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A. Eldaly et al.
identied where workers are estimated to have
100 times more risk of developing paranasal SCC
than the general population [9].
Human papillomavirus, specically subtypes
6 and 11, also seems to play a role in development of SCC by promoting malignant transformation of sinonasal inverted papilloma [10].
Histologically 80% are keratinizing (containing areas of keratin formation, either as sheets or
as epithelial pearls), while 20% are nonkeratinizing [11]. Transitional (Schneiderian) carcinoma
is a special type of nonkeratinizing SCC that has
no particular site of predilection. It is transitional
only in that it tends toward squamous cell differentiation [12].
Non salivary gland Adenocarcinoma:
Adenocarcinoma comprises about 15% of all
sinonasal malignancies. Adenocarcinomas
exhibit a striking male predominance (75–90%),
with a peak age incidence between 55 and
60years. The ethmoids are the most common site
of origin for these tumors. Adenocarcinomas are
divided into intestinal and nonintestinal types.
The intestinal-type adenocarcinoma (ITAC) is
identical to those arising in the intestinal tract. It
has been hypothesized that ITAC derives from a
stem cell capable of undergoing differentiation
into various type of epithelial cells [13]. Exposure
to hard wood dust is a well-recognized risk factor
since 1965 [14]. Acheson estimated that woodworkers in the furniture industry had an approximately 875-fold higher incidence in sinonasal
adenocarcinoma when compared to the normal
population [15]. Most series reveal a high rate of
ethmoid adenocarcinoma (90%) linked to wood
exposure and some European countries include it
with occupational diseases [16]. ITAC histologically and immunohistochemically resembles
intestinal neoplasms [17]. Barnes subdivided
those neoplasms into ve subtypes: papillary,
colonic, solid, mucinous, and mixed. The papillary type shows the less aggressive course while
mucinous adenocarcinomas have the highest
mortality [18].
The nonintestinal adenocarcinomas are typically seromucinous adenocarcinoma lacking any
histological or immunophenotypical features of
ITACs or salivary type adenocarcinomas. There
are no known occupational or environmental etiological factors.
Typically, they are characterized by a back-toback proliferation of glands without intervening
stroma. Based on the degree of cytomorphological characteristics, non-ITACs can be further
divided into low-grade and high-grade tumors.
Low-grade tumors commonly affect the ethmoids
while the high-grade tumors are more common at
the maxillary sinus [19]. Low-grade nonintestinaltype sinonasal adenocarcinomas have an excellent prognosis.
Adenoid cystic carcinoma (ACC) account for
about 10% % of sinonasal malignancies. It is
slightly more common among women and most
commonly present in the fth and sixth decades
of life. Those tumors are characterized by slowly
progressive relentless course. Late recurrence
can occur 10–20years after remission by initial
treatment [20]. Perineural spread, the hallmark of
adenoid cystic carcinoma, is usually evident and
provides avenues of spread to the cranial base
commonly through the maxillary division of trigeminal. Perineural invasion in ACC has been
considered as one of the determining factors for
locoregional recurrence or distant metastasis
[21]. The tumor also has a propensity for bony
invasion, which can lead to signicant involvement of the skull base. Distant metastasis is more
frequent than lymphatic metastasis, with an average incidence of 40%. The lungs and bones are
the sites most frequently involved in systemic
metastasis [22]. Adenoid cystic carcinoma exhibits three histologic subtypes based on tumor
architecture: cribriform, tubular, and solid. The
most common subtype is the cribriform, but the
solid subtypes are known to have the worst prognosis among the three subtypes [23].
Esthesioneuroblastoma is a rare malignant
tumor of neuroectodermal origin, arising from
olfactory bipolar cells. The tumor was rst recognized by Berger etal. in 1924, who coined the
term “esthesioneuroepitheliome olfactif” [24]. It
accounts for 3% of all intranasal malignancies.
The tumor exhibits a bimodal age incidence
showing peaks in age groups 11–20 years and
51–60years [25]. The sex distribution is roughly
equal. Most olfactory neuroblastomas arise in the
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467
superior nasal cavity and are intimately related to
the cribriform plate through which they readily
spread intracranially [26].
The incidence of metastasis is reportedly
10–33% at the time of diagnosis; cervical nodal
metastasis is the most common occurring in
15.6–20.2% [27]. Hyams’ developed a grading
system, which assigns ENB tumors a grade of I to
IV based on lobular architecture, mitosis, necrosis, nuclear pleomorphism, brillary matrix, and
rosettes formation. Grades I and II may be placed
together as low grade, and grades III and IV are
considered high grade [28].
Sinonasal undifferentiated carcinoma (SNUC)
was rst described in 1986 by Frierson and colleagues as a distinct pathological entity arising in
the nasal cavity and paranasal sinuses [29].
SNUC is a rapidly progressive epithelial
malignancy with an incidence of about 0.02 per
100,000 individuals and a median age of diagnosis in the sixth decade of life. These high-grade
neoplasms lack squamous or glandular differentiation and frequently arise from the ethmoid
sinuses. Immunohistochemistry analysis is often
required for diagnosis. Sinonasal undifferentiated carcinoma (SNUC) is composed of pleomorphic cells with a high nuclear-cytoplasmic
ratio, arranged in nests, sheets, and trabeculae
with central areas of central necrosis [30]. Most
patients with SNUC are typically diagnosed with
advanced disease extending beyond the paranasal sinuses to involve the orbit (53%) and skull
base (41%). In addition, cervical nodal and distant metastasis to the lungs and liver commonly
occur [31]. Although outcomes have improved
substantially from the median survival of
4 months originally reported by Frierson and
colleagues, the prognosis for SNUC remains
poor [32].
Rhabdomyosarcoma is the most common
sinonasal malignancy among children; it originates from primitive myogenic cells.
Histologically, These tumors appear as small
round blue cells and are further classied into
four distinct histologic groups (embryonic, alveolar, anaplastic, and undifferentiated)with varying prognosis [33]. Embryonal histology has a
favorable prognosis and 5-year survival rate of
80%, compared with a corresponding rate of only
52% for alveolar subtypes [34].
Malignant melanoma: The nasal cavity is the
most common site for mucosal melanomas in the
head and neck, it accounts for approximately 3%
of sinonasal cancers. The peak age of incidence is
between the fth and eighth decades [35].
Mucosal melanomas are less commonly pigmented than are their cutaneous counterparts.
Histologic appearance includes high mitotic rate
and vascular invasion. Immunostaining and electron microscopy are frequently needed to establish the diagnosis. Mucosal melanomas of the
paranasal sinuses are rapidly lethal neoplasms
[36].
Other less common malignant tumors of the
nasal cavity and paranasal sinuses are mucoepidermoid carcinoma, plasmacytoma, lymphoma,
germ cell tumors, and various sarcomas.
Metastases to the sinonasal region are rare.
Renal cell carcinoma is by far the most common
source of metastases to this area, followed by
lung and breast cancers [37].
40.3 Evaluation
40.3.1 Presentation
Because of the anatomical conguration of the
paranasal sinuses as air containing spaces in the
skull bones; early or small-sized sinus tumors
will produce no or nonspecic symptoms.
Clinician should have a high index of suspicion
to diagnose such early lesions which will dramatically improve the prognosis and the chances of
cure for such patients. It was estimated that
between 9% and 12% of patients diagnosed with
sinonasal malignancies are asymptomatic [38].
The presence of unilateral sinusitis associated
with pain and sinus pressure that is not responding well to medical treatment should raise the
suspicion for an early neoplasm involving that
sinus and causing obstructive phenomenon.
Unexplainable dental symptoms such as dental
pain, loosening of teeth, ill-tting denture or a
non-healing oroantral stula developing after
tooth extraction are possible suspicious signs
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that warrant further workup with a high resolution CT scan.
The most common symptoms of sinonasal
malignancies are unilateral nasal obstruction,
nasal discharge that may be bloody, epistaxis, or
anosmia. Such common complaints may be overlooked for a long time by patients and clinicians,
causing a signicant delay in the diagnosis.
It has been estimated that an average delay of
6–8months occurs between the onset of symptoms and the denitive diagnosis and, at this
time, more than half of the tumors have reached
an advanced stage with a poor prognostic outcome [39, 40].
Many patients present with an advanced
stage tumor that make the diagnosis very obvious. Maxillary tumors may extend inferiorly
causing a submucosal bulge or ulceration
involving the alveolar ridge or hard palate.
Anterior extension will breach the anterior maxillary wall causing evident facial swelling.
Medial extension to the nasal cavity producing
nasal obstruction and intranasal mass. Extension
to the orbit commonly occurs especially with
ethmoid tumors producing ocular symptoms in
about 50% of cases and is related to the site and
degree of invasion [41]. The occurrence of proptosis, epiphora (that might be bloody), diplopia, limited ocular motility, blindness or even
tumor fungation are all manifestations of orbital
involvement by malignant sinonasal neoplasms.
On the other hand, orbital involvement can be
completely asymptomatic and discovered only
on imaging.
Involvement of the infraorbital nerve commonly occurs with maxillary tumors leading to
hypoesthesia overlying the cheek. Posterior
extension will lead to trismus due to invasion of
pterygoid muscles.
Extension to the cranial base may lead to
blurred vision, diplopia, or in hypoesthesia along
the branches of the trigeminal nerves.
Nasal examination might reveal an intranasal
mass that is amenable to ofce examination using
the nasal speculum, on the other hand suspicious
cases not presenting with a frank nasal mass
should have a meticulous endoscopic intranasal
examination with the use of nasal decongestant
A. Eldaly et al.
Fig. 40.1 Endoscopic view of an esthesioneuroblastoma
and topical anesthetic. Endoscopic examination
may reveal the presence of a small intranasal
mass or a polyp (Fig.40.1), an ulcerative bleeding area in the nasal mucosa. Tumors may also
present as a submucosal mass without any mucosal changes or even a bulging lateral nasal wall
with overlying intact mucosa.
The presence of cervical adenopathy is not
common at the time of diagnosis (less than 10%).
Signicant adenopathy at initial presentation
should raise the suspicion of lymphoma.
40.3.2 Diagnostic Imaging
A non-contrast CT scan is the most commonly
request imaging modality for patients presenting
with nonspecic (suspicious) sinonasal symptoms. The presence of bone erosion or unilateral
soft-tissue shadow is enough to raise the suspension of a sinonasal neoplasm that mandates full
radiological evaluation. Contrast-enhanced CT
and magnetic resonance imaging (MRI) of the
paranasal sinuses are generally needed for the
accurate assessment of sinonasal neoplasia. CT
is better for evaluating bony changes, including
expansion, remodeling, and erosion or destruction, while MRI is more useful in assessing soft
tissues such as orbital invasion, intracranial
extension, and perineural spread. The
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Fig. 40.2 CT scan of a chondrosarcoma of the septum
Fig. 40.3 MRI scan demonstrating orbital invasion by
SCC of the ethmoid
information gained from both CT and MRI complement each other in dening the precise extent
of the tumor.
Bone destruction is seen with aggressive
malignant tumors. On the other hand, low-grade
malignancies may produce bone remodeling.
Tumors of cartilage and bone origin exhibit cartilaginous or bony matrix (Fig.40.2). Calcication
within the tumor mass is seen with esthesioneuroblastoma and chondrosarcoma. These radio-
469
graphic features can help in narrowing the
differential diagnosis of a tumor however, aggressive inammatory lesions (Wegener’s granulomatosis or granulomatous fungal sinusitis may
mimic a malignancy).
MRI is the most sensitive imaging modality in
assessment of orbital invasion (Fig.
40.3). The
condition of the periorbita is a key element in
assessment of early stages of orbital invasion.
The periorbita appears as a hypointense line
interspersed between the hyperintense extraconal
fat and the tumor. The presence of unsharp or
nodular tumor-fat interface predicts orbital invasion with high accuracy [
42]. In cases with cra-
nial base invasion; the condition of the dura is an
important determining factor. Linear enhancement at the site of contact with the tumor is generally a reactive change while dural invasion
appears as thickening (>5mm) or nodular dural
tumor interface with a sensitivity of 88% [43].
CT scans are much less sensitive in demonstration of such subtle changes.
Perineural tumor spread manifests as thickening or altered enhancement of a nerve segment,
widening or erosion of skull base foramina and
ssures, enlargement and bulging of the cavernous sinus.
Posterior extension to the pterygopalatine and
infratemporal fossa is shown equally by both CT
and MRI.Bone lysis and erosion are quite often
associated with partial or complete effacement of
fat pads in both fossae.
Functional imaging (PET-CT and the newly
emerging PET-MRI) does not generally play an
important role in the initial assessment of sinonasal tumors. However, they are particularly useful
in post-treatment follow-up. The high negative
predictive value of the technique allows recurrent
tumors to be safely ruled out, whereas positive
studies need to be viewed cautiously because of
the high rate of false-positive results [
44].
In the postoperative follow-up settings MRI
has greater potential in the differentiation
between scar tissue and recurrence. The wide
array of pulse sequences available (including diffusion weighted imaging) allows collection of
information quantitatively and qualitatively superior to that obtained with multislice CT [45].
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40.3.3 Biopsy
Biopsy and histopathological examination are
mandatory before embarking on any management of a malignant sinonasal mass. Biopsy
should be obtained after full imaging evaluation
of the case. An endoscopic transnasal biopsy is
the preferred method. It offers excellent visualization and minimal alteration of the tumor and
surrounding structures. However, the surgeon
should avoid attempts at either debulking or an
attempted resection of the tumor while taking the
biopsy because the resulting anatomical alteration will make denitive surgery more difcult.
Open biopsy is generally not needed even with
deeply located maxillary lesion can be reached
by the creation an astronomy and the use of endoscopes with different viewing angles and curved
instruments.
An adequate biopsy should be obtained avoiding the core of bulky tumors (least viable) and
areas of inammatory polypoid mucosal changes
beside the tumor mass. The specimen should be
handled carefully to avoid crush artifacts and a
part of the specimen should be sent in saline
especially if lymphoma is suspected.
Because of the rarity of sinonasal tumors, the
diversity of the histological types, the high histological spectrum of differentiation among the
same histological type and the presence of overlapping pathological features with other entities;
reaching a correct histopathological diagnosis of
malignant sinonasal tumors is often difcult.
The use of immunostaining is frequently
needed to reach a denitive diagnosis which will
have a great impact on the management decision.
It is extremely important to have a skilled head
and neck pathologist and to consider the need for
a second opinion in many instances.
40.3.4 Staging
The extent of a cancer at time of diagnosis is an
important factor used to dene treatment and to
assess the chance of successful outcome. Cancer
staging systems were developed to code the
extent of cancer. In addition to its prognostic
value, it also allows homogeneous classication
to compare groups of patients in clinical trials
who receive standard care around the world facilitating communication and publication.
The most widely used staging system in the
current clinical practice is the TNM system maintained by the American Joint Committee on
Cancer (AJCC) and the International Union for
Cancer Control (UICC). The system codes the
extent of the primary tumor (T), regional lymph
nodes (N), and distant metastases (M) and provides a “stage grouping” based on T, N, and
M.The system is periodically updated based on
advances in understanding of cancer prognosis to
remain current and relevant to clinical practice.
The latest revision of TNM is the eighth edition that included many changes related to the
classication on nasopharyngeal and oropharyngeal carcinoma, on the other hand the classication of sinonasal malignancies remained the same
as the previous edition [46]. The seventh edition
of this classication includes two different grouping systems, one for carcinoma of the maxillary
sinus and one for malignant tumors of the ethmoid sinuses and the nasal cavity. This classication divides T4 lesions into T4a (moderately
advanced local disease) and T4b (very advanced
local disease), leading to the stratication of
stage 4 into stage 4A (moderately advanced local/
regional disease), stage 4B (very advanced local/
regional disease), and stage 4C (distant metastatic disease) [47].
The TNM is essentially an anatomically based
staging. However, the rapidly increasing knowledge of cancer biology provides prognostic information that is in many instances more relevant
than anatomic extent. This information need to be
incorporated into the TNM nomenclature.
A variety of alternative systems have been
proposed for use with individual histopathological types, including esthesioneuroblastoma,
SNUC, sinonasal mucosal melanoma and rhabdomyosarcoma. Many of these staging systems
have been found to be of great utility and accurately predict patient survival.
Several staging systems have been proposed
for esthesioneuroblastoma. The Kadish system
[48] is the most commonly used, and it classied
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471
tumors into three categories (A–C) by location
and extension; the system was later updated with
redened stage C and introducing a new stage D
(for metastases) [49]. A third classication system proposed by Dulguerov and Calcaterra is
based on the TNM system [50].
40.4 Treatment
The management of paranasal sinus tumors is a
multidisciplinary endeavor that involves a team
of specialists beside the head and neck surgeon
such as pathology, radiation oncology, medical
oncology, prosthodontists, neurosurgery, and
plastic surgery. The prime parameters that drive
management decisions are the tumor pathology,
the ability to achieve a gross total resection, and
the availability of adjunctive therapies.
Complete surgical resection (when feasible)
followed by postoperative irradiation is considered the standard of care in most cases of malignant sinonasal tumors.
40.4.1 Surgical Treatment
Irrespective of the surgical technique used, the
aim of curative surgery is to achieve complete
tumor resection with microscopically negative
resection margins. The extent of surgically resection is largely dependent on the extension of the
tumor and to a lesser extent on the known biological behavior of a particular tumor e.g., biologically aggressive versus none.
high doses required for primary irradiation [
54,
55].
It was not possible until the early sixties that
Mon bloc resection of the ethmoids was possible
through a combined transcranial and facial
approaches. In 1963, Ketcham and his colleagues
reported the rst series of 19 patients who had an
anterior craniofacial resection, but 80% of his
patients suffered some type of complications
[56]. The technique fell in disfavor until the pericranial ap was described to protect dural closure
after anterior craniofacial resection which has led
to marked reduction of intracranial complication
and the anterior craniofacial resection became a
safe surgical procedure [
57].
Anterior craniofacial resection is the standard
procedure for surgical management of ethmoidal
malignancies abutting or invading the anterior
cranial base. Intracranial exposure is obtained
through a bicoronal incision and bifrontal craniotomy. Cerebral dehydrating measures are
administered and the dura is lifted off the anterior
cranial base to expose the roof of the ethmoids
(Fig.40.4). An appropriate transfacial approach
is combined (according to tumor extension). The
ethmoid block is ostetomized and the ethmoid
block is delivered through the facial approach
(Fig.40.5), dura is reconstructed and closed in a
watertight manner and the pericranial ap is used
to separate the intracranial contents from the
nasal cavity. Transdural invasion into the brain
parenchyma is not a contraindication to surgical
resection, alternatively cavernous sinus or inter-
40.4.1.1 Nasoethmoidal Tumors
Historically, those tumors were managed by a
transfacial resection. The major surgical failure
was an inadequate excision of the tumor, most
commonly at the cribriform plate, with subsequent high local recurrence rates [51, 52] and
very low cure rates of 27–35% of malignancies
of the nasal vault and 9–10% for ethmoid tumors
[53]. Radiation therapy was also associated with
high failure rate and serious complications
because of the limited tolerance of the visual
pathway and other neuronal structures to the
Fig. 40.4 Operative photograph demonstrating intracra-
nial extension of ethmoid tumor through the ethmoid roof
(viewed through a bifrontal craniotomy)
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472
Fig. 40.5 The surgical defect of anterior craniofacial
resection
nal carotid artery invasion are not amenable to
curative aggressive resection especially with
high-grade malignancies.
Endoscopic Resection ofNasoethmoidal
Malignancies
Surgical treatment for nasoethmoidal malignancies has witnessed a dramatic change over the
last two decades with a paradigm shift toward the
application of transnasal endoscopic techniques.
This was largely due to an increase in surgical
expertise, advances in imaging techniques and
surgical instrumentation.
Early reports on endoscopic resection of nasoethmoidal malignancies included only patients
with centrally located lesions limited to their site
of origin without involvement of the adjacent
skull base. However, in the following years and
with increasing experience skull base involvement was also deemed amenable to a purely
endoscopic excision [58].
Endoscopic resection of malignant sinonasal
neoplasms have been extensively debated since
its introduction. This was mainly based on the
inability to perform a monbloc resection and that
a piece meal removal of tumor is not considered
oncologically sound in that it predisposes the
patient to positive margins postresection [59].
Theoretical advantages of endoscopic resection include superior illumination, magnication
and visualization of the surgical eld, wider
angles of vision using angled endoscopes, avoid-
A. Eldaly et al.
ance of facial incisions, shorter hospital stays,
and lower costs [60].
The limitations of endoscopic techniques
include the lack of stereoscopic visualization and
depth perception, the inability to repair or patch
dural defects with suture techniques, which limits
the reconstructive options after endoscopic resection of intradural tumors. Lund and coworkers do
not recommend endoscopic resection in isolation
if there is transdural extension—a craniofacial
resection is typically recommended [61]. Also in
cases with extensive invasion and perineural
spread an open technique is usually
recommended.
Many studies comparing endoscopic vs open
techniques demonstrated that endoscopic resection of sinonasal malignancies have oncologic
results equivalent to those of open surgery in
selected cases however most of the cases who
underwent endoscopic resection where of a lower
grade tumors and none of them were T4 tumors
[62–64]. Lu etal. in a recent meta-analysis concluded that “current pooled evidence suggested
that when compared to open resection, endoscopic resection is a comparable surgical
approach for sinonasal malignancies” and that it
is likely that “particular patients and presentations will benet more from one of the approaches
versus the other.” [65]
In experienced hands and in well-selected
patient populations, endoscopic resection of
sinonasal malignancies is safe, and survival and
recurrence data seem to be comparable with
those for open techniques.
40.4.1.2 Maxillary Tumors
Tumors originating in the maxillary sinus are
removed by some form of maxillectomy. The
maxillectomy operation represents one of the
earliest attempts at oncological resection of head
and neck cancer. The rst report of maxillectomy
appeared in 1826 by Lizars [66]. Arguably, the
most famous of maxillectomies was that performed on President Grover Cleveland on board
the yacht Oneida as it sailed up the East River on
the morning of July 1, 1893. A verrucous squa-
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mous carcinoma was removed, the patient was
tted an obturator and he remained tumor-free
until his death from cardiopulmonary disease
15years later [67].
To avoid confusing terms like extended and
radical maxillectomy, Spiro et al. developed a
simple classication of maxillectomy. A limited
maxillectomy indicated removal of one wall of
the maxilla (e.g. medial, inferior or superior maxillectomy), total maxillectomy indicated removal
of the entire maxilla while a subtotal maxillectomy describes removal of at least two walls of
the maxilla. In all cases any additional resection
of adjacent structures e.g., the orbit, facial skin,
pterygopalatine, or infratemporal fossa must be
identied [68].
Medial maxillectomy requires removal of the
entire lateral nasal wall and the ethmoids on one
side. This can be performed classically through a
lateral rhinotomy. Alternatively the operation can
be accomplished successfully through an endoscopic endonasal approach or through a transantral approach avoiding the facial incision. The
operation is commonly performed for early or
low-grade tumors involving the lateral nasal wall.
Malignancies conned to the lower half of the
maxilla are managed by limited (inferior) maxillectomy and this can be performed through a
transoral route. In both medial and inferior maxillectomy the infraorbital nerve is preserved.
Larger maxillary tumors would require a subtotal
maxillectomy, a procedure that removes at least
two walls of the sinus including a portion of the
hard palate or the orbital oor. The extent of
resection is dictated by the extent of the tumor.
More extensive tumors would require a total
maxillectomy where the entire maxilla is
removed, where tumors extend posteriorly to the
pterygopalatine or infratemporal fossa; the pterygoid plates may be included with the maxillectomy (Fig. 40.6) or an infratemporal fossa
dissection is required for complete tumor extirpation. Total maxillectomy is generally performed
through a Weber-Ferguson incision with a subciliary or transconjunctival extension (Fig.40.7).
473
Fig. 40.6 The surgical specimen of total maxillectomy
with the pterygoid plates
Fig. 40.7 The surgical defect of total maxillectomy after
reconstruction of preserved orbit (medial palpebral ligament reattached and a titanium mesh is used to support the
orbital oor)
Alternatively, the operation can be performed
through a combined wide sublabial and subciliary incisions incision to minimize facial
incisions.
Resection of the hard palate and alveolus
requires reconstruction this is commonly performed using a dental obturator; some centers
prefer the use of composite free aps that are
fashioned to replace missing bone.
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40.4.2 Non-surgical Treatment
40.4.2.1 Radiation Therapy
Postoperative radiotherapy is generally indicated
patients with high-grade tumors, microscopically
positive resection margin or histopathological
features of aggressive behavior such as
lymphovascular, bone or perineural invasion.
Postoperative radiotherapy is also indicated in
cases where the surgeon is not condent about
complete tumor resection (close surgical margin)
or tumor spillage during surgery [69].
Postoperative doses typically range from 50 to
66Gy, but doses of 70 to 74.4Gy or higher may
be necessary to control gross residual or unresectable disease. The necessity for high dose for
disease control and the sensitivity of adjacent
neural structures presents challenges to the treating radiation oncologist [70].
Historically, radiation therapy delivered via
conventional techniques has been associated with
signicant complications. Severe visual toxicity
has been observed with unilateral and bilateral
blindness rates reported to be as high as 30% and
10%, respectively [71].
Subsequent improvements in threedimensional conformal radiation therapy (3DCRT) techniques allowed planning based on
computed tomography anatomy and led to
improvements in target coverage and normal tissue sparing appeared to reduce the risk on optical
pathways [72].
Intensity-modulated radiation therapy (IMRT)
was one of the most important advances in modern radiotherapy planning it allows for better
sparing of optic and brain structures and improved
coverage of tumor [73, 74].
Charged particle therapy using protons or carbon ions have garnered particular interesting the
treatment of sinonasal cancer it have the potential
to maintain target coverage and further lower
dose to surrounding normal organs [75]. A recent
meta-analyses showed an increase in disease control with charged particle therapy compared to
photon radiation therapy [76].
40.4.2.2 Chemotherapy
Classically, the role of chemotherapy in the management of sinonasal malignancies has been lim-
ited to palliative treatment of locally advanced or
metastatic cancers [77]. This role has recently
expanded to be become a part of the multimodal
management where systemic chemotherapy is
administered in neoadjuvant, concurrent, or adjuvant settings.
Clinical studies have demonstrated a potential benet of induction chemotherapy in the
multimodal treatment of advanced cases [78].
The approach with induction chemotherapy
aims to reduce the local burden of disease, with
the two objectives of promoting a better
approach with radical surgery or radiotherapy,
and to reduce the risk of distant spread, for the
most aggressive forms. Favorable response to
induction chemotherapy is considered a strong
prognostic factor [79, 80]. Induction chemotherapy has become key aspect of orbit-sparing
protocols [81].
Concomitant chemotherapy and radiotherapy
achieved promising survival and locoregional
control rates in certain cases [82].
Chemotherapeutic agents may also be used as
radiosensitizers, enhancing the effects of radiation on tumor cells [83]. Most accepted protocols
currently used involve platinum-based agents
[84].
Intra-arterial delivery of chemotherapeutic
agents was developed in an effort to deliver
higher concentrations to the tumor site while
minimizing toxic reactions [85]. Despite exciting organ-preservation and local control rates,
intra- arterial chemotherapy carries substantial
risk of toxicity that was not justied, given that
the efcacy was similar to that of evolving
induction chemotherapy regimens [86]. And the
technique remains largely an experimental
option.
The development of many biologic agents
over the past decade, including cetuximab and
other monoclonal antibodies, harbors signicant
potential for targeted therapy [87].
40.4.3 Management ofOrbital
Invasion
The incidence of orbital invasion by malignancies of the sinonasal tract varies with the site of
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origin, histology, and aggressiveness of the
tumor. Invasion of the orbital wall is present in
66–82% of the patients with ethmoidal
malignancy, with involvement of the orbital periosteum in 30–50% of patients [88].
Till the early 1960s, orbital exenteration was
required for any degree of orbital invasion [89].
During the early 1970s, an emerging consensus
toward orbital preservation have emerged and the
criteria dening the indications for orbital preservation versus exenteration have evolved. In 1970,
Sisson introduced the concept of selective orbital
preservation surgery following adjunctive preoperative radiation for paranasal sinus malignancy
[90]. Conley had stated that “most patients are
willing to take extra risks to save the eye” [91].
Several investigators like Perry et al. [92],
McCarry etal. [93], and Sisson etal. [94] have
demonstrated that the periorbita is an effective
barrier to tumor invasion and they concluded that
the orbit can be preserved if the full thickness of
the periorbita is not breached by tumor. The
results showed no signicant adverse effect on
local recurrence using this strategy pushing the
limits of orbital preservation even further, Tiwari
has noted that a thin fascial layer exists around
the periorbital fat that is distinct from the periorbita and believes that invasion of this layer should
determine the need for exenteration [95].
Reconstruction. Reconstruction of the orbit is
frequently needed to maintain function of the
preserved eye and avoid sequelae such as enophthalmos, hypotropia, and diplopia. Reconstructive
goals include appropriate support and positioning
of preserved orbital contents. Techniques and
options for repairing orbital defects depend hon
the extent of resection. Resected periorbita is
reconstructed with a fascial graft, limited resection of the orbital oor requires no reconstruction. Larger defects involving the orbital oor
must undergo immediate rigid reconstruction
[96]. Titanium mesh and porous polyethylene
implants are among the commonly used materials in this regard [97]. Larger tumor resection
including maxillectomy, orbital exenteration, and
facial soft-tissue sacrice necessitate utilization
of free tissue transfer. Complementary strategies,
such as prosthetics, can be exceedingly helpful in
restoring form.
Take Home Messages
• Cancer of the nasal cavity and paranasal
sinuses is rare, representing less than
1% of all human malignancies.
• Sinonasal malignancies comprise a
wide variety of neoplasms with different
biologic behavior, ranging from slowgrowing and indolent to highly aggressive and lethal.
• Understanding the biologic behavior of
these tumors is of paramount importance in selecting the optimal treatment
strategy.
• The signs and symptoms of early stage
sinonasal malignancy are similar to
those of benign conditions and a high
index of suspicion is required for their
diagnosis.
• Both CT and MRI are complimentary in
the evaluation of patients with sinonasal
malignancies.
• Surgery plays an important role in the
management of most patients with sinonasal malignancies.
• Treatment of sinonasal tumors is frequently multimodal and requires close
ongoing multidisciplinary cooperation.
References
1. Youlden DR, Cramb SM, Peters S, Porceddu SV,
Moller H, et al. International comparisons of the
incidence and mortality of sinonasal cancer. Cancer
Epidemiol. 2013;3786:770–9.
2. Turner JH, Reh DD. Incidence and survival in
patients with sinonasal cancer: a historical analysis of
population- based data. Head Neck. 2012;34:877–85.
3. Muir CS, Nectoux J. Descriptive epidemiology of
malignant neoplasms of nose, nasal cavities, middle
ear and accessory sinuses. Clin Otolaryngol Allied
Sci. 1980;5:195–211.
4. Barnes L, Eveson J, Reichart P.Pathology and genetics of head and neck tumors. Lyon, France: Oxford
University Press; 2005.
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