management. Neurosurgery 1993;32:706–14. discussion 714–705. [10] Jethanamest D, Morris LG, Sikora AG, Kutler DI. Esthesioneuroblastoma: a population-based analysis of survival and prognostic factors. Arch Otolaryngol Head Neck Surg 2007;133:276–80 [PubMed: 17372086]. [11] Bell D, Saade R, Roberts D, Ow TJ, Kupferman M, DeMonte F, et al. Prognostic utility of Hyams histological grading and Kadish-Morita staging systems for esthesioneuroblastoma outcomes. Head Neck Pathol 2015;9(March (1)):51–9. [12] Van Gompel JJ, Giannini C, Olsen KD, Moore E, Piccirilli M, Foote RL, et al. Long-term outcome of esthesioneuroblastoma: hyams grade predicts patient survival. J Neurol Surg B Skull Base 2012;73:331–6. [13] Lund VJ, Howard D, Wei W, Spittle M. Olfactory neuroblastoma: past, present, and future? Laryngoscope 2003;113:502–7. [14] Devaiah AK, Andreoli MT. Treatment of esthesioneuroblastoma: a 16year meta-analysis of 361 patients. Laryngoscope 2009;119:1412–6.
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[15] Bak M, Wein RO. Esthesioneuroblastoma: a contemporary review of diagnosis and management. Hematol Oncol Clin North Am 2012;26:1185–207. [16] Fu TS, Monteiro E, Muhanna N, Goldstein DP, de Almeida JR. Comparison of outcomes for open versus endoscopic approaches for olfactory neuroblastoma: a systematic review and individual participant data meta-analysis. Head Neck 2015;30:2306–16. [17] Doty RL, Shaman P, Kimmelman CP, Dann MS. University of Pennsylvania Smell Identification Test: a rapid quantitative olfactory function test for the clinic. Laryngoscope 1984;94(2 Pt. 1):176–8. [18] Dulguerov P, Allal AS, Calcaterra TC. Esthesioneuroblastoma: a metaanalysis and review. Lancet Oncol 2001;2:683–90. [19] Battaglia P. Septal flip flap for anterior skull base reconstruction after endoscopic resection of sinonasal cancers: preliminary outcomes. Acta Otorhinolaryngol Ital 2016;36:194–8. [20] Schwartz JS, Palmer JN, Adappa ND. Contemporary management of esthesioneuroblastoma. Curr Opin Otolaryngol Head Neck Surg 2016;24:63–9. [21] Levine PA, Gallagher R, Cantrell RW. Esthesioneuroblastoma: reflections of a 21-year experience. Laryngoscope 1999;109:1539–43. [22] Zafereo ME, Fakhri S, Prayson R, Batra PS, Lee J, Lanza DC, et al. Esthesioneuroblastoma: 25-year experience at a single institution. Otolaryngol Head Neck Surg 2008;138:452–8. [23] Soler ZM, Smith TL. Endoscopic versus open craniofacial resection of esthesio neuroblastoma: what is the evidence? Laryngoscope 2012;122:244–5. [24] Stammberger H, Anderhuber W, Walch C. Possibilities and limitations of endoscopic management of nasal and paranasal sinus malignancies. Acta Otorhinolaryngol Belg 1999;53:199–205. [25] Batra PS, Citardi MJ, Worley S, Lee J, Lanza DC. Resection of anterior skull base tumors: comparison of combined traditional and endoscopic techniques. Am J Rhinol 2005;19(5):521–8. [26] Casiano RR, Numa WA, Falquez AM. Endoscopic resection of esthesioneuroblastoma. Am J Rhinol 2001;15(4):271–9. [27] Castelnuovo P, Delu` G, Sberze F, Pistochini A, Cambria C, Battaglia P, et al. Esthesioneuoblastoma: endonasal endoscopic treatment. Skull Base 2006;16:25–30. [28] Tajudeen BA, Arshi A, Suh JD, Palma-Diaz MF, Bergsneider M, Abemayor E, et al. Esthesioneuroblastoma: an update on the UCLA experience, 2002–2013. J Neurol Surg B Skull Base 2015;76:43–9. [29] Eloy JA, Vivero RJ, Hoang K, Civantos FJ, Weed DT, Marcos JJ, et al. Comparison of transnasal endoscopic and open craniofacial resection for malignant tumors of the anterior skull base. Laryngoscope 2009;119:834–40. [30] Gallia GL, Reh DD, Salmasi V, Blitz AM, Koch W, Ishii M. Endonasal endoscopic resection of esthesioneuroblastoma: the Johns Hopkins Hospital experience and review of the literature. Neurosurg Rev 2011;34:465–75. [31] Song CM, Won TB, Lee CH, Kim DY, Rhee CS. Treatment modalities and outcomes of olfactory neuroblastoma. Laryngoscope 2012;122:2389–95. [32] Nabili V, Kelly DF, Fatemi N, St John M, Calcaterra TC, Abemayor E. Transnasal, transfacial, anterior skull base resection of olfactory neuroblastoma. Am J Otolaryngol 2011;32:279–85. [33] Nalavenkata SB, Sacks R, Adappa ND, Palmer JN, Purkey MT, Feldman MD, et al. Olfactory neuroblastoma: fate of the Neck—a long-term multicenter retrospective study. Otolaryngol Head Neck Surg 2015;154(2):283–9. [34] Komotar RJ, Starke RM, Raper DM, Anand VK, Schwartz TH. Endoscopic endonasal compared with anterior craniofacial and combined cranionasal resection of esthesioneuroblastomas. World Neurosurg 2013;80(1–2):148–59. [35] Patel ZM, DelGaudio JM. Olfaction following endoscopic skull base surgery. Curr Opin Otolaryngol Head Neck Surg 2016;24:70–4. [36] Wessell A, Singh A, Litvack Z. Preservation of olfaction after unilateral endoscopic approach for resection of esthesioneuroblastoma. Neurol Surg Rep 2014;75:e149–53. [37] Nakagawa T, Kodama S, Kobayashi M, Sanki T, Tanaka S, Hanai N, et al. Endoscopic endonasal management of esthesioneuroblastoma: a
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retrospective multicenter study. Auris Nasus Larynx 2017;8146 (17):30348–56. [38] Tajudeen BA, Adappa ND, Kuan EC. Smell preservation following endoscopic unilateral resection of esthesioneuroblastoma: a multiinstitutional experience. Int Forum Allergy Rhinol 2016;6 (10):1047–50. [39] Kababri M, El Habrand JL, Valteau-Couanet D, Gaspar N, Dufour C, Oberlin O. Esthesioneuroblastoma in children and adolescent: experi-
ence on 11 cases with literature review. J Pediatr Hematol Oncol 2014;36:91–5 [PubMed: 24390450]. [40] Venkatramani R, Pan H, Furman WL, Marron JM, Haduong J, Friedrich-Medina P, et al. Multimodality treatment of pediatric esthesioneuroblastoma. Pediatr Blood Cancer 2016;63:465–70. [41] Loy AH, Reibel JF, Read PW, Thomas CY, Newman SA, Jane JA, et al. Esthesioneuroblastoma: continued follow-up of a single institution’s experience. Arch Otolaryngol Head Neck Surg 2006;132:134–8.
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ANL-2419; No. of Pages 6 Auris Nasus Larynx xxx (2018) xxx–xxx Contents lists available at ScienceDirect
Auris Nasus Larynx journal homepage: www.elsevier.com/locate/anl
Case report
Treatment of pediatric esthesioneuroblastoma with smell preservation Giandomenico Maggiore, Maria Silvia Lazio *, Oreste Gallo Clinic of Otolaryngology, Head and Neck Surgery, Department of Translational Surgery and Medicine, University of Florence, Italy
A R T I C L E I N F O
A B S T R A C T
Article history: Received 31 October 2017 Accepted 6 February 2018 Available online xxx
Olfactory neuroblastoma is a rare malignant tumor of neuroectodermal origin and represents the most common cancer of the nasal cavity in pediatric age. The gold standard of treatment consists of en bloc resection, numerous studies have shown as the endoscopic approaches permit good control of the disease improving the quality of life after the treatment. Herein we describe the case of a 13year-old patient referred to our outpatient clinic with a polypoid multi-lobed lesion occupying the left nasal cavity and imaging that confirmed a left-sided nasal mass without cribriform plate involvement (Kadish B). We performed an unilateral endoscopic resection with transnasal craniectomy and anterior skull base reconstruction with a flap from the contralateral nasal septum based on the septal branches of the anterior and posterior ethmoidal arteries (Septal Flip Flap, SFF), that provided a faster healing process with reduction of nasal crusting, improvement in the quality of life of patient in the postoperative period and the preservation of the contralateral olfactory bulb that has allowed to save the smell. This treatment strategy of pediatric esthesioneuroblastoma was analyzed in the context of the current literature. © 2018 Elsevier B.V. All rights reserved.
Keywords: Paranasal tumors Olfactory neuroblastoma Esthesioneuroblastoma Smell preservation Sinonasal malignances
1. Introduction Olfactory neuroblastoma (ON), also known as esthesioneuroblastoma (ENB) was described by Berger in 1924, who described an “esthesioneuroepitheliome olfactif” [1]. Since the first description about 1000 cases have been reported in the world literature [2]. It represents about 3%–5% of all malignant nasal tumors [3] and has a bimodal age distribution, between 10 and 20 years and between 50 and 60 years. In pediatric age, the estimated incidence of ON is 0.1/100.000 children up to 15 years of age, but it is the most common cancer of the nasal cavity [4,5]. Tumor etiopathogenesis of ON is not yet clear, there are no known etiologic agent(s) for human olfactory neuroblastoma demonstrated. The main presenting symptoms * Corresponding author at: Clinic of Otolaryngology, Head and Neck Surgery, University of Florence, via Largo Brambilla, 3-50134 Firenze, Italy. E-mail address: [email protected] (M.S. Lazio).
are unilateral nasal obstruction (70%) and epistaxis (46%); less common manifestations include anosmia, headache, pain, excessive lacrimation and ocular disturbances, these symptoms are related to the site and local invasion of the tumor. Diagnosis is often made late because they are asymptomatic or produce nonspecific symptoms in their early stages, the mean delay between the appearance of the first symptom and the diagnosis being 6 months [6]. ON does not have any specific radiologic appearance and when seen, it is a homogenous soft-tissue mass in the nasal vault, with uniform and moderate contrast enhancement. Computed tomography (CT) images are essential for correct staging and they should be carefully examined for erosion of the lamina papyracea, cribriform plate, and fovea ethmoidalis. Magnetic resonance imaging (MRI) enables a better estimate of tumor spread into surrounding soft-tissue areas and can differentiate mucus from tumor, also showing any possible intraorbital or intracerebral extension. Regional and metastatic dissemination occurs, with 8–20% of patients having
https://doi.org/10.1016/j.anl.2018.02.003 0385-8146/© 2018 Elsevier B.V. All rights reserved.
Please cite this article in press as: Maggiore G, et al. Treatment of pediatric esthesioneuroblastoma with smell preservation. Auris Nasus Larynx (2018), https://doi.org/10.1016/j.anl.2018.02.003
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clinical or occult cervical nodal involvement at presentation [7]. Kadish et al. [8] were the first to propose a staging classification, of 3 stages (A–C) for ON, which was later modified by Morita [9], who added stage D indicating metastatic disease. Optimal treatment is still discussed controversially. In adults, Kadish Stage and Hyam’s histological grade have been shown to predict prognosis [10–12]. This has not been validated in children that generally present with more advanced stage disease than in adults, however, their prognosis is better. Most children are treated based on reviews of adult cases and series and based on the findings of a limited number of studies, the gold standard for treatment of ON is craniofacial resection (CFR) followed by adjuvant radiotherapy and/or chemotherapy [13]. Most recently, with the advent of endoscopic technologies, use of a transnasal surgical approach has achieved comparable outcomes to traditional open craniofacial resection [14–16]. Although combined surgery and radiation therapy has produced the best outcomes in adults, in children it can lead to significant long-term morbidity. Herein we describe the pediatric case of a patient with ON treated by radical endoscopic surgery alone with preservation of the contralateral olfactory bulb in order to preserve olfaction. 2. Case report A 13-year-old male referred to our outpatient clinic with a 3 months history of recurrent epistaxis from the right nostril, unilateral nasal obstruction and congestion symptoms without pain or ocular disturbances. Parents referred a normal psychophysical growth, no prior cranio-facial trauma, surgery or hospitalizations and a non-significant family medical history. Antibiotics, systemic anti-inflammatory and topical therapy were before prescribed without benefit. The University of Pennsylvania Smell Identification Test (UPSIT) [17] was administered to assess olfactory function that resulted normal with a score of 35. The video-endoscopic examination with 0 rigid telescope showed a polypoid multi-lobed lesion occupying the right nasal cavity, of dark red color and easily bloody with mechanical stimulation. The base of implant of the lesion was impossible to identify. It was required a MRI plus gadolinium that revealed a lesion with marked enhancement occupying the right nasal cavity and involved the medial wall of the maxillary sinus, extending backwards to the posterior ethmoid and the frontal recess. There was no evidence of orbital, meningeal and cerebral invasion (Fig. 1). CT scan confirmed the presence of the mass occupying the right nasal cavity with ipsilateral involvement of maxillary and ethmoid sinuses, the mass was in contact with the medial orbital wall without evidence of cribriform plate erosion. Because the mass showed a marked enhancement both on CT and MRI, the patient underwent a video endoscopic assisted biopsy under general anesthesia in order to avoid an important bleeding in outpatient setting, in the suspect of a vascular mass. Intraoperative biopsy showed malignant features of the lesion. After fixation, histopathological and immunohistochemical examination were diagnostic for ON with Hyams grade II differentiation. Positron Emission Tomography (PET-CT) scan was performed, with evidence of high metabolisms areas in the right nasal cavity and in a single
right retro-angolo- mandibular lymph node. This latter was examined with a neck ultrasonography that showed a reactive morphologic features of the lymph node. The ON was stage B, according to Kadish classification and T2 according to Dulguerov TNM staging [18]. Treatment management was discussed in our Pediatric Tumor Board with indication to surgical endoscopic resection. The patient underwent an endoscopic sinuses surgery, as first step we realized a debulking of the sinonasal tumour in order to assess the extent of disease and its origin and exclude any involvement of the nasal septum. Then the base of implant of the tumor was removed using a subperiosteal dissection plane, with the centripetal technique obtaining a clean macroscopic surgical field. Intraoperative frozen sections of the contralateral nasal septum mucosa were negative for malignancy. Once the bony of the anterior skull base was exposed, the skull base was drilled out using a diamond burr and last, after resection of the ethmoidal roof and the fovea ethmoidalis, we removed the dura mater of the olfactory cleft and the olfactory bulb (Fig. 2a). The dura was then circumferentially incised with angled scissors and resected at a safe distance from the suspected area of tumour invasion. We verified the surgical field with 11 frozen sections to minimize the risk of recurrence, resulting all free of disease. In our patient, it was possible to anatomically spare the contralateral olfactory cleft. The resulting skull base defect was reconstructed transnasal in a multilayer fashion using free grafts of iliotibial tract. in detail, the first layer was placed in the intradural gap and the second in the epidural one. The duraplasty was then resurfaced using the septal flip flap (SFF), a pedicled flap based on the septal branches of the contralateral ethmoidal arteries. After the preparation of the flap according to the technique described by Battaglia et al. [19] was made a superiorly hinged and freely rotated to cover the anterior skull base defect as a third layer (Fig. 2b). The flap is then properly fixed with fibrin glue and absorbable hemostat and the nasal cavities are packed bilaterally with polyvinyl alcohol sponge for about 48 h. The operation was free of complications, the subsequent pathology report confirmed that all margins were free from disease, in particular we obtained 22 margins to valuate for the definitive examination. Immediate Postoperative MRI and a CT scan revealed no evidence of residual tumor and the preservation of the left olfactory bulb (Fig. 3), and after a new discussion in our Pediatric Tumor Board no adjuvant radiation therapy was prescribed. During clinical follow up olfactory function was investigated by an interview (preserved or loss) and during the last clinical control a new UPSIT test was assessed and shows a normal smell function with a score of 38 at 24 months after surgical treatment. The patient remained disease free at last follow-up of 24 months. 3. Discussion Pediatric ON is a rare disease that usually affects the adolescent age group and due to its rarity, there are no randomized, controlled studies investigating optimal treatment guidelines. First-line treatment for ON is CFR with postoperative radiation therapy, combining a bifrontal craniotomy and transfacial approach to achieve true en bloc resection performed
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Fig. 1. Preoperative CT scan and MRI images.
Fig. 2. a and b.
with removal of the sinonasal component of the tumor in conjunction with the cribriform plate, olfactory bulbs, and any involved extracranial and intracranial structures [19]. It still remains an invasive procedure with serious complications (intracranial hemorrhage, CSF leakage, pneumocephalus, and infection) and morbidity [20]. In recent times, the endoscopic endonasal approach has been used in order to decrease treatment-related morbidity to the maximum extent possible and to achieve positive esthetic and functional outcomes [21– 23]. Stammberger et al. [24] first have published in the English literature their experience with endoscopic treatment of nasal malignancies, including esthesioneuroblastomas. In english literature we found numerous other authors that described endoscopic ON resection, with oncologic results comparable
with that of traditional CFR [25,26]. Castelnuovo demonstrated that a purely endoscopic approach can achieve histologically negative surgical margins [27]. With the improvements in endoscopy and instrumentation, complete endoscopic resection of ON has now gained wider acceptance. Numerous studies from multiple tertiary care centers have shown comparable long-term survival between endoscopic and open approaches [10,18,28–33]. Komotar et al. performed a thorough literature review comparing endoscopic approach with CFR and combined open/endonasal (CN) ON resection. The study revealed a greater rate of gross total resection for endoscopic approach cases (98.1%) compared with CFR (81.3%). Negative surgical margins were achieved in 93.8%, 95.8%, and 77.3% of endoscopic approach, CN, and CFR cases, respectively
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Fig. 3. Postoperative CT scan and MRI images.
[34]. Rimmer et al. reported local recurrence in 25.3% of their patients overall, with a higher rate in the CFR group compared to the endoscopic group. In the CFR group, 5-year survival was 76.5% and 10-year 67.8%, compared to 100% at both time points in the endoscopic group. DFS for those who underwent CFR was 73.5% at 5 years and 57.1% at 10 years, compared to 96% and 75.6%, respectively, for those treated endoscopically [7]. Olfactory sensory loss is an often-undervalued morbidity for patients after endoscopic procedures at the skull base as highlighted by a recent review by Patel et al. [35] and it is due of the removal of the cribriform plate and bilateral olfactory bulbs because ON is considered to arise from the olfactory neuroepithelium, and thus this approach would remove all potential malignant progenitor cells. Several studies showed that smell preservation is possible with the sparing of the contralateral cribriform and olfactory bulb in early-stage tumors and select patients with unilateral disease without affecting long-term survival or compromising oncologic principles [36– 38]. For our patient we adopted an endoscopic unilateral ON resection, in fact he had a mono lateral disease, without invasion of the contralateral cribriform mucosa at the frozen section and at the definitive pathological examination. We were able to perform a complete and radical resection of the lesion with an endoscopic approach and a brief hospitalization. In the postoperative period, our patient, confirmed the maintenance of his sense of smell. This case provides further support that olfactory preservation should be considered as an end objective, above all in patients with low-grade tumors (Kadish stages A and B) and unilateral disease with a meticulous preoperative planning and respecting oncologic margins. Radiation therapy is generally administered in the postoperative setting, it is very effective for local control of ENB but is associated with the
development of late effects such as craniofacial abnormality, endocrine dysfunction and secondary malignancy. In some instances, radiation therapy was not given due to the patient’s age and due to the rarity of the disease, there is no established standard of care for pediatric ENB. In a pediatric series by El Kababri et al., a 10 month old was treated with surgery and chemotherapy alone due to age and was a long-term survivor [39]. Venkatramani et al. [40] reported three patients treated without radiation therapy; in two patients there was no local relapse while the third patient experienced local relapse one year after diagnosis. In our case after discussion with our Pediatric Tumor Board, due to the negative margins taken with sufficient distant from the tumor, the early stage of the cancer and the age of the patient no adjuvant radiation therapy was prescribed. A radiation therapy could be used also as a salvaged therapy if it is necessary. The use of the septal flip flap for the external layer rather then other autologous free grafts such as fascia lata or iliotibial tract ensured a faster healing process with reduction of nasal crusting and improvement in the quality of life of patients in the postoperative period. Our patient returned to practices a completely normal life with high intensity sport activities, such as soccer. Thorough evaluation of ON resection techniques requires long-term follow-up because recurrence and metastases have been reported up to 10 years after initial treatment [41] and for this reason the follow-up has to be extended over the entire life of the patient. 4. Conclusion ON is the most common cancer of the nasal cavity affected adolescents. An unilateral endoscopic resection in our selected case was possible and it allowed smell preservation with
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sparing of the contralateral cribriform and olfactory bulb. Endoscopic endonasal approach and negative margins demonstrated similar oncologic control, reducing postoperative morbidity, mortality and time of hospitalization over traditional transcranial approaches. The use of the septal flip flap ensured greater speed in the healing process, with a reduction of nasal crusting and corresponding patient discomfort. Because the complete resection of the tumour and the age of the patient, the adjuvant radiation therapy was not suggested by our Tumor Pediatric Board. But it remains an option of salvage treatment in case of necessity. Regarding the rarity of this tumor entity in children and adolescents futures studies must incorporate longterm follow up to adequately assess the rate of oncologic cure compared with traditional approaches and to personalize the way of reconstruction most suitable for the necessity of the patients. Ethical statement Our study was approved by the Institutional Review Board, and before submitting it we obtained written informed consent from our patient. The patient’s anonymity was preserved. References [1] Berger L, Luc R, Richard D. Olfactory neuroblastoma [in French]. Bull Assoc Fr Etude Cancer 1924;13:410–21. [2] Broich G, Pagliari A, Ottaviani F. Esthesioneuroblastomas: a general review of the cases published since the discovery of the tumor in 1924. Anticancer Res 1997;17:2683–706. [3] Bradley PJ, Jones NS, Robertson I. Diagnosis and management of esthesioneuroblastoma. Curr Opin Otolaryngol Head Neck Surg 2003;11:112–8. [4] Benoit MM, Bhattacharyya N, Faquin W, Cunningham M. Cancer of the nasal cavity in the pediatric population. Pediatrics 2008;121:141–5. [5] Eich HT, Hero B, Staar S, Micke O, Seegenschmiedt H, Mattke A, et al. Multimodality therapy including radiotherapy and chemotherapy improves event-free survival in stage C esthesioneuroblastoma. Strahlenther Onkol 2003;179:233–40. [6] Dulguerov P, Calcaterra T. Esthesioneuroblastoma: the UCLA experience 1970–1990. Laryngoscope 1992;102:843–9. [7] Rimmer J, Lund VJ, Beale T, Wei WI, Howard D. Olfactory neuroblastoma: a 35-year experience and suggested follow-up protocol. Laryngoscope 2014;124:1542–9. [8] Kadish S, Goodman M, Wang CC. Olfactory neuroblastoma. A clinical analysis of 17 cases. Cancer 1977;37:1571–6. [9] Morita A, Ebersold MJ, Olsen KD, Foote RL, Lewis JE, Quast LM. Esthesioneuroblastoma: prognosis and management. Neurosurgery 1993;32:706–14. discussion 714–705. [10] Jethanamest D, Morris LG, Sikora AG, Kutler DI. Esthesioneuroblastoma: a population-based analysis of survival and prognostic factors. Arch Otolaryngol Head Neck Surg 2007;133:276–80 [PubMed: 17372086]. [11] Bell D, Saade R, Roberts D, Ow TJ, Kupferman M, DeMonte F, et al. Prognostic utility of Hyams histological grading and Kadish-Morita staging systems for esthesioneuroblastoma outcomes. Head Neck Pathol 2015;9(March (1)):51–9. [12] Van Gompel JJ, Giannini C, Olsen KD, Moore E, Piccirilli M, Foote RL, et al. Long-term outcome of esthesioneuroblastoma: hyams grade predicts patient survival. J Neurol Surg B Skull Base 2012;73:331–6. [13] Lund VJ, Howard D, Wei W, Spittle M. Olfactory neuroblastoma: past, present, and future? Laryngoscope 2003;113:502–7. [14] Devaiah AK, Andreoli MT. Treatment of esthesioneuroblastoma: a 16year meta-analysis of 361 patients. Laryngoscope 2009;119:1412–6.
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