CASE REPORT
Jonathan Irish, MD, FRCSC, Section Editor
Possible esthesioneuroblastoma metastasis to paranasal sinuses: Clinical report and literature review Lamia Buohliqa, MD1 Smita Upadhyay, MD1 Piero Nicolai, MD3 Robert Cavalieri, MD4 Ricardo L. L. Dolci, MD1 Daniel Prevedello, MD1,2 Ricardo L. Carrau, MD1,2* 1
Department of Otolaryngology–Head and Neck Surgery, Wexner Medical Center at The Ohio State University, Columbus, Ohio, 2Department of Neurosurgical Surgery, Wexner Medical Center at The Ohio State University, Columbus, Ohio, 3Department of Otolaryngology–Head and Neck Surgery, University of Brescia, Brescia, Italy, 4Department of Medical Oncology, Neuro-Oncology Division, Wexner Medical Center at The Ohio State University, Columbus, Ohio.
Accepted 17 April 2015 Published online 14 July 2015 in Wiley Online Library (wileyonlinelibrary.com). DOI 10.1002/hed.24095
ABSTRACT: Background. Local recurrence, and regional and distant metastases, respectively, develop in 30% and 15% of patients with esthesioneuroblastoma (ENB). Methods. This case report includes 3 patients with unusual recurrences of ENB in the sinonasal tract. Results. Patient 1 developed ENB in the bilateral maxillary sinuses after unilateral endoscopic resection of a left ENB followed by postoperative proton radiotherapy. Patient 2 developed ENB at the left optic-carotid recess 7 years after a craniofacial resection and postoperative radiotherapy. Patient 3 developed ENB over the left zygomatic process of the maxilla 4 years after a cranioendoscopic resection and postoperative
INTRODUCTION Esthesioneuroblastoma (ENB), also known as olfactory neuroblastoma, is a rare tumor of neural crest origin comprising 6% of sinonasal tumors.1 ENB arises from the basal layer of the olfactory epithelium in the nasal vault over the cribriform plate, upper septum, and upper surface of the superior and middle turbinates. Occasionally, ENB develops ectopically outside the distribution of the olfactory epithelium. Great efforts have been made regarding the differentiation of ENB from other neoplasms with similar histological appearance but different clinical behavior, such as neuroendocrine tumors and sinonasal undifferentiated carcinomas.2 Nonetheless, ENB may display disparate biologic activity ranging from indolent growth, with survival rates exceeding 20 years, to a highly aggressive behavior capable of rapid widespread metastases and a survival that is limited to a few months. This article presents 3 cases of ENB with recurrences at the maxillary sinuses, sphenoid sinus, and the zygomatic process of the maxilla. All these sites had not been involved by the primary
*Corresponding author: R. L. Carrau, Department of Otolaryngology–Head and Neck Surgery, Comprehensive Skull Base Surgery Program, Arthur G. James Cancer Hospital and Robert Solove Research Institute, Wexner Medical Center at The Ohio State University, Starling Loving Hall, Room B221, 320 West 10th Avenue, Columbus, OH 43210. E-mail:
[email protected];
[email protected]
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radiation therapy for ENB of the ethmoid sinuses with intracranial extension. The possibility of venous tumor emboli must be considered as a likely etiology. However, alternative explanations include the development of a second primary or potential transformation because of tumor signaling. Conclusion. We present 3 cases that may represent metastasis of ENB C 2015 Wiley Periodicals, Inc. Head Neck 38: within the sinonasal tract. V E32–E36, 2016
KEY WORDS: endoscopic endonasal approach, esthesioneuroblastoma, skull base surgery, ectopic tumor, recurrence
tumor and had been spared during the initial approach and resection. To our knowledge, the possibility of metastasis to these extracranial ectopic sites has not been reported previously.
CASE REPORT Case 1 A 56-year-old man underwent an endoscopic resection of an ENB (T2N0M0) arising at the vault of the left nasal cavity (Figure 1A). The resection included the left vertical and horizontal lamella of the cribriform plate, left fovea ethmoidalis, upper nasal septum, left middle and superior turbinates, ethmoid sinuses, lamina papyracea, and a large mid-meatal antrostomy. The ipsilateral dura, olfactory bulb, and tract were also removed. The right lateral nasal wall, including the inferior, middle, and superior turbinates, uncinate process, and ethmoid sinuses were completely spared. Histopathological analysis revealed a Hyams grade III ENB with adequate resection (ie, negative) margins. In view of the ENB extension and grade, surgery was followed by adjuvant proton radiotherapy. A routine surveillance MRI 2 years after treatment, demonstrated heterogeneously enhancing soft tissue masses in both maxillary sinuses (Figure 1B). The left maxillary mass was 3.0 3 1.6 cm. The right maxillary mass was 3.9 3 3.5 cm extending toward the right alveolar ridge, pterygopalatine fossa, right pterygomaxillary fissure, and adjacent
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FIGURE 1. Postgadolinium T1weighted MRI sequences, coronal views. (A) Left-sided esthesioneuroblastoma (ENB) (T). (B) Postoperative MRI demonstrating ENB in both maxillary sinuses. (C) ENB (T) with intracranial extension. (D) Postoperative MRI demonstrating minimal polypoid lesion at the left opticocarotid recess, corresponding to known ENB.
right masticator and buccal space. Endoscopic biopsies of the left maxillary sinus tumor via the previously performed mid-meatal antrostomy and the right antral mass via a new mid-meatal antrostomy confirmed the diagnosis of ENB. A positron emission tomography/CT scan also revealed a metastasis to the lumbar spine. The patient was referred for palliative chemotherapy.
Case 2 A 50-year-old man was diagnosed with a Hyams grade I ENB of the left nasal cavity extending to the left anterior cranial fossa (Figure 1C). He underwent a traditional craniofacial resection, including the entire cribriform plate, fovea ethmoidalis, ethmoid sinuses, laminae papyracea, superior and middle turbinates, and bilateral midmeatal antrostomies and sphenoidotomies. The dura, olfactory bulbs, and tracts were also removed. Surgery was followed by adjuvant external-beam radiotherapy. Seven years after treatment, during a nasal endoscopy investigating an episode of epistaxis, a polypoid reddish
lesion was found in the lateral opticocarotid recess of the left sphenoid sinus (Figure 1D). An MRI revealed a nonspecific polypoid soft tissue density along the lateral aspect of the left sphenoid sinus with decreased T1 and T2 signal and diffuse enhancement. A CT scan revealed no associated osseous erosion. Biopsy of the lesion confirmed a Hyams grade II ENB. Subsequently, he underwent an endoscopic excision of the lesion over the left opticocarotid recess, including drilling of the adjacent bone to remove any possible remnants. At the time of surgery, a prior sphenoidotomy (limited to the medial aspect of the sphenoid rostrum) had to be extended laterally to enable visualization of the tumor with a 08 rod-lens endoscope.
Case 3 A 68-year-old man was referred for a progressively worsening bilateral nasal obstruction associated with an expansile ethmoid lesion. MRI revealed a solid lesion involving the ethmoid sinuses and extending to the anterior cranial HEAD & NECK—DOI 10.1002/HED
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FIGURE 2. Postgadolinium T1weighted MRI sequences. Ethmoid lesion with massive intracranial and intradural extension before (A) and after (B) neoadjuvant chemotherapy. Multiple left neck lymphadenopathies at levels II to III (C; black and white arrowheads). Submucosal intraosseous nodular lesion into the posterolateral wall of the left maxillary sinus (D; white arrows).
fossa, showing moderate enhancement after gadolinium administration (Figure 2A and 2B). A biopsy was consistent with ENB Hyams grade II with a clinical staging of Kadish C. In view of the extent of the lesion, neoadjuvant chemotherapy (etoposide, ifosfamide, and cisplatin) was scheduled. An MRI after 2 cycles of chemotherapy did not show any major change in the size of the lesion. Therefore, the patient underwent a combined cranio-endoscopic resection followed by adjuvant external-beam radiotherapy to the primary site (total dose of 60 Gy in 30 fractions). After 29 months of close follow-up with clinical evaluation and MRI, a regional recurrence involving levels II to III on the left side of the neck was detected (Figure 2C). A selective neck dissection (levels II–V) was performed and histologic examination confirmed the presence of metastatic ENB in 6 lymph nodes at levels II and III (extracapsular spread at level II). The patient underwent adjuvant radiotherapy to the neck with a total dose of 54 Gy and a boost of 10 Gy at level II. Twenty-two months later (51 months after initial treatment), an MRI revealed a 15- 3 9-mm solid mass arising at the posterolateral wall and zygomatic process of the maxillary sinus on the left side (Figure 2D). A sublabial endoscopic-assisted approach facilitated the resection of the lesion, which was found within the bone. Histologic analysis of the specimen was consistent with ENB. An MRI and positron emission tomography/CT 47 months after the latter surgery (98 months after initial treatment) detected multiple recurrences, including a nodular lesion in the left infratemporal fossa (Figure 2A), a 9-mm nodule medial to the right orbital apex (Figure 2B), and bilateral E34
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temporal leptomeningeal metastases (Figure 3A–3C). Concomitant with these 3 findings, the patient was treated for a sarcoma on the right thigh (ie, surgery and adjuvant radiotherapy). In view of the complexity of the oncologic history and the patient’s age, close follow-up was recommended, although a treatment plan was established in case he would become symptomatic. One year later, the patient remains asymptomatic, and surveillance MRI showed minimal increase in size of the lesions in the brain and paranasal sinuses.
DISCUSSION ENB is a rare malignancy of neural crest origin with only about 1400 cases reported since it was first described by Berger et al3 in 1924. Its exact genesis is controversial; however, the presence of neural filaments in the tumor and its immunohistochemistry suggest an origin deriving from the basal cells of the olfactory epithelium.4 Therefore, ENB is most commonly seen in the superior nasal vault. Ectopic ENBs are extremely rare but have been previously reported arising in the maxillary sinus, sphenoid sinus, pituitary gland, lateral nasal wall, nasopharynx, and parapharyngeal space.5–10 ENB has no predilection for sex or age; however, recent studies point to a higher incidence in the fifth decade. Its clinical presentation is nonspecific and includes nasal obstruction, epistaxis, and other symptoms and signs related to its space-occupying nature; therefore, a high index of suspicion is required to diagnose these tumors.
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FIGURE 3. Postgadolinium T1-weighted MRI sequences. Nodular lesion (23 3 12 3 24 mm) in the infratemporal fossa infiltrating the temporal muscle (A; black asterisk). Nodular lesion of 9-mm medial to the right orbital apex (B; white arrows). Bilateral temporal leptomeningeal lesions (C; white arrowheads).
Contrasted CT and MRI are complementary imaging studies. MRI better demonstrates intraorbital and intracranial involvement, identifies perineural spread, and differentiates among soft tissues. ENB is usually hypointense on T1-weighted MRI, isointense or hyperintense on T2weighted, and shows enhancement with gadolinium.3,11,12 Conversely, CT better delineates bony erosion and regional nodal metastasis; thus, both imaging studies are needed in the majority of patients. Histopathological distinction of ENB from other small cell neoplasms of the nasal cavity is difficult, requiring a panel of immunohistochemical stains and, sometimes, electron microscopy. Complete surgical excision of ENB is the mainstay of treatment. Postoperative radiotherapy seems to significantly improve local control. Chemotherapeutic regimens are generally used in the induction setting before surgery or concurrently with postoperative radiation therapy. Chemotherapy as a single modality is usually reserved for palliation. Despite aggressive surgical resection and postoperative radiation therapy, 5-year survival rates according to a recent meta-analysis is about 45%; however, most large series quote survival rates around 70%.11–14 Local recurrence occurs in about 30%13–15 and regional nodal and distant recurrences develop in 15% to 20% of patients with ENB. Distant metastasis with locoregional control carries a dismal prognosis. However, salvage after local or regional recurrence is possible in 33% to 50% of patients.3,11,16 A literature search revealed not a single study with a detailed description of the pattern of local recurrence, and no mention of extracranial recurrences at sites that had not been affected by the primary tumor or initial resection. Our patients had lesions at sites, which clearly had been uninvolved when the primary tumors were first diagnosed and their recurrences were not adjacent to the area involved with the resection. Therefore, they cannot be considered as a local recurrence or as “seeding” related to the surgical resection. In patient 1, a tumor developed at the medial wall of the left maxillary sinus and one could argue that it could be the result of tumor implantation during the surgery. However, its origin was at the lower area of the wall, at an area that, although close, did not adjoin the margins of the middle meatal antrostomy. Furthermore, the tumor in the right antrum was neither adjacent to the original tumor or
to the surgical boundaries. In patient 2, the recurrence aroused in the confines of the left opticocarotid recess in the lateral wall of the sphenoid sinus, a site that was untouched at the time of the initial surgery, confirmed by the deep site of origin within the recess and the fact that the sphenoidotomy had to be expanded laterally to visualize the tumor with a 08 rod-lens endoscope (the equivalent of a microscopic or direct view used during a craniofacial resection). In addition, tumor arising 7 years after the primary tumor resection would not be consistent with a pattern after implantation of tumor during surgery. Similarly, patient 3 developed a recurrence at a site distant from the original ENB and its resection. The authors believe that these tumors may be better explained by the phenomenon of embolic metastasis, such as seen intracranially. Other alternative explanations include a possible development of a second primary (ie, “field of cancerization”) or potential transformation because of tumor signaling.
CONCLUSION Recurrence of ENB in an extracranial ectopic site is extremely rare; nonetheless, this study presents 3 cases of ectopic recurrences. The authors believe that this recurrence pattern likely corresponds to embolic phenomena, although other alternative mechanisms are possible. Unfortunately, the rarity ENB is an impediment to the understanding of its clinical behavior, and these cases raise further questions about its biology. Genetic analysis may shed some light into this matter. In addition, further studies should evaluate the presence of olfactory tissue in areas of the sinonasal tract that are generally considered ectopic sites.
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