Recent Patents on Inflammation & Allergy Drug Discovery 2011, 5, 241-252 241

Nasal Polyposis: An Overview of Differential Diagnosis and Treatment

Cemal Cingi1, Duygu Demirbas2 and Ahmet Ural3,*

1
Osmangazi University, Medical Faculty, Department of Otorhinolaryngology, Eskisehir, Turkey, 2Acibadem Hospitals,
Department of Otorhinolaryngology, Istanbul, Turkey, 3 Karadeniz Technical University School of Medicine, Depart-
ment of Otorhinolaryngology, Trabzon, Turkey

Received: October 21, 2010; Accepted: July 8, 2011; Revised: July 11, 2011

Abstract: Nasal polyposis is a chronic inflammatory disease of the nasal and paranasal sinus mucosa. Etiology remains
unclear, but allergy, asthma, aspirin sensitivity, cystic fibrosis, and infection have been associated with the disease. Clini-
cally, nasal obstruction, anosmia/hyposmia, rhinorrhea, postnasal drainage, headaches, facial pain, and sleep disorders
constitute the main symptoms. Intranasal examination reveals bilateral, mobile, grey, smooth and semi translucent poly-
poid masses that usually originate in the ethmoid sinuses or the middle meatus. Differential diagnosis is important to rule
out congenital anomalies, as well as benign or malignant tumors. In the evaluation of nasal polyps, computerized tomo-
graphy is helpful especially in determining the extent of the disease and in planning the surgical approach. Management of
nasal polyposis consists of medical therapy and surgery. Surgical treatment is performed in cases that are refractory to
medical therapy. Recurrence of nasal polyps is quite common and medical therapy after surgery is often necessary for
avoiding recurrences. This paper aims to summarize the current trends in the diagnosis, management of nasal polyposis
and relevant patents.
Keywords: Diagnosis, nasal polyposis, pathopysiology, treatment.

INTRODUCTION indicate cystic fibrosis. There is a male predominance, with a

Nasal polyposis has been known for more than 4000
years, and inteersitngly it is the first disease in history where
both the doctor and patient names had been recorded [1].
Nasal polyposis is often associated with systemic diseases
and is characterized by nasal obstruction, anosmia/hyposmia,
rhinorrhea, postnasal drip, headache, facial pain, and im-
paired quality of life [2, 3].In case of a unilateral nasal polyp,
other possibilities such as benign or malignant tumors and
congenital abnormalities should be ruled out. Due to the
obscure etiology and high rate of recurrence; treatment of
nasal polyps has always been a challenge in ENT practice.
There is no consensus for a standard therapy, approach, or
algorithm; and the management of nasal polyposis remains
primarily medical. Topical steroids can be combined with
systemic corticosteroids in severe cases [4]. Surgery is indi-
cated in patients who are refractory to medical management
or in whom complications occur. Postoperative care needs to
be meticulous to avoid or at least to delay recurrences.
EPIDEMIOLOGY
The prevalence of nasal polyposis in the general popula-
tion has been estimated at 1-4% [2]. In autopsy studies, this
prevalence has been shown to be as high as 40% [5-8]. Nasal
polyps are usually present between the ages of 20 and 60
years. Nasal polyposis in children under 10 years of age may
*Address correspondence to this author at the Medical Faculty, Department
of Otorhinolaryngology Karadeniz Technical University, Trabzon, Turkey;
Tel: 0090 462 3775884; Fax: 00 90 462 3250518;
E-mail: ahmetural2001@yahoo.com
ratio of 2-4:1 [2].
ETIOPATHOGENESIS
Historically, allergy had been supposed to paly role in
nasal polyposis is allergy; due to the increased number of
eosinophils in nasal secretions and similarity of clinical
symptoms. Contemporarily, polyps are considered to occur
as a consequence of chronic inflammation that may be initi-
ated by both infectious and noninfectious causes. Several
hypotheses have been proposed to explain the pathogenesis
of nasal polyps.
ALLERGY
In the past, nasal polyps were associated with allergic
diseases, because of the high concentration of eosinophils in
polyp tissue and similarity of clinical symptoms to allergic
rhinitis. Recently, studies have suggested that polyps are, in
fact, more likely to be linked to non-allergic inflammation
rather than allergic disease [9] Table 1.
Some studies have shown that the incidence of allergic
disease and rates of prick test positivity among the patients
with nasal polyps are not higher than the general population.
Allergic disease in nasal polyp patients appears to be a coin-
cidence [10]. Patients with nasal polyps have specific IgE
manifested nasal mucosal allergy with no sign of systemic
allergy. This suggests that local allergic mechanisms, in the
absence of systemic features, could play role in the patho-
genesis [11]. Total and specific IgE levels have correlated
with levels of eosinophils but not with prick test positivity
[12].

1872-213X/11 $100.00+.00 © 2011 Bentham Science Publishers

242 Recent Patents on Inflammation & Allergy Drug Discovery 2011, Vol. 5, No. 3
Table 1. Prevalence of Nasal Polyposis in Different Popula-
tion Subgroups [9].
Aspirin intolerance 36-72%
Adult asthma 7%
IgE mediated 5%
Non-IgE mediated 13%
Chronic sinusitis in adults 2%
IgE mediated 1%
Non-IgE mediated 5%
Childhood asthma/sinusitis 0.1%
Cystic fibrosis
Children 10%
Adults 50%
Allergic fungal sinusitis 66-100%
Primary ciliary dyskinesia 40%
INFECTION
Many patients with nasal polyps have a history of chronic
rhinosinusitis; the pathogens isolated were common patho-
gens in rhinosinusitis such as Staphylococcus aureus, Strep-
tococcus pneumoniae, and Bacteroides fragilis. In addition
to these, Pseudomonas aeruginosa may be isolated in nasal
polyposis patients with cystic fibrosis [13]. S. aureus is de-
tected in the mucin of 60-70% of patients with nasal poly-
posis Enterotoxins (SEA, SEB) excreted by Staphyloccus
aureus may act as superantigens and cause clonal expansion
of lymphocytes. Increased levels of Th1 and Th2 cells may
lead to mucosal damage [14]. Nasal polyps occurring secon-
dary to infections exhibit a predominance of, neutrophils and
lymphocytes rather than an eosinophilic infiltration [13].
Fungal infections may contribute to the development of
nasal polyps, since eosinophils attack fungal elements and
release toxic mediators, resulting in secondary mucosal in-
flammation and polypoid changes [15]. Aspergillus sp. is the
most common fungal species found in paranasal sinuses. In
one study, 45% of patients with nasal polyps had a positive
skin prick test with mold extracts and 40% had a positive
skin prick test for Candida albicans. In contrary, only 11%
of control subjects were positive on skin prick test with mold
extracts [16]. To our knowledge, no viral etiology has been
demonstrated in the development of nasal polyposis yet.
VASOMOTOR IMBALANCE
In recent years, due to the fact that most of the nasal
polyposis patients were found to be not atopic; the vasomo-
tor imbalance theory has been postulated as a cause of nasal
polyposis, This theory is based on the idea of impaired vas-
cular regulation with increased vascular permeability, that
may subsequently cause edema and polyp formation [9].
Cingi et al.
BERNOULLI PHENOMENON
The Bernoulli phenomenon is based on the decreasing
pressure throughout a narrowing passage. When such a
change occurs in the nasal passage, the resulting pressure
difference sucks the mucosa outward. Thus, it appears that
the negative pressure induces the inflamed mucosa to project
into the nasal cavity, resulting in polyp formation [10].
NITRIC OXIDE
Nitric oxide is a free radical that is kept in balance by the
antioxidant defense system, which includes superoxide dis-
mutase (SOD), catalase, and glutathione peroxidase. In-
creased levels of nitric oxide and decreased SOD were found
in patients with nasal polyps compared to controls, suggest-
ing the presence of free radical damage in nasal polyps [17].
Conditions Associated with Nasal Polyposis
Asthma and Aspirin Intolerance
Nasal polyposis has been related to aspirin (ASA) intol-
erance and asthma, with an eosinophilic inflammatory
mechanism [2]. Seven% of asthmatic patients were found to
have nasal polyps [6], while 20-40% of patients with nasal
polyps have asthma. Among patients with ASA intolerance,
36% have nasal polyps [6,7].
The combination of nasal polyps, ASA intolerance, and
aspirin-induced-asthma was described by Samter in 1967 and
later named as Samter’s Triad. Inhibition of the cyclooxy-
genase enzymes (COX1 or COX2) with aspirin shunts ara-
chidonic acid metabolism towards the leukotriene pathway.
This leads to decreased levels of PGE2 and increased levels
of cysteinyl leukotriene (Cys-LT), which may lead to serious
inflammatory responses and chronic inflammation [8].
Genetic Predisposition
Cystic fibrosis (CF) is caused by an autosomal-recessive
defect of the CFTR gene on the long arm of chromosome 7.
Typical features of CF patients are high concentration of
chloride in sweat, recurrent pulmonary and paranasal sinus
infections, nasal polyposis, pancreatic insufficiency, and
infertility [18]. Among patients with CF, 10% of the children
and 50% of the adults have concomitant nasal polyps [9].
Nasal polyps are encountered in patients with other ge-
netic syndromes, such as primary ciliary dyskinesia, an auto-
somal recessive disorder in which patients are plagued with
recurrent upper respiratory tract infections including chronic
sinusitis. The maximal manifestation of the illness is known
as Kartagener’s syndrome.
Young’s Syndrome is another disease characterized by
recurrent respiratory infections, azoospermia and nasal pol-
yps. Churg-Strauss Syndrome is a granulomatous vasculitis
and one third of patients had been reported to suffer from
nasal polyps. Another study reported a genetic link in the
immune function through a significant association shown
between HLA-A74 and nasal polyps [18].
Nasal Polyposis Recent Patents on Inflammation & Allergy Drug Discovery 2011, Vol. 5, No. 3 243
Cellular Composition and Chemical Mediators
Nasal polyps are characterized by an edematous stroma,
pseudostratified ciliated columnar epithelium, thick epithe-
lial basement membrane, and few blood vessels with poor
vasoconstrictor innervation [19]. The most common type is
an edematous eosinophilic polyp; 85-90% of nasal polyps
are of this type [7]. Eosinophils are the major inflammatory
cells of nasal polyps found in 80-90% of all polyps. They
release inflammatory products that directly damage the epi-
thelium of the upper and lower respiratory tract [2].
Increased inflammatory cell infiltration causes increased
expression and production of numerous mediators in nasal
polyps. High concentrations of free histamine have been
found in fluid extracted from nasal polyps [20]. Th1 and Th2
type cytokines are up-regulated in polyp tissue, but in atopic
patients, polyps exhibit a predominance of Th2 cells and
eosinophils in comparison to nonatopic patients [21].
IL-1, IL-3, and IL-5 have been regularly found in polyp
stroma. IL-5 plays a key role in eosinophil migration, while
IL-8 can induce neutrophil infiltration [14]. IL-5 is the major
eosinophil survival factor, and treatment of eosinophil -
infiltrated polyp tissue with neutralizing anti-IL-5 mono-
clonal antibody resulted in eosinophil apoptosis [22].
Increased levels of GM-CSF (granulocyte/macrophage
colony-stimulating factor), RANTES (regulated upon activa-
tion, normal T-cell expressed and secreted), and VCAM-1
(vascular cell adhesion molecule 1) have strong eosinophil
chemotactic, activating effects and are regularly detected
within the polyp stroma [23]. VPF/VEGF (vascular perme-
ability/vascular endothelial growth factor) may contribute to
the edema, with induction of vascular hyperpermeability
[24]. Immunoreactivity for IGF-I (insulin-like growth fac-
tor I) immunoreactivity was found at high levels in patients
with nasal polyps [25]. The complement system was shown
to be involved in the pathogenesis of nasal polyposis; sig-
nificantly higher concentrations of C3a desArg and C5a
desArg were found in nasal secretions of patients with nasal
polyps compared to controls [26].
In antrochoanal polyps, eosinophilia can be found in 20-
65% of cases. Mucus glands, which are common in nasal
polyps, are almost never found in antrochoanal polyps.
The polyp stroma regularly contains neutrophils, lym-
phocytes, monocytes, plasma cells, and macrophages, in
addition to eosinophils and mast cells [19].
In patients with cystic fibrosis, primary ciliary dyskinesia
syndrome or Young’s syndrome, neutrophils are the domi-
nant cells in polyps [2].
DIAGNOSIS
History
The evaluation of nasal polyps begins with a history. The
most common symptom is nasal obstruction, which depends
on the size of the nasal polyp. Nasal polyps can cause watery
rhinorrhea, purulent postnasal drainage, hyposmia/anosmia,
headache, facial pain, and affect the quality of the voice and
sense of taste. Epistaxis does not occur with benign multiple
polyps and may suggest a more serious nasal cavity lesion.
Small polyps arising from the middle meatus may block the
outflow tract of the sinuses and cause chronic or recurrent
acute sinusitis symptoms [7]. Mucocele, which may be
caused by nasal polyps in the frontoethmoidal sinus, can
displace the globe laterally, inferiorly and anteriorly; result-
ing in diplopia [27].
Physical Examination
Careful examination of the nose is mandatory. Anterior
rhinoscopy mostly reveals bilateral, single or multiple, mo-
bile, grey, smooth and semi-translucent polypoid masses in
the nasal cavity. Nasal polyps most frequently arise from the
middle meatus, but also the mucosa of the ostia, anterior and
posterior ethmoidal clefts, frontal and sphenoethmoidal re-
cesses may be the site of origin [28]. Nasal endoscopy may
be performed with or without decongestion. Decongestion
and endoscopic examination provides excellent visualization
of the small polyps in the middle meatus, but is not essential
for gross polyps [29]. Endoscopic visualization of the polyps
and adjacent regions of the nasal and sinus cavities is neces-
sary for correct diagnosis and staging of the disease. The
most commonly used staging system, based on the endo-
scopic appearance of the sinonasal cavity, was described by
Lildholdt [29, 30] Table 2.
Table 2. Grading of Nasal Polyps [29, 30].
Endoscopic Appearance Score
No polyps 0
Polyps restricted to middle meatus 1
Polyps below middle turbinate 2
Massive polyposis 3
Radiology
Plain sinus X-ray, sinus computed tomography (CT)
scanning, and magnetic resonance imaging (MRI) can be
used for the diagnosis of nasal polyposis. X-rays have a
limited value in the diagnosis of nasal polyposis [31]; be-
cause they show generalized opacification of all sinuses, but
the true nature of an opaque sinus cannot be demonstrated.
Therefore, a plain radiograph cannot determine the nature of
lesion resulting in the opacification of the paranasal sinus
[7].
Computerized tomography scanning is not a primary
method in the diagnosis of nasal polyposis. It must be util-
ized in cases for which surgical treatment (especially revi-
sion surgery) is considered and in cases of unilateral disease.
A CT scan with 2-3 mm direct coronal sections is adequate
for diagnosis and before limited surgery for maxillary and
anterior ethmoid sinuses, complete CT (2 mm direct and
3 mm axial cuts) is useful if the disease extends beyond the
ground lamella into the posterior ethmoids and sphenoid to
define the relationship of the optic nerves and carotid arteries
prior to the surgery. Because of the poor resolution of bony
tissue, MRI is only preferred to differentiate meningocele or
encephalocele and to distinguish a tumor from retained se-
cretions and secondary inflammatory disease [32].
244 Recent Patents on Inflammation & Allergy Drug Discovery 2011, Vol. 5, No. 3
Other Tests
Anterior rhinomanometry, acoustic rhinometry and nasal
inspiratory peak flow are other measures that can be used to
quantify the restriction in the nasal airway [7]. Allergy test-
ing, pulmonary function tests, biopsies, sweat chloride test,
or genetic testing for the detection of cystic fibrosis, aspirin
intolerance test, fungal stains and cultures, and quantitative
tests of smell, such as by UPSIT [University of Pennsylvania
Smell Identification Test), can be used to assess the response
to treatment or to the evaluate the efficacy of the treatment as
well as to diagnose the accompanying diseases [7].
Differential Diagnosis
Presence of unilateral nasal polyp in a patient must arise
the suspicion of other clinical entitites. The similarities of
benign and malignant disorders at initial presentation lead to
a significant delay in the diagnosis of malignancy. Sinonasal
symptoms unresponsive to medical treatment, intranasal
bleeding or crusting, orbital symptoms, cranial neuropathies,
severe and unilateral frontal headache, signs of meningitis or
focal neurological signs must remind the other possibilities
to the physician.
Any benign or malignant tumor can mimic or coexist
with nasal polyps. All polyp tissue removed surgically or
biopsies obtained from polyp tissue must be examined his-
tologically to exclude the possibilty of neoplasia [7]. When a
dermoid, glioma, or encephalocele is presumed, a biopsy
should not be performed unless an intracranial connection is
ruled out. Otherwise, a surgical intervention may bring about
the risk of meningitis or cerebrospinal fluid (CSF) leak.
Imaging modalitites should be considered prior to biopsy
in order to avoid the distortion of tumor margins as well as to
assess the lesion in terms of vascularity and intracranial
connection. The advantage of CT scans is the detection of
bone erosion. Magnetic resonance imaging provides excel-
lent delineation of tumor from surrounding inflammatory
tissue and secretions within the sinuses. Typically, edema of
the inflamed tissue and retained secretions would be of low
intensity on T1 sections and of high intensity on T2 sections
secondary to the increased fluid content. In contrary, 95% of
sinonasal tumors are highly cellular with less fluid content
giving low to an intermediate signal intensity on both T1 and
T2 sections.
A unilateral nasal polyp should raise the suspicion of an
inverted papilloma or a tumor (nasal squamos cell carci-
noma, nasal lymphoma, melanoma, esthesioneuroblastoma,
and hemangiopericytoma) in adults, or congenital anomalies
like nasolacrimal canal cyst, gliomas, encephaloceles, or
tumors like juvenile nasopharyngeal angiofibroma, rhabdo-
myosarcoma, hemangioma and chordomas in children Table
3.
Antrochoanal polyp was initially described by Professor
Gustav Killian in 1906. It represents 4-6% of all nasal pol-
yps. It is a benign lesion originating from the mucosa of the
maxillary sinus, growing through the accessory ostium into
the middle meatus and subsequently protruding posteriorly to
the choana and nasopharynx. Incomplete excision of antro-
choanal polyp almost always leads to recurrence [33].
Cingi et al.
Table 3. Differential Diagnosis of Nasal Polyposis.
Adults
Inverted papilloma
Tumors
Squamous cell carcinoma
Nasal lymphomas
Nasal melanoma
Esthesioneuroblastoma
Hemangiopericytoma
Children
Turbinate hypertrophy
Congenital
Nasolacrimal duct cysts
Nasal gliomas
Encephaloceles
Tumors
Juvenile nasopharyngeal angiofibroma (JNA)
Rhabdomyosarcoma
Hemangioma
Chordoma
Inverted papilloma (Cylindrical cell papilloma, Schnei-
derian cell papilloma) is a true epitelial neoplasm character-
ized by hyperplastic epithelium inverted into the underlying
stroma. It occupies approximately 0.5% of the nasal tumors
and 4% of all nasal polyps. The typical presentation is a
unilateral polyp. Malignant transformation is possible. Early-
stage and limited tumors can be managed with endoscopic
excision. For widespread, recurrent and rapidly growing
tumors; lateral rhinotomy with medial maxillectomy is the
treatment of choice. Close postoperative follow up is manda-
tory not to skip the recurrences [34].
Squamous cell carcinoma is the most common malig-
nant tumor of the paranasal sinuses (80%). In In %70 of
cases, the tumor arises from the maxillary sinus, followed by
nasal cavity (20%), and ethmoid sinuses (10%). The presen-
tation is variable and the complaints may include a nasal
mass or obstruction, rhinorrhea, epistaxis, cranial neuropa-
thies, or pain. 90% of cases exhibit local invasion at presen-
tation. Surgical resection followed by postoperative radio-
therapy is recommended in resectable cases [35].
In general, non-Hodgkin lymphomas are primarily found
in patients at 6th and 7th decades. Clinically, symptoms of
nasal obstruction may be accompanied by rhinorrhea and
epistaxis. After the identification of the tumor, radiotherapy
and chemotherapy may be utilized. The prognosis is
Nasal Polyposis Recent Patents on Inflammation & Allergy Drug Discovery 2011, Vol. 5, No. 3 245
variable, depending on the type and stage. Median survival
time ranges from 1 year to 5 years in 80% of cases.
Melanomas are arising from melanocytes and those
arising in the nasal cavity or paranasal sinus are relatively
rare. The incidence of melanomas arising from the mucosal
surface of the aerodigestive tract varies from 0.4 to 4%. The
majority of these lesions arise in the nasal cavity or paranasal
sinuses. The peak incidence is between the fifth and eighth
decades. They are more common in malesi and age and sex
do not affect the prognosis [35]. Immunogenic peptides
derived from the Melanoma antigen recognized by T lym-
phocytes (MART-1) had been developed recently. Hope-
fully, they are expected to serve as a vaccine to prevent or
treat melanoma [36].
Esthesioneuroblastoma is a rare and malignant tumor
originating from the olfactory neuroepithelium in the nasal
cavity. Esthesioneuroblastoma is the term used most com-
monly. Tumor may invade the nasal cavity, paranasal si-
nuses, the orbit and the cranial cavity. Nasal obstruction
(65%) and epistaxis (55%) are the common symptoms. Pa-
tients with esthesioneuroblastoma are older than 40 years in
most cases [37].
Hemangiopericytoma is an uncommon vascular tumor
originating from the pericytes of Zimmerman. Less than one-
third of these tumors occur in the head and neck, while a
minor proportion can involve the sinonasal tract. Sinonasal
hemangiopericytomas are borderline tumors which clinically
appear as pale, gray-white, well-circumscribed masses with a
soft, rubbery consistency. Nasal obstruction with epistaxis is
common. The mean age of onset is 55, and the gender distri-
bution is roughly equal. Treatment is a complete surgical
resection followed by radiation if the surgical margin is
positive [35].
Nasal duct cysts occur in advance to the congenital ob-
struction of the nasolacrimal drainage system. It is common,
but symptomatic cases are rare. The most common site of
obstruction is the most distal part of the duct beside its exit
into the nose. The obstruction is usually unilateral. A bluish-
gray cyst can appear beneath the inferior turbinate. A large
nasolacrimal duct cyst filingl the nasal cavity may lead to
nasal obstruction and inferior turbinate may be pushed medi-
ally toward the nasal septum. Because infants are preferen-
tially nose breathers, this displacement can cause significant
respiratory distress, ending up with cyanotic spells and poor
feeding, these symptoms usually subside with crying. The
treatment of choice for symptomatic cases is endoscopic
marsupialization or resection. Outfracturing of a medially
displaced inferior turbinate might further improve the
patency of the nasal airway [38].
Nasal gliomas are rare, benign, congenital masses which
are actually sequestered glial tissue. Of the gliomas, 60% are
extranasal, 30% are intranasal, and 10% are both intra and
extranasal. Extranasal gliomas are mobile and usually do not
swell upon crying or Valsalva maneuver. Extranasal gliomas
appear near the nasion. The overlying skin may be discol-
ored or telangiectatic [38].
Encephaloceles are herniation of the neural tissue
through a defect in the skull. They may contain meninges
(meningocele) or brain matter and meninges (encephalomen-
ingocele) or they may communicate with a ventricle (en-
cephalomeningocystocele). Twenty percent of all encephalo-
celes occur in the cranium. Of these, 15% are nasal. Nasal
encephaloceles can be divided into 2 types: syncipital (60%)
and basal (40%). Syncipital encephaloceles typically present
as soft compressible masses over the glabella. Basal en-
cephaloceles may remain clinically dormant. Both CT scan
and MRI are useful in diagnosis and a treatment modality
involving craniotomy is necessary to provide sufficient ex-
posure for the encephalocele [38].
Juvenile nasopharyngeal angiofibroma (JNA) is a rare,
benign, vascular neoplasm that accounts for less than 0.5%
of all head and neck tumors. They are classically present
with unilateral nasal obstruction, epistaxis, and a naso-
pharyngeal mass in adolescent males. Treatment options
include surgery, radiation therapy, chemotherapy, and hor-
mone therapy. Surgery is the gold standard of treatment [39].
Rhabdomyosarcoma originates in the soft tissue and it
appears as a nasal mass resembling a polyp. The tumor is
slightly more common in males than females. Early presenta-
tion of head and neck lesions allows early diagnosis, which
in turn facilitates complete surgical resection and effectivity
of chemotherapy, thereby reducing the mortality and avoid-
ing recurrence. Increased alertness for a nasal mass and thor-
ough clinical assessment is the key to diagnosis [38].
Hemangiomas are benign vascular tumors originating
from the skin, mucosa, bones, muscles and glands. Although
hemangiomas are common lesions of the head and neck,
those of the nasal cavity and paranasal sinuses are relatively
rare. Neoplasms arising in the nasal cavity are predominant
capillaries and they may be attached to the nasal septum. On
the other hand, cavernous hemangiomas are more likely to
be found on the lateral wall of the nasal cavity [39].
Chordomas are malignant, nonepithelial neoplasms de-
rived from notochordal tissue. Primary chordoma of the
paranasal sinuses or nasal cavity is extremely rare. The pre-
senting signs and symptoms of chordoma are related to the
site of origin and the area of extension. Intranasal chordoma
presents with nasal obstruction caused by the mass effect of
the tumor. Radiographically, chordomas are associated with
bony destruction and an extraosseous soft-tissue mass with
intralesional destruction. Treatment of the lesion depends on
the location and pattern of extension. An anterior lesion
appears to be amenable to wide local excision, ending up
with good results. Clival or sphenoid lesions are usually
more advanced on presentation and are treated with debulk-
ing and postoperative radiation. New therapeutic agent
“Gamma-secretase inhibitor”, that has intramembranous
proteolytic activity, has been patented for treatment of chor-
doma and other solid tumors [40, 41].
TREATMENT
Management of nasal polyps involves medical, surgical,
or a combination of medical and surgical therapy. Better
knowledge on the cause and pathogenesis of nasal polyposis
is mandatory in the treatment of nasal polyps Medical treat-
ments include topical or systemic steroid regimens, as well
as nasal saline lavage and allergen immunotherapy. The
current consensus among specialists is that benign nasal
246 Recent Patents on Inflammation & Allergy Drug Discovery 2011, Vol. 5, No. 3
polyps should initially be treated conservatively, as many
patients may not require surgery. Surgery has a role when
themedical treatment fails [42]. Treatment should be deter-
mined on an individual basis. Surgery is considered when
medical therapeutic options fail. The goal of surgery is to
reduce of the size of the nasal polyp, Ito improve sinus
drainage, restoration of the ventilation of sinuses and restora-
tion of olfaction and taste and also to remove the fungal
debris in cases with Allergic Fungal sinüsitis and to prevent
the complications in cases with erosion of the lamina pa-
pyracea and the skull base.The surgical approach alone is not
entirely curative, and usually repeated procedures and addi-
tional long-term medical treatment is essential. However, it
must be kept in mind that polyps cannot be compeletely
eradicated and main aim of surgery is mostly to provide a
nasal passage for airway and drainage [7, 43] Fig. (1).
Nevertheless, for all nasal polyposis patients, recurrences
still comprises of a serious problem and neither option pro-
vides the ideal solution. In recent years a change in treatment
strategy has lead to greater use of medication, with good
evidence of the eficacy of nasal corticosteroids
MEDICALTREATMENT
Medical treatment should be determined on an individual
basis. Treatment options in nasal polyposis include topical
and systemic steroids, nasal lavage, antibiotic therapy, anti-
fungal therapy, antihistamines, antileukotrienes, and aspirin
desensitization. Despite this long list, topical and oral sys-
temic corticosteroids constitute the mainstay of contempo-
rary medical management. While the other approaches may
offer alternatives to corticosteroid treatment or surgery, at
present largescale controlled trials are lacking and further
evaluation is required before they could be considered a
viable alternative to steroids.
Several studies have demonstrated the clinical efficacy of
corticosteroids in patients with nasal polyps [43-51].
CORTICOSTEROID TREATMENT
Corticosteroids have a broad anti-inflammatory activity
and are most effective drugs in the medical treatment of
nasal polyposis. Corticosteroids bind the cytoplasmic gluco-
corticoid receptors in the target tissue. They exert their effect
by reducing the acting on both the secretion of chemotactic
cytokines and inhibiting the activity of T cells and eosino-
phils [43,44]. Corticosteroids may be used both as a primary
treatment modality and as an adjunctive measure to prevent
recurrence.
Intranasal Corticosteroids
The use of topical corticosteroids for several months in
untreated nasal polyps,as well as in therapeutic attempts to
avoid surgery and for relapse prevention after surgical treat-
ment (6-12 months),is therefore to be recommended [45]
Topical nasal steroids are delivered by drops or sprays.
Some patients with nasal polyps do not respond to topical
steroids because of the complete nasal obstruction due to
gross polyps. Nasal drops deliver a higher dose of medica-
tion to the middle meatus and application of the drug in the
Cingi et al.
supine position has been shown to be both comfortable and
effective [44, 46].
Many studies have been performed to evaluate the effects
of topical steroids in nasal polyposis. Beclomethasone
dipropionate (BDP) has provided significant improvement in
nasal symptoms, but no significant difference could be ob-
served in the size of polyps [46].
Budesonide was shown effective for not only reducing
the symptom scores and polyp size, but also improving ol-
factory function [47].
Fluticasone propionate (FP) has provided relief in nasal
blockage and improved peak nasal respiratory flow. Impact
on the size of polyps was not significant compared to pla-
cebo. In terms of side effect, only a few epistaxis cases were
reported [48].
Mometasone furoate (MF) was found to be effective in
improving nasal congestion, polyp size, sense of smell, peak
nasal inspiratory flow, and quality of life [49].
The effects of these steroid regimens have been com-
pared in the literature. However no obvious superiority of
one compound over the other could be demonstrated [31].
Topical administration of corticosteroids can rarely cause
epistaxis and nasal septal perforation [50]. Long term use
(>1 year) of steroids have been accused for suppressing
growth via affecting the hypothalamic-pituitary-adrenal axis
in children [51, 52].
All in all, topical corticosteroid sprays are effective on
polyp size and nasal symptoms associated with nasal poly-
posis, but the impact on olfaction is limited [44].
Systemic Corticosteroids
Systemic corticosteroids are effective in reducing the size
of polyps, alleviating nasal symptoms like sneezing, nasal
blockage, secretion and improving olfaction. They are usu-
ally preferred in extensive nasal polyposis for preparing the
patient for surgery or in refractory cases especially when
allergy co-exists. Systemic corticosteroids can be adminis-
tered either in the form of depot injections or tablets pero-
rally in tapered doses. There is no standard protocol regard-
ing the systemic corticosteroid treatment. Prednisolone is the
most preferred corticosteroid in systemic therapy. Some
surgeons advocate use of 30 mg of prednisolone daily in
reducing doses for 10-14 days prior to surgery. Short-term
treatment with systemic corticosteroids can be used in con-
junction with topical steroids. Such a regimen can reduce the
size of polyps preoperatively and the efficacy of the topical
therapy may be enhanced. This model is an effective method
and has been named “medical polypectomy.”
Use of 50 mg prednisolone daily for 14 days was found
to be beneficial in terms of nasal symptoms (obstruction,
secretion, sneezing, and sense of smell), endoscopic findings
of polyp size, and MRI scores compared to placebo [39, 42,
43, 53].
Oral steroids must be cautiously and very carefully used
in patients with diabetes mellitus, hypertension, psychiatric
disorders, advanced osteoporosis, tuberculosis, glaucoma,
and peptic ulcer disease. Steroid injection into inferior
Nasal Polyposis Recent Patents on Inflammation & Allergy Drug Discovery 2011, Vol. 5, No. 3 247

One or more symptoms: Consider other diagnosis

 Nasal blockage  Unilateral symptoms
 Purulent discharge  Bleeding
 Smell disturbance  Crusting
 Rinoscopic or  Cacosmia
endoscopic nasal polys Orbital symptoms
 Periorbital edema
 Displaced globe
 Double or reduced
Severe vision
Nasal polyps Comorbidities
Mild  Ophtalmoplegia
 Asthma Severe frontal headache
 Anosmia Frontal swelling
 Severe nasal Signs of meningitis

Moderate blockage
Comorbidities
 Asthma
 Anosmia
 Nasal blockage

Saline douching Oral steroids

Topical steroid
Saline douching (short course)
spray Topical steroid drops Topical streoids

Review after 6 Review after 3 months

months

Test for aspirin sensitivity,

No improvement allergic fungal sinusitis. Treat
specifically if present
CT scan/ plan surgery

Topical steroids
Nasal irrigation
+/- oral steroids
Surgery +/- long term
antibiotics

Fig. (1). Management of chronic rhinosinusitis with nasal polyposis [42].

turbinates is not advised due to the risk of fat necrosis or
blindness [51,53].
NON-STEROIDAL TREATMENT
Antibiotic Therapy
Antibiotic therapy can be used if chronic or recurrent
acute sinusitis due to the obstruction of the sinus ostiums
occurs. The treatment should be directed against the Staphy-
lococcus species, Streptococcus species and anaerobes, as
well as Pseudomonas aeruginosa, which is common in cys-
tic fibrosis. Aggressive antimicrobial therapy in cystic fibro-
sis has also been reported to reduce the need for surgery in
chronic sinusitis and polyposis. The effect of macrolides is
thought to be anti-inflammatory, rather than antimicrobial.
Macrolides both inhibit the expression of adhesion molecules
involved in the recruitment of inflammatory cells and accela-
rate the apoptosis of neutrophils. Macrolides have been
shıown to diminish the levels of IL-8 in nasal lavage and
reduce the size of nasal polyp. Roxithromycin has been re-
ported to inhibit fibrosis and prevent the progression of nasal
polyposis [54]. Trials of long-term oral antibiotics (12
weeks), especially macrolides, have demonstrated sympto-
matic and objective improvement similar to endoscopic
sinus surgery. The improvement shown increases with time
and may relate to anti-inflammatory reactions in macrolides
[55].
Antifungal Therapy
Fungi and their spores are present in the air at all times,
are naturally part of the respired air and can be detected in
the normal nose. it was suggested that immune response to
248 Recent Patents on Inflammation & Allergy Drug Discovery 2011, Vol. 5, No. 3
fungal elements may be the cause of most chronic sinusitis
and nasal polyposis [56].
Surgery has played an important role in the management
of allergic fungal sinusitis (AFS). An aggressive surgical
procedure is needed because of a perceived risk of fungal
invasion. Complete extirpation of all allergic mucin and
fungal debris, permanent drainage and ventilation of the
affected sinuses and postoperative access to the previously
diseased areas are the goals of the surgery
To minimize recurrence, for ameliorating the underlying
inflammatory process the use of limited systemic and topical
steroid preparations are important. Postoperative care begins
immediately following surgery with nasal saline irrigation.
Frequent clinic visits are required to allow regular inspection
of the operative site and debridement of crusts and retained
fungal debris. It recently was postulated that immunotherapy
may be beneficial, rather than harmful, as a component of
treatment for allergic fungal sinusitis (AFS). Clinical experi-
ence from a large practice suggests that if patients comply
with their immunotherapy, they will need less systemic ster-
oid usage and fewer revision surgeries [57,58].
Promising results have been reported with specific im-
munotherapy, effectivity of intranasal amphotericin in the
treatment of nasal polyposis remains obscure [58].
For invasive fungal rhinosinusitis; surgery is the main
treatment option; topical and systemic antifungal agents can
be used additionally [57,58].
Antihistamines
Antihistamines are not the first line drug of choice in
nasal polyposis. However, when a patient with polyps also
suffers from seasonal or perennial allergic rhinitis, there is an
increased risk of exacerbations of polyps during allergen
exposure [59]. Exposure to allergen exacerbates the symp-
toms in nasal polyposis patients with allergic rhinitis. These
patients benefit from antihistamines especially during expo-
sure to allergens in the pollen season. In a placebo-controlled
study, an antihistamine, cetirizine, provided significant re-
duction in sneezing, rhinorrhea, and obstruction, but did not
affect the size or number of polyps [60].
Antileukotrienes
Leukotriene receptor antagonists and leukotriene synthe-
sis inhibitors have been used for the therapy of nasal polyps.
Parnes and Chuma found that zafirlukast and zileuton sig-
nificantly improves symptoms in 75% patients an objective
stabilization of polyposis was detected by endoscopic ax-
amination in 50% of patients [61] Leukotriene antagonists
are showed to be effective in reducing the symptoms of se-
vere nasal polyposis and chronic sinusitis, but further inves-
tigations are needed [62].
ASPIRIN DESENSITIZATION THERAPY
Apirin desensitization therapy can alleviate the symp-
toms in nasal polyposis patients with aspirin-exacerbated
respiratory disease. Aspirin desensitization not only to re-
duces the number of sinusitis episodes and decreases recur-
rence rates; but also decreases the need for additional sur-
Cingi et al.
gery. The rate of polyp recurrences is higher in patients in-
tolerant to aspirin and NSAIDs [63].
Oral doses as low as 100mg daily may be effective and
this could potentially prevent some of the adverse effects
including gastrointestinal bleeding associated with oral aspi-
rin [57]. In a study aspirin-sensitive patients were treated
perorally for up to 6 years with aspirin. clinical reduction of
sinus infections and asthma exacerbations, as well as im-
proved nasal olfaction were experienced by the patients.
Furthermore, the numbers of sinus and polyp operations
were clearly reduced[64].
Saline nasal irrigation Nasal douching is a safe, inex-
pensive treatment commonly used in patients who suffer
from hypersecretion or postnasal drainage. It improves nasal
mucociliary clearance measured by the saccharine test in
both NP and healthy volunteers [65]. In all patients the addi-
tion of simple saline nasal douching to help cleanse the nose
prior to topical medications is beneficial [39]. But it is not
effective in the medical management of uncomplicated nasal
polyposis [44].
Other Therapies
Topical capsaicin application causes depletion of pep-
tides in the nasal mucosa and degeneration of non-
myelinated sensory C branches. A case study by Baudoin
et al. has demonstrated significant reduction of sinonasal
polyposis after 5 consecutive days treatment with increasing
doses (30-100 mmol/L) of topical capsaicin in massive poly-
posis measured by CT scans at entry and after 4 weeks The
sensation of burning in nasal mucosa administration of cap-
saicin can cause burning of the nasal mucosa, limiting its
acceptability to patients [66].
Topically administered lysine acetylsalicylate (LAS)
appears to be effective in nasal polyp patients with aspirin
intolerance, especially those with the Samter’s triad (asthma,
aspirin intolerance and nasal polyposis). Reduction in fre-
quency of rhinosinusitis, and asthma attacks were observed
in patients with aspirin sensitization treated with oral aspirin
for 6 years [67]. Intranasal treatment with LAS after poly-
pectomy (2000 mcg weekly for 24 months) was effective in
aspirin intolerant patients [67]. In conclusion, intranasal
treatment with oral aspirin and topically administered LAS
appears to be effective in patients with aspirin intolerance,
especially within the aspirin triad. Local treatment with LAS
has no effect in patients without aspirin intolerance [68].
Mucolytics can be used as adjuncts to antibiotics in acute
sinusitis to reduce viscosity of sinus secretion but no clinical
trials have tested their effects in NP [69].
IL-5 is the major eosinophil survival factor, and treat-
ment of eosinophil - infiltrated polyp tissue with neutralizing
anti -IL-5 monoclonal antibody resulted in eosinophil apopi-
tosis [22].
INVESTIGATIONAL THERAPIES
There are numbers of therapies which are investigational;
Pilon described recombinant human CC10 for treatment of
nasal polyposis. It has anti-inflammatory and immunomodu-
latory effects. Intranasally administered rhCClO is found to
Nasal Polyposis Recent Patents on Inflammation & Allergy Drug Discovery 2011, Vol. 5, No. 3 249
be safe and well-tolerated for alleviating the symptoms of
nasal polyposis, rhinitis, nasal sinusitis [70].
Cyclosporin has been patented for the treatment of nasal
polyps it blocks the synthesis and secretion of certain lym-
phokines. A 52- year- old male patient was treated with
topical cyclosporin (0.2% in a spray form, three times a day
for two weeks), and eventually the size of the nasal polyps
was reduced that subsequently resulted in the resolution of
the nasal blockage [71].
SURGICAL TREATMENT
Most authors primarily prefer conservative medical ther-
apy with steroids, but because of the side effects of systemic
steroids and the strong recurrence tendency of polyposis.
Surgery is often necessary for complicated cases, persistant
or recurrent infections, and unilateral nasal polyps. The aims
of treatment are elimination or at least significantly reduction
of the size of the nasal polyp, improvement of sinus drain-
age, restoration of the ventilation of sinuses and restoration
of olfaction and taste. Patients with polyps and asthma may
benefit from surgery by elimination of a contributory factor
for asthma [7]. Surgical techniques have been signifi cantly
refined over the past 20 years with the advent of endoscopic
sinus surgery (ESS). ESS is now the mainstay surgical
method of treatment for NP. It is important postoperatively
to regularly douche the nasal cavity with saline to prevent
crusting and adhesions. Topical intranasal steroids are also a
routine part of aftersurgery care to prevent recurrence [72].
Intranasal (Simple) Polypectomy
Simple polypectomy is traditionally performed using a
snare or forceps, removing the polyp by either avulsion or
cutting. Formerly, this technique was unsafe because of the
lack of proper examination and surgical instruments. Intrana-
sal polypectomy had become a more conservative method
after the development of endoscopes [73].
Intranasal Ethmoidectomy
Intranasal ethmoidectomy was described by Mosher in
1913. In 1929, he eventually concluded that the operation
was theoretically easy, but in practice it had proven to be one
of the easiest interventions to kill the patient. Mortality oc-
curred due to the poor visualisation of anterior cranial fossa
during surgery. Contemporarily, intranasal ethmoidectomies
have been replaced by endoscopic approaches. The proce-
dure is mostly performed under general anesthesia, but local
anesthesia with sedation can also be used. The eyes should
be inspected during surgery. Subsequently, middle turbinate
is medialized, the bulla is opened with a small curette and
the anterior ethmoids are removed. A toal middle turbinec-
tomy is usually necessary to provide sufficient exposure to
the ethmoids. Great care must be taken to preserve the orbit
or the skull base. The safety of the intranasal ethmoidectomy
has been questioned. Most surgeons now do not perform this
procedure [73].
External Ethmoidectomy
The procedure is generally performed under general
anesthesia. External ethmoidectomy is performed through an
incision between the medial canthus and the midline of the
nose. The periosteum is elevated posteriorly into the orbit
until the anterior ethmoidal artery is identified. Identification
of the basal lamella guides the limits of the dissection. The
skull base can usually be identified clearly in the posterior
ethmoids. Once the ethmoids are opened, any diseased mu-
cosa, polyps, or tumors should be removed. All ethmoid cells
should be removed once the orbit has been displaced later-
ally [73].
Caldwell-Luc
The Caldwell-Luc procedure is usually performed under
general anesthesia. The incision is made in the gingivobuccal
sulcus, above the canine fossa, and extended through the
periosteum over the maxilla. The periosteum is elevated
superiorly until the infraorbital nerve is identified. A 4-mm
osteotome or a drill is used to outline a window into the
maxillary antrum. Once the window is opened, a punch for-
ceps or a drill can be used to enlarge the window as required.
Injury to the secondary dentition and the infraorbital nerve
must be avoided. The Caldwell-Luc operation was primarily
designed for chronic maxillary sinusitis, but it can also be
used in generalized polypoid disease, fungal sinusitis, antro-
choanal polyps, pterygomaxillary space surgery, trauma,
foreign bodies, and benign tumors [73].
Endoscopic Sinus Surgery (ESS)
The mainstay of surgical treatment for nasal polyposis is
actually endoscopic sinus surgery (ESS), which requires a
high degree expertise to achieve optimum results without
complications [7].
Two approaches have been defined in ESS. In the “front-
to-back” approach (Messeklinger technique), the procedure
begins with visualization with a 0-degree endoscope. The
operation starts with uncinectomy and afterwards removal of
the ethmoid bulla, exposure of the frontal sinus ostium, and
identification of the roof of the ethmoid are done. Once the
skull base is identified, the dissection continues posteriorly
with removal of the anterior ethmoid cells and the posterior
ethmoid cells, and finally opening of the sphenoid sinus. The
ostium of the maxillary sinus is identified with a 30-degree
telescope, and this ostium may be widened if necessary [73].
In the “back-to-front” approach (Wigand technique), the
sphenoid sinus is initially identified. Using the skull base and
lateral wall as landmarks, the ethmoid sinuses are cleaned
from posterior to the anterior. early exposure to the skull
base is the major advantage of this technique [74].
A microdebrider may reduce the blood loss and improve
the visualization due to the rapid removal of the nasal pol-
yps. The instrument also functions as suction, and it keeps
the surgical field clear. In cases with extensive polyposis,
removal of the polyps may be performed anteriorly and infe-
riorly until the middle turbinate and other landmarks
250 Recent Patents on Inflammation & Allergy Drug Discovery 2011, Vol. 5, No. 3
are identified. Surgery should progress in parallel with the
identification of the orbit and skull base. Polyp recurrence
tends to occur more in the upper frontal area.
Preoperative CT scans are necessary for planning the
surgical strategy [7]. Computer-assisted surgical navigation
allows the sinus surgeon to more effectively remove disease
and preserve normal tissue and avoid vital structures, espe-
cially in tumor and revision cases.
Sinus surgery should be reserved for patients who do not
respond to medical treatment [7].
Several studies were performed to compare the efficacy
of surgical treatment to medical treatment. In a study, it was
proposed that olfaction improved better with systemic and
topical steroids, whereas surgery had a more prominent
beneficial effect on nasal obstruction and secretion [75].
At 6 and 12 months, significant improvements in quality
of life, nasal symptoms, and polyp size were observed after
both medical and surgical treatment [76].
Functional endoscopic surgery is superior to minimal
conventional procedures such as polypectomy and antral
irrigations. But its superiority to inferior meatal antrostomy
or conventional sphenoethmoidectomy has not yet been
demonstrated [44].
Recurrence occurs in 5-10% of patients with severe dis-
ease [77]. Revision endonasal sinus surgery is indicated if
medical treatment after surgery does not work. Complication
and recurrence rates are higher after revision surgery than
after primary surgery [44].
Powered instrumentation with microdebriders enable
accurate removal of nasal polyps, preserves normal anatomi-
cal structures, and minimize inadvertent mucosal trauma
[76].
Complications
The most common complications in surgical treatment
are bleeding and, postoperatively synechia. Cerebrospinal
fluid leak, lacrimal and orbital injuries have also been re-
ported [76]. Serious complications of ESS are rare, but the
patient must be counseled preoperatively about the potential
risks [30].
In the postoperative follow-up, prevention of synechia
formation and ostial obstruction are main goals. In addition
to the prevention of persistent inflammation, infection, and
further polyp growth, stimulation of normal mucosal devel-
opment is necessary to replace the diseased tissue. Irrigation
of the nasal cavity with saline can overcome crusting and
adhesion. Topical intranasal steroids are a part of routine
postoperative care. Antibiotics are administered during the
acute healing phase. Patients with aspirin intolerance, aller-
gic fungal sinusitis, asthma or cystic fibrosis are under high
risk for recurrence [72, 76].
CURRENT & FUTURE DEVELOPMENTS
New approaches specifically target the eosinophilic re-
cruitment (chemokine receptor 3, eotaxin, eosinophilic major
basic protein), inflammation (interleukin-4, -5, and -13) and
tissue remodeling by reducing the activity of metalloprotein-
Cingi et al.
ases [77, 78]. Advanced oxidation protein products are found
to be significantly higher in patients with nasal polyposis;
therefore efficacy of antioxidant therapy needs to be investi-
gated [79]. Recently, some tissue proteins such as Cu/Zn
SOD and PLUNC are thought to be involved in airway in-
flammation. They may be utilized not only for exploring the
pathophysiology but also for monitoring disease progression
or response to treatment [80]. Possible role of biofilms in
pathogenesis of nasal polyposis needs to be determined [78].
Weakening of desmosomal junctions in the nasal mucosa
due to exposure to the inflammatory cytokines may enhance
the pathogenesis of nasal polyposis [81]. Molecules such as a
disintegrin and metalloproteinase 33 (ADAM-33) and metal-
lothionein were supposed to contribute to the pathogenesis of
polyps in nasal mucosa [82,83]. These issues can help devel-
oping new treatment options in the management of nasal
polyposis.
CONFLICT OF INTEREST
Authors state that there is no conflict of interest for this
article.
ACKNOWLEDGEMENTS
Author has not made any acknowledgements.
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