Impact of Successful Choanal Atresia Repair onthe Nasal Mucosa: A Preliminary StudyEzzeddin Elsheikh1 Mohammad Waheed El-Anwar1 Hesham Radwan Abdel-aziz2

1Otorhinolaryngology-Head and Neck Surgery Department,Faculty of Medicine, Zagazig University, Egypt

2Pathology Department, Faculty of Medicine,Zagazig University, Egypt

Int Arch Otorhinolaryngol 2017;21:276–280.

Address for correspondence Mohammad Waheed El-Anwar,Otorhinolaryngology, Head and Neck Surgery Department, Faculty ofMedicine, Zagazig University, Egypt (e-mail: mwenteg@yahoo.com).

Introduction

Congenital choanal atresia causes deprivation of nasal airflowandmucus transport,1,2 and one of its features is accumulatedtenacious mucous secretion in the nasal cavity.3

The main found histological features of the nasal mucosain choanal atresia are distorted cilia,3,4 marked increase ofmucous submucosal glands associated with marked reduc-tion of goblet cell density, and lymphocytic cellular infiltra-tion.3 This raised a question: are these found featurespermanent, and will these patients complain of thick mucussecretion for life? Or will these features reverse after success-ful surgery?

Therefore, the aim of this work was to investigate theimpact of the successful permanent repair of the choanalatresia on these histological features.

Patients and Methods

This study was conducted at the Otorhinolaryngology–Headand Neck Surgery and Pathology departments in the periodbetween March 2011 and February 2015 on patients diag-nosed with choanal atresia. Patients with systemic muco-ciliary diseases were excluded from the study.

The patients who needed general anesthesia for anothersurgical reason 6 months or more after the successful repair

Keywords

► choanal atresia► nasal mucosa► endoscopes

Abstract Introduction Themain histological features of the nasal mucosa in choanal atresia aredistorted cilia, marked increase of mucous submucosal glands associated with markedreduction of goblet cell density, and lymphocytic cellular infiltration.Objective To study the nasal mucosal changes in cases of choanal atresia aftersuccessful repair compared with pre-repair mucosal histological features.Methods Tissue samples were taken from the inferior turbinate of 3 patients (1bilateral and 2 unilateral) who were successfully operated. Then, the biopsies weresubjected to histopathological, histochemical and immunohistochemical studies. Afterthat, the results were compared with pre-repair findings in the choanal atresia side andin the normal side.Results Four biopsies (4 repaired choanal atresia sides) of the mucosa of the inferiorturbinate revealed that 1 patient (who had a bilateral choanal atresia repaired), afterachieving a patent choana for 8 months, had not completely recovered a normal nasalmucosa. The other 2 patients, after 18 and 23 months of achieving a patent choana,showed normal nasal cavities.Conclusion The main histological features of the nasal mucosa in choanal atresiacould be reversed by surgery, making the patients regain their choanal patency, withtheir mucosae changing back to normal gradually with time.

receivedMay 20, 2016acceptedJanuary 29, 2017published onlineMarch 28, 2017

DOI https://doi.org/10.1055/s-0037-1601404.ISSN 1809-9777.

Copyright © 2017 by Thieme RevinterPublicações Ltda, Rio de Janeiro, Brazil

Original ResearchTHIEME

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of the choanal atresia were the candidates in this study whoallowed for the performance of a biopsy of their inferiorturbinate mucosae. The repair was considered successful ifthe patient showed easy nasal breathing, non-interruptedoral feeding, a patent nasal airway, and an open new choana.Patency was defined as less than 50% restenosis.5–7

The patients were subjected to full history taking, generaland local examinations, and routine preoperative laboratorytests. A written informed consent to participate in the studywas signed by the relatives of the patients, and the univer-sity’s institutional review board approved the study.

With the patients under general anesthesia, a biopsy ofthe inferior turbinate mucosa (0.5 cm behind its anteriorend) was obtained. Then, the biopsies were subjected tohistopathological, histochemical and immunohistochemicalstudies, as described by Elsheikh et al.4

Results

A total of three patients who were successfully operated forchoanal atresiawere included in this study (onewas repairedfor bilateral choanal atresia, and two for unilateral choanalatresia); their demographic data are summarizedin ►Table 1. The repair was performed by stentless transna-sal endoscopic approach, with resection of the posterior partof the vomer in all cases.

The histopathological study of the 4 biopsies of themucosa of the inferior turbinate (4 repaired choanal atresiasides) revealed that in 1 patient (who had bilateral choanalatresia) after 8 months of repair, the findings were similarto the ones prior to the repair in the form of pseudostra-tified columnar ciliated covering epithelium with focalmucosal atrophy and ulceration, and with intact basementmembrane (►Fig. 1). But the mucosa had features unlikethe ones found prior to the repair, because the basementmembrane was of normal thickness. Moreover, the overallnumber of goblet cells increased significantly after therepair, to 17–21 cells per high power field (HPF). Thesubmucosa also showed less lymphocytic infiltrate thanbefore the repair (►Figs. 1 and 2).

Comparedwith thefindings prior to surgery, in the other 2patients (2 unilateral choanal atresias), after 18 months and23 months of the repair with patent choana, the coveringepithelium was pseudostratified columnar ciliated epithe-lium with no mucosal atrophy or ulceration, and with an

intact basementmembrane of normal thickness. The numberof goblet cells also increased, to 20–25 cells per HPF (►Fig. 3).The submucosal glands were found in lower numbers andless active than before the repair, mainly of the mucous type

Table 1 Patient data

Patients Patient 1 Patient 2 Patient 3

Atretic side8 months afterrepair (patent)

Atretic side8 months afterrepair (patent)

Atretic side 1.5 yearafter repair (patent)

Atretic side23 months afterrepair (patent)

Gender Male Male Male Male

Age at the time ofthe biopsy

8 months 8 months 6.5 years 9 years

Side Bilateral Bilateral Unilateral Unilateral

Nature of the atresia Pure bony Pure bony Mixed Pure bony

Fig. 1 Photomicrograph shows the pseudostratified columnar ci-liated epithelium with focal mucosal atrophy and ulceration (blackarrow) with an intact basement membrane (red arrow), H&E x 400.

Fig. 2 Photomicrograph showing an increased number of gobletcells (bold arrow) mild lymphocytic infiltrate in the submucosa (star),H&E x 400.

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and showing faint periodic acid-Schiff (PAS) - positive, faintAlcian blue - periodic acid shift (PAS) positive material(►Fig. 4). The submucosa showed less lymphocytic infiltratethan before the repair (►Figs. 3, 5) (►Table 2).

Collectively in all biopsies, the mean of goblet cells was21.5 � 1.9, which was nearly similar to the levels of anormal mucosa.3 On the immunohistochemical studies,the nerve terminals (using neuron specific enolase, NSE,immunostaining) were found to be intact. In addition,lymphocytic infiltrate proved by CD45 immunostaining(►Fig. 5).

After 18 months of achieving a patent choana, themucosa had the same features as it does in healthy subjects.

Discussion

Basal, goblet and columnar cells are usually identified inthe respiratory airway epithelium. Goblet cells are mucusproducing cells with an important role in mucociliary

Fig. 3 In the second case (18 months after the repair), photomi-crograph showing the pseudostratified columnar ciliated epitheliumwith no mucosal atrophy or ulceration, and with an intact basementmembrane of normal thickness and more goblet cells (arrow).

Fig. 4 (A) Photomicrograph showing faint staining for neutral mucin, periodic acid-Schiff (PAS) X 400; (B) faint staining for acidic mucin, Alcian-PAS X 400.

Fig. 5 (A) Immunostained for neuron specific enolase (NSE) showing intact wavy nerve bundles (star), (B) mild lymphocytic infiltrate,Hematoxylin counterstain X 400.

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clearance and in the local mucosal immune system. Gobletcell density differs in various sites of the respiratory tract,and is affected by different factors, such as genetic factorsand the impact of air currents, as well as infection orinflammation.8

The effect of airflow deprivation on the nasal mucousmembrane is an issue of wide disagreement in the literature.In experimental animals, studies showed an increase ingoblet cells in the closed side, and loss of ciliawith squamousmetaplasia.9,10 Mogenson and Tos10 detected an inverserelationship between the number of goblet cells and theair current, and found abundant goblet cells in regions withscanty airflow and vice versa. Contrary to that, Berger et al11

detected more goblet cells in the lateral wall of the inferiorturbinate compared with the medial wall, and She et al8

reported more goblet cells in the lateral wall of the uncinateprocess compared with the medial wall, and this reducednumber was attributed to epithelial changes caused by aircurrents.

A former study found that the nasal mucosa in the atresiaside in both unilateral and bilateral choanal atresias is nothistologically different, and is characterized by histologicalfeatures such as thickened basement membrane, markedincrease of mucous submucosal glands associated withmarked reduction of goblet cell density, and lymphocyticcellular infiltration.3 The choanal atresia side is also char-acterized by accumulated tenacious mucous secretion in thenasal cavity.4,12

Compared with serous glands, abundant submucosalactive mucous glands increase mucous viscosity13, lead-ing to stasis of the thick mucus as result of the lowviscosity of the periciliary sol, which allows the cilia tobeat and propel the mucous blanket to the mouth. Thelack of mucous drainage could also be increased by theconstricted glandular excretory ducts of the thick basalmembrane that was detected in the nasal mucosa of thechoanal atresia side.4

The current study aimed to evaluate the impact of thepermanent repair of the choanal atresia on these histo-logical features. We found that the mucosal features ofchoanal atresia reversed after achieving a permanentpatent airway, and the mucosa became close to normalwith more patency time. Thus, the histological features ofthe nasal mucosa associated with the choanal atresia aremostly secondary to complete nasal obstruction. There-fore, the successful repair of the choanal atresia not onlyrecreates nasal airflow and breathing, but also restoresthe features of the normal nasal mucous membrane andthe mucus gradually with time after achieving a persistentnasal patency.

The limitation of this preliminary work is the smallnumber of biopsies, as it was difficult to find choanal atresiapatients successfully operated who underwent surgery un-der general anesthesia for another reason and accepted tohave a biopsy performed on them. However, this study opensthe door for further studies on large series of patients, and forthe comparison of the results in bilateral and unilateralchoanal atresias.Ta

ble

2Cha

nges

inthehistop

atho

logical

resultsaftertherepa

irof

thech

oan

alatresia

Histopa

thological

resu

lts

ASbefore

surgery

ASafter8m

onths

(paten

t)ASafter8m

onths

(paten

tbu

tna

rrow

er)

ASafter1.5ye

ar(paten

t)(unila

teral,

6.5ye

ars)

ASafter23

months

(paten

t)(unilateral,

9ye

ars)

Patentside

(noatresia)

Epithelium

Foca

lmuc

osal

atroph

yan

dulce

ration

Focalm

ucos

alatro-

phyan

dulce

ration

Focalm

ucos

alatroph

yan

dulce

ration

Noatroph

yor

ulce

ration

Noatroph

yor

ulce

ration

Noatroph

yor

ulce

ration

Basemen

tmem

brane

Thicke

ned

Normal

thickn

ess

Normal

thickn

ess

Norm

althickn

ess

Normal

thickn

ess

Normal

thickn

ess

Subm

uco

salg

land

sDiffuse

andmarke

dincrea

sein

numbe

rMod

erate

Mod

erate

Asno

rmal

Asno

rmal

Less

than

theatretic

side

Lympho

cytic

infiltrate

Mode

rate

increa

sein

lymph

ocy

ticinfiltrate

inthesubmuc

osa

Minim

alMinim

alMinim

alMinim

alMinim

al

Abbrev

iation

:AS,

atreticside.

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Conclusion

Themain histological features of the nasalmucosa in choanalatresia could be reversed by surgery, with the patientsregaining choanal patency, and the mucosa going back tonormal gradually with time.

Financial SupportThe authors declare no financial support for this study.

Conflicts of InterestThe authors have no conflicts of interest to declare.

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