10.14639/0392-100X-suppl.1-41-2021-08
Orbital invasion is frequently observed in tumors involving the maxillary, ethmoid and frontal sinuses given the proximity of the orbit to the sinonasal tract and ventral skull base. The main objective of the present review is to determine the existing evidences on the frequency, treatment, and outcomes of orbital invasion in benign and malignant sinonasal tumors. A systematic review of the literature published from 1995 to 2020 was performed and data sources included PubMed, Cochrane library, NCBI Bookshelf, National Guideline Clearinghouse. Orbital invasion was reported in 2-4% of inverted papillomas, 12-15% of fibro-osseous lesions, 27-32% of juvenile angiofibromas, 35-45% of low-grade malignancies, and 50-80% of high-grade cancers. Surgical resection with negative margins represents the cornerstone of management for benign and low-grade malignant tumors. Histology-specific induction chemotherapy can be used for high-grade sinonasal cancers in order to downstage the tumor and increase the possibility of orbital preservation. When a significant response to induction chemotherapy is observed, exclusive chemoradiation should be offered to improve overall survival rates. Appropriate reconstruction of any surgical defects is essential in order to minimize complications and optimize functional and aesthetic outcomes. Orbital apex invasion represents a negative prognostic factor. In conclusion, a multidisciplinary teamwork is mandatory to maximize local control, minimize morbidity and improve orbital preservation rates.
application/xml
1827-675X
1689
en
Mario Turri-Zanoni
https://creativecommons.org/licenses/by-nc-nd/4.0
ACTA Otorhinolaryngologica Italica
sinonasal tumors
Critical review of multidisciplinary approaches for managing sinonasal tumors with orbital involvement
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2021-05-10
2021-05-14
2021-05-14
76-89
1
Mario Turri-Zanoni
2021/05/14
10.14639/0392-100X-suppl.1-41-2021-08
76
Division of Otorhinolaryngology, Department of Biotechnology and Life Sciences, University of Insubria, Varese, Italy; Head and Neck Surgery & Forensic Dissection Research center (HNS&FDRc), Department of Biotechnology and Life Sciences, University of Insubria, Varese, Italy
1827-675X
sinonasal tumors
89
Critical review of multidisciplinary approaches for managing sinonasal tumors with orbital involvement
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ACTA OTORHINOLARYNGOLOGICA ITALICA 2021;41(SUPPL.1):S76-S89; doi: 10.14639/0392-100X-suppl.1-41-2021-08




Critical review of multidisciplinary approaches for
managing sinonasal tumors with orbital involvement
Approcci multidisciplinari per la gestione dei tumori nasosinusali con invasione
orbitaria: revisione critica della letteratura
Paolo Castelnuovo1,2, Alessia Lambertoni1, Giorgio Sileo1, Marco Valentini1, Apostolos Karligkiotis1, Paolo Battaglia1,2,
Mario Turri-Zanoni1,2
1
  Division of Otorhinolaryngology, Department of Biotechnology and Life Sciences, University of Insubria, Varese, Italy; 2 Head and
Neck Surgery & Forensic Dissection Research center (HNS&FDRc), Department of Biotechnology and Life Sciences, University of
Insubria, Varese, Italy


SUMMARY
Orbital invasion is frequently observed in tumors involving the maxillary, ethmoid and
frontal sinuses given the proximity of the orbit to the sinonasal tract and ventral skull base.
The main objective of the present review is to determine the existing evidences on the
frequency, treatment, and outcomes of orbital invasion in benign and malignant sinonasal
tumors. A systematic review of the literature published from 1995 to 2020 was performed
and data sources included PubMed, Cochrane library, NCBI Bookshelf, National Guideline
Clearinghouse. Orbital invasion was reported in 2-4% of inverted papillomas, 12-15% of
fibro-osseous lesions, 27-32% of juvenile angiofibromas, 35-45% of low-grade malignancies,          Received: November 8, 2020
and 50-80% of high-grade cancers. Surgical resection with negative margins represents the           Accepted: February 4, 2021
cornerstone of management for benign and low-grade malignant tumors. Histology-specific
induction chemotherapy can be used for high-grade sinonasal cancers in order to downstage           Correspondence
the tumor and increase the possibility of orbital preservation. When a significant response to      Mario Turri-Zanoni
induction chemotherapy is observed, exclusive chemoradiation should be offered to improve           Unit of Otorhinolaryngology, Department of
overall survival rates. Appropriate reconstruction of any surgical defects is essential in order    Biotechnology and Life Sciences, University of
to minimize complications and optimize functional and aesthetic outcomes. Orbital apex inva-        Insubria, Ospedale di Circolo e Fondazione Macchi,
                                                                                                    via Guicciardini 9, 21100 Varese, Italy
sion represents a negative prognostic factor. In conclusion, a multidisciplinary teamwork is
                                                                                                    E-mail: tzmario@inwind.it
mandatory to maximize local control, minimize morbidity and improve orbital preservation
rates.
                                                                                                    Funding
KEY WORDS: anterior skull base, endoscopic endonasal surgery, induction chemotherapy,               None.
orbital exenteration; sinonasal tumors
                                                                                                    Conflict of interest
                                                                                                    The Authors declare no conflict of interest.
RIASSUNTO
La vicinanza anatomica dell’orbita con il compartimento nasosinusale e la base cranica
giustifica il fatto che un’invasione orbitaria possa essere frequentemente osservata nei tu-          How to cite this article: Castelnuovo P, Lamber-
mori che originano dall’etmoide, dal seno mascellare e dal seno frontale. L’obiettivo prin-           toni A, Sileo G, et al. Critical review of multi-
                                                                                                      disciplinary approaches for managing sinonasal
cipale di questa review è quello di analizzare le evidenze scientifiche a oggi disponibili in
                                                                                                      tumors with orbital involvement. Acta Otorhi-
letteratura circa la frequenza, le strategie di trattamento e i risultati ottenuti nella gestione     nolaryngol Ital 2021;41(SUPPL.1):S76-S89.
dei tumori nasosinusali benigni e maligni con invasione orbitaria. È stata condotta una               https://doi.org/10.14639/0392-100X-sup-
revisione sistematica della letteratura scientifica pubblicata dal 1995 al 2020. Un’invasio-          pl.1-41-2021-08
ne dell’orbita è stata osservata nel 2-4% dei papillomi invertiti, nel 12-15% delle lesioni
fibro-ossee, nel 27-32% degli angiofibromi giovanili, nel 35-45% dei tumori maligni ben             © Società Italiana di Otorinolaringoiatria
differenziati, e nel 50-80% delle neoplasie maligne scarsamente differenziate. L’asporta-           e Chirurgia Cervico-Facciale
zione chirurgica radicale con margini di resezione negativi rappresenta il caposaldo per
il trattamento delle neoplasie benigne e maligne a basso grado. Schemi di chemioterapia                            OPEN ACCESS
di induzione specifici per ogni sottotipo istologico rappresentano invece il trattamento di         This is an open access article distributed in accordance with
scelta per i tumori maligni scarsamente differenziati, nel tentativo di ridurre il volume di        the CC-BY-NC-ND (Creative Commons Attribution-Non-
malattia e aumentare le possibilità di preservazione del contenuto orbitario. Nei casi in           Commercial-NoDerivatives 4.0 International) license. The
                                                                                                    article can be used by giving appropriate credit and mentio-
cui si osservi una risposta significativa alla chemioterapia di induzione, un trattamento           ning the license, but only for non-commercial purposes and
radio-chemioterapico esclusivo con intento radicale è in grado di migliorare i risultati di         only in the original version. For further information: https://
sopravvivenza oncologica, lasciando alla chirurgia solo un ruolo di salvataggio in caso di          creativecommons.org/licenses/by-nc-nd/4.0/deed.en




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                                                                                     Multidisciplinary treatments for sinonasal tumors invading the orbit




persistenza o recidiva di malattia. In caso di preservazione dell’orbita, appropriate strategie di ricostruzione devono essere pianificate durante
l’intervento chirurgico al fine di minimizzare possibili complicanze post-operatorie e per ottimizzare i risultati estetici e funzionali a lungo ter-
mine. L’infiltrazione dell’apice orbitario rappresenta il fattore prognostico negativo principale nel trattamento di queste neoplasie. Un lavoro
di squadra all’interno di un gruppo multidisciplinare è indispensabile per ottimizzare il controllo locale di malattia, ridurre la morbilità per il
paziente e aumentare le possibilità di preservazione dell’orbita.
PAROLE CHIAVE: base cranica anteriore, chirurgia endoscopica endonasale, chemioterapia di induzione, exenteration orbitae, tumori
nasosinusali



Introduction                                                                keywords as follows: “sinonasal neoplasm”; “orbit”; “or-
                                                                            bital involvement”; “sinonasal benign tumors”; “sinonasal
The proximity of the orbit to the sinonasal tract and ven-                  malignant tumors”; “orbital management”. Our research
tral skull base facilitates tumoral infiltration of the orbital             was focused on the time period ranging from January
content via preformed pathways (e.g. inferior and superior                  1995 to June 2020, in order to avoid discrepancy and to
orbital fissure, anterior and posterior ethmoidal foramina,                 promote data consistency. Among the 137 selected arti-
nasolacrimal duct), neurovascular structures (e.g. infraor-                 cles, only the studies that met the following criteria were
bital and supratrochlear nerves; ethmoidal arteries), or by                 included: 1) English language articles; 2) adequate number
direct extension through the bone (e.g. lamina papyracea,                   of patients for significant statistical analysis; 3) appropriate
orbital floor and roof, nasal bones). The periorbit is a highly             survival analysis to compare data; 4) accurate description
resistant barrier against invasion but, once the tumor has                  of orbital invasion and concerning survival data. Follow-
passed through it, no further barriers are able to prevent or-              ing these inclusion criteria, 21 articles were selected to be
bital content infiltration. Orbital involvement poses unique                reviewed.
challenges in the management of sinonasal benign and ma-
lignant tumors since the eye represents a borderline ana-
tomical region, between the intracranial and extracranial                   Diagnosis
compartment, containing many neurovascular structures,                      Symptoms can result from orbital compression, nasolacri-
with also relevant functional and aesthetic implications.                   mal duct obstruction, and real infiltration of the orbital con-
Traditionally, the standard treatment for sinonasal tumors                  tent. Therefore, diplopia, epiphora, chemosis, visual chang-
in close proximity to the orbit was radical excision with                   es, and proptosis may be observed in approximately 50%
orbital exenteration 1. Over the past 20 years, the increased               of the cases 4. However, the absence of these findings does
attention to patient’s quality of life along with the develop-              not rule out the occurrence of tumoral invasion of the orbit.
ment of endoscopic surgery and advances in multimodal                       Computerized tomography (CT) of the paranasal sinuses is
treatment strategies have led to significant progresses in the              paramount for identification of orbital bone erosion or reab-
management of sinonasal tumors with orbital invasion. As                    sorption, and enlargement of fissures and foramina. Moreo-
a result, in recent years, treatment protocols including or-                ver, bony lesions such as fibro-osseous tumors can be easily
bital preservation have been increasingly adopted 2,3.                      detected using the CT scan. Magnetic resonance imaging
However, there are still several open issues. The definition                (MRI) is superior for analyzing orbital soft tissues, and
of “orbital invasion” represents a source of confusion since                distinguishing inflammatory secretions (e.g. in the lacrimal
a universally accepted stratification of the degrees of or-                 sac) from tumor. In addition, by comparing T1-weighted
bital invasion is lacking. Moreover, data emerging from the                 contrast enhanced and T2-weighted sequences, periorbital
case-series available in literature are difficult to compare                and extraocular muscles invasion can be distinguished from
and sometimes conflicting in terms of surgical and non-sur-                 other changes such as peritumoral edema. The MRI pro-
gical treatments adopted, indications for orbital preserva-                 tocol may be further refined by adding dynamic contrast-
tion, needs for orbital reconstruction and recurrence rates.                enhanced (DCE) and diffusion-weighted sequences (DWI)
In the present review, we analyze the multidisciplinary ap-                 in order to better analyze the interface between orbit and tu-
proaches currently available for managing benign and ma-                    mor in difficult cases of recurrences after previous surgery
lignant sinonasal tumors invading the orbit, in an effort to                and/or radiotherapy 5. In the suspect of a vascular tumor
critically appraise their survival, functional and aesthetic                (e.g. juvenile angiofibroma), an angio-MRI and/or an angi-
outcomes. The systematic review of the literature was con-                  ography should be also performed in order to study the dis-
ducted in accordance with current guidelines. Data sources                  tribution of the arterial feeders to the tumor and, possibly,
including PubMed, Cochrane library, NCBI Bookshelf,                         embolize them. With the exception of fibro-osseous lesions
National Guideline Clearinghouse were searched using                        and of vascular tumors, where the diagnosis is exclusively



                                                                                                                                                   S77
P. Castelnuovo et al.




based on radiology, all other cases of sinonasal tumors need                                approaches, which could overcome the limits of a single
an endoscopic endonasal evaluation with multiple biopsies                                   surgical technique in the management of lesions affecting
to define the tumoral histology and plan the most appropri-                                 such a complex anatomical compartment. Orbital exentera-
ate range of multimodal treatment. In case of malignancy,                                   tion is rarely required for benign tumors and orbital preser-
neck ultrasound and total body contrast-enhanced CT scan                                    vation is generally obtained. Globally, when selecting the
or positron emission tomography (PET) scan are obtained                                     surgical approach, it is necessary to carefully balance the
to rule out regional or systemic spread, respectively.                                      complete excision with the associated surgical morbidity,
                                                                                            taking also into account that some selected residual benign
Benign tumors                                                                               tumors, usually tend to remain stable over time.

Benign tumors of the paranasal sinuses are a heterogeneous                                  Fibro-osseous lesions (FOLs)
group of diseases, that reflects the wide spectrum of differ-                               Benign sinonasal fibro-osseous tumors involving the orbit
ent tissues present in the sinonasal cavities from which they                               commonly arise from the frontal and ethmoidal bones, with
could originate. Rare pathologies per se, they might involve                                osteomas representing the most frequent subtypes 6. While
the orbit in a small percentage of cases, ranging from 2 to                                 osteomas generally originate or involve the orbital bony
15%; therefore, few data are available in literature (Tab. I).                              walls, without invasion of the orbital contents, other FOLs
These tumors are generally slow growing lesions that com-                                   such as fibrous dysplasia and ossifying fibroma may pre-
press without infiltrating the surrounding anatomical struc-                                sent higher rates of intraorbital invasion and related clinic 7.
tures, invading the orbital compartment by means of bone                                    A common feature in this group of lesions is the slow rate
reabsorption or via preformed skull fissures or foramina. In                                of growth, which often makes patients asymptomatic for
the majority of cases, the integrity of the periorbital layer                               a long period of time; for this reason, the “wait and scan”
is maintained, while the displacement of the orbital con-                                   policy could be a valid option while the choice of surgi-
tent can cause proptosis, diplopia due to extrinsic muscles                                 cal resection should be based on the site of the tumor, its
abnormal mobility, decreased visual acuity until blindness                                  growth pattern as well as on the clinical presentation 8-10.
secondary to optic nerve compression, ocular pain and epi-                                  The endoscopic endonasal technique has been proposed by
phora 6.                                                                                    many authors as a minimally invasive and effective surgical
The standard treatment of benign tumors is surgical resec-                                  approach to treat these tumors, by using the drill cavita-
tion, using endoscopic endonasal techniques, transfacial/                                   tion technique. In this regard, the intraorbital component
transcranial resection, transorbital surgery or combined                                    of the lesion can be used as a corridor to pass through


Table I. Literature review of the main case-series describing treatment outcomes of sinonasal benign tumors with orbital involvement.
 Author, year         N. of cases         Histology             Endoscopic or external          Mean             Recurrences &                       Orbital
                                                              surgical approach & other       follow-up      persistences/treated               preservation rate
                                                                      treatments              (months)                cases
 Wang, 2014 9                14            Ossifying fibroma                 10, EEA (71%)                     25                 6/14 (43%)     14/14 (100%)
                                                                              4, TTA (29%)
 Ye, 2017 11                 12            Ossifying fibroma                12, EEA (100%)                    43.1                2/12 (17%)     12/12 (100%)
 Turri-Zanoni,                6                Osteoma                        4, EEA (66%)                    72.6                     -          6/6 (100%)
 2012 12                                                                   1, EEA+TTA (17%)
                                                                              1, TTA (17%)
 Bertin, 2020 48             12            Fibrous dysplasia                  6, TTA (50%)                    20.8               12/12 (100%)    12/12 (100%)
                                                                          3, Bifosfonate (25%)
                                                                          3, Wait&scan (25%)
 Ricalde, 2001 10             6             Fibrous dysplasia                6, TTA (100%)                     NA                     NA           6/6 (100%)
 Elmer, 1995 15              10            Inverted papilloma                 2, TTA (20%)                    51.6                8/10 (80%)       2/10 (20%)
                                                                         8, Orbital exenteration
 Saldana, 2013 18             6            Inverted papilloma                6, TTA (100%)                    22.8                    -            5/6 (84%)
                                                                                 +(3, RT)
 Xu, 2012 23                 18          Juvenile angiofibroma               10, EEA + TTA                     NA                 6/18 (34%)     18/18 (100%)
                                                                                  8, TTA
                                                                                 +(4, RT)
EEA: endoscopic endonasal approach; TTA: transfacial/transcranial approach; RT: adjuvant radiotherapy; NA: not available data.




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                                                                                          Multidisciplinary treatments for sinonasal tumors invading the orbit




                                                                                   of the periorbital layer prevents diplopia, enophthalmos, or
                                                                                   facial deformity; however, in case of major removal of the
                                                                                   periorbit or in extensive intraorbital dissection, the place-
                                                                                   ment of a silastic sheet as a protection while pushing the
                                                                                   orbital content into the orbital cavity may be sufficient to
                                                                                   avoid postsurgical orbital complications and the need for
                                                                                   secondary revision surgeries 13. In some cases of fibrous
                                                                                   dysplasia, the lesion may involve the optic canal and orbital
                                                                                   apex with optic nerve compression, resulting in progressive
 A                                        B
                                                                                   loss of visual acuity, color vision and peripheral and central
                                                                                   field defects. Although elective surgery is not indicated for
                                                                                   asymptomatic cases of optic nerve encasement, due to the
                                                                                   potential risk of impaired optic nerve function, an immedi-
                                                                                   ate referral for surgical optic nerve decompression should
                                                                                   be recommended if there is evidence of visual loss and pe-
                                                                                   riodic follow-up is essential to monitor any recurrences 10,14.
                                                                                   It appears clear that such critical patients should be man-
                                                                                   aged in a multidisciplinary way, by means of periodical
                                                                                   radiological, ophthalmological and surgical evaluations to
                                                                                   define the best treatment strategy.
 C                                        D

Figure 1. Coronal (A) and axial (B) CT scan of a 32 year-old male affected
                                                                                   Inverted papilloma (IP)
by ivory osteoma with right intraorbital extension. White arrows in A and B        Sinonasal IP may invade the orbit in 2-4% of cases, involv-
highlight the displacement of the extrinsic ocular muscles. The patient was        ing frequently also the nasolacrimal system. However, es-
submitted to endoscopic endonasal resection of the lesion using the cavitation     pecially in huge tumors spreading into the orbit, it’s dif-
technique. The early post-operative CT scan performed 24 hours after surgery
(panels C and D) ruled out any intraorbital complication. White asterisks in C
                                                                                   ficult to define whether the IP has been originated from the
and D indicate silicon roll sheets placed to maintain the orbital content within   lacrimal structures or from the paranasal sinuses, since the
the orbital cavity and therefore prevent postoperative sequelae.                   nasolacrimal duct also represents one of the most common
                                                                                   route of diffusion of sinonasal tumors to the orbit 15,16. In
                                                                                   the largest case-series of IPs invading the orbit currently
without needing to expose all the external boundaries of                           available in literature, 10 cases were described and foci of
the lesion (Fig. 1), which could be selectively separated                          malignant transformation were found in all cases, respec-
from the orbital periosteum and carefully collapsed and                            tively six squamous cell carcinomas and four transitional
removed 11,12. Nevertheless, additional external approach-                         cell carcinomas 15. The high rate of malignant transforma-
es may be required when the tumor extends anteriorly to                            tion observed in IP involving the orbit was confirmed also
the nasolacrimal duct or in cases of fronto-orbital tumors                         by other authors reporting smaller case-series 17-19. Having
not easily manageable with an exclusive endoscopic treat-                          in mind these critical issues, when dealing with a histolog-
ment, as described by Georgalas et al. 8. In order to achieve                      ically-proven IP that shows an intraorbital extension at the
complete resection, different approaches through differ-                           preoperative MRI, one should keep in mind the possibil-
ent orbital structures (eyelid, eyebrow, conjunctiva) were                         ity that this lesion might harbor foci of malignant transfor-
successfully employed with minimal residual morbidity                              mation. Although in literature the mean recurrence rate is
and aesthetic defects. In cases with massive involvement                           around 5-10% for sinonasal IPs 18, when the tumor invades
of the anterior and/or posterior wall of the frontal sinus,                        the orbit the reported incidence of recurrence is consider-
an osteoplastic flap or Riedel-Mosher approach is neces-                           ably higher, ranging from 20 to 80% 18,19. This finding can
sary to reach a complete and safe surgical excision. This                          be explained by the more frequent occurrence of malignant
is the reason why a teamwork including maxillofacial sur-                          transformation compared to other IPs. In this regard, John-
geons, neurosurgeons and ophthalmologists is generally re-                         son et al. 17 reported four cases of IP with orbital invasion,
quired. Generally, no reconstruction of the orbital walls is                       of whom three experienced recurrences after the initial sur-
performed, except in case of massive removal of the bony                           gery in a period ranging from 4 months to 6 years; simi-
orbital floor (more than 50%) 8. A limited intranasal herni-                       larly, Elner et al. 15 described a recurrence rate of 80% in
ation of the orbital content may occur but the preservation                        a series of 10 cases. Considering such significant rates of



                                                                                                                                                        S79
P. Castelnuovo et al.




recurrences, a multidisciplinary approach is recommended
when dealing with sinonasal IPs invading the orbit. The
radiologist should be consulted in order to exactly define
the grade of orbital involvement and signs of clear infiltra-
tion; the pathologist plays a crucial role in analyzing the
surgical specimen to find out possible signs of malignant
transformation; medical and radiation oncologists should
be also included in the design of treatment’s strategy when-
ever cancerization is detected. Few data are available in the
                                                                  A                                       B
current literature about the proper surgical management of
these tumors but, taking into account their aggressive be-
havior, there is a general consensus that aggressive surgi-
cal resection is recommended in order to obtain complete
removal of the lesion. Radical surgical treatment, even in-
cluding orbital exenteration, may be required (Fig. 2) 15,18.
No evidences are currently available regarding indications
for adjuvant treatments in such cases; however, some au-
thors suggested the importance of adjuvant radiotherapy in
case of orbital involvement by an IP harboring signs of ma-
                                                                  C                                       D
lignant transformation in order to improve long-term local
control of disease 20,21.

Juvenile angiofibroma (JA)
This vascular tumor is supposed to originate from vascular
embryonic remnants in the cancellous bone around the vid-
ian canal and basisphenoid, typically showing an expansive
and destructive pattern of growth with spread to adjacent
anatomical compartments throughout foramina and fis-
sures. Tumoral extension to the orbit, across the inferior or-
bital fissure, turns out to be a common finding in advanced        E                                      F

staged lesions, ranging from 27 to 32% of cases 22. Oph-
thalmological disorders and visual defects are caused by
direct compression of the eye, optic nerve and chiasm, with
proptosis reported as the most frequent symptom 23. Con-
sidering that JA is a vascular lesion and its surgical removal
carries a high risk of profuse bleeding, preoperative embo-
lization is advised in advanced-stage cases, paying special
attention to the feeding vessels coming from the internal
carotid artery (ICA) which can be more frequently involved
                                                                  G                                       H
when the JA extends to the orbital compartment. Xu et al. 23,
in a series of 18 patients affected by JA involving the orbit    Figure 2. Contrast-enhanced MRI in coronal (A) and axial views (B) of a 46
and optic nerve, described the occurrence of blood supply        year-old man affected by left ethmoid-maxillary inverted papilloma eroding the
to the tumor from small arterial vessels branching from the      floor of the left orbit (black arrow in A), who underwent endoscopic endonasal
ophthalmic artery, which should be properly recognized by        resection with left medial maxillectomy type III. Postoperative MRI (C and D)
                                                                 excluded residual disease with hyperintense signal (black asterisk) at the left
the interventional radiologist and not embolized, in order to    orbital floor, interpreted as post-surgical scar tissue requiring close radiological
avoid vision loss due to central retinal artery occlusion 24.    follow up. MRI performed 3 months after the surgery (E and F) demonstrated
Different treatment strategies have been proposed in the         an extensive recurrence of disease involving the orbital floor (black arrowheads
                                                                 in E), anterior orbital content (black asterisk in F), hard palate and lateral bony
last decades, such as radiotherapy, chemotherapy and hor-
                                                                 wall of the left maxilla (black arrows in E), thus the patient was submitted to
mone therapy, with little or no success. Surgical excision is    transfacial radical maxillectomy associated with orbital exenteration and re-
considered as the best treatment option, aiming complete         construction with an anterolateral thigh (ALT) flap. Final histology revealed an
tumor excision to avoid persistent disease and therefore         invasive SSC arising on IP. The MRI performed 3 years after the surgery (G and
                                                                 H) excluded local recurrences of disease (white asterisks indicate ALT flap).


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                                                                          Multidisciplinary treatments for sinonasal tumors invading the orbit




minimize recurrence rates. Nowadays, the increase of en-           (nasolacrimal duct, orbital fissures, optic canal, ethmoidal
doscopic surgical skills together with advances in surgical        foramina), neurovascular structures (infra- e supraorbital
instrumentation, imaging and intraoperative surgical navi-         nerves) or by direct invasion transgressing surrounding
gation systems allows a minimally invasive endoscopic              bones (e.g. erosion of the lamina papyracea in most cas-
endonasal resection even in advanced staged lesions, like          es) 3,6. This condition inevitably impacts on survival rate,
those with orbital involvement. Compared to traditional            functional outcomes and therapeutic strategies. It has been
transfacial approaches, the endoscopic endonasal surgery           widely accepted that the grade of orbital infiltration strong-
improves surgical results, with limited blood loss, reduced        ly impacts on prognosis, with worst survival rates in case
postoperative sequelae and minimized recurrence rates 25-28.       of extensive orbital involvement 3,34. Different case series
In the surgical management of JA involving the orbit and           in literature reported 5-year disease free survival of 69%
orbital apex, particular care must be taken to avoid injury        for tumors abutting the lamina papyracea, 51% for tumors
of the optic nerve, III, V2, and V1 cranial nerves. Similarly,     invading the periorbital layer, 34% for tumors involving the
adequate endoscopic surgical skills are required in order to       orbital content and, lastly, down to nearly 0% in case of
manage intraoperative bleeding, especially for tumor feed-         orbital apex involvement 3.
ers originating from the ophthalmic artery, which should be
coagulated without damaging any intraorbital neurovascu-           Grade of orbital invasion
lar structures.                                                    Orbital invasion must be preoperatively graded, by means
Another crucial aspect is the management of a recur-               of an accurate radiological imaging, as minimal (erosion of
rent or persistent intraorbital JA, since tumoral regrowth         lamina papyracea, loss of the fat plane between tumor and
in such areas has not been described frequently in litera-         extraconal muscles, periorbital irregularities) or massive,
ture and small remnants might undergo an involution over           often accompanied by clinical signs of orbital involvement
time. Therefore, in case of a partial resection with a sta-        (proptosis, visual loss, restriction of ocular motility) 35. The
ble asymptomatic intraorbital JA persistence (e.g. inferior        recent 8th edition of the AJCC (American Joint Committee
orbital fissure), there is not a strict indication for an im-      on Cancer) cancer staging system considers orbit involve-
mediate revision surgery unless there is measurable tumor          ment as a significant factor upgrading tumor classification:
growth or new symptoms 26.                                         tumor is staged as T3 when invasion is limited to orbital
In the light of all these aspects, JAs should be treated in ter-   bony wall, as T4a in case of invasion of the anterior or-
tiary-care referral centers, specialized in skull base surgery,    bital contents, and as T4b when the orbital apex is involved.
by a multidisciplinary team including ENT surgeon, neuro-          The lack of an officially recognized classification defining
surgeons, ophthalmologist, neuroradiologists and interven-         the depth of orbital involvement by the tumor poses some
tional radiologists, in order to achieve best results in terms     challenges. Firstly, comparison of results from different
of complete resection and low morbidity for the patient.           studies can be challenging 29. Secondly, the lack of a clear
                                                                   definition as to what constitutes orbital invasion has been a
                                                                   source of confusion, and an accurate distinction should be
Malignant tumors
                                                                   made between bony erosion, orbital soft tissues involve-
Malignant sinonasal tumors are extremely rare, account-            ment and apex infiltration. Thirdly, considering that surgi-
ing about 3% of all head and neck tumors and less than             cal resection has always been considered as the cornerstone
1% of all malignant neoplasms. They include a variety of           in the management of sinonasal tumors invading the orbit, a
different histotypes with different behaviors, survival out-       recognized classification is needed in order to correctly de-
comes and treatment protocols 29-31. The most frequentely          fine indications whether to preserve or exenterate the orbit.
encountered are squamous cell carcinoma, intestinal type           In fact, orbital exenteration appears to be an invasive pro-
adenocarcinoma (ITAC), esthesioneuroblatoma (ENB) and              cedure conditioning a significant functional defect, esthetic
sinonasal undifferentiated carcinoma (SNUC) 32.                    deformity and, consequently, emotional impact 29. Over the
Sinonasal tumors are frequently diagnosed in advanced              years, different classifications have been proposed, aimed
stages due to their delayed symptoms that easily mimick            to stratify patients according to tumor aggressiveness and
inflammatory diseases. The incidence of orbital invasion           to guide adequate treatment planning (Tab. II) 3,33,36,37. Cur-
by sinonasal malignancies depends on the site of origin,           rent indications for orbital exenteration are: gross orbital
histology, and aggressiveness of the specific tumor and it is      contents invasion; extensive infiltration of the extraconal
reported between 62 and 82% of all ethmoidal tumors, 55%           fat, extraocular muscles; intraconal and retrobulbar fat in-
of maxillary neoplasms, and 46% of nasal cavity tumors 33.         vasion; eye bulb and optic nerve involvement; bulbar con-
Tumors may invade the orbit through preformed pathways             junctiva or sclera, eyelid, and/or proximal lacrimal path-



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Table II. Grading systems of orbital invasion and relative treatments.
 Author, year of publication                                         Grading of orbital invasion                                           Treatment
 McCary et al., 1996 35                             A           Tumor adjacent the orbit without infiltration of the orbital            RT/CT + surgery
                                                                                            wall
                                                    B              Tumor eroding the orbital wall without ocular bulb
                                                                                       displacement
                                                    C           Tumor eroding, infiltrating and displacing the orbital wall
                                                                             without periorbital invasion
                                                    D              Tumor invading the orbit with periorbital invasion          RT/CT + surgery with resection of
                                                                                                                               involved periorbita (exenteration if
                                                                                                                                     extensive involvement)
 Iannetti et al., 2005 36                           1                 Erosion or destruction of medial orbital wall              Resection of medial orbital wall
                                                    2                      Extraconal invasion of periorbital fat
                                                    3          Invasion of medial rectal muscle, optic nerve, ocular bulb             Orbital exenteration
                                                                                or skin overlying the eyelid
 Neel et al., 2016 32                               1             Tumor adjacent to orbital wall, which may be thinned,        Drilling and resection of involved
                                                                      bowed or eroded without periorbital invasion                            bone
                                                    2          Tumor eroding the orbital wall, with resectable periorbital        Resection of periorbita and
                                                                                         involvement                           underlying extraconal orbital fat
                                                    3            Tumor with extraocular muscle, intraconal fat, globe or                Orbital clearance
                                                                                   orbital apex invasion
                                                    4             Tumor invading the nasolacrimal system, eyelids duct                Orbital exenteration
                                                                                          and/or sac
                                                    5              Tumor with cavernous sinus, optic canal or massive               Unresectable, pallation
                                                                                    intracranial invasion
 Turri-Zanoni et al., 2018 3                        1                  Erosion or destruction of lamina papyracea               Endoscopic endonasal surgery
                                                    2           Invasion of the periorbital layer and/or focal invasion of
                                                                               the extraconic periorbital fat
                                                    3                    Invasion of the anterior 2/3 of the orbit                   Orbital exenteration
                                                    4                        Involvement of the orbital apex                        Unresectable, palliation
RT: radiotherapy; CT: chemotherapy.



ways infiltration. Although orbital apex involvement has                          opment of multimodal treatment protocols have led to sig-
been considered in the last decades as an indication to or-                       nificant progress in managing such patients, with an ever-
bital exenteration 6,30,33, recent scientific reports found that,                 growing trend to orbital preservation. Currently, available
in such cases, prognosis remains poor regardless the extent                       treatments include surgical removal (via pure endoscopic
of surgery and, in general, any kind of multimodal treat-                         surgery or open endoscopic-assisted surgery), chemothera-
ment adopted 3. Thus, current trends tend to exclude orbital                      py in an induction or adjuvant setting, and adjuvant radio-
exenteration when orbital apex is massively involved by the                       therapy. All these therapeutic options must be previously
cancer.                                                                           discussed during a multidisciplinary tumor board 3,33.
                                                                                  Based on these assumptions, a histology-driven treatment
Management of sinonasal tumors invading the orbit                                 algorithm has been proposed (Fig. 3) in order to offer tai-
The gold standard treatment of sinonasal malignancies in-                         lored therapies to high-grade tumors (poorly differentiated
vading the orbit still remains controversial, and it has been                     squamous cell carcinoma, neuroendocrine carcinoma, es-
widely debated in recent literature. The main reasons are                         thesioneuroblastoma Hyams grade IV, sinonasal undiffer-
the small amount of available data and the lack of a stand-                       entiated carcinoma, ITAC p53 wild type) and other specific
ardized universally-accepted classification of orbital inva-                      treatments to well differentiated malignancies (adenocarci-
sion, as previously mentioned 29. Traditionally, the standard                     noma, adenoid cystic carcinoma, low-grade esthesioneuro-
treatment of sinonasal tumors invading the orbit was radi-                        blastoma and squamous cell carcinoma) and to chemore-
cal excision with orbital exenteration 1. In recent years, in-                    sistant tumors (mucosal melanoma) 3. High-grade tumors
creased attention to patient’s quality of life, the refinement                    might be submitted to induction chemotherapy 30, up to a
of minimally invasive endoscopic techniques and the devel-                        maximum of five cycles, conducted with different protocols



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                                                                                                 Multidisciplinary treatments for sinonasal tumors invading the orbit




 ACC: adenoid cystic carcinoma; ONB: olfactory neuroblastoma; SCC: squamous cell carcinoma; SNUC: sinonasal undifferentiated carcinoma; NEC: neuroendocrine carcinoma;
 p53wt ITAC, p53 wild type intestinal type adenocarcinoma

Figure 3. Flowchart describing the multimodal management of sinonasal cancers with orbital invasion.


based on the specific histotype (TPF, PE/AI regimen, PFL                               response (> 80% reduction of initial tumor volume) can
regimen) 3; the response rate to induction chemotherapy                                be treated with exclusive orbital-sparing chemoradiation
is radiologically evaluated by seriated contrast-enhanced                              with curative intent (Fig. 4). Conversely, patients achiev-
MRI and can be used to segregate “good responders” from                                ing partial response (tumor reduction inferior to 80%),
“non-responders”. Patients achieving complete or good                                  non-responder patients (reduction inferior to 30%), and pa-



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P. Castelnuovo et al.




                                                                                    A                                      B
 A                                      B




                                                                                    C                                      D


 C                                      D

Figure 4. Contrast-enhanced MRI in coronal views (panels A and B) of a 30
year-old female affected by poorly-differentiated small cells neuroendocrine
carcinoma, with intracranial involvement (black asterisk) and bilateral orbital
invasion (black arrows). The patient received induction chemotherapy (cispl-
atin/etoposide scheme, 5 cycles) with complete response. The patient was
therefore submitted to exclusive chemoradiation with curative intent. The con-
trast-enhanced MRI performed 2 years after treatment excluded recurrences           E                                      F
of disease (C and D).
                                                                                  Figure 5. Contrast-enhanced MRI in coronal views (A and B) of a 69 year-old
                                                                                  man affected by locally advanced sinonasal undifferentiated carcinoma involv-
tients with disease progression might be directed to surgi-                       ing the left orbit (white arrows). The patient underwent induction chemotherapy
cal resection, followed by adjuvant radiotherapy or chemo-                        (TPF scheme, 5 cycles) obtaining partial response (black asterisks in panels
                                                                                  C and D indicate the persistence of disease). A left unilateral endoscopic re-
radiation (Fig. 5). On the other hand, patients affected by                       section with transnasal craniectomy and skull base reconstruction (white ar-
low-grade tumors, chemoresistant tumors, and high-grade                           rowheads) was performed to remove the residual disease. Finally, the patient
tumors non-susceptible to systemic chemotherapy due to                            received adjuvant irradiation using intensity-modulated radiotherapy (62 Gy).
age and/or severe comorbidities, can be submitted to up-                          The contrast-enhanced MRI performed 5 years after treatment showed no evi-
                                                                                  dence of disease (E and F).
front surgery. When a surgical resection is planned, an en-
doscopic endonasal approach must be preferred when fea-
sible, eventually combined with a traditional transfacial or                      extensive invasion of the extraconal fat, extraocular mus-
craniofacial surgery in case of massive intracranial or facial
                                                                                  cles, intraconal and retrobulbar fat invasion, eye bulb and
skeleton involvement, always respecting the oncological
                                                                                  optic nerve involvement, bulbar conjunctiva or sclera infil-
principle of complete excision. The surgical management
                                                                                  tration, eyelid involvement, proximal lacrimal pathways in-
and the decision whether to preserve or exenterate the orbit,
must be carefully discussed and planned according to the                          vasion 3,30 (Fig. 6). When dealing with such advanced-stage
extent of orbital invasion. In case of limited orbital involve-                   sinonasal tumors, a postoperative radio(chemo)therapy is
ment (tumor abutting the orbital bones, erosion of lamina                         adopted almost invariably, according to the final histol-
papyracea, orbital periosteum, minimal extraconal fat in-                         ogy report. Orbital apex infiltration by sinonasal cancer
filtration), an orbital-sparing endoscopic surgery might be                       deserves separate consideration since it has been reported
adopted and intraoperative frozen sections examination                            how orbital apex involvement is dramatically related to
should be used to assess the free-margins resection. Con-                         poor prognosis regardless the treatment strategy adopted
versely, orbital exenteration should be planned in case of                        and extent of surgery 3. A free-margins resection is virtually



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                                                                                                         Multidisciplinary treatments for sinonasal tumors invading the orbit




  A                                                             B                                                         C




 D                                                              E                                                          F


  Abbreviations: ON: optic nerve; OB: olfactory bulb; SS: sphenoid sinus; ICA: internal carotid artery

Figure 6. Contrast-enhanced MRI in coronal (A, T1 contrast-weighted and B, T2-weighted sequences) and axial (C, T1 contrast-weighted) views of a 51 year-
old man affected by locally advanced well-differentiated squamous cell carcinoma involving the left orbit (white arrows indicate medial and inferior rectus muscles
infiltration) and encroaching the anterior skull base. The patient underwent a bilateral endoscopic endonasal resection associated with skull base reconstruction
and left orbital exenteration, followed by adjuvant irradiation (66 Gy). The contrast-enhanced MRI performed 3 years after treatment excluded recurrences of dis-
ease (panels D, E and F).


impossible in such cases due to the complex neurovascular                                      rates 38-40. Suarez et al. reported disease-specific survival
anatomy of this site. Indeed, in such advanced cases, cura-                                    rates of 41% in patients affected by sinonasal cancers with
tive treatments are excluded and different forms of pallia-                                    orbital invasion compared to 75% for those without or-
tive surgery and/or chemoradiation should be adopted 3. Tu-                                    bital involvement 38. Although a clear consensus regarding
mors with cavernous sinus invasion, internal carotid artery                                    the oncological safety of orbital preservation has not yet
encasement or massive intracranial involvement should be                                       been reached, trends encouraging orbit-sparing surgery are
considered unresectable as well 33,38.                                                         renowned since many years. In this regard, Carrau et al.
                                                                                               found that orbit preservation, when a full-thickness peri-
Prognostic significance of orbital invasion                                                    orbit infiltration was excluded, did not downgrade onco-
To date, it is widely accepted that orbital invasion by sinon-                                 logical outcomes, while a full-thickness periorbit invasion
asal tumors affects negatively the survival rates, as sum-                                     was associated with a decreased prognosis. Their results
marized by data emerging from the largest case-series cur-                                     suggested that eye preservation, in the absence of orbital
rently available in literature (Tab. III). Several worldwide                                   soft tissues invasion, did not compromise the local control
case series have supported the evidence that progressive                                       rate 4. In 2002, Imola and Schramm reported no differences
involvement of the orbital structures decreases survival                                       in terms of survival rates between orbital preservation and



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Table III. Literature review.
 Authors           N. of               Degree of                         Treatment                             Oncological                              Conclusions
                   cases            orbital invasion                     strategies                             outcomes
 Carrau                 58    36% orbital invasion (bone           Surgical resection +                NED 56% cases after orbital               Orbital sparing is possible
 1999 4                           and soft tissues)                 adjuvant treatment                       preservation                          when soft tissues are
                                                                                                                                                uninvolved, without affecting
                                                                                                     NED 50% cases after orbital                   oncological outcomes
                                                                                                            exenteration
 Imola and              66       54 pt with bony wall or                 Surgery                  LRR 29.6% after orbital preservation         Selective orbital preservation
 Schramm                         periorbital involvement             poRT in 44 cases                                                           does not seem to adversely
 2002 40                                                                                          LRR 33.3% after orbital exenteration         affect survival or local control
                                 12 pt with intraorbital
                                     involvement
 Iannetti               29     24.1% medial orbital wall                   CFS                    5y OS 71.4% with medial orbital wall     Orbital exenteration is
 2005 36                               invasion                         poRT 37.9%                            invasion                 necessary in case of intraconal
                                                                                                                                                fat invasion
                                  20.7% extraconal fat                                              5y OS 33.3% with extraconal fat
                                       invasion                                                               invasion

                               37.9% intraconal or eyelid                                           5y OS 50.9% with intraconal fat
                                    skin invasion                                                             invasion
 Ganly                334           33.8% bone                              CFS                   5y DSS 75% with no orbital invasion          Orbital contents invasion was
 2005 49                                                                 poRT 48%                                                               a negative PF in univariate
                                   16.5% periosteum                                               5y DSS 40.7% with bone/periosteum            analysis, but not statistically
                                                                                                              invasion                           significant in multivariate
                                  15% orbital contents                                                                                                    analysis
                                                                                                     5y DSS 44.4% with intraorbital
                                                                                                               invasion
 Patel               1306             24.6% bone                            CFS                      5y DSS 66.2% with no orbital               Orbital contents invasion is
 2003 38                                                                 poRT 39%                              invasion                          a negative PF in univariate
                                   10.5% periosteum                                                                                             analysis, but not statistically
                                                                                                   5y DSS 59.2% with bone/periosteal              significant in multivariate
                                 22.5% orbital content                                                         invasion                                    analysis

                                                                                                   5y DSS 48.2% with orbital contents
                                                                                                               invasion
 Howard               308       No orbital involvement in                  CFS                         5y OS 52% with no orbital              Orbital spread is a negative PF
 2006 39                               56% of pt                 Adjuvant treatment 40%                      involvement
                                                                       (mainly RT)
                                                                                                   5y OS 45% with periosteal invasion

                                                                                                   5y OS 14% with orbital involvement
 Suarez               100           36% periosteum                         CFS                       5y OS 44% with no deep orbital            Deep orbital involvement is a
 2004 37                                                         Adjuvant treatment 55%                        invasion                                negative PF
                                   14% deep orbital                    (mainly RT)
                                     involvement                                                  5y OS 16% with deep orbital invasion
 Safi                   52      100% invading the orbit                    CFS                    5y OS 14% after orbital preservation           In case of orbital content
 2017 28                       beyond orbital periosteum              Surgery + poRT                           + poRT                          invasion, exenteration shows
                                                                                                                                                  better survival rate than
                                                                                                        5y OS 65.5% after orbital                  conservative surgery
                                                                                                              exenteration
 Turri-Zanoni         196            Grade 1: 44 pt               27 pt orb. exenteration                5y OS 84% for grade 1                 Orbital invasion represents a
 2018 3                                                                                                                                         negative prognostic factor.
                                     Grade 2: 46 pt              112 pt orb. preservation               5y OS 64.1% for grade 2               Neoadjuvant chemotherapy can
                                                                                                                                              downstage the local extension
                                     Grade 3: 49 pt             5 cases treated with CTRT               5y OS 48.9% for grade 3                 of the tumor and maximize
                                                                                                                                                 orbital preservation rates
                                     Grade 4: 24 pt                 Grade 4 patients:                   5y OS 14.6% for grade 4                Cancers invading the orbital
                                                                  11 pt orb. exenteration                                                        apex must be considered
                                                                  13 pt orb. preservation                                                                 incurable
CFS: craniofacial surgery; RT: radiotherapy; poRT: postoperative radiotherapy; preRT: preoperative radioteraphy; CT: chemotherapy; CTRT: chemoradiotherapy; LRR: local recurrence
rate; LCR: local control rate; DSS: disease specific survival; OS: overall survival; NED: non evidence of disease; PF: prognostic factor.


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                                                                           Multidisciplinary treatments for sinonasal tumors invading the orbit




orbital exenteration in patients with tumor invasion lim-           be placed to keep the orbital content into the orbital cavity
ited to the bony orbital walls 41. In 2006, Howard et al., as       and prevent its prolapse into the sinonasal region 13. In se-
well, demonstrated that patients with preserved orbit didn’t        lected cases, fascial grafts (temporalis or fascia lata), mu-
have worst prognosis when the orbital periosteum was not            coperiosteum harvested from the middle turbinate or nasal
breached yet by the tumor; thus, removal of the infiltrated         floor/septum, or commercially available acellular dermis
periorbit with the conservation of the orbital content could be     layer can be used to this purpose 33. Larger defects involv-
oncologically feasible 40. Therefore, sparing the soft tissues of   ing the orbital floor must undergo rigid reconstruction to
the orbit when the periorbit have not been deeply transgressed      avoid post-operative enophthalmos, globe malposition,
by the tumor generally does not appear to adversely affect          ptosis, diplopia and ectropion 41. Titanium mesh or porous
cure or local control 38. On the other hand, when dealing with      polyethylene implants can be used when post-operative ir-
advanced-stage tumors with invasion of the orbit beyond the         radiation is not scheduled (e.g. benign tumors) while bony
orbital periosteum, the orbital exenteration is considered as a     free flap (e.g. scapular tip flap, iliac crest and fibular free
safe oncological procedure with better oncological rates than       flap) should be preferred in case of malignancies. Larger
conservative surgery 29. In addition, recent reports have shown     resections involving total maxillectomy, skull base re-
how orbital apex involvement appeared to be an independent          moval, orbital exenteration and facial soft tissue removal
prognostic factor, negatively impacting the survival rates and      require both structural and aesthetic reconstruction using
precluding any kind of curative treatment 3,33,42. Turri-Zanoni     distant free tissue transfer, such as chimeric anterolateral
et al. described 24 patients with orbital apex infiltration by      thigh flap 45, radial forearm flap or rectus abdominis flap. In
sinonasal cancer, reporting a 95.8% rate of recurrence and          addition to flap, prosthetic rehabilitation can be also helpful
death from disease within a mean period of 21 months 3. Sim-        in these cases to restore form. Secondary procedures may
ilarly, Nishino et al. described oncologic outcomes of mul-         be required for remodeling of the flap’s soft tissues and to
timodality treatments for patients with advanced-stage ma-          provide adequate space where prosthetics can be applied.
lignant tumors with orbital invasion, reporting significantly
worse local control rates in patients with disease involving the    Functional outcomes
orbital apex 42. In conclusion, a multidisciplinary approach is
mandatory for the correct management of sinonasal cancers           Functional sequelae which may be observed in case of or-
invading the orbit and to thoroughly define precise indica-         bital preservation may include enophthalmos, diplopia, lid
tions to orbital exenteration.                                      ectropion, epiphora, canthal dystopia, exposure keratitis and
                                                                    visual loss. Imola and Schramm described a grading system
                                                                    to assess the eye function, which stratified cases as follows:
Reconstruction of orbital defects                                   grade I, functional vision without impairment; grade II,
The main reconstructive goal is the support and position-           functional vision with impairment (chronic ophthalmologi-
ing of the preserved eye, since it sits adjacent to the air-        cal sequelae); and grade III, nonfunctional eye (blindness,
filled cavities of the maxillary, ethmoid and frontal sinuses.      nonserviceable visual acuity, intractable diplopia, patched
Other objectives are aesthetic restoration of bony and soft         eye, or delayed exenteration) 41. In their study on 54 pa-
tissue defects, and skull base reconstruction of associat-          tients, eye function was reported as grade I in 54%, grade II
ed dural defects, when present 43. Reconstructive options           in 37%, and grade III in 9%. The most common problem
range from no reconstruction to grafts positioning, and, in         observed was orbit malposition due to lack of adequate rigid
selected cases, to free flap transfer, based on the extent of       reconstruction of the orbital floor. However, the enophthal-
resection. Immediate reconstruction is recommended in or-           mos was not frequently associated with persistent diplopia,
der to improve healing and mitigate soft tissue contraction,        which was reported only in 9% of cases. Similarly, Turri-
especially if radiation therapy has or will be administered.        Zanoni et al. reported a case-series of 125 patients where the
Isolated papyracea defects and limited bony orbital floor           orbital preservation was achieved, obtaining functional eye
defects, medial to the course of the infraorbital nerve, do         without impairment in 63.2%, functional with impairment in
not require rigid reconstruction, since the periorbit integ-        32.8%, and nonfunctional only in 4% 3. Both of these stud-
rity itself is able to keep the position of the orbital content.    ies concluded that postoperative radiation increased the risk
Even in case of periorbital defects, the reconstruction is not      of orbital sequelae, especially for optic atrophy, cataract for-
routinely required since orbital stability is warranted by the      mation, eye dryness, and ectropion. This is supported also
intraorbital connective septal system and postoperative scar        by Rajapurkar et al. who described two cases of decreased
tissue is enough to restore the orbital continence 44. To pro-      visual acuity and radiation-induced retinopathy from a series
mote such healing process, a U-shaped silastic sheet can            of 19 patients with preserved orbit 46.



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Table IV. Summary of evidences available in literature concerning the multidisciplinarymanagement of sinonasal benign and malignant tumours with orbital invasion.
 Pathology                                        Rate of orbital invasion               Multidisciplinary                              Orbital
                                                             (%)                          management                                 preservation
    IP                                                         2-4%                             Recommended                                 Almost invariably
    FOLs                                                      12-15%                            Recommended                                 Almost invariably
    JNA                                                       27-32%                            Recommended                                 Almost invariably
    Low grade cancer (adenocarcinoma, ACC,                    35-45%                              Mandatory                      Highly selected cases (according to the
    low grade ONB, SCC); chemoresistant tumor                                                                                           grade of orbital invasion)
    (MM)
    High grade cancer (SNUC, SCC-G3, NEC,                     50-80%                              Mandatory                   Selected case (according to the response to
    ONB grade IV, p53wt ITAC)                                                                                                          induction chemotherapy)
IP: inverted papilloma; FOLs: fibro-osseus lesions; JNA: juvenile nasopharyngeal angiofibroma; ACC: adenoid cystic carcinoma; ONB: olfactory neuroblastoma; SCC: squamous cell
carcinoma; MM: mucosal melanoma; SNUC: sinonasal undifferentiated carcinoma; NEC: neuroendocrine carcinoma, p53wt ITAC, p53 wild type intestinal type adenocarcinoma.



Epiphora can result from stenosis of the nasolacrimal duct,                                2
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                                                                                                Turri-Zanoni M, Lambertoni A, Margherini S, et al. Multidisciplinary
decreased epiphora rate of 13% using a prophylactic stent-                                      treatment algorithm for the management of sinonasal cancers with or-
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                                                                                                https://doi.org/10.1002/hed.25759
                                                                                           4
                                                                                                Carrau RL, Segas J, Nuss DW, et al. Squamous cell carcinoma of the
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                                                                                                Jørgensen M, Heegaard S. A review of nasal, paranasal, and skull base
                                                                                                tumors invading the orbit. Surv Ophthalmol 2018;63:389-405. https://
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                                                                                                Duan C, Dai Q, Liu Q, et al. Characteristics of sinonasal fibrous
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                                                                                           8
                                                                                                Georgalas C, Goudakos J, Fokkens WJ. Osteoma of the skull base and
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                                                                                                Wang H, Sun X, Liu Q, et al. Endoscopic resection of sinonasal os-
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                                                                                                014-2972-z
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                                                                                                Ricalde P, Magliocca KR, Lee JS. Craniofacial fibrous dysplasia.
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                                                                                                Turri-Zanoni M, Dallan I, Terranova P, et al. Frontoethmoidal and in-
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