Skull base low-grade non-intestinal adenocarcinoma in a paediatric patient*

Background: Non-intestinal adenocarcinomas of the sinonasal tract are uncommon neoplasms in adults, and particularly rare in the paediatric population. Case presentation: A 10-year-old male presented to the Paediatric Otolaryngology clinic with symptoms of recurrent epistaxis, persistent clear nasal discharge, and a left-sided polypoidal swelling causing nasal obstruction. An endoscopic biopsy of the polyp under general anaesthesia found a mass arising from the anterior olfactory cleft, and the histology report described the mass as a low-grade non-intestinal adenocarcinoma. CT and MRI of the sinuses post-biopsy demonstrated no bony structure infiltration. The patient underwent a further endoscopic operation for definitive excision of the nasal mass, and the histology findings confirmed a complete resection of the tumour. Conclusion: This case demonstrates the first case of a primary low-grade non-intestinal adenocarcinoma originating from the olfactory cleft.


Introduction
Sinonasal tumours present similarly in the adult and paediatric population, with unilateral symptoms of nasal blockage, anosmia, and blood-stained nasal discharge or epistaxis. Subsequent extension into adjacent structures may present with symptoms of proptosis, diplopia, epiphora, trismus, pain, or paraesthesia.
Patients who present with these symptoms should be assessed with endoscopy, imaging, and biopsy (1,2) . Paediatric patients tend to present with rhabdomyosarcomas of the nasal cavity (3,4) , whilst adults more commonly present with squamous cell carcinomas (1) .
Primary adenocarcinomas of the sinonasal tract are a heterogeneous group of malignancies representing 10%-20% of all primary malignant neoplasms of the nasal cavity and paranasal sinuses in adults (5) . They can be classified as salivary or non-salivary, and further divided from non-salivary adenocarcinomas to intestinal-type adenocarcinomas (ITACs) and non-intestinal-type adenocarcinomas (non-ITACs) (6) .
Adenocarcinomas of the sinonasal cavity have previously been reported in the adult population (7) , but never for a paediatric patient. This case reports describes the first low-grade non-ITAC originating from the olfactory cleft in a child. infection. The left nasal mass was found to be arising from the nasal septum, medial to the middle turbinate, and adjacent to the olfactory mucosa. A limited biopsy was taken as the atypical appearance of the lump suggested a neoplasm and it is known that incomplete resection of nasal tumours leads to worse outcomes (1) .

Case presentation
The specimen was submitted for histology, and was described as polypoid mucosa covered by respiratory epithelium, infiltrated by an unencapsulated neoplasm with a lobular architecture forming tubular ductal glands. The glands were arranged in a 'back-to-back' pattern, with minimal intervening stroma in the majority of the tumour. The tumour cells were uniformly roundto-ovoid, with minimal pleomorphism. There was no evidence of communication of the tumour with the surface epithelium and no surface invagination.

Discussion
Adenocarcinomas of the sinonasal tract are defined by their histopathological features and immunohistochemical staining.
Sinonasal salivary-type adenocarcinomas arise from the seromucinous glands and surface epithelium of the nasal cavity and paranasal sinuses. They are, therefore, histologically well-defined and resemble major and minor salivary glands.
ITACs have histological and immunohistochemical features of normal intestinal mucosa, or features of intestinal neoplasms.

Skull base low-grade non-ITAC paediatrics
Non-ITACs can be further divided into low-grade or high-grade types. Low-grade non-ITACs present histopathologically in an exophytic papillary and tubular, or glandular pattern. They commonly occur in the nasal cavity, ethmoid and maxillary sinus (8) , are more common in individuals above the age of 50 years, and not associated with sex or race (12) .
High-grade non-ITACS display diverse morphologic patterns such as blastomatous, apocrine, oncocytic, mucinous, poorly differentiated or undifferentiated (13) . They more frequently affect male patients with a mean age around 60 years and a wide range (8) .
Although nasal adenocarcinomas are occasionally seen in the adult population, there are no documented cases of a nasal non-ITAC that present in childhood. A literature search on PubMed with key words and terms (paediatric, sinonasal, nasopharyngeal, nasopharynx, non-intestinal, adenocarcinoma) found no preceding case.
Histopathology examination of the initial specimen showed a consistent adjoining cellular arrangement and strong positive staining for CK7, indicative of non-ITAC, but also variably positive staining for CK20 suggestive of an ITAC. S-100 staining of the specimen was also positive though this is reported to be absent in ITACs and present to varying degrees in most non-ITAC and all sinonasal seromucinous hamartomas (14) .
The latter differential diagnosis was suggested as there is no clear criterion to differentiate this from a low-grade non-ITAC (7,14) . The final diagnosis favoured a low-grade non-ITAC due to the histopathological pattern, and the positive CK20 and S-100 staining results. The specimen was reviewed by two other pathologists who concurred with the diagnosis. This is there-fore the first reported paediatric case of a low grade non-ITAC of the olfactory cleft. This case demonstrates the potential of a non-ITAC to arise in the nasal cavity in paediatric patients. This should therefore be a consideration in the differential diagnosis of a sinonasal mass.
Sinonasal adenocarcinomas are described on CT as a soft tissue mass with areas of calcification representing the mucin content within the mass. CT provides detailed bony images that can identify tumour erosion through surrounding bony structures that high-grade adenocarcinomas often present with. MRI has greater contrast resolution for margins, with tumour intensity being related to mucin content, cellularity, and the presence of haemorrhage. Unilateral adenocarcinomas arising from the olfactory cleft demonstrate enlargement of the olfactory cleft and contralateral bulging of the nasal septum, whilst ethmoid sinus adenocarcinomas may present with extension to the skull base and intracranially to the frontal lobes (1,2) . In this case, staging CT and MRI was performed after the initial biopsy, and did not show any bony erosion or extension into the skull base.
The treatment standard for sinonasal low-grade non-ITACs is complete surgical removal (2) , with optional postoperative radiotherapy (11,15) . Non-ITACs are usually localised and prognosis is therefore favourable in comparison to ITACs that tend to be aggressive malignancies (6) . This case was managed with an initial biopsy and complete excision of the tumour with no adjuvant treatment. Biopsy for tumour staging should deliberately leave residual tumour as an indicator to ensure a complete subsequent excision, as poorer patient outcomes occur with incomplete resection (1) . Post-operative radiotherapy was not considered as this was a low-grade tumour with no skull base extension (5) , and due to the complications of ocular and lacrimal toxicity that would have arisen (16,17) .

Conclusion
This case describes the first paediatric presentation of a low grade non-ITAC of the olfactory cleft, and demonstrates the potential of a non-ITAC to arise in the nasal cavity in paediatric patients. We therefore suggest consideration of this diagnosis in a paediatric patient who presents similarly in future.

Authorship contribution
KM is the main author who is responsible for conception, drafting and revision of the article. CT has contributed in the conception and revision of the article. PS has approved the final version of the article.

Funding
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Ethics approval and consent to participate
Written informed consent for publication of their clinical details and clinical images has been obtained from the parent of the patient.

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