Endoscopic endonasal resection of sinonasal and skull base malignancies in children: feasibility and outcomes

ORIGINAL PAPER

Endoscopic endonasal resection of sinonasal and skull base

malignancies in children: feasibility and outcomes

Abdulaziz AlQahtani & Mario Turri-Zanoni &

Iacopo Dallan & Paolo Battaglia & Paolo Castelnuovo

Received: 12 June 2012 /Accepted: 17 July 2012# Springer-Verlag 2012

Abstract

Background The aim of this study is to present our experi-

ence in treating paediatric sinonasal and skull base malig-

nancies with exclusively endonasal endoscopic approach

and measure its feasibility.

Methods This study is a retrospective review of seven

patients under age of 19 years who have sinonasal and skull

base malignancies and treated with endoscopic endonasal

approach. The main outcome measures are the surgical

resection, complications, survival rate, recurrence and gross

facial growth.

Results Radical tumour resection was achieved in all cases

with negative margins; no major complications were ob-

served. Mean follow-up was 65 months and no evidence

of recurrences. Facial growth assessment showed no gross

changes.

Conclusion In selected cases, endoscopic endonasal ap-

proach of paediatric sinonasal and skull base malignancies

could be an alternative approach. Despite of our few cases, it

showed a feasibility of this technique with satisfactory on-

cological control. A further collaborative study with larger

number is needed to have more valid conclusion.

Keywords Endoscopic endonasal . Paediatric .

Malignancy . Sinonasal . Skull base

Introduction

Skull base and sinonasal malignancies (SNM) are infrequent

conditions [1]. Fortunately, these lesions are extremely rare

in children, who show many differences with their adult

counterparts, especially in the histology and biological be-

haviour of the tumour [2, 3]. Another difference that con-

cerns the surgeons is the anatomical dissimilarity resulting

from the developing craniofacial complex [3].

Owing to the infrequency of this disease, sufficient and

significant data focusing on the different surgical approaches

is difficult to obtain. Only a few series, describing external

approaches, have been published on this topic [3].

The resection of malignant tumours via conventional

approaches harbours difficulties because of the importance

of the structures involved and the complexity of the anatom-

ical sites [4]. Needless to say, these external approaches carry

considerable risks, which may give rise to complications such

as intracranial, orbital, neural, skin and many others [4–6].

Not less important, especially in a paediatric population, is the

concern regarding the future skeletal development of the

child; this can be significantly impaired in cases of disruption

of the craniofacial complex growth centres [2, 7, 8].

On the other hand, the endoscopic endonasal resection

(EER) procedure is well established in inflammatory and

benign lesions in the paediatric population [9–11]. Nowa-

days, it is applied with satisfactory oncological outcome in

sinonasal and skull base malignancies in adults [12, 13].

To our knowledge, no series focusing on the use of EER

in paediatric skull base and SNM have been published. The

aim of this study is to show the feasibility and safety of the

technique by reporting our experience in this field.

A. AlQahtani (*)

Department of Otorhinolaryngology, Riyadh Military Hospital,

Riyadh, Saudi Arabia

e-mail: [email protected]

M. Turri-Zanoni : P. Battaglia : P. Castelnuovo

Department of Otorhinolaryngology, University of Insubria,

Varese, Italy

I. Dallan

Second Otorhinolaryngology Unit, Azienda Ospedaliera

Universitaria Pisana,

Pisa, Italy

Childs Nerv Syst

DOI 10.1007/s00381-012-1866-x

Material and methods

This retrospective analysis was carried out in a single aca-

demic tertiary care centre from 2001 to 2010. All patients

with skull base and SNM, treated with curative intent and

who were ≤18 years old at the time of presentation, repre-

sent the cohort of this study. Patients who had been submit-

ted to surgical palliative treatment, diagnostic procedures,

exclusively medical treatment and conventional or com-

bined surgical approaches were excluded from the study.

Imaging workup included computed tomography (CT)

and magnetic resonance imaging (MRI) for all patients,

while positron emission tomography was performed in

patients with aggressive histotypes. Diagnostic biopsy is

part of our pretreatment protocol.

The American Joint Committee on Cancer staging system

(seventh edition) was used for all histotypes [14]. In the case

of olfactory neuroblastoma, the Kadish staging system was

used as well [15].

The parents of all the patients were fully informed about

our surgical proposal and of the possibility of shifting to the

conventional external approach, and they gave their consent

to the treatment.

In this respect, the patients were prepared in the operating

theatre for both the endoscopic and a possible external

approach. Dedicated instrumentations were used. A magnet-

ic image guidance system was used in the last four patients

since it became available in our department. We used the

standard transnasal endoscopic approach that has been de-

scribed previously by our group [12, 16, 17]. Frozen sec-

tions guided the extent of the surgical resection. The status

of the margins was defined post-operatively according to the

definitive results of the histological evaluation. Resection

was considered either radical or partial, as determined

during surgery and post-operative MRI. Margins were con-

sidered R0 if there was no evidence of disease, and either R1

or R2 if infiltration was evident microscopically or macro-

scopically respectively.

Demographic data, presenting symptoms, length of hos-

pitalisation, complications, previous treatment, adjunctive

therapy, site of pathology, histology, recurrence and gross

facial growth were all collected and analysed. The follow-up

interval was calculated in months from the date of surgical

intervention to the date of the last examination. Follow-up

observations were based on monthly endoscopic examina-

tions and MR imaging every 4 months during the first year,

endoscopic examinations and MR imaging every 2 and

6 months, respectively, during the second year and, subse-

quently, both examinations at 6-month intervals. The last

follow-up reported was March 2012. Statistical analysis like

overall survival and disease-specific survival rates were

calculated. The local ethical board approved this retrospec-

tive evaluation.

Results

Seven patients fitted the inclusion criteria. These patients

were aged from 3 to 18 years (mean: 11.1 years) with a

female predominance ratio (2:1) as shown in the demo-

graphic chart (Table 1). None of the patients had received

previous surgery. The tumour location was in the sinonasal

cavity in four patients and in the nasopharynx in three of

them. Further details about tumour location, origin and

extension are given in Table 1.

Nasal obstruction was the main complaint in 57 % of the

patients (4/7). Interestingly, only one patient showed epi-

staxis and rhinorrhea. Different histopathologies were found

Table 1 Demographic distribution of the tumour, location and staging

Case Age Sex Histopathology Subtype Grading Site of origin Extension Staginga

1 4 F Osteosarcoma – 2 Right ethmoid Orbital

compression

T3-N0-M0

2 17 F Adenocarcinoma Adeno-

salivary

1 Right ethmoid – T1-N0-M0

3 14 F Olfactory neuroblastoma – 1 Right ethmoid Right periorbita T3-N0-M0 (Kadish

C)b

4 8 M Adenoid cystic

carcinoma

Tubular 1 Left inferior

turbinate

– T1-N0-M0

5 3 F Rhabdomyosarcoma – 2 Left nasopharynx Sphenoid &

ethmoid

T3-N0-M0

6 14 F Adenocarcinoma Tubulo-

papillary

2 Median

nasopharynx

Septum &

sphenoid

T3-N0-M0

7 18 M Muco-epidermoid

carcinoma

– 2 Left nasopharynx – T1-N0-M0

a 2010 American Joint Committee on Cancer staging systembKadish staging system

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among the patients. All cases had localised pathology with

no evidence of loco-regional or distant metastases at the

time of presentation (Table 1).

All patients affected by sinonasal malignancies under-

went exclusively EER (Figs. 1 and 2). In this series, there

was no bony invasion of the ethmoidal roof in any of the

cases, so a craniectomy was never required. In patients with

nasopharyngeal lesions, a nasopharyngeal endoscopic

resection, tailored to the extension of disease, was per-

formed (type 2 resection in two cases; type 3 resection in

one case) [17].

All surgeries were considered radical. No intraoperative

complication occurred. In one case, the results of the histo-

logical evaluation showed presence of microscopic disease

in the margin (R1). In this case, adjuvant chemotherapy was

administered. Detailed data are given in Table 2.

Fig. 1 Pre-operative MR scan, in coronal (a), axial (b), and sagittal (c)

view, of a right ethmoidal neuroblastoma with periorbital extension,

staged T3N0M0. Postoperative MR scan, in coronal (d), axial (e), and

sagittal (f) view, performed 7 years after the endoscopic endonasal

resection (EER) of the lesion. (Case number 3) 191×106 mm (300×

300 DPI)

Fig. 2 Coronal (a) and sagittal

(b) MR images showing a

nasopharyngeal

adenocarcinoma extended to

the sphenoid and nasal septum

staged T3N0M0. Post-operative

MR scan, in coronal (c) and

sagittal (d) view, performed

3 years after the endoscopic

endonasal resection (EER) of

the lesion. (Case number 6)

176×128 mm (300×300 DPI)

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Mean hospitalisation time was 6.2 days (2–17 days).

Regarding the complications, one patient developed a septic

fever 2 days after surgery that required an intravenous

antibiotic. Another patient with osteosarcoma of the ethmoi-

dal sinus compressing the orbit had a late complication

(after 1 month) of transient diplopia that was treated con-

servatively. No significant deformity in facial appearance

was observed in any of the cases during follow-up.

None of the patients received neoadjuvant therapy. The

patient with recurrent nasopharyngeal rhabdomyosarcoma

received primary chemo-radiation as first line treatment.

Four patients received adjuvant therapy: chemotherapy

alone (two patients), radiotherapy alone (one patient) and

both chemo-radiotherapy (one patient), as summarised in

Table 3.

According to the last follow-up, performed in March

2012, 6/7 (85.7 %) patients were alive with no evidence of

disease; only one patient died of causes other than SNM.

Notably, oncologic control of the sinonasal disease was

obtained in all the cases, without evidence of loco-regional

or distant recurrences. The mean follow-up was 67.7 months

(ranging from 24 to 109 months).

In detail, the patient who died during the follow-up was a

4-year-old girl who had previously received radiotherapy for

acute T-cell lymphoblastic leukaemia. She then developed a

radio-induced sinonasal osteosarcoma that was resected

endoscopically. Surgery along with adjuvant chemotherapy

achieved good oncologic control of the sinonasal osteosar-

coma but the patient died after 97 months due to a radio-

induced meningosarcoma of the spinal cord.

Discussion

Sinonasal and skull base malignancies are rare diseases in

the general population, characterised by histological hetero-

geneity, late diagnosis and poor prognosis [18]. The inci-

dence of the disease in children is unknown, but it is

probably less frequent in this population [19, 20].

The choice of treatment depends upon many aspects like

tumour biology, behaviour, histotype, and the consequences

of the treatment modality on the patient. It is commonly

accepted that aggressive tumours are better treated primarily

with radiotherapy, chemotherapy or both. Surgical treatment

is unfavourable when it ends up with poor outcome or

devastating complications, especially in children. On the

other hand, the best surgical outcome is obtained when the

tumour is resected radically, the margins maintain negative

results and when there are no serious complications.

These considerations are extremely important in the pae-

diatric population, in which physicians must be concerned

about future skeletal development and the incidence of

radiation-induced secondary lesions [21].

In our series, we were able to achieve radical tumour

resection despite narrow spaces. EER gives us the opportu-

nity to view the origin of the tumour and then resect it

radically while preserving the adjacent vital structures.

According to our long follow-up (mean: 67.7 months), there

is no clinical or radiological evidence of residual disease or

recurrence. Statistically, the survival rate and oncological

control rate were 85.7 and 100 %, respectively. Due to the

rarity of these tumours and our small number of cases, the

impact of these statistical outcomes is difficult to ascertain.

EER of SNM and skull base tumours without tragic com-

plications can be considered a therapeutic option, either as a

Table 2 Intraoperative measures with post-operative complications

Case Location Type of resection Frozen

sections

Margins Complications Treatment of

complication

Hospitalisation

(days)

1 Sinonasal EER Negative R0 Diplopia Conservative 8

2 Sinonasal EER Negative R0 – – 3

3 Sinonasal EER Negative R0 Septic fever Antibiotics 17

4 Sinonasal EER Negative R0 – – 2

5 Nasopharynx NER type 3 Negative R1 – – 7

6 Nasopharynx NER type 2 Negative R0 – – 3

7 Nasopharynx NER type 2 Negative R0 – – 4

EER endoscopic endonasal resection, NER nasopharyngeal endoscopic resection, R0 no infiltration, R1 micro-infiltration, R2 macro-infiltration

Table 3 Adjuvant therapy and follow-up

Number Adjuvant therapy F/U (months) Status

1 CHT 97 DOC

2 – 109 NED

3 RT + CHT 91 NED

4 – 74 NED

5 CHT 40 NED

6 – 36 NED

7 RT 27 NED

DOC died of other causes, NED no evidence of the disease

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single or a dual modality protocol, as well as a palliative

option in advanced or aggressive malignancies.

Almost all the available data regarding the surgical man-

agement of SNM in children have discussed the convention-

al approach. Kassam et al. reported applying EER not only

to malignant lesions but also to different sinonasal patholo-

gies [11]. In this series, six cases were malignant tumours

and most of them underwent either diagnostic biopsy or

subtotal resection with subsequent adjuvant therapy.

The M.D. Anderson Cancer Centre presented 44 paedi-

atric cases of malignant lesions, eight of which were

resected through an endoscopic approach. Unfortunately,

no specific data about histology, extension of disease, type

of resection and status of the margins are given for these

endoscopically treated patients [21].

Long-standing complications following the conventional

approach may reach 25 % in some series [22]. A recent

international collaborative study reported 84/1,307 paediatric

patients (≤21 years old) and confirmed the efficacy and safety

of the CFR technique [19]. However, this approach has been

associated with a morbidity and perioperative mortality rate

that is not negligible. Moreover, CFR can potentially disrupt

growth centres in the craniofacial skeleton [20].

This is of particular interest in the case of nasopharyngeal

lesions, in which external approaches are particularly de-

manding and require facial disassembling or an infratempo-

ral fossa approach [23–25]. In the largest series of external

nasopharyngectomies published to date, no paediatric

patients were treated [23]. In this respect, again we point

out that endoscopic nasopharyngectomy has never been

described in children before.

The absence of facial incisions, needs for osteotomies,

less post-operative pain, decreased hospitalisation time and

reduced morbidity and mortality rates are the major advan-

tages of endoscopic endonasal surgery compared to the

external approach. Furthermore, avoidance of the growing

craniofacial skeleton should be considered [26, 27]. This

statement is corroborated by our results, which show that no

facial growth disorders were seen in any of the cases during

the follow-up.

Our patients had a mean hospitalisation time of 6.2 days.

This is in contrast to the mean hospitalisation of 13 days

reported in the series describing external conventional

approaches [27]. No complications were encountered apart

from septic fever in case number 3 (Fig. 1), and transient

diplopia in case number 1 which was related to the com-

pressive effect of the tumour and which resolved

spontaneously.

It is beyond the scope of our study to assess the patient’s

quality of life. However, it has been demonstrated that the

endoscopic endonasal technique offers a better tolerance com-

pared to external microsurgical techniques in paediatric patients

when dealing with a trans-sphenoidal approach [26, 27].

The milestones in presurgical planning remain imaging

with CT scan and contrast enhanced MRI, which are recom-

mended even in children to understand the tumour extension

and its relationship with the surrounding neurovascular

structures [28]. The need for an external or combined pro-

cedure may be suggested by the preoperative imaging stud-

ies but, in some cases, a definite decision can be made only

during the surgical procedure itself.

Hence, based on the above-mentioned considerations, we

think that in well-selected cases, EER can be proposed as an

alternative to the traditional external approach for either

therapeutic or palliative purposes. Obviously, EER can be

included in a multimodality treatment plan according to the

specific necessities of the case.

Conclusion

According to our preliminary experience, we consider EER

as a potential option in selected cases of paediatric skull

base malignancies. Our long follow-up, low complication

rate and apparent good oncologic outcomes stimulate us to

continue investigating this option. Further collaborative

studies with larger groups of patients are necessary for

determining the validity and comparability of EER to the

conventional approach.

Conflict of interest The authors declare that they have no conflict of

interest.

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