Neuroradiology (2009) 51:841–850 DOI 10.1007/s00234-009-0581-0

DIAGNOSTIC NEURORADIOLOGY

Esthesioneuroblastoma methods of intracranial extension: CT and MR imaging findings Tian Yu & Yi-Kai Xu & Long Li & Fei-Ge Jia & Gang Duan & Yuan-Kui Wu & Hua-Yu Li & Rui-Meng Yang & Jie Feng & Xiang-Hua Ye & Ying-Wei Qiu

Received: 9 July 2009 / Accepted: 23 July 2009 / Published online: 11 August 2009 # Springer-Verlag 2009

Abstract Introduction Esthesioneuroblastoma (ENB) is an aggressive neuroectodermal malignancy in the upper nasal cavity with local infiltration and lymphatic or hematogenous metastasis. The purpose of this paper is to document three types of direct intracranial extensions by ENB using computed tomography (CT) and magnetic resonance imaging (MRI). Methods Eleven patients with pathologically confirmed ENB were admitted in our hospital between December 2002 and December 2008. Their magnetic resonance (MR; n=10) and CT (n=8) images were retrospectively reviewed, and particular attention was paid to tumor location and extension, enhancement pattern, cervical lymph node metastasis, and Kadish stage. Results The majority of patients were male (8/11) with Kadish stage C tumor (10/11). Three types of direct

intracranial extension by ENBs were put forward according to their MR and CT findings. The primary tumors were well-defined soft-tissue masses centered in the roof of the nasal cavity eroding into the paranasal sinuses (11/11), the contralateral nasal cavity (4/11), the cranial cavity (5/11), and the fossa orbitalis (3/11). The tumor parenchyma were hypointensity on T1-weighted images, heterogeneous hyperintensity on T2-weighted images, and isodensity or slight hyperdensity on CT images with scattered necroses (4/11) and marginal cysts(4/11). Their enhancements were significant and inhomogeneous. Cervical lymph nodes metastases were observed in four patients (4/11), but no pathologically proved distant metastasis was observed. Conclusion Three types of direct intracranial extensions by ENB can be found on CT and MRI: cranio-orbital-nasalcommunicating ENB, cranio-nasal-communicating ENB, and orbital-nasal-communicating ENB.

T. Yu : Y.-K. Xu (*) : F.-G. Jia : R.-M. Yang : J. Feng : X.-H. Ye : Y.-W. Qiu Department of Medical Imaging Center, Nan Fang Hospital, Southern Medical University, No. 1838 Guangzhou Avenue North, Guangzhou, Guangdong 510515, China e-mail: [email protected]

Keywords Esthesioneuroblastoma . Olfactory neuroblastoma . Magnetic resonance imaging . X-ray . Computed tomography . Neoplasm . Nasal tumor . Otolaryngology

L. Li Department of Radiology, Guangdong Provincial Corps Hospital, Chinese People’s Armed Police Forces, Guangzhou, China G. Duan : Y.-K. Wu Department of Radiology, Nan Fang Hospital, Southern Medical University, Guangzhou, China H.-Y. Li Department of Medical Imaging Center, No. 458 Hospital of PLA, Guangzhou, China

Introduction Esthesioneuroblastoma (ENB) is a rare, aggressive neuroectodermal malignancy of the upper nasal cavity [1–4]. It accounts for 3–5% [5–9] of all nasal malignant tumors, and its incidence is estimated at 0.4 per million [10]. Since it was first described by Berger et al. in 1924 [11], controversy has been surrounding its exact cytopathologic origin [12] and classification [13–17]. Recently, immunohistochemical and histological examinations imply that ENB is of neuroendocrine cell origin and is

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classified as a subtype of olfactory neuroblastomas (ONBs). ONBs are uncommon neuroectodermal malignancies assumed to arise from olfactory receptor cells high in the nasal cavity and are generally considered to be APUDomas. Other proposed histological subtypes of ONBs include olfactory neuroepithelioma (esthesioneuroepithelioma) and esthesioneurocytoma differing from ENB in morphological appearance. ENB has a propensity of locally infiltrating into the paranasal sinuses, brain, and sometimes the orbit [16]. Resection and radiotherapeutic techniques, similar to those applied for paranasal sinus tumors, thus, risk damaging these critical structures and result in late sequelae [18, 19]. Furthermore, it has the probability of disseminating to the cervical lymph nodes and rarely other distant organs. Hence, optimistic management of an ENB patient depends in a large degree on accurate tumor locating and staging. To date, magnetic resonance imaging (MRI) and computed tomography (CT) are the mainstream cross-sectional imaging modalities for its evaluation [20]. Till now, more than 1,000 cases have been reported [16, 21–25], including a meta-analysis of 390 cases from publications between 1990 and 2000 [2], but most of them are single case reports focusing on the histogenetic, pathologic, and clinical characteristics. However, data of its imaging characteristics are still scarce. Therefore, this paper mainly documents the magnetic resonance (MR) and CT findings of 11 pathologically confirmed ENBs, aiming to increase the dataset and evaluate the application of MRI and CT in its diagnosing and staging. Besides, three types of direct intracranial extension by ENB are put forward, which have not been proposed before, as far as we know.

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gap; and matrix size, 256 × 224). Preenhanced T1weighted spin-echo images (repetition time/echo time (TR/TE), 450–700/8–12 ms) and T2-weighted spin-echo images (TR/TE, 4,500–5,500/80–100 ms) were obtained. Fluid-attenuated inversion recovery sequence images (FLAIR; TR/TE, 8,000/120 ms; inversion time, 110 ms) were available in two cases. After the intravenous administration of gadopentetate dimeglumine (Magnevist; Bayer Schering, Berlin, Germany; 0.1–0.2 mmol/kg (body weight) b.w.), T1-weighted spin-echo images were obtained in the axial, coronal, and sagittal plane. All CT scans were performed with a Somatom Plus 4 scanner (Siemens, Enlargen, Germany) with contiguous 3-mm-thick axial slices before and after the intravenous administration of contrast agent (Omnipaque 300 mg I/ml; 1.5~2.0 ml/kg b.w.; injection rate, 2.0~2.5 ml/s). Image analysis Each MR and CT image was jointly reviewed by two experienced radiologists retrospectively blind to the histological diagnosis and reached decisions by consensus. Images were assessed mainly for tumor location and local extension, signal and density, enhancement pattern, as well as lymph-node metastasis. The primary clinical stages were classified as A, B, and C, according to the criteria established by Kadish et al. [26]: stage A tumors are limited to the nasal cavity, stage B tumors involve the nasal cavity and paranasal sinuses, and stage C tumors extend beyond these structures.

Results Materials and methods Patients From December 2002 to December 2008, 11 patients (eight males and three females; 11~59 years old; mean age, 44 years) with pathologic diagnosis of ENB were admitted in our hospital. Ten of them took pretreatment MR examination and eight underwent pretreatment and/or post-treatment CT scanning of the brain and sinonasal area (seven patients had both modalities). Imaging techniques All MR scans were performed on a 1.5-T system (Magnetom vision plus; Siemens, Erlangen, Germany) using a standard quadrature head coil (field of view, 22 cm; slice thickness, 5~8 mm with 0.1-mm interslice

The MR and CT findings of the 11 ENB patients together with their clinical data are detailed in Table 1. The majority of patients presented were male (8/11) with Kadish stage C disease (10/11). On MR and CT images, all 11 cases exhibited welldefined soft-tissue masses within the unilateral (10/11) or bilateral (1/11) nasal cavity (centered in the superior nasal meatus and cribriform plate) with adjacent structure invasion, including one cranio-orbital-nasal-communicating tumor (Fig. 1), four cranio-nasal-communicating tumors (Figs. 2, 3, 4) and two orbital-nasal-communicating tumors. Compared with the gray matter, the tumor parenchyma appeared as hypointensity on T1-weighted images, hyperintensity on T2-weighted images, and isodensity or slight hyperdensity on precontrast CT images. Contrast enhancement was usually significant and inhomogeneous with multiple necrotic and cystic areas. Scattered intratumoral necroses (Figs. 1 and 3) were observed in four cases with

+ NA + L+R

L + + + + + + + + L+R L L+R + C

+ NA − L

L + + − − + + − − − − L + C

+ positive, − negative, L left, R right, NA not available

Lamina erbitalis (n=3) Regional lymphadenopathy (n=4) Kadish stage

Frontal sinus (n=2) Frontal lobe (n=5)

15 M 1 month

11 F 8 days

Age Gender History prior to diagnosis Symptoms Nasal obstruction and epistaxis (n=9) Hyposmia (n=5)/anosmia (n=1) Unsteadiness/headache (n=6) Ophthalmalgia, exophthalmos, dacryorrhea, visual disturbance (n=3) Nasal location of primary tumor Unilateral (n=10)/bilateral (n=1) Superior nasal meatus (n=11) Middle nasal meatus (n=9) Inferior nasal meatus (n=3) Local invasion Contralateral nasal cavity (n=4) Paranasal sinuses invasion (n=11) Ethmoid sinus (n=11) Sphenoid sinus (n=6) Maxillary sinus (n=6)

2

1

Patient no.

Table 1 The MR and CT features together with clinical data of 11 ENB patients.

− − − C

−

+ + + + −

L+R + + −

+ A − −

28 M 3 days

3

− − − C

−

+ + + +

L + + −

+ NA − −

38 F 6 months

4

− L − C

−

+ + + + +

L + + +

+ H + L

39 M 4 years

5

R − − C

−

+ + − −

− − − C

−

− + + − −

R + + −

+ H − −

− H + −

R + − −

47 M NA

7

44 M 6 days

6

− − + B

−

− + + + +

L + + −

+ H − −

47 M 1 month

8

R − − C

−

− + + − −

R + − −

− NA + −

54 M 6 months

9

L − + C

−

− + + − +

L + + -

+ NA + −

55 F 1 month

10

L − − C

L

+ + + + +

L + + +

+ H + −

59 M 40 days

11

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complicated hemorrhage (Fig. 1) in two. And all five intracranial tumors exhibited mild peritumoral edema (Figs. 1, 2, 3); four of which had marginal cystic components (Figs. 1, 2). Besides, obliterative paranasal sinusitis was found in ten cases (10/11). Moreover, enlarged cervical lymph nodes (>1 cm in short diameter) were observed in four patients (4/11; Fig. 4c) and proved to be tumor metastases. Skin involvement was found in one patient (1/11). Ovary and liver problems were found in two patients (2/11), but they are not pathologically proved.

Discussion ENB is an uncommon (3–5% of all nasal tumors) and aggressive malignant neurogenic tumor located high in the nasal cavity. It can affect all age groups with some researches reporting a bimodal age distribution [27] peaking first between 11 and 20 years and later from 41 to 60 years of age [28] and others; a single peak in the fifth [22, 29] or sixth [30] decade. Our patient group with age ranging between 11 and 59 years old (mean, 44 years) was basically consistent with the former. There is still a lack of consensus over the incidence of both genders. Some reported that ENB affect male and female patients equally [13]; some thought that it is slightly more common in males [16, 18, 30, 31] or otherwise [32]. Our study exhibited a male predominance (eight males versus three females), although the patient series was a bit small. In general, the clinical symptoms of ENB were not specific and related to tumor sites and invasion [27]. It was reported that the commonest presenting symptoms were unilateral nasal obstruction, epistaxis, and anosmia [2, 23, 25, 33–39]. In our study, nine patients (82%) were presented with nasal obstruction and epistaxis lasting from 3 days to 4 years (mean, 1 month), and they, as were shown on MR images (Figs. 1, 2, 5), all developed masses in the superior and middle nasal meatus with or without the inferior nasal meatus involvement. The other two patients (18%) presented with headache (without nasal obstruction or epistaxis) had neoplasma in the superior nasal meatus without the middle and inferior nasal meatus involvement (Fig. 3). Hence, nasal obstruction and epistaxis might suggest blockage and encroachment of the superior and middle nasal meatus. Hyposmia (5/6) or anosmia (1/6) suggests involvement of either unilateral or bilateral olfactory placode. Encroachment of the brain leads to headache and/or unsteadiness (6/11; Figs. 1, 2, 3). Orbital extension (3/11; Fig. 1) caused ophthalmological symptoms such as ophthalmalgia, exophthalmos, epiphora, visual impairment, or limitation of ocular movement. Rare case

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reports of ear ache, tympanitis [40], and Cushing's syndrome [41, 42] or SiADH [14, 43] have been published; unfortunately, they were not found in our present patient series. Owing to its nonspecific symptoms and slowgrowing nature, ENB patients often have a long history of progressive symptomatology for months, sometimes years, prior to diagnosis [2]. The average duration from symptom onset to management is 1 month (3 days–4 years) in our study and 6 months (0–18 months) in the USA, reportedly [16]. The fact that most of our patients presented with advanced Kadish stage C disease (10/11) is in support of this point of view. Our study confirmed that MRI and CT appearance of ENB are nonspecific, sharing similar signal and density features, and enhancement patterns with other nasal neoplasms [2, 33]. The predominant site of primary tumor is the roof of the unilateral nasal cavity in the region of the cribriform plate, or laterally above the middle turbinate. Uncommon sites of initial occurrence such as the sellar and parasellar region, nasopharynx, maxillary, and sphenoid sinuses were not found in our study [44–47]. Locally, ENB extended laterally and upwards to the paranasal sinuses (n=11; Figs. 1, 2, 5) or medially to the contralateral nasal cavity (n=4; Figs. 1, 2), and even into the cranial cavity (n=10; Figs. 1, 2, 3, 4, 5) or fossa orbitalis (n=3; Fig. 1). Furthermore, ENB can also metastasize by lymphatic and hematogenic routes. It is reported that approximately 5% of patients have cervical lymph node metastasis, with a cumulative cervical metastases rate of 25% or so [28, 29], and approximately 10–30% of patients will develop distant metastases to the central nervous system (about 20–30%), lung, liver, skin, eye, bone, and parotid [9, 33, 36, 37, 39, 48]. In our study, lymph nodes metastases (ranging from 1.0 to 3.0 cm in minimal diameter) were noticed in four patients (36%) over the parapharyngeal space, the upper cervical, and submaxillary region (Fig. 4c). In addition, the 11-year-old girl with craniofacial skin involvement (Fig. 4) underwent abdominal ultrasound examination revealing a soft-tissue lump within the right cavitas pelvis which might suggest distant metastasis to the right ovary although not pathologically confirmed. Also, a 54-year-old man's abdominal ultrasound examination demonstrated a low echo-level mass in the left lobe of the liver. This report mainly concentrates on the ten cases with direct intracranial extension and categorizes them into three types based on the depth of invasion: brain parenchyma type (5/10; Figs. 1, 2, 3), leptomeninges type (1/10; Fig. 4), and base-of-skull type (4/10; Fig. 5). The brain parenchyma type had the primary tumor extend across the cribriform plate, grow through the dura, and then infiltrate into the anterior frontal lobe. Even though the bulk of the tumor may lie intracranial, it is still attached to the cribriform plate (Fig. 3). It is reported that

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Fig. 1 a–i (Case 2) Cranio-orbital-nasal-communicating ENB in a 15-year-old boy (brain parenchyma type). MR images show a highaggressive tumor centered in the roof of the left nasal cavity penetrating into bilateral fossa orbitalis, left frontal lobe, and frontal sinus. Compared with the gray matter, the tumor parenchyma appear as hyperintensity on T2-weighted images (a–c) and FLAIR image (d), hypointensity on T1-weighted image (e). FLAIR image (d) exhibits

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the peritumoral edema more clearly, but gadolinium-enhanced T1weighted images (f–i) visualize the tumor boundary best due to significant enhancement of all involved soft tissues. Multiple cysts (arrowheads) along the intracranial tumor margin are portrayed clearly. The necrotic component (short arrows) and complicated intratumoral hemorrhage (long arrow) can be identified

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Fig. 2 a–i (Case 11) Cranio-nasal-communicating ENB in a 59-year-old male (brain parenchyma type). MR and CT images show that the tumor located high in the left nasal cavity extends through the left cribriform plate and invades the ipsilateral frontal lobe. The tumor parenchyma is hyperintense to gray matter on T2-weighted image (a) and hypointense on T1-weighted images (b, c) with remarkable enhancement on gadolinium-enhanced T1-weighted images (d–g). A cyst (short arrows)

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along the margin of the intracranial tumor is portrayed clearly. Precontrast coronal CT image (h) shows an isodensity endonasal mass with slight high density to the surrounding soft tissue. Postcontrast coronal CT image (i) shows that the tumor enhances significantly and inhomogeneously. Erosion of the ethmoid labyrinth and left cribriform plate is well demonstrated (long arrows), although the margin and cyst of the tumor can not be seen as clearly as that on MRI

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Fig. 3 a–f (Case 6) Cranio-nasal-communicating ENB in a 44-year-old male (brain parenchyma type). MR images reveal a well-defined mass with multiple intratumoral necroses (short arrows) in the right upper nasal cavity and frontal lobe. Although the bulk of the tumor lies intracranially, it is still attached to the cribriform plate (long arrows). The tumor parenchyma is hyperintense to gray matter on T2-weighted image (a) and hypointense on T1-weighted image (b) with remarkable

enhancement on gadolinium-enhanced T1-weighted images (c–e). No intratumoral cyst is observed. Photomicrograph (f) shows that the tumor consists of uniform, small, round-to-oval blue cells with coarsely granular chromatin, multiple small nucleoli, prominent nuclear membranes, and scant cytoplasm (hematoxylin–eosin, original magnification ×400)

the presence of cysts along the intracranial tumor margin [49] and intralesional calcification [50, 51] can be considered pathognomonic for ENB. In our study, marginal cysts were observed in four of five intracranial tumor masses (Figs. 1, 2) while no definite intralesional calcification was detected. The leptomeninges type was found only in one patient showing a locally lamellar enhancement lining the brain surface (Fig. 4a), which may indicate diffuse seeding of the dural and subdural spaces. The base-of-skull type was revealed in four cases, where bulging duramatral were demonstrated on MRI (Fig. 5b, c), and thinned or destroyed cribriform complex were discovered during operation. In cases in which CT scanning reveals nasal roof erosion evidence of intracranial extension (Fig. 5d), Oskouian et al. [19] recommend acquiring MR images because they provide a more sensitive assessment for unrecognized intracranial lesions.

From our experience, whether the dura is invaded or not can be determined preoperatively via carefully assessing the coronal and sagittal MR images. And the present of cerebral edema may imply the existence of intracranial extension, especially when the patient complains about either unsteadiness or headache. Due to the high aggressive behavior and recurrence rate [23, 37] of ENB, early diagnosis, accurate staging, and close follow-ups are essential for optimistic patient management [22]. In these aspects, both MR and CT scanning are helpful in providing necessary information as to the tumor location and extension and proximity to the adjacent structures. Specifically, MRI is more accurate in depicting the exact margins of intracranial and intraorbital tumor extension on account of its multiplanar display and superior tissue contrast. And CT, especially coronal CT scanning, is excellent in evaluating the encroachment of lamina papy-

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Fig. 4 a–c (Case 1) ENB in an 11-year-old girl (leptomeninges type). Postcontrast axial CT images (a–c) show a locally lamellar enhancement lining the surface of bilateral frontal lobe suggesting leptomeninges involvement. Besides, thickened craniofacial soft tissue (short arrows)

and intradermal nodules (long arrows) can be found. The enhancing nodule (1 cm in short diameter) over the left submaxillary region indicates a focally enlarged lymph node (arrowhead)

racea, cribriform plate, and anterior cranial base, thanks to its sensitivity to osseous structure. In Kadish stage C disease, it is important to perform MRI, especially gadolinium-enhanced T1-weighted MR imaging, to obtain essential additional information, particularly when walls of the bones are thinned or eroded. By and large, MRI is the imaging method of choice for demonstration of ENB, especially for identifying intracranial and intraorbital extension. And CT scanning can supplement MRI in further

depicting bony involvement. Further studies on the management and prognosis will be summarized in our next study.

Fig. 5 a–d (Case 4) ENB in a 38-year-old female (base-of-skull type). Gadolinium-enhanced T1-weighted MR images show a well-defined tumor mass within the superior and middle nasal meatus. The axial MR image (a) shows an enhancing round signal (arrowhead) in the gyrus rectus mimicking an intracranial tumor. Nevertheless, coronary (b) and sagittal (c) MR images show bulge of the dura (short arrows). Ten days later, the operation confirmed that the ethmoid plate was destroyed by the tumor and that the cerebral dura mater was exposed, but the brain parenchyma had not been encroached by then. Posttreatment sagittal CT image (d) depicts the destruction of the left ethmoid plate directly

Conclusions Three types of direct intracranial extensions by ENB can be found on CT and MRI: cranio-orbital-nasal-communicating

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ENB, cranio-nasal communicating ENB, and orbital-nasalcommunicating ENB. Although ENB exhibits no specific MR and CT characteristics, the combined use of MR and CT techniques is excellent in providing necessary information, such as the extent of tumor and the involvement of cervical lymph nodes, which are of vital importance for treatment planning and assessing. According to our study, if the images reveal upper nasal cavity-centered polypoid mass invading the paranasal sinuses, anterior cranial fossa, or the lamina erbitalis plus enlarged cervical lymph nodes, ENB should be therefore listed in the differential diagnoses, especially when the patient complains of persistent nasal obstruction, recurrent epistaxis, hyposmia, or even anosmia. Further studies are still necessary to correlate the image findings with the surgical findings of this high aggressive malignancy. Acknowledgement Conflict of interest statement of interest.

We declare that we have no conflict

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