10.14639/0392-100X-suppl.1-41-2021-16
Nose vestibule malignancies, mainly SCCs, are considered rare neoplasms. In the present paper, we review the current state of the art concerning classification and treatment, and describe current evidence supporting a paradigm shift. In the current AJCC classification nose vestibule is considered part of nasal cavity/ethmoid. In daily clinical practice, nose vestibule lesions are often misclassified as skin primaries. This leads to an underestimation of the real incidence and to a mis-management. When nose vestibule primaries are correctly classified as nose primaries, the current AJCC TNM appears inadequate for prognostic stratification and an old staging system described 4 decades ago by Wang has been demonstrated to be more reliable in the literature and is preferred in centers with the largest volume of cases treated. The principles of Wang classification should be applied and nose vestibule acknowledged as a new distinct subsite of nose and paranasal sinuses by the AJCC/ UICC. Surgery, External Beam RadioTherapy (EBRT) and Interventional RadioTherapy (IRT, BrachyTherapy BT) are the current therapeutic options for nose vestibule (NV) SCC. Increasing evidence demonstrates that IRT, with a proper multidisciplinary approach, is at least equivalent to surgery and EBRT for treatment of the primary lesions in terms of oncological outcomes, but markedly superior in terms of cosmetic and functional results, supporting HDR (high dose rate) IRT as the new standard for the treatment of the primary lesion in these malignancies. To optimize the advantages of IRT as primary therapeutic modality we set up a new approach to the implantation phase of IRT exploiting the anatomic planes of esthetic and functional nose surgery and the potential of intensity modulated and image guided brachytherapy to avoid septal and alar perforation (anatomic implantation).
application/xml
1827-675X
1697
en
Gaetano Paludetti
https://creativecommons.org/licenses/by-nc-nd/4.0
ACTA Otorhinolaryngologica Italica
interventional radiotherapy
Multidisciplinary approach to nose vestibule malignancies: setting new standards
Text.Serial.Journal
https://www.actaitalica.it/
41
Annual congress report
2021-05-14
2021-05-10
2021-05-14
2021-05-14
158-165
1
Gaetano Paludetti
2021/05/14
10.14639/0392-100X-suppl.1-41-2021-16
158
UOC di Otorinolaringoiatria, Dipartimento Scienze dell’Invecchiamento, Neurologiche, Ortopediche e della testa collo, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, Rome, Italy
1827-675X
interventional radiotherapy
165
Multidisciplinary approach to nose vestibule malignancies: setting new standards
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ACTA OTORHINOLARYNGOLOGICA ITALICA 2021;41(SUPPL.1):S158-S165; doi: 10.14639/0392-100X-suppl.1-41-2021-16




Multidisciplinary approach to nose vestibule
malignancies: setting new standards
Approccio multidisciplinare ai tumori maligni del vestibolo del naso:
verso la definizione di nuovi standard
Francesco Bussu1,4, Luca Tagliaferri2, Antonio Piras1, Davide Rizzo3, Nicola Tsatsaris1, Eugenio De Corso4,
Claudio Parrilla4, Gaetano Paludetti4
1
  Otolaryngology Division, Azienda Ospedaliero Universitaria, Sassari, Italy; 2 Fondazione Policlinico Universitario “A. Gemelli”
IRCCS, UOC Radioterapia Oncologica, Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia,
Rome, Italy; 3 Otolaryngology, Dipartimento delle Scienze Mediche, Chirurgiche e Sperimentali, Università di Sassari, Italy; 4 UOC
di Otorinolaringoiatria, Dipartimento Scienze dell’Invecchiamento, Neurologiche, Ortopediche e della Testa Collo, Fondazione
Policlinico Universitario “A. Gemelli” IRCCS, Rome, Italy


SUMMARY
Nose vestibule malignancies, mainly SCCs, are considered rare neoplasms. In the present
paper, we review the current state of the art concerning classification and treatment, and
describe current evidence supporting a paradigm shift. In the current AJCC classification
nose vestibule is considered part of nasal cavity/ethmoid. In daily clinical practice, nose
vestibule lesions are often misclassified as skin primaries. This leads to an underestimation
of the real incidence and to a mis-management. When nose vestibule primaries are correct-
ly classified as nose primaries, the current AJCC TNM appears inadequate for prognostic
stratification and an old staging system described 4 decades ago by Wang has been demon-          Received: October 10, 2020
strated to be more reliable in the literature and is preferred in centers with the largest vol-   Accepted: January 15, 2021
ume of cases treated. The principles of Wang classification should be applied and nose ves-
tibule acknowledged as a new distinct subsite of nose and paranasal sinuses by the AJCC/          Correspondence
UICC. Surgery, External Beam RadioTherapy (EBRT) and Interventional RadioTherapy                  Luca Tagliaferri
(IRT, BrachyTherapy BT) are the current therapeutic options for nose vestibule (NV) SCC.          Fondazione Policlinico Universitario “A. Gemelli”
                                                                                                  IRCCS
Increasing evidence demonstrates that IRT, with a proper multidisciplinary approach, is
                                                                                                  largo F. Vito 1, 00168 Rome, Italy
at least equivalent to surgery and EBRT for treatment of the primary lesions in terms of          E-mail: ent.brachytherapy@gmail.com
oncological outcomes, but markedly superior in terms of cosmetic and functional results,
supporting HDR (high dose rate) IRT as the new standard for the treatment of the primary          Funding
lesion in these malignancies. To optimize the advantages of IRT as primary therapeutic mo-        None.
dality we set up a new approach to the implantation phase of IRT exploiting the anatomic
planes of esthetic and functional nose surgery and the potential of intensity modulated and       Conflict of interest
image guided brachytherapy to avoid septal and alar perforation (anatomic implantation).          The Authors declare no conflict of interest.
KEY WORDS: nasal vestibule carcinoma, brachytherapy, total rhinectomy, interventional
radiotherapy                                                                                        How to cite this article: Bussu F, Taglia-
                                                                                                    ferri L, Piras A, et al. Multidisciplinary ap-
                                                                                                    proach to nose vestibule malignancies: set-
RIASSUNTO                                                                                           ting new standards. Acta Otorhinolaryngol
I tumori maligni del vestibolo del naso, principalmente SCC, sono considerati neoplasie             Ital 2021;41(SUPPL.1):S158-S165. https://doi.
rare. Nel presente lavoro, rivediamo lo stato attuale dell’arte per quanto riguarda la clas-        org/10.14639/0392-100X-suppl.1-41-2021-16
sificazione e il trattamento, e descriviamo le evidenze attuali a supporto di un cambiamento
di paradigma. Nell’attuale classificazione AJCC il vestibolo del naso è considerato parte         © Società Italiana di Otorinolaringoiatria
della cavità nasale/etmoide. Nella pratica clinica quotidiana, le lesioni del vestibolo del       e Chirurgia Cervico-Facciale
naso sono spesso erroneamente classificate come primarie della pelle. Questo porta a una
sottovalutazione della reale incidenza e a una cattiva gestione. Quando i tumori primitivi                       OPEN ACCESS
del vestibolo del naso sono correttamente classificati come a origine dal naso/seni pa-           This is an open access article distributed in accordance with
ranasali, l’attuale AJCC TNM appare inadeguato per la stratificazione prognostica e un            the CC-BY-NC-ND (Creative Commons Attribution-Non-
vecchio sistema di stadiazione descritto 4 decenni fa da Wang ha dimostrato di essere più         Commercial-NoDerivatives 4.0 International) license. The
                                                                                                  article can be used by giving appropriate credit and mentio-
affidabile ed è preferito nei centri con il maggior volume di casi trattati. I principi della     ning the license, but only for non-commercial purposes and
classificazione di Wang dovrebbero essere applicati e il vestibolo del naso dovrebbe essere       only in the original version. For further information: https://
riconosciuto dall’AJCC/UICC come una nuova sottosede distinta di naso e seni paranasali.          creativecommons.org/licenses/by-nc-nd/4.0/deed.en




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La chirurgia, la radioterapia a fasci esterni (EBRT) e la radioterapia interventistica (IRT, BrachyTherapy BT) sono le attuali opzioni terapeu-
tiche per il carcinoma del vestibolo del naso (NVSCC). Sempre più evidenze dimostrano che la IRT, da effettuarsi in un contesto rigorosamente
multidisciplinare, è almeno equivalente alla chirurgia e all’EBRT per il trattamento delle lesioni primarie in termini di esiti oncologici, ma net-
tamente superiore in termini di risultati estetici e funzionali, supportando l’HDR (high dose rate) IRT come nuovo standard per il trattamento
della lesione primaria in questi tumori maligni. Per ottimizzare i vantaggi della IRT come modalità terapeutica primaria abbiamo impostato
un nuovo approccio alla fase di impianto della IRT sfruttando i piani anatomici della chirurgia estetica e funzionale del naso e le potenzialità
della brachiterapia a intensità modulata e guidata dalle immagini, per evitare la perforazione del setto e dell’ala (impianto anatomico).
PAROLE CHIAVE: carcinoma del vestibolo nasale, brachiterapia, rinectomia totale, radioterapia interventistica



Introduction                                                                       spread make such criteria clearly inadequate for nose vesti-
                                                                                   bule 1-6. In fact skin invasion through the nasal valve (mostly
The present work is a critical review of the state of the art                      deep to alar and superficial to lateral nasal cartilage) is very
concerning nose vestibule squamous cell carcinomas (SCC)                           frequent among SCC of the NV, and makes most of them
with the aim to outline recent evidence supporting a para-                         cT4a for AJCC. On the other hand, paradoxically, bony in-
digm shift in the domains of classification (1), treatment                         vasion, which, according to the AJCC, can be present also
strategy (2), and therapeutic technique (3, brachytherapy                          in cT1 ethmoid/nasal cavity lesions, is typical only of the
implantation technique).                                                           bulkiest, most difficult to treat and with the worst progno-
                                                                                   sis, vestibular SCC 1,4-6. Wang, back in 1976, outlined that
Nose vestibule malignancy, current                                                 “there is no acceptable classification for tumors of the nasal
classification and misclassification                                               vestibule” and proposed a classification of primary lesions
                                                                                   (T), specific for the nose vestibule 7 (Tab. I). Wang classi-
The nasal vestibule (NV) is defined as that part of the an-                        fication has been reported to predict prognosis better than
terior nasal cavity that is lined by squamous epithelium up                        more recent AJCC/UICC T classification and remains the
to the limen nasi, which is the muco-cutaneous junction 1.                         most used for nose vestibule malignancies 1,4-6,8,9 even if it
SCC of the nasal vestibule (NV) is a relatively rare condi-                        can result difficult to apply (especially for the distinction
tion believed to account for about 1% of all head and neck                         between T2 and T3, see Table I).
malignancies. Primary epithelial malignancies, ad in par-
ticular SCCs, of the nasal vestibule, according to the AJCC/                       Rethinking classification and staging of nose vestibule ma-
UICC staging system 2, are classified together and assigned                        lignancies
the same topography code (C30.0) than those of the rest                            Basing upon the above considerations a shared internation-
of the nasal cavity (nasal cavity proper). A Danish group                          al standard for classification and staging of nose vestibule
recently estimated, as a rounded down approximation, an                            malignancies and in particular SCC is needed. We propose
annual incidence of squamous cell of the nasal vestibule of                        2 modifications of the current TNM.
0.41 per 100.000 inhabitants 3. Anyway, the absence in the                         1. Define the nose vestibule as the portion of the nasal cav-
AJCC classification of a specific topography code for nose                            ity extending from the pyriform aperture to the external
vestibule malignancies which most often are not discrimi-                             skin of the nose, cheek, superior lip, and assign a spe-
nated from all the other nasal cavity primaries, as well as the                       cific topography code as a site distinct from nasal cavity
frequent misdiagnosis and misclassification of these lesion                           proper/ethmoid and from maxillary sinus, which are cur-
as cutaneous neoplasms are likely to produce a relevant un-                           rently the two sites with different T classification criteria
derestimation of their incidence. When TNM staging sys-                               for nose and paranasal sinuses. It will allow to better de-
tem is concerned, staging criteria for the primary lesion (T)                         fine the incidence and also to better consider the peculiar
according to AJCC are the same as nasal cavity proper and                             aspects of malignancies of the nose vestibule.
ethmoid, but anatomical features and peculiar pattern of                           2. Set up specific T classification criteria for the newly de-


Table I. Staging of the primary lesions of the nose vestibule according to Wang.
 T1      The lesion is limited to the nasal vestibule, relatively superficial, involving one or more sites within
 T2      The lesion has extended from the nasal vestibule to its adjacent structures, such as the upper nasal septum, upper lip, philtrum, skin of the nose and/
         or nasolabial fold, but not fixed to the underlying bone
 T3      The lesion has become massive with extension to the hard palate, buccogingival sulcus, large portion of the upper lip, upper nasal septum, turbinate
         and/ or adjacent paranasal sinuses, fixed with deep muscle and bone involvement




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Table II. A preliminary proposal for redefinition of T classification in nose vestibule malignancies.
 T1      The lesion is limited to the nasal vestibule internal surface (skin and or mucosa)
 T2a     The lesion invades superficial structures outside the nasal cavity (skin and subcutaneous) and in particular upper lip, philtrum, skin of the nose and/or
         nasolabial fold, but does not destroy cartilage, nor invades bony structures, nor structures beyond the plane of the pyriform aperture (septum, lateral
         wall, turbinates, etc.)
 T2b     Disruption of cartilages is evident, without invasion of bony structures, nor of structures beyond the plane of the pyriform aperture (septum, lateral
         wall, turbinates, etc.)
 T3      The lesion extends beyond the pyriform aperture (septum, lateral wall, turbinates, etc.)
 T4a     The lesion invades bony structures as hard palate, nasal bones, frontal process of the maxilla, ethmoid, and the orbit
 T4b     Tumor invades any of the following: orbital apex, dura, brain, anterior and middle cranial fossa, cranial nerves other than (V2), nasopharynx, or clivus



   fined subsite, starting from the Wang classification, to                         for oncological results (OS over 90% in cT1 and cT2 ac-
   better define prognosis and guide treatment selection. A                         cording to Wang).
   hypothetical draft of the new T classification is reported                       In the absence of oncological evidences supporting one
   in table II, considering that, in our experience, cartilage                      versus another modality, functional issues become funda-
   is not usually disrupted in the early phases, but somehow                        mental for treatment selection.
   guides tumor spread (posteriorly along the septum, su-
   perficially below the alar and above the lateral cartilages                      Cosmetic outcomes
   to the skin of the dorsum, inferiorly to the superior lip)                       Among such functional issues there is for sure the aesthetic
   to different areas of the midface (Fig. 1).                                      appearance, which have obvious social implications and
                                                                                    can be deeply impacted by any therapeutic procedure in-
                                                                                    volving the nose and the nose vestibule in particular 1,4,6.
Current treatment options for nose vestibule                                        In fact, reconstruction of the nose tip, which shares the
SCCs: evidence supporting brachytherapy                                             cartilaginous framework with the vestibule after ablative
as the new standard for treatment of the                                            surgery, is notoriously extremely difficult for at least 2 rea-
primary lesion                                                                      sons:
                                                                                    • it is the most exposed and noticed area of the entire
Oncological outcomes                                                                   body, where light and human eyes always land. There-
Surgery, External Beam RadioTherapy (EBRT) and Inter-                                  fore, minimal imperfections, scars, color mismatches,
ventional RadioTherapy (IRT, BrachyTherapy BT) are the                                 and deformities exhibit the highest esthetical and social
current therapeutic options in clinical practice 3,9-14, as there                      impacts;
are not clear evidences of superiority for any modality. Re-                        • it is practically impossible to faithfully reproduce the
cent papers focusing on the comparison between surgery                                 complex pattern of relieves and hollows created by the
and IRT 4 and on IRT alone 5,15,16 showed that brachytherapy                           nose cartilage and underlying maxillary and nasal bones
as primary treatment of the T is not inferior to surgery as                            using surgical procedures. Free flaps, which have drasti-
                                                                                       cally changed head and neck surgical oncology in the
                                                                                       last few decades, do not have a resolutive impact here.
                                                                                       According to several authors 3,12,18 bone anchored pros-
                                                                                       theses remain the best option under an esthetical point of
                                                                                       view in case of total rhinectomy defects.
                                                                                    Therefore, anatomical preservation of the osteocartilagi-
                                                                                    nous framework is the most successful option in midface
                                                                                    and nose vestibule malignancies from an aesthetic point of
                                                                                    view 4,12. If we consider in addition that nose cartilage itself
Figure 1. Preferential pattern of local spread of malignancies arising in the
nose vestibule. Cartilagineous structures are not usually disrupted in the early    is generally pretty resistant to radiation, the markedly bet-
phases, as tumor spread rather occurs along them to different areas of the          ter cosmetic results reported for high dose rate (HDR) IRT
face. Posterior spread along the septum for primaries of the columella and an-      (Fig. 2) when compared to surgery (Fig. 3) 4 can be easily
terior septum is shown in A. Preferential pattern of spread of primaries of the
                                                                                    explained. For the same reasons also EBRT, with similar
lateral side of the vestibule, between alar and lateral cartilages or (more rare)
between lateral cartilage and nasal bones is shown in B. Spread of primaries        survival figures than IRT 3,13,14, is considered a valid alterna-
from columella and inferior side of the vestibule is shown in C.                    tive option also under an esthetical point of view 8,10,12,19,20



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                                                                                                                     New standards for nose vestibule malignancies




and is probably the most frequently recommended primary                              the first section to be passed through by inhaled air. Thus,
treatment in Western countries at present 10,19.                                     the nose has evolved multiple physiologic strategies to regu-
                                                                                     late flow speed, temperature, and humidification (somehow
Functional outcomes                                                                  conditioning the inhaled air headed to bronchi and alveoli)
The nose is primarily part of the respiratory system, being                          of the inspired air, as well as to tightly modulate its ability


 A                                      B                                              H                                                                          I




                                                                                       L
 C




                                                                        D

                                            E
                                                                                                                                                                 M

                                                                                                                                                                 O
                                                                                                                            N


  F


                                                 G




Figure 2. Pretreatment findings (A, B, H, I), catheter positioning (C, D, L, M) and postoperative results (E, F, G, N, O) in 2 patients treated by primary brachyther-
apy are shown. Case 1 came to our observation with a primary SCC arising from the columella without a clear cartilagineous involvement (cT1 stage according to
Wang). Plastic tubes were placed parallel along the main axis of the nose (C, D) with a complete coverage of the tumor volume. The patient is currently alive with no
evidence of disease (60 month follow up) (E). The aesthetic result appears very good (F, G) (pictures have been taken 9 months after treatment). Case 2 displayed
a bulky primary SCC (cT2 according to Wang classification, pN1 after concomitant neck dissection), involving all the walls of the nasal vestibule and infiltrating the
skin of the nasal dorsum and of the superior lip, and alar and septal cartilages (H, I). The patient underwent primary brachytherapy and bilateral selective neck
dissection. At the time of neck surgery plastic tubes were placed parallel along the main axis of the nose (L, M) with a complete coverage of the tumor volume).
The patient is currently alive with no evidence of disease (30 month follow up). The aesthetic results appear acceptable (N, O) (pictures have been taken 7 months
after treatment) with no further loss of cartilage deriving from IRT.



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F. Bussu et al.




        A                                        B                                     C                                         D



                                                 F




                                                 G


                                                                                                                                       L



        E                                                               H                                    I

Figure 3. Preoperative findings (A, B, E, F, G) and postoperative results (C, D, H, I, L) in 2 patients treated by primary surgery are shown. Case 1 came to our
observation with a primary SCC arising from the limen nasi and spreading to the tip and the alar skin with cartilagineous involvement (A, B) (T2 stage according to
Wang). R0 resection was performed, with the preservation of nostril rims, but the aesthetic result without a prosthesis 12 months after surgery is not satisfactory at
all (C, D). Case 2 displayed at physical exam (E) and at MR imaging (F, G) a SCC of the columella spreading towards the superior lip (T2 stage according to Wang).
6 weeks after the R0 resection, the results of the primary closure are objectively better (H, I, L) but still not fully satisfactory for the patient.


to protect and defend itself and the respiratory system as                           view, evidence supporting EBRT versus IRT is lacking, we
a whole. Among such physiologic strategies, there are the                            recently compared the 2 irradiation modality as for out-
maintenance of adequate intranasal resistances within the                            comes on nasal function 15. The nasal functions are notori-
physiologic variations due to the nasal cycle 21, the sneeze                         ously affected by irradiation 23-25, and many complaints, as
reflex 22, and the complex immunological and mechanical                              crusting 25, dry nose 26, dysosmia 24,27, dysgeusia 24, in pa-
defensive system constituted by nasal mucosa, with all its                           tients with a previous irradiation of nasal region, are clearly
cellular components (both in the ciliated epithelium and                             linked to the disruption of physiological mechanisms by
in the stroma) and by the mucous itself. One of the most
                                                                                     mucosal toxicity of radiotherapy 26,28,29. Most of these pre-
characteristic and well-known expression of such defensive
                                                                                     vious data have been recently confirmed with specific test
system is the mucociliary clearance.
                                                                                     after EBRT but not after IRT 15, with a substantial pres-
Disruption of any of the above-cited physiologic functions
can be secondary to gross anatomic variations, as after on-                          ervation of nasal function and cytological findings. The
cological surgery, or to other pathological processes involv-                        rapid dose fall off of the IRT, exploited also in the adjuvant/
ing and impairing one or more of the above cited mecha-                              perioperative setting 30,31, with a drastic reduction of the ir-
nisms, mainly at the level of nose mucosa, as in case of                             radiated mucosal surface inside the nasal/paranasal cavi-
irradiation, which notoriously harbours well known acute                             ties, may be decisive factors. Nevertheless such favourable
and, most of all, late toxicities.                                                   toxicity profile is well known and exploited also in geriatric
For this reason, knowing that, under a cosmetic point of                             population 17.



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The new standard
Such evidence, together with the confirmation of oncologi-
cal effectiveness, which remains of course the most relevant
argument, supports the establishment of interstitial IRT as
the new standard for the treatment of the primary lesion in
cT1 and cT2 (according to the Wang staging) NV SCCs.
Still, it must not be forgotten that IRT is a multidiscipli-
nary tool at the border between surgery and radiotherapy,
and close cooperation between surgeons and radiation on-
cologists during every phase, from the recommendation of
treatment and implantation in the operating theater to the
prescription and dose painting at the radiotherapy depart-
ment, is mandatory to perform high-quality IRT 6.

Implantation technique for nose vestibule
                                                                 Figure 4. The plastic tubes ideally lie along a subperichondral route, cartilages
primaries                                                        and perichondrium should not be disrupted and the tubes pass from a submu-
                                                                 cosal to a subcutaneous plane through the junction between alar and lateral car-
The aim of functional and, even more, cosmetic preservation      tilages. Such an implant is particularly fit for a primary lesion invading skin along
of patients with nose vestibule carcinoma passes as written      the same route. More rarely the primary can reach skin through the junction be-
above through the preservation of the nose tip cartilaginous     tween nasal bone and lateral cartilages, also in this case the implant should fol-
framework not already eroded by tumour growth. It is well        low the same route as malignancy (drawing realised by Nicola Tsatsaris).
known also from laryngeal oncology 32 that cartilage itself
is particularly resistant to tumour invasion also because it
is devoid of blood vessels and fed through the interstitium      selves and that the final geometry of the implant is dictated
by direct diffusion from vascularized perichondrium 33. In       primarily by the anatomy of the nose tip (and not by the
fact, as blood vessels are brought in by ossification, prob-     Paris system rules). Such anatomic implantation technique
ability of invasion drastically increases. Nose cartilages,      resulted in no septal perforation in our series (39 cases by
differently from laryngeal ones, and thyroid cartilage in        now) with markedly better functional and cosmetic results
particular, do not usually get ossified even in the elderly,     than in previous series 13. The “anatomic” implantation
and in fact, as observed above, direct invasion is very late     technique may contravene the “classical” Paris system 38
in nose vestibule SCCs. This fact and the resistance and the     whose rules and principles remain valid to obtain an opti-
low toxicity of radiotherapy on nose cartilages 4,15,34-37 are   mal dose distribution, especially with LDR linear sources,
clear advantages for the cosmetic results after irradiation of   but the potential of the intensity dose modulation, thanks
these malignancies.                                              to the stepping source brachytherapy treatment planning
However, the main reported long-term toxicity of IRT in          combined with the image guided IRT, can improve dose
this area is known to be chondronecrosis and consequent          distribution after “anatomic” implantation in order to ob-
septal and even alar perforations 13. These sequelae are         tain optimal local control, which in fact is not inferior to
reportedly more frequent when an interstitial delivery is        other brachytherapy series 4,6,9,13,15,16.
chosen, than in endocavitary/mold technique 13, suggesting
that chondronecrosis is likely due to the mechanical dam-        Conclusions: towards new standards
age and interruption of the perichondrium which feeds the
cartilage by the implants, more than to the dose to carti-       The evidence and the considerations expressed above push
lage itself. Starting from this assumption, we modified our      for a paradigm shift in different management phases of
implantation technique following the principle to avoid as       nose vestibule carcinomas:
much as possible the piercing of the perichondrium and of        • Diagnosis and staging. Nose vestibule should be consid-
the cartilages. To this aim, we leave the implantation phase        ered a distinct site of nose and paranasal sinuses, with
of nose vestibule SCCs to skilled nose surgeons who brings          specific T staging and criteria borrowed from the most
the plastic tubes along the subperichondral planes, which           used Wang staging (Tab. I) with some improvements
are the main dissection routes of the functional and aesthet-       (Tab. II);
ic surgery of the nose (Fig. 4). This implies that the planes    • Treatment choice. There are three options available for
of the implant are ideally the subpericondral planes them-          the treatment of the primary lesion in nose vestibule SC-



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F. Bussu et al.




  Cs (surgery, EBRT, IRT), without any clear difference                       12
                                                                                   Goepfert H. The vex and fuss about nasal vestibule can-
                                                                                   cer. Head Neck 1999;21:383-384. https://doi.org/10.1002/
  in term of oncological outcomes, but IRT (administered                           (sici)1097-0347(199908)21:5<383::aid-hed1>3.0.co;2-#
  with HDR) offers clear advantages in terms of cosmetic                      13
                                                                                   Lipman D, Verhoef LC, Takes RP, et al. Outcome and toxicity pro-
  and functional results and we consider it the standard for                       file after brachytherapy for squamous cell carcinoma of the nasal
  cT1 and cT2 (according to Wang) primary lesion. When                             vestibule. Head Neck 2015;37:1297-303. https://doi.org/10.1002/
                                                                                   hed.23758
  there is indication to neck treatment (elective or thera-                   14
                                                                                   Koopmann M, Weiss D, Savvas E, et al. Clinicopathological and im-
  peutic) we recommend concomitant neck dissection, to                             munohistochemical characteristics of surgically treated primary carci-
  be performed in the same session as implantation, being                          noma of the nasal vestibule- an evaluation of 30 cases. Clin Otolaryn-
  IRT a localized treatment, and in case or local/regional                         gol 2015;40:240-247. https://doi.org/10.1111/coa.12359
  recurrence EBRT remains a fully available option;                           15
                                                                                   Bussu F, Tagliaferri L, De Corso E, et al. Functional results of exclu-
                                                                                   sive interventional radiotherapy (brachytherapy) in the treatment of
• IRT technique. The main long term toxicity of IRT on                             nasal vestibule carcinomas. Brachytherapy 2021;20:178-184. https://
  the nose vestibule, which is chondronecrosis deriving                            doi.org/10.1016/j.brachy.2020.08.008
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