Journal of military pharmaco-medicine n
o
7-2018 
 113 
INVESTIGATION OF CLINICAL, PARACLINICAL SYMPTOMS 
AND CONVERTED PREVALENCE TO CARCINOMA OF 
SINONASAL INVERTED PAPILLOMA PATIENTS 
 Nguyen Ba Khoa*; Ho Anh Son**; Do Tram Anh*** 
 Nguyen Thi Ngoc Dung*; Nguyen Linh Toan** 
SUMMARY 
Objectives: To investigate the sinonasal inverted papilloma clinical, paraclinical symtoms and 
prevalence of inverted papilloma conveted to carcinoma. Subjects and method: A cross-
sectional study was carried on 81 subjects with sinonasal inverted papilloma. Data of main 
clinical, paraclinical symptoms (endoscopy and histopathology data) were collected and 
analyzed by independent - sample t-test or Pearson’s χ2 test or Fisher’s exact test. Results: 
The main symptoms of inverted papilloma patient were nose obstruction (96.5%); runny nose 
(42%); headache occurred in 38.3% of patients. Nose bleeding occurred in 13.6% of patients 
with statistically significant differences between male and female (p < 0.05). In 81 inverted 
papilloma patients, 16%; 17.3% and 8.6% of them had a history of smoking; alcohol 
consumption and allergy, respectively. Stage T3 was predominant in inverted papilloma patients 
(37%). Other stages, T2, T4 and T1 were 28.4; 24.7 and 9.9%, respectively. The recurrent rate 
of inverted papilloma was 28.4%; malignant transformation rate was 10.5%. Conclusion: 
Inverted papilloma is poor in symptom but rich in recurrence and malignant transformation rate. 
* Keywords: Sinonasal inverted papilloma; Clinical, paraclinical symptoms. 
INTRODUCTION 
Sinonasal inverted papilloma (IP) is a 
benign and relatively rare tumor of the 
nasal cavity and paranasal sinuses, that 
usually originates in the nasal mucosa 
and nasal sinus wall. This disease has 
been documented in the literature for 
more than a century, but so far, IP is still a 
matter of debate due to the complex 
nature of the disease, the high prevalence 
of recurrence. and the coordination with 
the cancer. With an incidence between 
0.2 and 1.5 cases per 100,000 persons 
per year, IPs account for 0.5 - 4% of all 
sinonasal neoplasms [1, 2]. IP tumors 
usually occur on one side of the nose and 
the incidence of papillary sinus reversal is 
more common in men than in women. 
The disease is more common among 
whites than blacks and is most common 
in the 50s and 60s of ages. In Vietnam, 
IPs is a rare disease that has not been 
studied yet, even in the ear, nose and 
throat specialist. We conducted this study: 
To investigate the IP clinical, paraclinical 
symtoms and prevalence of IPs converted 
to carcinoma. 
* Ear, Nose, Throat Hospital, Hochiminh City 
** Vietnam Military Medical University 
*** 103 Military Hospital 
Corresponding author: Nguyen Linh Toan (
[email protected]) 
 Date received: 01/07/2018 
 Date accepted: 20/08/2018 
Journal of military pharmaco-medicine n
o
7-2018 
 114
SUBJECTS AND METHODS 
1. Subjects. 
The study was conducted on 81 cases 
of sinonasal inverted papilloma. 
2.Methods. 
A cross-sectional study and analysis 
were carried on 81 subjects with IPs. 
* Data collection: 
- Clinical: Stuffy nose, runny nose, 
nose bleeds, loss of smell, headache... 
- Sinonasal endoscopy: The surface 
was classified to grape-like, strawberry-
like or polyp-like tumor. 
- CT-scan: All patients underwent CT-
scan to assess the location and extent of 
tumor invasion in the nasal cavity with the 
surrounding organism. It was useful for 
appropriate surgery. 
- Histopathology: All IP tumors were 
sliced and histo-staining before and after 
surgery. All slices were checked in 
Histopathology Department, Hochiminh 
Medical Phamaceutical University. 
* Data analysis: Data was collected 
and analyzed by STATA software for 
Pearson’s χ2 test or Fisher’s exact test, 
student t-test to compare continuous 
variables. 
RESULTS AND DISCUSTION 
 IPs patients were more concentrated in the age group 50 - 59 (33.3%), followed by 
the age group 40 - 49 (23.5%). Mean age of the group was 50.9. Men with sinonasal 
inverted papilloma accounted for 63% and female was 37% (male:female ratio was 
1.7:1.0). 
Table 1: Some characters of IPs symptom. 
Signs of nose obstruction appeared quite common in IPs patients (96.5%). There 
were no statistically significant differences between the male and female group. 
Runny nose and headache occurred in 42% and 38.3% of patients, respectively. There 
were no statistically significant differences between the male and female group. Nose 
bleeding occurred in 13.6% of patients with statistically significant differences between 
male and female (p < 0.05). 
Male (n = 51) Female (n = 30) Total (n = 81) Sex 
Characters n % n % n % 
Nose obstruction 48 94.1 30 100.0 78 96.3 
Runny nose 21 41.2 13 43.3 34 42.0 
Nose bleeding 10 19.6 1 3,3 11 13.6 
Headache 22 43.1 9 30.0 31 38.3 
Journal of military pharmaco-medicine n
o
7-2018 
 115 
Table 2: Historical disease of IPs patients. 
In patients with IPs disease, 16%; 17.3% and 8.6% of them had a history of 
smoking; alcohol consumption and allergy, respectively. The difference between male 
and female groups was not statistically significant. Similar to other head and neck 
tumors, smoking has been identified as a risk factor of IPs recurrence. Outdoor and 
industrial occupations may be another potential environmental risk factors, particularly 
exposure to organic solvents, including diethylnitrosamine. Other risks such as alcohol 
consumption, allergy history are controversy in mechanism of IPs [6]. 
Table 3: IPs tumor stage. 
Stage T3 was predominant in IPs patients (37%). Other stages, T2, T4 and T1 were 
28.4; 24.7 and 9.9%, respectively. The clinical stage of IPs has been defined using the 
Krouse staging system [3]. Many authors have emphasized the role of stage system on 
IP recurrence. 
Table 4: Location of IPs tumor. 
Male (n = 51) Female (n = 30) Total (n = 81) Sex 
Characters n % n % n % 
Smoking 13 25.5 0 0 13 16.0 
Alcohol 14 27.5 0 0 14 17.3 
Allergy 4 7.8 3 10.0 7 8.6 
Male (n = 51) Female (n = 30) Total (n = 81) Sex 
Stage n % n % n % 
T1 3 5.9 5 16.7 8 9.9 
T2 14 27.5 9 30.0 23 28.4 
T3 20 39.2 10 33.3 30 37.0 
T4 14 27.5 6 20.0 20 24.7 
Male (n = 51) Female (n = 30) Total (n = 81) Sex 
Site n % n % n % 
Right 22 43.1 11 36.7 33 40.7 
Left 29 56.9 19 63.3 48 59.3 
Both sites 0 0 0 0 0 0 
Location of IPs tumor was 40.7% on right site. In opposite site, IPs tumor was 
59.3%. None of patient tumor was located on both sites. Other study also found that, 
tumor site distribution was not predominant factor to estimate the recurrence or 
dysplasia of the cell in IP patients. 
Journal of military pharmaco-medicine n
o
7-2018 
 116
Table 5: Recurrent rate among subjects. 
The recurrence rate of IPs was very high, 28.4% of patients undergoing surgery had 
a history of IPs. Of the 23 patients with IPs recurrence, the average number of 
recurrences was 1.8 times and there was a patient had recurrence in 6 times. IP is a 
benign tumor which originates from the sinonasal Schneiderian mucosa. Unlike other 
benign tumors, IPs exhibit remarkable aggressive behaviors, including invasiveness, 
recurrence and malignant transformation (~10%) [6]. 
Table 6: Sinonasal endoscopy of IPs tumor. 
Under endoscopy, we found that IPs showed 44.2% of mulberry shape. Grape 
shape accounted for the second most popular category with 32.5% of cases. In 
addition, polyp-like images were also common in IPs with 23.4% of cases. 
Pre-surgery IPs tumor histology After surgery IPs tumor histology 
Figure 1: Pre-surgery and after surgery tumor histology. 
Male (n = 51) Female (n = 30) Total (n = 81) Sex 
Characters n % n % n % 
Number of recurrent patients 15 29.4 8 26.7 23 28.4 
Number of IPs recurrence 1.5 ± 0.8 2.3 ± 1.8 1.8 ± 1.2 
First surgery 36 70.6 22 73.3 58 71.6 
Male Female Total Sex 
Characters n % n n n % 
Grape 14 29.2 11 37.9 25 32.5 
Strawberry 23 47.9 11 37.9 34 44.2 
Polyp-like 11 22.9 7 24.1 18 23.4 
Total 48 100 29 100 77 100 
Journal of military pharmaco-medicine n
o
7-2018 
 117 
In preoperative IPs patients, the prevalence of polyps was 4.2%. After the surgery, 
tissue fragments were checked by histologist, three preoperative polyps were 
diagnosed as IPs. There were 8 cases (10.5%) diagnosed as carcinoma after 
operation, meanwhile they were diagnosed as IPs preoperation. 
Figure 2: Preoperative IPs histology. 
(Huynh Van P; left: 40X, right 200X) 
(Huynh Van P was biopsy before surgery through endoscopy, was diagnosed as IP, 
including Malpighi epidermis, papillae and deep invasion into the connective tissue and 
leukocyte infiltration) 
Figure 3: Histology of Aenoid-cystic carcinoma. 
(Huynh Van P after surgery: left: 40X, right 200X) 
However, histopathological findings of postoperative tumors revealed small, round, 
dark, cytoplasmic small cells, arranged in a variety of tubular, hollow, and small 
rounded structures. The lining was lined with one or two rows of adenoid cells. The 
cushion has a mucosal area. This was a histology of Aenoid cystic carcinoma. 
The mechanisms leading to the recurrence and malignant transformation of IP 
remain unclear. Malignant transformation of IP may be associated with the following 
factors: HPV genotype 16 and 18 chronic infections, the epidermal growth factor 
receptor mutations, abnormal cell cycle proteins [6]. 
Journal of military pharmaco-medicine n
o
7-2018 
 118
CONCLUSION 
The main symptom of IP patient were 
nose obstruction (96.5%); runny nose (42%); 
headache occurred in 38.3% of patients. 
Nose bleeding occurred in 13.6% of patients 
with statistically significant differences 
between male and female (p < 0.05). In 
81 IP patients, 16%; 17.3% and 8.6% of 
them had a history of smoking; alcohol 
consumption and allergy, respectively. 
Stage T3 was predominant in IPs patients 
(37%). Other stages, T2, T4 and T1 were 
28.4; 24.7 and 9.9%, respectively. The 
recurrent rate of IPs was 28.4%; malignant 
transformation rate was 10.5%. 
REFERENCES 
1. Scheel A, Lin G.C, McHugh J.B et al. 
Human papillomavirus infection and biomarkers 
in sinonasal inverted papillomas: Clinical 
significance and molecular mechanisms. Forum 
Allergy Rhinol. 2015, 5, 701e-707. 
2. Pajor AM, Danilewicz M, Stasikowska-
Kanicka O, Jo´zefowicz-Korczynska M. The 
immunoexpression of CD34, Bcl-2, and Ki-67 
antigens in sinonasal inverted papillomas. Am 
J Rhinol Allergy. 2014, 28, e31-e34. 
3. Krouse J.H. Development of a staging 
system for inverted papilloma. Laryngoscope. 
2000, 110, pp.965-968. 
4. Moon I.J, Lee D.Y, Suh M.W, Han D.H, 
Kim S.T, Min Y.G, Lee C.H, Rhee C.S. 
Cigarette smoking increases risk of 
recurrence for sinonasal inverted papilloma. 
Am J Rhinol Allergy. 2010, 24, pp.325-329. 
5. Hong S.L, Kim B.H, Lee J.H, Cho K.S, 
Roh H.J. Smoking and malignancy in 
sinonasal inverted papilloma. Laryngoscope. 
2013, 123, pp.1087-1091. 
6. Sun Q, An L, Zheng J, Zhu D. Advances 
in recurrence and malignant transformation of 
sinonasal inverted papillomas. Oncol Lett. 
2017, 13 (6), pp.4585-4592.