Otolaryngology Case Reports (2017) 33e36 Contents lists available at ScienceDirect Otolaryngology Case Reports journal homepage: www.otolaryngologycasereports.com Multifocal inverting papilloma of the sinonasal cavity and temporal bone Jonnae Y Barry, MD a, *, Christopher H Le, MD a, Rihan Khan, MD b, Abraham Jacob, MD a, Alexander G Chiu, MD a, a Department of OtolaryngologyeHead and Neck Surgery, Banner University Medical Center, 1501 N Campbell Ave., PO Box 245074, Tucson, AZ 85724, United States Department of Radiology, Banner University Medical Center, 1501 N Campbell Ave., PO Box 245067, Tucson, AZ 85724, United States b a r t i c l e i n f o a b s t r a c t Article history: Received September 2016 Accepted January 2017 Available online 16 February 2017 Introduction: Inverting papillomas (IPs) represent the most common benign neoplasm of the sinonasal cavity and are known for local invasion, proclivity for recurrence, and risk of malignant transformation IP of the temporal bone (TBIP) is exceptionally rare, with 32 reported cases We present a new case of multifocal IP of the sinonasal cavity and temporal bone Methods: Case report and review of the literature Results: A 45-year-old man presented with a left sided biopsy proven IP and associated left sided hearing loss Imaging demonstrated a left sided nasal mass and a separate non-contiguous soft tissue mass filling the left middle ear without involvement of the eustachian tube He underwent an endonasal endoscopic gross total resection of the sinonasal lesion and biopsy of the middle ear mass with pathology showing IP He subsequently underwent a left sided transtemporal resection of the TBIP Review of the literature, revealed 32 TBIP cases, with 59% having history of associated sinonasal IP and 41% with isolated temporal bone disease Over half of the patients demonstrated recurrence In comparison to patients with history of sinonasal IP, isolated TBIP occurred in younger patients, was more common in females, and had less association with HPV and malignant transformation Conclusion: TBIP is extraordinarily rare and usually presents with a history of sinonasal IP Isolated TBIP may be a distinctly different disease process Disease recurrence is common and risk of malignant transformation is present, so aggressive initial surgical treatment with gross total resection is advocated © 2017 Published by Elsevier Inc This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/) Keywords: Inverted papilloma Sinonasal tumor Schneiderian Introduction Inverting papilloma within the temporal bone (TBIP) is extremely rare with only 32 reported cases in the literature [1] Sinonasal inverted papilloma (IP) is a benign, but locally aggressive neoplasm, which most often originates from the lateral nasal wall and represents between 0.5% and 4% of all sinonasal tumors [2] There is a risk for transformation into squamous cell carcinoma and recurrence is common [3e7] TBIP has a higher rate of * Corresponding author Department of Otolaryngology-Head and Neck surgery, The University of Arizona College of Medicine, 1501 N Campbell Ave., PO Box 245074, Tucson, AZ 85724, United States E-mail address: jonnaeb@oto.arizon.edu (J.Y Barry) Present address: Department of OtolaryngologyeHead and Neck Surgery University of Kansas Medical Center 3901 Rainbow Boulevard Kansas City, KS 66160, United States transformation to SCC at 36% compared to IP within the nasal cavity which has been estimated to have rates between 5% and 21% [8] Involvement of the temporal bone is hypothesized to occur via several mechanisms including transmission of cells via the eustachian tube, direct extension through the eustachian tube, iatrogenic implantation or seeding, or from stimulation or conversion of residual Schneiderian mucosa within the middle ear by such triggers as chronic otitis media [1,9] Of the 32 cases previously reported, 13 had isolated TBIP without sinus involvement [1] The mean age of presentation was 52 and most commonly patients presented with hearing loss and otorrhea [1] We present a case of TBIP in a patient with concurrent IP of the sinonasal cavity Case report A 45-year-old man presented with two-year history of left-sided nasal obstruction, anosmia and diminished hearing The referring http://dx.doi.org/10.1016/j.xocr.2017.01.004 2468-5488/© 2017 Published by Elsevier Inc This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/) 34 J.Y Barry et al / Otolaryngology Case Reports (2017) 33e36 community ENT had obtained a biopsy of a left-sided nasal mass, which was consistent with IP A computed tomography (CT) scan demonstrated a large mass filling the entire left nasal cavity, ethmoid, and sphenoid sinuses, extension into nasopharynx with thinning of the medial orbital wall and cribiform plate Magnetic resonance imaging (MRI) demonstrated characteristic findings of IP including frond-like heterogeneous enhancement of the lesion (Fig 1A and B) Additionally, a similar soft tissue mass was seen in the left middle ear surrounding the ossicles (Fig 1C, E, F) The nasal mass appeared separate from the soft tissue mass filling the left middle ear, and there was no involvement of the Eustachian tube (Fig 1D) The patient underwent an endonasal endoscopic gross total resection of the sinonasal tumor The lesion was pedicled off of the posterior superior septum and did not extend into the Eustachian tube (Fig 2) The mass abutted but did not erode through the cribiform plate or involve the mucosa of the anterior skull base, and final pathology was consistent with inverted papilloma having high-grade dysplasia (Fig 4B) At the end of the endonasal endoscopic surgical resection, the left ear was examined and myringotomy performed revealing a polypoid mass within the middle ear space A biopsy of this mass was obtained and demonstrated IP The patient subsequently underwent left transotic resection of the extradural TBIP approximately two months after his sinonasal resection, allowing him time to heal from his endonasal operation and come to terms with the multifocal nature of his disease (Fig 3) Unfortunately, in these intervening two-months, the patient had progression of disease in his temporal bone with new symptoms of worsening hearing and vertigo/disequilibrium To remove the entire lesion, which was found to extend into the vestibule and cochlea, the ear canal was closed, a fallopian bridge technique was utilized, and complete labyrinthectomy was performed The Eustachian tube was also dissected mm from its protympanic orifice prior to obliteration; here biopsies obtained that were negative for IP Final pathology of the main tumor mass demonstrated inverted papilloma with high-grade dysplasia (Fig 4A), similar to the specimens previously obtained from the nose The patient has healed well from his operation and has been disease free for 9-months Discussion Ward first described sinonasal inverting papilloma in 1854 The pathogenesis of the disease, however, remains largely unclear Historically, risk factors for IP were smoking, allergy, occupational exposures, or viral infection, particularly HPV [10e12] Although extensively studied, HPV infection as an etiology is still controversial A recent study by Roh and colleagues argues against its involvement This study utilized PCR to target HPV DNA from sinonasal IP specimens, which was then genotyped They found only 14.8% of their study participants tumors contained HPV DNA, and none of the HPV positive patients were found to have recurrence with mean follow-up of 34.1 months [13] Their study group population contained 13% smokers Interestingly, of the patients with recurrent IP, 42.9% of them were smokers e suggesting that smoking may be a greater risk factor than HPV [13] A recent metaanalysis examined HPV infection and risk for malignant transformation in sinonasal IP and found a significant association between the two, especially with those infected with HPV-18 types [14] Fig A Axial T1 MRI with contrast and B Axial T2 MRI demonstrate a large intranasal mass (asterisk) A portion of the mass at the sphenoid sinuses (circle) demonstrates frond like heterogeneous enhancement with a “mini-brain” appearance characteristic of inverted papilloma More anteriorly the heterogeneity is lost consistent with pathologic findings of degeneration to high grade dysplasia C Axial T2 MRI demonstrating the large intranasal mass (asterisk) and trapped secretions in the left maxillary sinus (short arrow) as well as effusion of the left mastoid (long arrow), inverted papilloma (circle) with a more dark appearance D Coronal T1 MRI with contrast enhancing inverted papilloma throughout the middle ear cavity, surrounding the ossicles (tip of arrow) E DWI shows bright signal (circle) and ADC map (F.) Show dark signal (circle) indicative of restricted diffusion from tumor cellularity in the middle ear J.Y Barry et al / Otolaryngology Case Reports (2017) 33e36 35 Fig A Characteristic irregular grey to brown gelatinous and frond like mass of inverted papilloma filling the left nasal cavity B Tumor site of attachment (asterisk) to the left superior septum (arrow) C Left nasopharynx with mass (asterisk) and uninvolved eustachian tube (arrow) Fig A Inverted papilloma (arrow) seen extending into the external auditory canal through a perforation in the left tympanic membrane (asterisk) B Tumor (asterisks) involving the epitympanum and mastoid antrum (asterisk), with extension to the tegmen tympani (arrow) C Tumor extending into the cochlea through the round window (long arrow) The protympanic eustachian tube orifice (short arrow) is free of disease Fig H&E stained specimens consistent with inverted papilloma in both (A) the middle ear and (B) The intranasal mass C Immunostaining for p16 was negative The pathogenesis of multifocal IP is perplexing A recent systematic review by Carlson et al revealed 32 TBIP cases, with 59% having history of associated sinonasal IP and 41% with isolated temporal bone disease [1] Of the patients with TBIP, over half of the patients demonstrated recurrence of disease following microsurgical resection [1] They also found that in comparison to patients with history of sinonasal IP, isolated TBIP occurred in younger patients, was more common in females, and had less association with HPV and malignant transformation [1] Patients with secondary TBIP had an associated carcinoma 47% of the time in their review [1] Attempts to identify differences between sinonasal and temporal bone IP have also failed to differentiate them as separate pathologic entities [15] Proposed mechanisms for development of multifocal disease include direct extension, multicentric primary development, and rests of ectopic Schneiderian mucosa; however, no dominant hypothesis has emerged The mainstay of treatment for IP of the paranasal sinuses is aggressive primary resection with surveillance given the proclivity for recurrence [16] Although surgical resection should serve as the primary treatment option for IP, there may be a role for radiation therapy Some recommend the consideration of radiation therapy for those patients with malignant conversion, multiple recurrent IPs, or in those in whom complete resection is not possible [17] Unlike head and neck malignancies, there are no established guidelines for surveillance IP, although benign in and of itself, does carry the risk of transformation to squamous cell carcinoma and also has a high recurrence rate for incompletely resected lesions As such, surveillance for early detection of recurrence is critical As recommended by Suh and Chiu in 2014, it may be judicious to base surveillance for IP on the more standardized recommendations for squamous cell carcinoma of the head and neck [18] Though IP can recur > years after initial treatment, the majority of recurrences will occur within the first years following surgery [19] 36 J.Y Barry et al / Otolaryngology Case Reports (2017) 33e36 Additionally, Mirza and coworkers identified 7.1% synchronous carcinoma and 3.6% metachronous carcinomas and that the mean time to metachronous lesion development was 52-months, further supporting that long-term follow-up and close surveillance is prudent [20] An example surveillance regimen may include complete examination including nasal endoscopy every 1e3 months for the first year, every 2e6 months for the second year, every 4e8 months for years 3e5 and yearly thereafter [21] Post-treatment imaging may also serve an important role in surveillance especially when patients develop concerning signs or symptoms or when sites previously involved are difficult to visualize e frontal sinuses or middle ear spaces A contrast enhanced magnetic resonance image (MRI) is thought to be the best imaging modality to detect recurrence [18] Formal recommendations for imaging or surveillance when the temporal bone is involved are also lacking, even with risk for malignant transformation being much higher than for isolated sinonasal IP Conclusion TBIP is exceptionally rare and typically presents with a history of sinonasal IP Clinicians should consider the possibility of multifocal disease, especially in patients presenting with seemingly unrelated symptoms such as hearing loss Isolated TBIP may be a distinct disease process, and its pathogenesis is not clear Disease recurrence is common and risk of malignant transformation is high; therefore, aggressive surgical treatment with diligent and longterm surveillance is prudent Source of funding None Conflicts of interest None Presentations This manuscript was presented as a poster at the American Rhinologic Society Spring meeting in Chicago, Illinois on September 16 and 17, 2016 Acknowledgements The authors thank Dr Zahra Aly MD, PhD for her technical assistance and provision of pathologic specimen photographs contained within this manuscript References [1] Carlson ML, Sweeney AD, Modest MC, Van Gompel JJ, Haynes DS, Neff BA Inverting papilloma of the temporal bone: report of four new cases and systematic review of the literature Laryngoscope 2015;125:2576e83 [2] Mitchell CA, Ebert CS, Buchman CA, Zanation AM Combined transnasal/ transtemporal management of the eustachian tube for middle ear inverted papilloma Laryngoscope 2012;122:1674e8 [3] Liu ZW, Walden A, Lee CA Sinonasal inverted papilloma involving the temporal bone via the eustachian tube: case report J Laryngol Otol 2013;127: 318e20 [4] Ramey SJ, Russo JK, Condrey 3rd JM, Coulter B, Sharma AK Synchronous bilateral inverted papilloma of the temporal bone: case report and review of the literature Head Neck 2013;35:E240e5 [5] Dingle I, Stachiw N, Bartlett A, Lambert P Bilateral inverted papilloma of the middle ear with intracranial involvement and malignant transformation: first reported case Laryngoscope 2012;122:1615e9 [6] Shen J, Baik F, Mafee MF, Peterson M, Nguyen QT Inverting papilloma of the temporal bone: case report and meta-analysis of risk factors Otol Neurotol 2011;32:1124e33 [7] Gaio E, Marioni G, Blandamura S, Staffieri A Inverted papilloma involving the temporal bone and its association with squamous cell carcinoma: critical analysis of the literature Expert Rev Anticancer Ther 2005;5:391e7 [8] de Filippis C, Marioni G, Tregnaghi A, Marino F, Gaio E, Staffieri A Primary inverted papilloma of the middle ear and mastoid Otol Neurotol 2002;23: 555e9 [9] Kainuma K, Kitoh R, Kenji S, Usami S Inverted papilloma of the middle ear: a case report and review of the literature Acta Otolaryngol 2011;131:216e20 [10] Buchwald C, Franzmann MB, Tos M Sinonasal papillomas: a report of 82 cases in Copenhagen County, including a longitudinal epidemiological and clinical study Laryngoscope 1995;105:72e9 [11] Scheel A, Lin GC, McHugh JB, Komarck CM, Walline HM, Prince ME, et al Human papillomavirus infection and biomarkers in sinonasal inverted papillomas: clinical significance and molecular mechanisms Int Forum Allergy Rhinol 2015;5:701e7 [12] d'Errico A, Zajacova J, Cacciatore A, Baratti A, Zanelli R, Alfonzo S, et al Occupational risk factors for sinonasal inverted papilloma: a case-control study Occup Environ Med 2013;70:703e8 [13] Roh HJ, Mun SJ, Cho KS, Hong SL Smoking, not human papilloma virus infection, is a risk factor for recurrence of sinonasal inverted papilloma Am J Rhinol Allergy 2016;30:79e82 [14] Zhao RW, Guo ZQ, Zhang RX Human papillomavirus infection and the malignant transformation of sinonasal inverted papilloma: a meta-analysis J Clin Virol 2016;79:36e43 [15] Blandamura S, Marioni G, de Filippis C, Giacomelli L, Segato P, Staffieri A Temporal bone and sinonasal inverted papilloma: the same pathological entity? Arch Otolaryngol Head Neck Surg 2003;129:553e6 [16] Sharma J, Goldenberg D, Crist H, McGinn J Multifocal inverted papillomas in the head and neck Ear Nose Throat J 2015;94:E20e3 [17] Rutenberg M, Kirwan J, Morris CG, Werning JW, Mendenhall WM Radiation therapy for sinonasal inverted papilloma Pract Radiat Oncol 2013;3:275e81 [18] Suh JD, Chiu AG What are the surveillance recommendations following resection of sinonasal inverted papilloma? Laryngoscope 2014;124:1981e2 [19] Busquets JM, Hwang PH Endoscopic resection of sinonasal inverted papilloma: a meta-analysis Otolaryngol Head Neck Surg 2006;134:476e82 [20] Mirza S, Bradley PJ, Acharya A, Stacey M, Jones NS Sinonasal inverted papillomas: recurrence, and synchronous and metachronous malignancy J Laryngol Otol 2007;121:857e64 [21] Network NCC Head and neck cancers 2016 ... ear, and there was no involvement of the Eustachian tube (Fig 1D) The patient underwent an endonasal endoscopic gross total resection of the sinonasal tumor The lesion was pedicled off of the. .. 59% having history of associated sinonasal IP and 41% with isolated temporal bone disease [1] Of the patients with TBIP, over half of the patients demonstrated recurrence of disease following... AD, Modest MC, Van Gompel JJ, Haynes DS, Neff BA Inverting papilloma of the temporal bone: report of four new cases and systematic review of the literature Laryngoscope 2015;125:2576e83 [2] Mitchell