Isolated primary maxillary sinus esthesioneuroblastoma presenting as idiopathic syndrome of inappropriate antidiuretic hormone

Abstract

Esthesioneuroblastoma is an uncommon tumour, and isolated primary involvement of the maxillary sinus is exceedingly rare. Esthesioneuroblastoma has infrequently been reported as a source of paraneoplastic ectopic hormone production. We report a case of isolated primary maxillary esthesioneuroblastoma, presenting as idiopathic syndrome of inappropriate antidiuretic hormone (SIADH). A 17-year-old girl presented with symptoms consistent with SIADH and no sino-nasal symptoms. MRI to exclude pituitary tumour revealed an isolated lesion of the right maxillary sinus. Biopsy demonstrated esthesioneuroblastoma. The lesion was removed endoscopically as a single en bloc specimen. Following resection, the sodium level returned to normal. This is only the third report in the literature of a primary maxillary esthesioneuroblastoma presenting as SIADH.

Background

Esthesioneuroblastoma is a rare malignancy, thought to originate from the neuroepithelium of the upper nasal vault.¹ Approximately 1000 cases of this neuroectodermal tumour have been reported since it was first described in 1924.

Ectopic primary presentation outside the region of the cribriform plate is exceedingly rare, with only 11 cases being reported in the literature.^{2 3} There have been four reported cases thought to originate in the maxillary sinus.^{2 4}

Esthesioneuroblastoma may rarely be associated with paraneoplastic syndromes, including ectopic hormone production. Eighteen cases of the syndrome of inappropriate anti-diuretic hormone (SIADH) associated with esthesioneuroblastoma have been reported to date.^{5 6} Most of these cases involved primary tumours located in the region of the cribriform plate.

Isolated maxillary sinus involvement, particularly when localised, calls for an alternate resection strategy.

Case presentation

We report the case of a 17-year-old woman who presented to her primary care physician with a 1 year history of lethargy, nausea and pre-syncopal symptoms. The patient had no sino-nasal symptoms, nor headaches, facial pain or parasthesia. Physical examination was unremarkable. Routine blood investigations revealed significant hyponatraemia, with a serum sodium level of 111 mmol/L. Following consultant endocrinologist review, a diagnosis of SIADH was made based on being euvolaemic, euthyroid and having normal adrenal function. Serum antidiuretic hormone (ADH) levels were not performed and were not considered necessary by the endocrinologist and accepted diagnostic criteria for the diagnosis of SIADH in this patient. She was subsequently managed with fluid intake restriction, while further investigations were undertaken.

Investigations

An MRI was performed primarily to investigate for pituitary pathology. This demonstrated a normal pituitary. However, an incidental right maxillary sinus high-signal intensity lesion was seen on contrast-enhanced T1 sequences (figure 1).

Figure 1.

Preoperative imaging. (A) T1 MRI demonstrating contrast-enhancing lesion in the right maxillary sinus; (B) CT paranasal sinuses demonstrating opacification with an area of presumed calcification (arrow).

Subsequent CT of the paranasal sinuses demonstrated a soft tissue density lesion within the right maxillary sinus with areas of presumed calcification (figure 1). Positron emission tomography (PET) scan confirmed a high-activity lesion with no regional or distant disease.

Examination under anaesthesia demonstrated a pedunculated lesion arising from the roof of the maxillary sinus (figure 2). Endoscopic biopsy was performed. Histology demonstrated a Hyam’s grade 1 esthesioneuroblastoma (figure 3). The lesion was staged as Kadish B and Dulgerov T1N0M0.

Figure 2.

Intra-operative endoscopic view of right maxillary sinus, following medial maxillectomy. Pedunculated tumour (arrow) arising from maxillary roof. (A) View following wide middle meatal antrostomy. (B) View following modified medial maxillectomy

Figure 3.

Microscopic examination of tumour biopsy. (A) Hyam’s grade one esthesioneuroblastoma; (B) Low-power microinvasion of the orbital floor bone (arrow).

Treatment

Following presentation at a multidisciplinary head and neck oncology meeting, surgical resection with adjuvant radiotherapy was recommended.

In view of the tumour’s location, a completely endoscopic approach was used. Following complete right spheno-ethmoidectomy, middle turbinectomy and access septoplasty, a right endoscopic medial maxillectomy was performed. The lesion was excised en bloc along with partial resection of the orbital floor, medial orbital wall and surrounding mucosa of the maxillary sinus. The uninvolved periorbita was left intact, as was the infraorbital nerve. No reconstructive procedure was performed.

Histopathology confirmed a Hyam’s grade 1 esthesioneuroblastoma, as demonstrated by a proliferation of small cells arranged as nests and islands on a neurofibrillary stromal background. The tumour cells were found to contain uniform round and oval nuclei with scant cytoplasm, fine nuclear chromatin and inconspicuous nucleoli. Excision margins were clear but microinvasion of the orbital floor bone marrow was identified.

The patient’s serum sodium level subsequently returned to normal after removal of the tumour. The premorbid diagnosis SIADH was considered to have been resolved by the consulting endocrinologist as serum sodium and osmolalities and urine osmolalities returned to the normal ranges following cessation of the fluid restriction protocol.

Adjuvant intensity-modulated radiation therapy of 50 Gy was administered.

Outcome and follow-up

The patient was followed up every 6 months for the first 3 years, then yearly thereafter. At each follow-up visit, thorough flexible nasendoscopic examination of the patent sinus cavities and MRI was performed to assess for recurrence. The patient remains disease-free at 7 years postoperatively. No postoperative morbidity, such as hypoglobus, has been experienced by the patient.

Discussion

Esthesioneuroblastoma is a rare condition. Primary maxillary involvement is exceptionally rare. The tumour’s origin is thought to be neuroectodermal, in particular from neuroepithelial elements of the olfactory placode.⁷

Olfactory neuroepithelium is primarily found at the cribriform plate. Primary maxillary sinus esthesioneuroblastoma is therefore thought to develop within ectopic olfactory tissue, formed during embryological development.⁸

Neuroendocrine tumours, including esthesioneuroblastoma, may cause paraneoplastic syndromes through the ectopic secretion of hormones such as ADH. Primary presentation with paraneoplastic symptoms, however, is uncommon, with only two previously reported cases of esthesioneuroblastoma of the sinuses presenting primarily as idiopathic SIADH.^{6 9}

In Rasool et al’s case,⁶ a 28-year-old patient presented with non-specific sinonasal symptoms of nasal congestion, postnasal discharge and headache associated with a low serum sodium and high urine osmolality. Despite oral sodium chloride tablets and water restriction, SIADH persisted. As a result, a CT and PET scan was performed, confirming a lesion in the maxillary sinus, which was confirmed to be an aesthesioneuroblastoma. In a similar manner to this case, SIADH resolved within 24 hours postoperatively. Jiang et al ⁹ also describe a maxillary sinus aesthesioneuroblastoma, presenting primarily with symptoms from SIADH, with lethargy, aphasia and ataxia. However, only near-complete removal of the mass was able to be performed, and resolution of SIADH occurred at a later stage, approximately 2 weeks postoperatively.

In view of the typical site of origin, surgical management of esthesioneuroblastoma generally involves cranio-facial resection through an open approach. This is typically performed through a lateral rhinotomy incision (with or without a Weber-Ferguson extension), craniotomy and appropriate skull base reconstruction. The endoscopic approach has recently been described as an alternative.

Indications for endoscopic resection have been defined as tumours limited to the nose and paranasal sinuses without deep infiltration of the orbit and pterygopalatine fossa and without any involvement of the posterior wall of the frontal sinus.¹⁰

Esthesioneuroblastoma arising within the maxillary sinus requires an alternative resection strategy. Options include open resection (lateral rhinotomy or mid-face degloving approach) or endoscopic resection. In this 17-year-old girl, the isolated site of origin represented the ideal scenario for an endoscopic approach, resulting in no visible scar, no facial parasthesia and reduced morbidity.

Learning points.

• Esthesioneuroblastomas are a rare sinonasal neuroendocrine malignancy thought to arise from neuroepithelium.

• Like other neuroendocrine malignancies, esthesioneuroblastoma may cause paraneoplastic syndromes such as syndrome of inappropriate antidiuretic hormone (SIADH).

• In cases where patients present with SIADH with no obvious cause, a differential diagnosis of an indolent neuroendocrine tumour should be considered.