Journal of Otology & RhinologyISSN: 2324-8785

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Case Report, J Otol Rhinol Vol: 2 Issue: 4

Maxillary Sinus Olfactory Neuroblastoma presenting as a Schwartz-Bartter Syndrome

Rafaela Veloso-Teles1*, Søren Daugaard2, Henrik Bredahl-Sørensen3 and Christian von Buchwald3
1Department of Otorhinolaryngology-Head and Neck Surgery, Alto Ave Hospital Center, Guimarães, Portugal
2Department of Pathology, Rigshospitalet - Copenhagen University Hospital, Copenhagen, Denmark
3Department of Otorhinolaryngology-Head and Neck Surgery, Rigshospitalet-Copenhagen University Hospital, Copenhagen, Denmark
Corresponding author : Rafaela Veloso-Teles
Centro Hospitalar do Alto Ave, Rua dos Cutileiros, 4835-044 Creixomil, Guimarães, Portugal
E-mail: [email protected]
Received: August 26, 2013 Accepted: October 22, 2013 Published: October 28, 2013
Citation: Veloso-Teles R, Daugaard S, Bredahl-Sørensen H, von Buchwald C (2013) Maxillary Sinus Olfactory Neuroblastoma presenting as a Schwartz-Bartter Syndrome. J Otol Rhinol 2:4. doi:10.4172/2324-8785.1000137

Abstract

Maxillary Sinus Olfactory Neuroblastoma presenting as a Schwartz-Bartter Syndrome

Background: Olfactory Neuroblastoma, also known as Esthesioneuroblastoma, is a rare neuroectodermal malignant tumour, which is believed to have its origin in the olfactory epithelium. It usually presents as a mass in the roof of the nasal cavity. On rare occasions, an association between these tumours and paraneoplastic syndromes has been reported.

Methods: We present an atypical case and a review of the literature about the etiology, pathology, clinical manifestations, treatment options and prognosis of these tumours.

Keywords: Olfactory neuroblastoma; Esthesioneuroblastoma; Maxillary sinus; Olfactory epithelium; Schwartz-Bartter syndrome; Syndrome of inappropriate antidiuretic hormone secretion (SIADH)

Keywords

Olfactory neuroblastoma; Esthesioneuroblastoma; Maxillary sinus; Olfactory epithelium; Schwartz-Bartter syndrome; Syndrome of inappropriate antidiuretic hormone secretion (SIADH)

Introduction

Olfactory Neuroblastoma (ONB) is a rare malignant neuroectodermal tumour, which represents 3% of all intranasal tumours and is believed to originate from olfactory epithelium. It commonly arises in the superior part of the nasal cavity, close to the cribriform plate [1,2]. It was first described in 1924 by Berger and Luc [3], and since then more than 1000 cases have been reported [4]. In one of the largest series of ONBs published [5], the annual incidence was estimated to be 0.4 cases per million inhabitants. It follows a bimodal distribution - peaks from 10 to 30 and 50 to 70 years of age - with a slightly male predominance and no known risk factors [6]. The diagnosis is often delayed because many of the initial symptoms are nonspecific, such as nasal obstruction, epistaxis, rhinorrhoea and anosmia. It is locally aggressive and frequently invades paranasal sinuses, the orbit and the skull base, with potential for regional and distant metastases [7].
We describe a case of an ONB presenting with atypical clinical features: a low-grade tumour with primary location in the maxillary sinus. It first manifested as a syndrome of inappropriate antidiuretic hormone secretion (SIADH), also known as Schwartz-Bartter Syndrome, 17 years before the final diagnosis. This is the fourth case of an isolated maxillary Olfactory Neuroblastoma published in the medical English literature and the first ectopic ONB of the maxillary sinus manifesting as a SIADH.

Case Report

In 2010, a 36-year-old man was referred to the Department of Otorhinolaryngology of Rigshospitalet, because of a right maxillary opacification in an Orthopantomography (Figure 1A) performed because of self-limited right upper jaw pain. He denied nasal obstruction, epistaxis, rhinorrhoea, facial pain or hyposmia.
Figure 1: (A) Orthopantomography showing a right maxillary sinus opacification; (B) CT showing a calcified tumour in the right maxillary sinus with extension to the middle meatus, (C) Sagittal CT plane cut showing that the tumor did not reach the level of the cribriform plate.
The patient had been consulting an endocrinologist since 2009 due to asthenia, muscle cramps and multiple bone fractures, symptoms that began when he was 21 years old. The work-up study revealed osteoporosis in the DEXA scan, and the laboratory investigation disclosed plasma hyposmolality, hyponatraemia ([Na+] of 130 mmol/L), hyperkalaemia ([K+] of 4.7 mmol/l), and hypocalcaemia ([Ca2+] of 1.16 mmol/L). There were also abnormal urinalysis results showing high urinary sodium and calcium concentration. Determination of serum cortisol, thyroid and renal function were all within normal levels, whereas the plasma vasopressin was inappropriately high, > 30 pmol/l (<1.51 pmol/l). The endocrinologist diagnosed a SIADH and attributed it to excessive alcohol intake. The patient was placed on supplemental calcium, bisphosphonates and vitamin D, with normalization of calcium levels but persistent hyponatraemia.
In the physical examination, the otolaryngologist noticed diminished air patency in the right nasal cavity with a deviated septum and a prominent middle right turbinate. A Computerized Tomography (CT) of the paranasal sinuses showed opacification of the right maxillary sinus with a partially calcified tumour obliterating the osteomeatal complex and extending to the middle meatus, resembling an osteoma (Figure 1B and 1C). He was proposed for a combined endoscopic sinus surgery (ESS) and Caldwell-Luc procedure. For uncertain reasons the surgery was not scheduled.
In 2012, the patient was re-referred to the ENT department by the endocrinologist. Symptoms and objective findings were similar to the previously described ones. A new CT scan showed the partially calcified tumour located in the right maxillary sinus, without visible growth. The patient was submitted to a Caldwell-Luc procedure combined with ESS to obtain a histological diagnosis and remove the tumor. Histopathological examination demonstrated small round cells with uniform oval hyperchromatic nuclei and a very low mitotic count, in a background of fibrillar neuropil matrix and multiple calcifications (Figure 2A and 2B). Imunohistochemical staining was positive for synaptophysin, chromogranin A and calretinin and negative for cytokeratines. Electron microscopy showed dense secretory granules in the cytoplasm (Figure 2D and 2E). The final pathological diagnosis was consistent with an Olfactory Neuroblastoma.
Figure 2: (A) Densely packed sheet of tumour cells and focal calcifications (haematoxylin-eosin stain, original magnification x100); (B) Small round tumour cells with scant cytoplasm, uniform hyperchromatic nuclei and low mitotic count (HE, x400); (C) Dense secretory granules (arrowheads) in the cytoplasm of the tumor cells (Electronic Microscopy, x22000); (D) Immunohistochemical staining for neurofilament showing fibrillary neuropil matrix (x400), (E) Immunohistochemical staining for Chromogranin A (x400), and (F) Nests of submucosal tumor cells exhibiting strong cytoplasmic staining for Vasopressin (x100).
Postoperative magnetic resonance (MR) with enhanced gadolinium contrast showed tumour remnants in the right maxillary sinus with extension to the middle meatus (Figure 3), but no intracranial or skull base involvement, and no cervical metastases.
Figure 3: MR showing persistence of the tumour after the initial surgery in the right maxillary sinus/ middle right meatus.
One month after the first surgery, the patient was submitted to an endonasal endoscopic medial maxillectomy including the lacrimal bone, middle and inferior turbinate, combined with a revision of the Caldwell-Luc procedure. The remnants of the tumour and maxillary mucosa were removed with sacrifice of the infraorbital nerve, which was invaded by the tumour, and the maxillary bone walls were drilled.
After reviewing the past medical history, we speculated that the SIADH was related to the ONB as a paraneoplastic syndrome. After surgical intervention, biochemical tests revealed normal plasma osmolality, sodium and calcium levels, and a large drop in vasopressin values to 5.8 pmol/l. To confirm our hypothesis, tumour sections were incubated with a rabbit polyclonal antibody against vasopressin (Millipore catalog no. AB1565). The tumour tissue stained positive for this hormone (Figure 2F). Postoperative CT scan demonstrated signs of a complete resection of the medial wall and a defect in the anterior wall of the right maxillary sinus, according to the performed surgery (Figure 4). At an oncological multidisciplinary meeting, it was decided to proceed with adjuvant radiotherapy.
Figure 4: Post-surgery CT scan, following revision surgery, demonstrating complete resection of the medial wall of right maxillary sinus and defect in its anterior wall.

Discussion

In this case the ONB had its primary location in the maxillary sinus; there are few reports about ONBs arising from ectopic regions such as sphenoid sinus, sella turcica, inferior nasal cavity, nasopharynx, maxillary sinus and pterygopalatine fossa [1,7-9]. Since its first description in 1924, the primary site of origin is still debated. The most accepted theory [10] refers to the basal cells of the olfactory mucosa, embryologically derived from neural crest cells. One explanation for the existence of ectopic ONBs is the presence of ectopic olfactory cell rests; another is the possible origin from a separate neuroendocrine cell population as there is a report of a patient with Kallmann’s syndrome (in whom olfactory cells are absent) with a maxillary ONB [10]. The vomeronasal organ of Jacobson, sphenopalatine ganglion, ectodermal olphactory placode, autonomic ganglia in the nasal mucosa, have all been mentioned in the literature as other potential sites of origin [1].
Our patient did not have any rhinologic symptoms, but exhibited other signs such as asthenia and cramps for more than 17 years, due to the electrolytic imbalance caused by SIADH. There have been few reports of ONBs associated with paraneoplastic syndromes, reflecting the secretory potentials of its cells of origin, namely 14 cases of SIADH and nine case reports of ectopic Cushing Syndrome [11-13].
CT and MR scans are helpful for tumour staging and for planning its management. On CT imaging, it appears as a contrast-enhancing mass, occasionally with calcified or cystic areas, with adjacent bone erosion or expansion [14]. On MR, this tumour usually demonstrates intermediate signal intensity with tendency to iso- or hypointense signal in T1 and iso- or hyperintense signal in T2 weighted images [15].
The Kadish classification has traditionally been used for staging Olfactory Neuroblastoma since its proposal in 1976 [16]. However, this staging system does not anticipate an isolated ONB of the maxillary sinus. Another staging method was proposed by Dulguerov et al. (2001), a classification based in TNM system that resolved many of the shortcomings of the previous staging system [17].
We reviewed the English literature and found only three previous cases of ONBs in the maxillary sinus (Table 1). All cases together included three males and one female, with ages ranging from 14 to 38 years. In two cases the patients presented with pain, periorbital and/ or face swelling and epistaxis; in the third case the patient presented with long term anosmia and delayed puberty, confirmed with MR to be a Kallmann’s Syndrome (absence of olfactory bulbs), with an ONB being only incidentally discovered. Using the Dulguerov and Calcaterra’s classification they were all staged as a T1N0M0. Thus, this ectopic localization seems to present in an earlier stage than the other ONBs. Interestingly, a similar review of ectopic ONBs of the sellar region has been recently published [18].
Table 1: Clinical data from four patients with maxillary Olfactory Neuroblastoma. NER (no evidence of recurrence); OMC (osteomeatal complex); RT (radiotherapy).
Histopathology with immunohistochemical staining is essential in establishing the diagnosis of ONBs. Differential diagnoses include: sinonasal undifferentiated carcinoma (SNUC), sinonasal neuroendocrine carcinoma (SNEC), metastatic small cell lung carcinoma, malignant melanoma, lymphoma, rhabdomyosarcoma and extramedullary plasmocytoma [13,19]. Another, mainly clinical, differential diagnosis is the “Brown Tumour” which is a focal bony lesion that results from excess parathyroid hormone [20]. Olfactory Neuroblastomas consist of uniform small round-to-oval cells with minimal cellular pleomorphism, coarsely granular chromatin, small or indistinct nucleoli and scanty cytoplasm, set in fibrillar neuropil and with Homer-Wright pseudorosettes in about 50% of cases, or more rarely Flexner-Wintersteiner rosettes. It can also contain calcifications. In electron microscopy, dense-core cytoplasmic granules can be identified. Immunohistochemically, these tumours can be positive for various tumor markers including neuron specific enolase, calretinin, S-100, synaptophysin and chromogranin [2,14]. In our case, immunostaining was positive for calretinin, synaptophysin and chromogramin, and negative for cytokeratines (CK 5/6, P63, EMA), thus eliminating the above-mentioned differential diagnoses.
Hyams [8] proposed a histological grading in order to predict survival, based on degree of differentiation, cellular anaplasia and mitotic rate, with grades from 1 through 4, those showing less differentiation receiving higher grades [21]. Five-year survival rate for low-grade tumours (Hyams grade I and II), as our case, is approximately 70%, and approximately 40% for high grade (III and IV) Olfactory Neuroblastoma [21].
Surgery is the mainstay of treatment, and the advent of craniofacial resection in 1970’s has dramatically improved survival rates [7]. Optimal therapy for Olfactory Neuroblastoma has traditionally been considered surgery combined with adjuvant radiotherapy, resulting in better local control and survival rates than surgery or radiotherapy alone [22]. Recently, favourable results have been reported using endoscopic surgical techniques with benefits that include improved quality of life, decreased short-term morbidity, and fewer long-term side effects [4]. Chemotherapy is reserved for recurrent, inoperable or widely metastatic disease [7].
Long-term follow-up is crucial for diagnosing and treating any early recurrence. Recurrent disease in ONB has been reported to occur even after 10 years [5]. A cost-effective method in the follow-up of this patient might be the periodic measurement of plasma sodium levels.

Conclusion

Despite its rarity, ONB should be considered in ectopic locations beyond the olfactory cleft and included in the differential diagnosis of maxillary tumours.
Its presentation as a paraneoplastic syndrome is rare but both physicians and ENT surgeons must be aware of this possibility. Besides, the causes of SIADH and Cushing Syndrome are quite varied and ONB should always be excluded.
This case is to our knowledge the first report of an ectopic Olfactory Neuroblastoma of the maxillary sinus associated with SIADH.

Bullet Point Summary

• Olfactory Neuroblastomas (ONB) can occur in ectopic locations.
• ONBs can manifest as paraneoplastic syndromes: Schwartz- Bartter Syndrome / SIADH or Cushing Syndrome.
• Published evidence indicates that ectopic ONBs of maxillary sinus tend to occur in younger people and present in earlier stages.
• This case is the first to describe an ONB of the maxillary sinus associated with SIADH.

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