Surg Radiol Anat DOI 10.1007/s00276-014-1375-6
ORIGINAL ARTICLE
Olfactory neuroblastoma behavior inside and outside the olfactory cleft Roger Jankowski • Adrien Russel • Patrice Gallet Philippe Henrot • Jean Michel Vignaud • Duc Trung Nguyen
•
Received: 29 May 2014 / Accepted: 8 September 2014 Ó Springer-Verlag France 2014
Abstract Purpose Olfactory neuroblastoma (ONB) is a rare malignant tumor of the nose. The currently available evidence links this disease with cells of the olfactory epithelium. The detailed description of tumor site and its extension is the key of treatment. The aim of the present study was to describe the way ONB develops inside and outside the olfactory cleft. Methods Thirteen consecutive patients treated between 2004 and 2014 for ONB with unequivocal pathologic diagnosis, complete diagnostic imaging and endonasal endoscopy surgery were enrolled in this retrospective study. The site of origin and local extension of each tumor were studied in detail based on computed tomography/ magnetic resonance imaging, surgical report, registered videotape of the surgery, and pathological reports. Results This series shows the behavior of a tumor arising either in the olfactory clefts (11 cases) or in the ethmoidal labyrinth (2 cases). When the setting begins with a tumor located in the olfactory cleft (below or in contact with the cribriform plate), the further step can be the extension to the ethmoidal labyrinth before intracranial or intraorbital extension. When tumors originate inside the ethmoidal R. Jankowski A. Russel P. Gallet D. T. Nguyen (&) Department of Otorhinolaryngology - Head and Neck Surgery, University hospital of Nancy - Hospital of Brabois, Morvan street, 54511 Vandoeuvre les Nancy cedex, France e-mail: [email protected] P. Henrot Department of Radiology, Cancer Institute of Lorraine, Vandoeuvre Les Nancy Cedex, France J. M. Vignaud Department of Pathology, University hospital of Nancy, University of Lorraine, Nancy, France
labyrinths, the extension can first be into frontal sinus or orbital cavity. Conclusions This fine anatomic and radiologic description shows the natural behavior of ONB inside and outside the olfactory cleft. As a consequence, the staging system developed by Kadish seems inadequate and Dulguerov’s staging system could be improved. However, the preliminary proposed modification has to be evaluated in a prospective and large, multicenter cohort of patients. Keywords Olfactory neuroblastoma Ethmoid bone Nose neoplasms Olfactory cleft
Introduction Olfactory neuroblastomas (ONB) are malignant tumors emanating from cells belonging to the olfactory mucosa of the olfactory recess. The currently available evidence links ONB with the basal progenitor cell of the olfactory neuroepithelium [2], which is located at the upper part of the olfactory cleft in humans [4, 10]. Two different mucosae are found in the olfactory cleft [6]: the upper part under the cribriform plate (i.e. olfactory recess) is covered with olfactory mucosa, the lower part (i.e. olfactory vestibule) with respiratory mucosa. The behavior of tumors originating in the olfactory cleft has become a matter of attention only recently [1, 11, 14]. Understanding of the tumoral behavior helps surgeons to accurately classify the tumor staging and to plan an adequate treatment, specially preparation of surgical procedure. All ONB of this series were operated under endoscopic control during the ten-year period (2004–2014). Despite the small number of cases, the description of this series gives clues to understand the natural behavior of ONB development inside and outside the olfactory cleft.
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Age, gender
33 years, female
54 years, male
69 years, female
82 years, male
42 years, male
73 years, male
39 years, male
Patients
1 (Fig. 1a)
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2 (Fig. 1b)
3 (Fig. 2a, b)
4 (Fig. 2c, d)
5 (Fig. 3a, b)
6 (Fig. 3c, d)
7 (Fig. 4a, b)
Left exophthalmos diplopia with normal visual acuity
Left rhinorrhea, bilateral nasal obstruction, and anosmia since 6 months
Anosmia and ageusia since 3 months
nasal obstruction, right recurrent epistaxis, nasal polyposis
Bilateral nasal obstruction
Left nasal obstruction
Left nasal obstruction
Symptoms
A suspect left cervical lymph node was found on CT and PET scan
The tumor developed inside the left anterior ethmoid labyrinth and invaded left orbit and left frontal sinus without intracranial extension
The tumor invaded both posterior ethmoidal labyrinths and protruded into the anterior cranial fossa through the dura but did not invade the cerebral hemispheres of the brain
The tumor was involving both olfactory recess. On left side, the tumor destroyed the conchal lamina to invade the ethmoid labyrinth and penetrated the left olfactory groove both through the cribriform plate and lateral lamina
The PET scan showed multiple, hypermetabolic lymph nodes in the right side of the neck. The pathological analysis confirmed metastatic lymph nodes
The tumor (after debulking) was stemming from the right turbinate wall, reaching the mucosa of the cribriform plate but without invading it. The tumor invaded some superior ethmoidal cells through the right superior meatus. Both ethmoidal roofs were unharmed
The mass enlarged the left OC, from sphenoid to frontal process of maxilla with extension to the left ethmoidal labyrinth. Both bony cribriform plates looked intact
Tumor in the left OC with radiological extension to the left cribriform plate. The left turbinate wall was lateralized but remained preserved. MRI showed retention in the left ethmoidal labyrinth
Insertion at 3 mm below the left cribriform plate on the middle nasal septum without invasion of the ethmoidal labyrinth
Tumor localization
Table 1 Description of clinical feature, imaging, and treatment in each patient
C
C
C
B
B
A
A
Kadish’s staging
T3N1M0
T3 or T4 N0M0
T3 or T4 N0M0
T2N1M0
T2N0M0
T2N0M0
T1N0M0
Dulguerov’s staging
Chemotherapy (with complete response) followed by exenteration of left OC and orbit associated to homolateral neck dissection and radiotherapy
Bilateral endoscopic exenteration of OC associated to EECR, followed by radiotherapy
Bilateral endoscopic exenteration of OC associated to EECR, followed by radiotherapy
Exenteration of the right OC without bony cribriform plate removal and neck dissection followed by radiotherapy
Exenteration of the left OC without bony cribriform plate removal followed by radiotherapy
Exenteration of the left OC without bony cribriform plate removal, followed by radiotherapy
Exenteration of the left OC without bony cribriform plate removal, followed by radiotherapy
Treatment
2 years without recurrence
2 years without recurrence
5.5 years without recurrence
2 years without recurrence
5.5 years without recurrence
8.5 years without recurrence
7.5 years without recurrence
Follow-up
Surg Radiol Anat
16 years, male
21 years, male
69 years, male
77 years, male
63 years, male
40 years, Male
8
9 (Fig. 5a)
10 (Fig. 5b)
11
12 (Fig. 5c)
13 (Fig. 4c)
Left recurrent epistaxis
Anosmia, Left recurrent epistaxis, nasal obstruction, Cushing’s syndrome
Left recurrent epistaxis, nasal obstruction
Left recurrent epistaxis, nasal obstruction
Right facial pain, edema of the right upper eyelid, and left cervical lymph node (3 cm)
Right lateral lymph nodes ([6 cm) associated to nasal obstruction, mild epistaxis and anosmia
Symptoms
The tumor developed inside the left anterior ethmoid labyrinth. This tumor protruded into the left frontal infundibulum and left maxillary sinus. The left OC was free
The tumor invaded both ethmoidal labyrinths and protruded into the anterior cranial fossa through the dura but did not invade the cerebral hemispheres of the brain. The tumor was separated with the brain by marginal tumors cysts
Tumor in the left OC with radiological extension to the left cribriform plate without evident bone erosion. The left turbinate wall was lateralized but remained preserved. MRI showed retention in the left ethmoidal labyrinth
The tumor developed inside the bilateral nasal cavity with left orbital and bilateral craniofacial extensions involving the brain tissue. The PET scan showed bilateral, hypermetabolic, cervical lymph nodes and diffuse pulmonary metastasis
The PET scan revealed hypermetabolic, bilateral, cervical lymph nodes and a spot in the right ilium
The voluminous tumor was in the posterior ethmoids with right intraorbital extension, bilateral intracranial extension running over the two orbital roofs
The tumor involved both nasal fossae, ethmoidal labyrinths and right orbit, extending into the anterior cranial fossa with no clear delineation between tumor and brain hemispheres The PET scan revealed left cervical, hypermetabolic lymph nodes that were metastatic confirmed by pathological analysis
Tumor localization
OC olfactory cleft, EECR endoscopic ethmoido-cranial resection
Age, gender
Patients
Table 1 continued
B
C
A
C
C
C
Kadish’s staging
T2N0M0
T4N0M0
T2N0M0
T4N1M1
T4N1M1
T4N1M0
Dulguerov’s staging
Complete exenteration of left ethmoidal labyrinth
Chemotherapy (without response) followed by bilateral endoscopic exenteration of OC associated to EECR and radiotherapy.
Exenteration of the left OC without bony cribriform plate removal, followed by radiotherapy
Palliative chemotherapy
Chemotherapy followed by surgery with neck dissection and radiotherapy
Chemotherapy (with partial response) followed by surgery with homolateral neck dissection and radiotherapy
Treatment
6 months without recurrence
6 months without recurrence
9 months without recurrence
Died after 8 months of uncontrolled disease
Died of disseminated metastasis 2 years later
Died of carcinomatous meningitis 3 years later
Follow-up
Surg Radiol Anat
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Surg Radiol Anat
Case # 2
Case # 1
A
B Kadish A; T1 (Dulguerov); T1 (modified)
Kadish A; T2 (Dulguerov); T2 (modified)
Fig. 1 Olfactory Neuroblastomas located in the olfactory cleft. a Below cribriform plate: Case #1 CT scan showed an elongated opacity widening the left olfactory cleft; top of opacity remained separated from left cribriform plate (arrow) by an air bubble; below right cribriform plate (arrow), right olfactory cleft appeared narrowed by a bulging nasal septum; below left lateral lamina, turbinate wall of left ethmoidal labyrinth was not identifiable, but sinuous, regular aspect of the opacity was not suggestive of invasion; both ethmoidal labyrinths remained normally aerated. b In contact with cribriform
plate: Case #2 CT scan revealed an opacified, enlarged left olfactory cleft; turbinate wall appeared lateralized onto the orbit, but ethmoidal perpendicular plate was not displaced; cribriform plate remained visible on all coronal sections; superior ethmoidal labyrinth appeared opacified, but middle turbinate attachment under ethmoidal roof showed no disruption; lateral lamella appeared well preserved (arrow). Sphenoid, maxillary and frontal sinuses remained fully aerated
Patients and methods
circumscribe the pedicle of the tumor in the olfactory cleft; (2) complete exenteration of the ethmoidal labyrinth with transethmoidal sphenoidotomy, frontotomy and maxillotomy; (3) resection of the middle turbinate; (4) exenteration of the olfactory cleft [10]; and (5) if necessary, endoscopic endonasal resection of the anterior cranial base and intracranial extension (endoscopic ethmoido-cranial resection) followed by reparation with fascia lata and biologic glue. The staging of tumors was classified according to Kadish’s [9] as well as Dulguerov’s staging systems [3]. This study was approved by the Institutional Review Board of University Hospital of Nancy, France.
A retrospective review of medical records of all patients with ONB treated in our tertiary care center during the period 2004–2014 was carried out. Inclusion criterions were an unequivocal pathologic diagnosis, complete diagnostic imaging of the tumor with craniofacial computed tomography (CT) and magnetic resonance imaging (MRI), and endonasal surgery under endoscopic control. Wholebody positron emission tomography-computed tomography (PET/CT) using [18F]-fluorodeoxyglucose (18FDG) and cervical CT were systematically performed in preoperative check-up to look for distant metastasis. The therapeutic protocol was proposed to each patient after multidisciplinary decision. If the tumor seemed resectable, surgery with additional radiotherapy was the standard protocol. When tumors seemed unresectable, patients were first treated with chemotherapy, followed by surgery if possible [preoperative chemotherapy can reduce tumor size (downstaging)] and radiotherapy. The site of origin and local extension of the tumor were retrospectively re-evaluated by confronting CT and MR images to the data obtained by the surgical report, registered videotape of the surgery, and pathological report. Since 2004, endonasal endoscopic surgery for malignant tumors of the olfactory cleft was performed in our department according to the following systematic procedure [5, 7, 8]: (1) debulking of the tumor with the objectives to identify middle turbinate and nasal septum, and to
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Results Fourteen patients with an ONB [11 males, 2 females; median age 54 years (16–82 years)] were treated in our center between 2004 and 2014. One patient (a 47-year-old man) was excluded because the initial imaging of the tumor could not be found. The 13 remaining cases were ordered to understand and illustrate the natural behavior of ONB inside and outside the olfactory cleft. These 13 cases with detailed description of the localization and the extension of each tumor inside and outside the olfactory clefts were summarized in Table 1. Descriptions were based on the CT and MR imaging, PET scan, registered video of surgery, operative and pathological reports.
Surg Radiol Anat Case # 3
Case # 3
Right
Kadish B T2 (Dulguerov) T3 (modified)
B
A Case # 4-CT
Case # 4-MRI T2-weighted Right
Kadish B T2 (Dulguerov) T3 (modified)
C
D
Fig. 2 Olfactory Neuroblastomas extended to the ethmoidal labyrinth, without intraorbital or intracranial invasion. a On case #3 coronal CT, both nasal fossae were obstructed by a mass expanding under left cribriform plate, lateralizing nasal septum onto right turbinate wall, crushing both ethmoidal labyrinths onto medial orbital walls, and reaching left nasal floor; both cribriform plates looked intact and upper part of right olfactory cleft seemed also preserved (arrow). b On case #3 axial, enhanced CT, the mass enlarged left olfactory cleft, from sphenoid (protruding smoothly inside) to frontal process of maxilla; right olfactory cleft remained aerated at anterior and posterior extremities (arrows); right ethmoidal labyrinth was crushed onto medial orbital wall with seemingly retention opacities; the medial cells of left ethmoidal labyrinth (asterisk) appeared
contrast enhanced while the lateral cells in contact with orbit were not. c Case #4 coronal CT showed complete opacification of right nasal fossa and paranasal sinuses, but opacities limited to ethmoidal labyrinth and olfactory cleft on left side. Floor of anterior cranial fossa (both ethmoidal roofs, lateral laminas and cribriform plates) looked thin but preserved on all coronal CT scans. d Case #4 MRI showed a tumor occupying the right olfactory cleft without intracranial extension. Body of the tumor was bulging into right middle meatus and reaching the nasal floor. Nasal septum (arrows) separating both olfactory clefts was easy to identify except postero-superiorly. MRI signals were similar in both ethmoidal labyrinths, but different from signals of the olfactory cleft tumor (patient had also bilateral nasal polyposis). No intracranial extension was detected
In two patients (cases #7 and 13), ONB arose in the ethmoidal labyrinth. In one of these two patients (case #7), the tumor invaded the frontal sinus and orbital cavity without evident tumor observed in the olfactory cleft. This patient had only ophthalmologic complaints without sinonasal symptom [12]. Three patients died from metastasis of disease. In the last three patients, the follow-up is less than a year. The follow-up in survival patients goes up to 8.5 years without recurrence of the disease.
be the step before intracranial extension (cases #5 and 6). Intracranial extensions appear either delimited by a safe edging ribbon from the brain tissue (cases #5 and 6) or associated to radiological signs of leptomeninges (cases #8 and 9) or brain tissue involvement (like marginal tumor cysts [13, 15], case #10). Two patients had tumor arising in the ethmoidal labyrinth only without evident tumor observed in the olfactory cleft. Does this means that ONB can primarily develop from a cell located in the ethmoidal labyrinth? Could ONB develop from cells which are not belonging to the olfactory mucosa or could it be that olfactory cells can be found in the ethmoidal labyrinth? The evo-devo origin of the ethmoidal labyrinth is in favor of the second hypothesis [6]. In this theory, the ethmoidal labyrinth was formerly covered with olfactory mucosa, which regressed in humans to be located in the olfactory recess of the human olfactory cleft [6]. Thus, rare and inconstant cells belonging to the former olfactory mucosa may still remain in the ethmoidal
Discussion This series shows the behavior of a tumor which arises in most of the cases (11/13) inside the olfactory cleft, which can develop either below the cribriform plate (case #1) or in contact with the cribriform plate (cases #2 and 11). Extension to the ethmoidal labyrinth (cases #3 and 4) can
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Surg Radiol Anat
A
Case # 5-contrast CT B
Case # 5-MRI
Kadish C T3 or T4? (Dulguerov) T4a (modified)
C
Case # 6-CT
D
Case # 6-MRI
Kadish C T3 or T4? (Dulguerov) T4a (modified)
Fig. 3 Olfactory Neuroblastomas with intracranial extension, without brain tissue invasion. a Case #5 enhanced CT showed a lesion involving both olfactory fossae, left olfactory groove and superomedial ethmoidal cells with lysis of lateral lamina; the tumor appeared separated from orbital wall by crushed ethmoidal cells (arrow). b Case #5 MRI confirmed the extension of the tumor and revealed an edging ribbon separating tumor and brain parenchyma
(arrows). c Case #6 CT showed extensive lysis of the anterior cranial base by a tumor involving both nasal fossae. d Case #6 MRI showed a tumor involving both olfactory clefts and ethmoidal labyrinths, with intracranial extension but without brain invasion: an edge ribbon (arrows) could be found separating tumor and brain tissue. Tumor was in close contact with periorbita on both sides but no intraorbital extension was observed
labyrinth of some people, who therefore can primarily develop ONB in the ethmoidal labyrinth. Adequate treatment of ONB depends on locating and staging accurately the tumor. In these aspects both MR and CT imaging are helpful. CT, especially coronal CT scanning, is appropriate in evaluating the encroachment of the osseous structures of the anterior cranial base and orbital wall. Specifically, MRI is more accurate in depicting the margins of the tumor on account of its tissue contrast; in fact, this is probably true for the margins of intracranial and intraorbital extensions, but the correct differentiation between tumor and edematous tissue/retention seems more uncertain inside the nasal cavities. This is why we decided in this study to confront the data of CT/MR imaging to the observations during endoscopic surgery. The endoscopic surgical approach developed since 2004 to remove adenocarcinomas of the olfactory cleft [1, 7, 8] appeared well suited also for the surgical management of ONB and in the observation of the different stages of extension of the tumor.
Each tumor was staged by two currently used staging systems according to Kadish [9] and Dulguerov [3]. The Kadish staging system (in 1976) is as follow: ‘A’ meaning tumor limited to the nasal cavity, ‘B’ meaning tumor involving the nasal and paranasal cavities, and ‘C’ meaning tumor extending beyond the nasal and paranasal cavities. The staging system developed by Kadish seems, however, inadequate because group C includes tumor with very different spread and prognosis (cases #5–10, 12 illustrated by Figs. 3, 4 and 5) (Table 1). Dulguerov’s classification in 2001 (Table 2) is based on the TNM staging system, which was developed to achieve consensus on one globally recognized standard for classifying the extension of cancer. Dulguerov’s stages 1 and 2 deal with tumors involving ‘‘the nasal cavity and/or paranasal sinuses.’’ Extension of the tumor into the sphenoid sinus is proposed as a feature to differentiate T1 (no extension into the sphenoid sinus) and T2 (extension into the sphenoid sinus). Our series show that the invasion of the sphenoid sinus is rare. Moreover, protrusion of the tumor inside the sphenoid sinus without
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Surg Radiol Anat Fig. 4 Olfactory Neuroblastoma with intraorbital invasion. a Coronal CT (case #7) showed a round opacity in the left anterior ethmoidal labyrinth with extraperiosteal collection under orbital roof and complete opacification of frontal sinus. b Coronal MRI (case #7) showed two ovoid masses, one in the anterior ethmoidal labyrinth, one in the orbit, linked together by a tiny bridge (arrow) under the junction between ethmoidal and orbital roofs. No intracranial extension was noted. c Coronal MRI T2 (case #13) showed that the tumor grown inside left ethmoidal labyrinth. It tended to develop upward and downward in the ethmoidal labyrinth and protruded in left maxillary sinus as well as infundibulum of left frontal sinus. The left olfactory cleft was free of tumor
B
A
Case # 7-MRI (T1 gado fast sat)
Case # 7-CT
T4a
C
Kadish C; T3 (Dulguerov); T4a (modified)
Case # 13-MRI (T2 )
Fig. 5 Olfactory neuroblastomas with intracranial and brain tissue invasion. a Coronal MRI (case #9) showed a voluminous tumor of the posterior ethmoids with right intraorbital extension, bilateral intracranial extension running over the two orbital roofs (arrows) without clear delineation with the brain on the right side. b Coronal MRI (case #10) showed a bilateral nasal tumor with left orbital and bilateral craniofacial extensions involving the brain tissue. The presence of cysts along the intracranial margin of the tumor suggested the diagnosis of neuroblastoma. c Coronal MRI T2 (case #11) showed a tumor involving both olfactory clefts and ethmoidal labyrinths, with intracranial extension. The tumor was separated from the brain by intracranial marginal tumor cysts
A
B
Case # 9 MRI
Case # 10
Kadish C; T4 (Dulguerov); T4b (modified)
C
Case # 12
Kadish C; T4 (Dulguerov); T4a (modified)
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Surg Radiol Anat Table 2 Staging after Dulguerov and its modified staging Dulguerov staging system [3]
Dulguerov modified staging system
T1: Tumor involving the nasal cavity and/or paranasal sinuses (excluding sphenoid), sparing the most superior ethmoidal cells
T1: Tumor limited to the olfactory cleft without extension to the cribriform plate
T2: Tumor involving the nasal cavity and/or paranasal sinuses (including the sphenoid) with extension to or erosion of the cribriform plate
T2: Tumor limited to the olfactory cleft in contact with the cribriform plate
T3: Tumor extending into the orbit or protruding into the anterior cranial fossa, without dural invasion
T3: Tumor involving the ethmoidal labyrinth, without intracranial or intraorbital extension
T4: Tumor involving the brain
T4a: Tumor with intraorbital or intracranial extension without leptomeninges or brain tissue invasion T4b: Tumor with intraorbital or intracranial extension with leptomeninges or brain tissue invasion
N0: No cervical lymph node metastasis N1: Any form of cervical lymph node metastasis
N0: No cervical lymph node metastasis N1: Any form of cervical lymph node metastasis
M0: No metastasis
M0: No metastasis
M1: Distant metastases
M1: Distant metastases
bony wall involvement is usually easy to remove with endoscopic surgery. The extension to the cribriform plate is the second feature to differentiate T1 from T2. Our series show that this element may be a major criteria to differentiate T1 from T2 (Fig. 1), as a tumor that develops without extension to the cribriform plate (Fig. 1a) can easily be removed endoscopically with safe anatomical margins. In contrast to Dulguerov’s proposition, our series shows that the most superior ethmoidal cells should be free of any disease to classify T1 and T2 tumors, as involvement of the ethmoidal cells is at risk for intracranial or intraorbital extension. Case #3 and 4 showed involvement of the inferior ethmoidal cells (Fig. 2) without intracranial or orbital extension. In contrast, case #5 (Fig. 3a, b) had very small and difficult to observe tumor in the nasal fossae, but invasion of the most superior ethmoidal cells was already associated with intracranial extension. Cases #7 and 13 had massive unilateral superior ethmoidal cells invasion. Therefore, ethmoidal cell involvement is at risk of intracranial or intraorbital invasion and should be affected a staging different than T2, thus T3. The therapeutic approach is different according to the resectability of the intracranial or intraorbital extensions. When the resection seems mutilating, the chemotherapy has to be considered first. Patients have to be radiologically reevaluated after chemotherapy to consider a resection of tumor residual followed by radiotherapy. As tumor extension into the ethmoidal labyrinth should be staged T3, intracranial or intraorbital extension should be staged T4, with T4a when resection seems possible (Fig. 5c) and T4b when resection is impossible or in case with leptomeninges or brain tissue invasion (Fig. 5a, b). In this study, each tumor was described in detail on the basis of CT/MR imaging, endoscopic observation during surgery and pathological reports of the surgical specimens
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removed methodically during the surgery: (1) debulking, (2) ethmoidal labyrinth, (3) middle turbinate, (4) olfactory cleft, and (5) ±anterior cranial fossa. Moreover, the followup is relatively long for a few patients, arguing in favor of our therapeutic approach. Of course, our study with its quite small number of patients is underpowered to modify the Dulguerov’s staging system, which should still stay used as it is. Our study just shows that there could be some interests in considering the origin of ONB either in the olfactory cleft (majority of cases) or in the ethmoidal labyrinth. In olfactory cleft originating ONB, the relationship between the tumor and the cribriform plate would, at least from a surgical point of view, represent the criteria to differentiate T1 from T2 stages (Table 2). Whatever origin, ONB developed in the ethmoidal labyrinth seems to be exposed to intracranial or intraorbital extension and could be labeled as stage T3. Both intracranial and intraorbital invasion change the therapeutic approach and may be also prognosis, and could be labeled T4, with T4a for resectable tumor and T4b for unresectable tumor.
Conclusion The proposition to modify the Dulguerov’s staging system according to this preliminary study which has tried to understand the behavior of ONB inside and outside the OC will be proposed in a future prospective multicenter study. Acknowledgments The authors wish to thank Drs Bruno TOUSSAINT, M.D. and Ce´cile RUMEAU, M.D., Ph.D. (Otorhinolaryngology, Head and Neck Surgery, University hospital of Nancy, University of Lorraine, France), Drs Marie Christine KAMINSKY, M.D. and Lionnel GEOFFROIS, M.D. (Oncology, Cancer Institute of Lorraine, Vandoeuvre les Nancy, France)), Dr Pierre GRAFF, M.D.,
Surg Radiol Anat Ph.D. (Radiotherapy, Cancer Institute of Lorraine, Vandoeuvre les Nancy, France), Dr Be´atrice MARIE, M.D. (Department of Pathology- University hospital of Nancy, University of Lorraine, France) for their expert opinion both in clinical setting, multidisciplinary decision and for their participation in this manuscript. Conflict of interest interest.
The authors declare they have no conflict of
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ORIGINAL ARTICLE
Olfactory neuroblastoma behavior inside and outside the olfactory cleft Roger Jankowski • Adrien Russel • Patrice Gallet Philippe Henrot • Jean Michel Vignaud • Duc Trung Nguyen
•
Received: 29 May 2014 / Accepted: 8 September 2014 Ó Springer-Verlag France 2014
Abstract Purpose Olfactory neuroblastoma (ONB) is a rare malignant tumor of the nose. The currently available evidence links this disease with cells of the olfactory epithelium. The detailed description of tumor site and its extension is the key of treatment. The aim of the present study was to describe the way ONB develops inside and outside the olfactory cleft. Methods Thirteen consecutive patients treated between 2004 and 2014 for ONB with unequivocal pathologic diagnosis, complete diagnostic imaging and endonasal endoscopy surgery were enrolled in this retrospective study. The site of origin and local extension of each tumor were studied in detail based on computed tomography/ magnetic resonance imaging, surgical report, registered videotape of the surgery, and pathological reports. Results This series shows the behavior of a tumor arising either in the olfactory clefts (11 cases) or in the ethmoidal labyrinth (2 cases). When the setting begins with a tumor located in the olfactory cleft (below or in contact with the cribriform plate), the further step can be the extension to the ethmoidal labyrinth before intracranial or intraorbital extension. When tumors originate inside the ethmoidal R. Jankowski A. Russel P. Gallet D. T. Nguyen (&) Department of Otorhinolaryngology - Head and Neck Surgery, University hospital of Nancy - Hospital of Brabois, Morvan street, 54511 Vandoeuvre les Nancy cedex, France e-mail: [email protected] P. Henrot Department of Radiology, Cancer Institute of Lorraine, Vandoeuvre Les Nancy Cedex, France J. M. Vignaud Department of Pathology, University hospital of Nancy, University of Lorraine, Nancy, France
labyrinths, the extension can first be into frontal sinus or orbital cavity. Conclusions This fine anatomic and radiologic description shows the natural behavior of ONB inside and outside the olfactory cleft. As a consequence, the staging system developed by Kadish seems inadequate and Dulguerov’s staging system could be improved. However, the preliminary proposed modification has to be evaluated in a prospective and large, multicenter cohort of patients. Keywords Olfactory neuroblastoma Ethmoid bone Nose neoplasms Olfactory cleft
Introduction Olfactory neuroblastomas (ONB) are malignant tumors emanating from cells belonging to the olfactory mucosa of the olfactory recess. The currently available evidence links ONB with the basal progenitor cell of the olfactory neuroepithelium [2], which is located at the upper part of the olfactory cleft in humans [4, 10]. Two different mucosae are found in the olfactory cleft [6]: the upper part under the cribriform plate (i.e. olfactory recess) is covered with olfactory mucosa, the lower part (i.e. olfactory vestibule) with respiratory mucosa. The behavior of tumors originating in the olfactory cleft has become a matter of attention only recently [1, 11, 14]. Understanding of the tumoral behavior helps surgeons to accurately classify the tumor staging and to plan an adequate treatment, specially preparation of surgical procedure. All ONB of this series were operated under endoscopic control during the ten-year period (2004–2014). Despite the small number of cases, the description of this series gives clues to understand the natural behavior of ONB development inside and outside the olfactory cleft.
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Age, gender
33 years, female
54 years, male
69 years, female
82 years, male
42 years, male
73 years, male
39 years, male
Patients
1 (Fig. 1a)
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2 (Fig. 1b)
3 (Fig. 2a, b)
4 (Fig. 2c, d)
5 (Fig. 3a, b)
6 (Fig. 3c, d)
7 (Fig. 4a, b)
Left exophthalmos diplopia with normal visual acuity
Left rhinorrhea, bilateral nasal obstruction, and anosmia since 6 months
Anosmia and ageusia since 3 months
nasal obstruction, right recurrent epistaxis, nasal polyposis
Bilateral nasal obstruction
Left nasal obstruction
Left nasal obstruction
Symptoms
A suspect left cervical lymph node was found on CT and PET scan
The tumor developed inside the left anterior ethmoid labyrinth and invaded left orbit and left frontal sinus without intracranial extension
The tumor invaded both posterior ethmoidal labyrinths and protruded into the anterior cranial fossa through the dura but did not invade the cerebral hemispheres of the brain
The tumor was involving both olfactory recess. On left side, the tumor destroyed the conchal lamina to invade the ethmoid labyrinth and penetrated the left olfactory groove both through the cribriform plate and lateral lamina
The PET scan showed multiple, hypermetabolic lymph nodes in the right side of the neck. The pathological analysis confirmed metastatic lymph nodes
The tumor (after debulking) was stemming from the right turbinate wall, reaching the mucosa of the cribriform plate but without invading it. The tumor invaded some superior ethmoidal cells through the right superior meatus. Both ethmoidal roofs were unharmed
The mass enlarged the left OC, from sphenoid to frontal process of maxilla with extension to the left ethmoidal labyrinth. Both bony cribriform plates looked intact
Tumor in the left OC with radiological extension to the left cribriform plate. The left turbinate wall was lateralized but remained preserved. MRI showed retention in the left ethmoidal labyrinth
Insertion at 3 mm below the left cribriform plate on the middle nasal septum without invasion of the ethmoidal labyrinth
Tumor localization
Table 1 Description of clinical feature, imaging, and treatment in each patient
C
C
C
B
B
A
A
Kadish’s staging
T3N1M0
T3 or T4 N0M0
T3 or T4 N0M0
T2N1M0
T2N0M0
T2N0M0
T1N0M0
Dulguerov’s staging
Chemotherapy (with complete response) followed by exenteration of left OC and orbit associated to homolateral neck dissection and radiotherapy
Bilateral endoscopic exenteration of OC associated to EECR, followed by radiotherapy
Bilateral endoscopic exenteration of OC associated to EECR, followed by radiotherapy
Exenteration of the right OC without bony cribriform plate removal and neck dissection followed by radiotherapy
Exenteration of the left OC without bony cribriform plate removal followed by radiotherapy
Exenteration of the left OC without bony cribriform plate removal, followed by radiotherapy
Exenteration of the left OC without bony cribriform plate removal, followed by radiotherapy
Treatment
2 years without recurrence
2 years without recurrence
5.5 years without recurrence
2 years without recurrence
5.5 years without recurrence
8.5 years without recurrence
7.5 years without recurrence
Follow-up
Surg Radiol Anat
16 years, male
21 years, male
69 years, male
77 years, male
63 years, male
40 years, Male
8
9 (Fig. 5a)
10 (Fig. 5b)
11
12 (Fig. 5c)
13 (Fig. 4c)
Left recurrent epistaxis
Anosmia, Left recurrent epistaxis, nasal obstruction, Cushing’s syndrome
Left recurrent epistaxis, nasal obstruction
Left recurrent epistaxis, nasal obstruction
Right facial pain, edema of the right upper eyelid, and left cervical lymph node (3 cm)
Right lateral lymph nodes ([6 cm) associated to nasal obstruction, mild epistaxis and anosmia
Symptoms
The tumor developed inside the left anterior ethmoid labyrinth. This tumor protruded into the left frontal infundibulum and left maxillary sinus. The left OC was free
The tumor invaded both ethmoidal labyrinths and protruded into the anterior cranial fossa through the dura but did not invade the cerebral hemispheres of the brain. The tumor was separated with the brain by marginal tumors cysts
Tumor in the left OC with radiological extension to the left cribriform plate without evident bone erosion. The left turbinate wall was lateralized but remained preserved. MRI showed retention in the left ethmoidal labyrinth
The tumor developed inside the bilateral nasal cavity with left orbital and bilateral craniofacial extensions involving the brain tissue. The PET scan showed bilateral, hypermetabolic, cervical lymph nodes and diffuse pulmonary metastasis
The PET scan revealed hypermetabolic, bilateral, cervical lymph nodes and a spot in the right ilium
The voluminous tumor was in the posterior ethmoids with right intraorbital extension, bilateral intracranial extension running over the two orbital roofs
The tumor involved both nasal fossae, ethmoidal labyrinths and right orbit, extending into the anterior cranial fossa with no clear delineation between tumor and brain hemispheres The PET scan revealed left cervical, hypermetabolic lymph nodes that were metastatic confirmed by pathological analysis
Tumor localization
OC olfactory cleft, EECR endoscopic ethmoido-cranial resection
Age, gender
Patients
Table 1 continued
B
C
A
C
C
C
Kadish’s staging
T2N0M0
T4N0M0
T2N0M0
T4N1M1
T4N1M1
T4N1M0
Dulguerov’s staging
Complete exenteration of left ethmoidal labyrinth
Chemotherapy (without response) followed by bilateral endoscopic exenteration of OC associated to EECR and radiotherapy.
Exenteration of the left OC without bony cribriform plate removal, followed by radiotherapy
Palliative chemotherapy
Chemotherapy followed by surgery with neck dissection and radiotherapy
Chemotherapy (with partial response) followed by surgery with homolateral neck dissection and radiotherapy
Treatment
6 months without recurrence
6 months without recurrence
9 months without recurrence
Died after 8 months of uncontrolled disease
Died of disseminated metastasis 2 years later
Died of carcinomatous meningitis 3 years later
Follow-up
Surg Radiol Anat
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Surg Radiol Anat
Case # 2
Case # 1
A
B Kadish A; T1 (Dulguerov); T1 (modified)
Kadish A; T2 (Dulguerov); T2 (modified)
Fig. 1 Olfactory Neuroblastomas located in the olfactory cleft. a Below cribriform plate: Case #1 CT scan showed an elongated opacity widening the left olfactory cleft; top of opacity remained separated from left cribriform plate (arrow) by an air bubble; below right cribriform plate (arrow), right olfactory cleft appeared narrowed by a bulging nasal septum; below left lateral lamina, turbinate wall of left ethmoidal labyrinth was not identifiable, but sinuous, regular aspect of the opacity was not suggestive of invasion; both ethmoidal labyrinths remained normally aerated. b In contact with cribriform
plate: Case #2 CT scan revealed an opacified, enlarged left olfactory cleft; turbinate wall appeared lateralized onto the orbit, but ethmoidal perpendicular plate was not displaced; cribriform plate remained visible on all coronal sections; superior ethmoidal labyrinth appeared opacified, but middle turbinate attachment under ethmoidal roof showed no disruption; lateral lamella appeared well preserved (arrow). Sphenoid, maxillary and frontal sinuses remained fully aerated
Patients and methods
circumscribe the pedicle of the tumor in the olfactory cleft; (2) complete exenteration of the ethmoidal labyrinth with transethmoidal sphenoidotomy, frontotomy and maxillotomy; (3) resection of the middle turbinate; (4) exenteration of the olfactory cleft [10]; and (5) if necessary, endoscopic endonasal resection of the anterior cranial base and intracranial extension (endoscopic ethmoido-cranial resection) followed by reparation with fascia lata and biologic glue. The staging of tumors was classified according to Kadish’s [9] as well as Dulguerov’s staging systems [3]. This study was approved by the Institutional Review Board of University Hospital of Nancy, France.
A retrospective review of medical records of all patients with ONB treated in our tertiary care center during the period 2004–2014 was carried out. Inclusion criterions were an unequivocal pathologic diagnosis, complete diagnostic imaging of the tumor with craniofacial computed tomography (CT) and magnetic resonance imaging (MRI), and endonasal surgery under endoscopic control. Wholebody positron emission tomography-computed tomography (PET/CT) using [18F]-fluorodeoxyglucose (18FDG) and cervical CT were systematically performed in preoperative check-up to look for distant metastasis. The therapeutic protocol was proposed to each patient after multidisciplinary decision. If the tumor seemed resectable, surgery with additional radiotherapy was the standard protocol. When tumors seemed unresectable, patients were first treated with chemotherapy, followed by surgery if possible [preoperative chemotherapy can reduce tumor size (downstaging)] and radiotherapy. The site of origin and local extension of the tumor were retrospectively re-evaluated by confronting CT and MR images to the data obtained by the surgical report, registered videotape of the surgery, and pathological report. Since 2004, endonasal endoscopic surgery for malignant tumors of the olfactory cleft was performed in our department according to the following systematic procedure [5, 7, 8]: (1) debulking of the tumor with the objectives to identify middle turbinate and nasal septum, and to
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Results Fourteen patients with an ONB [11 males, 2 females; median age 54 years (16–82 years)] were treated in our center between 2004 and 2014. One patient (a 47-year-old man) was excluded because the initial imaging of the tumor could not be found. The 13 remaining cases were ordered to understand and illustrate the natural behavior of ONB inside and outside the olfactory cleft. These 13 cases with detailed description of the localization and the extension of each tumor inside and outside the olfactory clefts were summarized in Table 1. Descriptions were based on the CT and MR imaging, PET scan, registered video of surgery, operative and pathological reports.
Surg Radiol Anat Case # 3
Case # 3
Right
Kadish B T2 (Dulguerov) T3 (modified)
B
A Case # 4-CT
Case # 4-MRI T2-weighted Right
Kadish B T2 (Dulguerov) T3 (modified)
C
D
Fig. 2 Olfactory Neuroblastomas extended to the ethmoidal labyrinth, without intraorbital or intracranial invasion. a On case #3 coronal CT, both nasal fossae were obstructed by a mass expanding under left cribriform plate, lateralizing nasal septum onto right turbinate wall, crushing both ethmoidal labyrinths onto medial orbital walls, and reaching left nasal floor; both cribriform plates looked intact and upper part of right olfactory cleft seemed also preserved (arrow). b On case #3 axial, enhanced CT, the mass enlarged left olfactory cleft, from sphenoid (protruding smoothly inside) to frontal process of maxilla; right olfactory cleft remained aerated at anterior and posterior extremities (arrows); right ethmoidal labyrinth was crushed onto medial orbital wall with seemingly retention opacities; the medial cells of left ethmoidal labyrinth (asterisk) appeared
contrast enhanced while the lateral cells in contact with orbit were not. c Case #4 coronal CT showed complete opacification of right nasal fossa and paranasal sinuses, but opacities limited to ethmoidal labyrinth and olfactory cleft on left side. Floor of anterior cranial fossa (both ethmoidal roofs, lateral laminas and cribriform plates) looked thin but preserved on all coronal CT scans. d Case #4 MRI showed a tumor occupying the right olfactory cleft without intracranial extension. Body of the tumor was bulging into right middle meatus and reaching the nasal floor. Nasal septum (arrows) separating both olfactory clefts was easy to identify except postero-superiorly. MRI signals were similar in both ethmoidal labyrinths, but different from signals of the olfactory cleft tumor (patient had also bilateral nasal polyposis). No intracranial extension was detected
In two patients (cases #7 and 13), ONB arose in the ethmoidal labyrinth. In one of these two patients (case #7), the tumor invaded the frontal sinus and orbital cavity without evident tumor observed in the olfactory cleft. This patient had only ophthalmologic complaints without sinonasal symptom [12]. Three patients died from metastasis of disease. In the last three patients, the follow-up is less than a year. The follow-up in survival patients goes up to 8.5 years without recurrence of the disease.
be the step before intracranial extension (cases #5 and 6). Intracranial extensions appear either delimited by a safe edging ribbon from the brain tissue (cases #5 and 6) or associated to radiological signs of leptomeninges (cases #8 and 9) or brain tissue involvement (like marginal tumor cysts [13, 15], case #10). Two patients had tumor arising in the ethmoidal labyrinth only without evident tumor observed in the olfactory cleft. Does this means that ONB can primarily develop from a cell located in the ethmoidal labyrinth? Could ONB develop from cells which are not belonging to the olfactory mucosa or could it be that olfactory cells can be found in the ethmoidal labyrinth? The evo-devo origin of the ethmoidal labyrinth is in favor of the second hypothesis [6]. In this theory, the ethmoidal labyrinth was formerly covered with olfactory mucosa, which regressed in humans to be located in the olfactory recess of the human olfactory cleft [6]. Thus, rare and inconstant cells belonging to the former olfactory mucosa may still remain in the ethmoidal
Discussion This series shows the behavior of a tumor which arises in most of the cases (11/13) inside the olfactory cleft, which can develop either below the cribriform plate (case #1) or in contact with the cribriform plate (cases #2 and 11). Extension to the ethmoidal labyrinth (cases #3 and 4) can
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Surg Radiol Anat
A
Case # 5-contrast CT B
Case # 5-MRI
Kadish C T3 or T4? (Dulguerov) T4a (modified)
C
Case # 6-CT
D
Case # 6-MRI
Kadish C T3 or T4? (Dulguerov) T4a (modified)
Fig. 3 Olfactory Neuroblastomas with intracranial extension, without brain tissue invasion. a Case #5 enhanced CT showed a lesion involving both olfactory fossae, left olfactory groove and superomedial ethmoidal cells with lysis of lateral lamina; the tumor appeared separated from orbital wall by crushed ethmoidal cells (arrow). b Case #5 MRI confirmed the extension of the tumor and revealed an edging ribbon separating tumor and brain parenchyma
(arrows). c Case #6 CT showed extensive lysis of the anterior cranial base by a tumor involving both nasal fossae. d Case #6 MRI showed a tumor involving both olfactory clefts and ethmoidal labyrinths, with intracranial extension but without brain invasion: an edge ribbon (arrows) could be found separating tumor and brain tissue. Tumor was in close contact with periorbita on both sides but no intraorbital extension was observed
labyrinth of some people, who therefore can primarily develop ONB in the ethmoidal labyrinth. Adequate treatment of ONB depends on locating and staging accurately the tumor. In these aspects both MR and CT imaging are helpful. CT, especially coronal CT scanning, is appropriate in evaluating the encroachment of the osseous structures of the anterior cranial base and orbital wall. Specifically, MRI is more accurate in depicting the margins of the tumor on account of its tissue contrast; in fact, this is probably true for the margins of intracranial and intraorbital extensions, but the correct differentiation between tumor and edematous tissue/retention seems more uncertain inside the nasal cavities. This is why we decided in this study to confront the data of CT/MR imaging to the observations during endoscopic surgery. The endoscopic surgical approach developed since 2004 to remove adenocarcinomas of the olfactory cleft [1, 7, 8] appeared well suited also for the surgical management of ONB and in the observation of the different stages of extension of the tumor.
Each tumor was staged by two currently used staging systems according to Kadish [9] and Dulguerov [3]. The Kadish staging system (in 1976) is as follow: ‘A’ meaning tumor limited to the nasal cavity, ‘B’ meaning tumor involving the nasal and paranasal cavities, and ‘C’ meaning tumor extending beyond the nasal and paranasal cavities. The staging system developed by Kadish seems, however, inadequate because group C includes tumor with very different spread and prognosis (cases #5–10, 12 illustrated by Figs. 3, 4 and 5) (Table 1). Dulguerov’s classification in 2001 (Table 2) is based on the TNM staging system, which was developed to achieve consensus on one globally recognized standard for classifying the extension of cancer. Dulguerov’s stages 1 and 2 deal with tumors involving ‘‘the nasal cavity and/or paranasal sinuses.’’ Extension of the tumor into the sphenoid sinus is proposed as a feature to differentiate T1 (no extension into the sphenoid sinus) and T2 (extension into the sphenoid sinus). Our series show that the invasion of the sphenoid sinus is rare. Moreover, protrusion of the tumor inside the sphenoid sinus without
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Surg Radiol Anat Fig. 4 Olfactory Neuroblastoma with intraorbital invasion. a Coronal CT (case #7) showed a round opacity in the left anterior ethmoidal labyrinth with extraperiosteal collection under orbital roof and complete opacification of frontal sinus. b Coronal MRI (case #7) showed two ovoid masses, one in the anterior ethmoidal labyrinth, one in the orbit, linked together by a tiny bridge (arrow) under the junction between ethmoidal and orbital roofs. No intracranial extension was noted. c Coronal MRI T2 (case #13) showed that the tumor grown inside left ethmoidal labyrinth. It tended to develop upward and downward in the ethmoidal labyrinth and protruded in left maxillary sinus as well as infundibulum of left frontal sinus. The left olfactory cleft was free of tumor
B
A
Case # 7-MRI (T1 gado fast sat)
Case # 7-CT
T4a
C
Kadish C; T3 (Dulguerov); T4a (modified)
Case # 13-MRI (T2 )
Fig. 5 Olfactory neuroblastomas with intracranial and brain tissue invasion. a Coronal MRI (case #9) showed a voluminous tumor of the posterior ethmoids with right intraorbital extension, bilateral intracranial extension running over the two orbital roofs (arrows) without clear delineation with the brain on the right side. b Coronal MRI (case #10) showed a bilateral nasal tumor with left orbital and bilateral craniofacial extensions involving the brain tissue. The presence of cysts along the intracranial margin of the tumor suggested the diagnosis of neuroblastoma. c Coronal MRI T2 (case #11) showed a tumor involving both olfactory clefts and ethmoidal labyrinths, with intracranial extension. The tumor was separated from the brain by intracranial marginal tumor cysts
A
B
Case # 9 MRI
Case # 10
Kadish C; T4 (Dulguerov); T4b (modified)
C
Case # 12
Kadish C; T4 (Dulguerov); T4a (modified)
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Surg Radiol Anat Table 2 Staging after Dulguerov and its modified staging Dulguerov staging system [3]
Dulguerov modified staging system
T1: Tumor involving the nasal cavity and/or paranasal sinuses (excluding sphenoid), sparing the most superior ethmoidal cells
T1: Tumor limited to the olfactory cleft without extension to the cribriform plate
T2: Tumor involving the nasal cavity and/or paranasal sinuses (including the sphenoid) with extension to or erosion of the cribriform plate
T2: Tumor limited to the olfactory cleft in contact with the cribriform plate
T3: Tumor extending into the orbit or protruding into the anterior cranial fossa, without dural invasion
T3: Tumor involving the ethmoidal labyrinth, without intracranial or intraorbital extension
T4: Tumor involving the brain
T4a: Tumor with intraorbital or intracranial extension without leptomeninges or brain tissue invasion T4b: Tumor with intraorbital or intracranial extension with leptomeninges or brain tissue invasion
N0: No cervical lymph node metastasis N1: Any form of cervical lymph node metastasis
N0: No cervical lymph node metastasis N1: Any form of cervical lymph node metastasis
M0: No metastasis
M0: No metastasis
M1: Distant metastases
M1: Distant metastases
bony wall involvement is usually easy to remove with endoscopic surgery. The extension to the cribriform plate is the second feature to differentiate T1 from T2. Our series show that this element may be a major criteria to differentiate T1 from T2 (Fig. 1), as a tumor that develops without extension to the cribriform plate (Fig. 1a) can easily be removed endoscopically with safe anatomical margins. In contrast to Dulguerov’s proposition, our series shows that the most superior ethmoidal cells should be free of any disease to classify T1 and T2 tumors, as involvement of the ethmoidal cells is at risk for intracranial or intraorbital extension. Case #3 and 4 showed involvement of the inferior ethmoidal cells (Fig. 2) without intracranial or orbital extension. In contrast, case #5 (Fig. 3a, b) had very small and difficult to observe tumor in the nasal fossae, but invasion of the most superior ethmoidal cells was already associated with intracranial extension. Cases #7 and 13 had massive unilateral superior ethmoidal cells invasion. Therefore, ethmoidal cell involvement is at risk of intracranial or intraorbital invasion and should be affected a staging different than T2, thus T3. The therapeutic approach is different according to the resectability of the intracranial or intraorbital extensions. When the resection seems mutilating, the chemotherapy has to be considered first. Patients have to be radiologically reevaluated after chemotherapy to consider a resection of tumor residual followed by radiotherapy. As tumor extension into the ethmoidal labyrinth should be staged T3, intracranial or intraorbital extension should be staged T4, with T4a when resection seems possible (Fig. 5c) and T4b when resection is impossible or in case with leptomeninges or brain tissue invasion (Fig. 5a, b). In this study, each tumor was described in detail on the basis of CT/MR imaging, endoscopic observation during surgery and pathological reports of the surgical specimens
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removed methodically during the surgery: (1) debulking, (2) ethmoidal labyrinth, (3) middle turbinate, (4) olfactory cleft, and (5) ±anterior cranial fossa. Moreover, the followup is relatively long for a few patients, arguing in favor of our therapeutic approach. Of course, our study with its quite small number of patients is underpowered to modify the Dulguerov’s staging system, which should still stay used as it is. Our study just shows that there could be some interests in considering the origin of ONB either in the olfactory cleft (majority of cases) or in the ethmoidal labyrinth. In olfactory cleft originating ONB, the relationship between the tumor and the cribriform plate would, at least from a surgical point of view, represent the criteria to differentiate T1 from T2 stages (Table 2). Whatever origin, ONB developed in the ethmoidal labyrinth seems to be exposed to intracranial or intraorbital extension and could be labeled as stage T3. Both intracranial and intraorbital invasion change the therapeutic approach and may be also prognosis, and could be labeled T4, with T4a for resectable tumor and T4b for unresectable tumor.
Conclusion The proposition to modify the Dulguerov’s staging system according to this preliminary study which has tried to understand the behavior of ONB inside and outside the OC will be proposed in a future prospective multicenter study. Acknowledgments The authors wish to thank Drs Bruno TOUSSAINT, M.D. and Ce´cile RUMEAU, M.D., Ph.D. (Otorhinolaryngology, Head and Neck Surgery, University hospital of Nancy, University of Lorraine, France), Drs Marie Christine KAMINSKY, M.D. and Lionnel GEOFFROIS, M.D. (Oncology, Cancer Institute of Lorraine, Vandoeuvre les Nancy, France)), Dr Pierre GRAFF, M.D.,
Surg Radiol Anat Ph.D. (Radiotherapy, Cancer Institute of Lorraine, Vandoeuvre les Nancy, France), Dr Be´atrice MARIE, M.D. (Department of Pathology- University hospital of Nancy, University of Lorraine, France) for their expert opinion both in clinical setting, multidisciplinary decision and for their participation in this manuscript. Conflict of interest interest.
The authors declare they have no conflict of
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