EGFR Exon 20 Insertion Mutations in Sinonasal Squamous Cell Carcinoma

Recurrent epidermal growth factor receptor (EGFR)-activating mutations have been identified in a rare form of head and neck cancer known as sinonasal squamous cell carcinoma (SNSCC), a malignant disease with a 5-year mortality rate of ~40%. Interestingly, the majority of EGFR mutations identified in patients with primary SNSCC are exon 20 insertions (Ex20ins), which is in contrast to non-small-cell lung cancer (NSCLC), where the EGFR exon 19 deletion and L858R mutations predominate. These studies demonstrate that EGFR Ex20ins mutations are not exclusive to lung cancer as previously believed, but are also involved in driving SNSCC pathogenesis. Here we review the landscape of EGFR mutations in SNSCC, with a particular focus on SNSCC associated with inverted sinonasal papilloma (ISP), a benign epithelial neoplasm. Taking lessons from NSCLC, we also discuss potential new treatment options for ISP-associated SNSCC harbouring EGFR Ex20ins in the context of targeted therapies, drug resistance and precision cancer medicine. Moving forward, further basic and translational work is needed to delineate the biology of EGFR Ex20ins in SNSCC in order to develop more effective treatments for patients with this rare disease.

Mismatch Repair Deficiency and Somatic Mutations in Human Sinonasal Tumors

Due to limitations in local therapy approaches for sinonasal tumors, improvement in systemic therapies plays a pivotal role for prolongation of the patient’s survival. The aim of this study was to examine potential biomarkers, including deficiency in mismatch repair proteins (dMMR)/microsatellite instability (MSI-H) in sinonasal cancers and their precancerous lesions. A comprehensive analysis of 10 sinonasal cancer cell lines by whole exome sequencing, screening 174 sinonasal tumors by immunohistochemistry (IHC) for mismatch repair deficiency and next generation sequencing (NGS) of 136 tumor samples revealed a dMMR/MSI-H sinonasal squamous cell carcinoma (SNSCC) cell line based on a somatic missense mutation in MLH1 and an overall frequency of dMMR/MSI-H SNSCC of 3.2% (4/125). Targetable EGFR mutations were found in 89.3% (25/28) of inverted sinonasal papilloma (ISP) and in 60% (6/10) of ISP-associated carcinomas. While PIK3CA and EGFR mutations were not mutually exclusive, KRAS mutated tumors were an EGFR-wildtype. The effect of potential driver mutations in FGFR2, FGFR3, BRAF, HRAS, MAP2K1, PTEN, NOTCH1 and CARD11 need further investigation. Our results suggest that biomarker testing, including MMR-IHC and NGS panel analysis, should be integrated into the diagnostics of clinically aggressive ISPs and SNSCC to assess prognosis and facilitate therapeutic decisions.

Bilateral Schneiderian (sinonasal) papilloma: An uncommon rare entity

Sinonasal papilloma is a benign surface mucosal neoplasm with variable growth pattern and cytological features. It is a rare benign tumor with tendency to recur and also malignant transformation. The most common sites of inverting papillomata are lateral nasal wall and middle meatus and are usually unilateral. Rarely Bilateral disease can occur, which may be due to direct extension of the tumour, but can also occur as two distinct lesions. The etiology still remains unclear, eventhough the morphology and clinical behavior of this lesion has been well described. Here we report a case of recurrent bilateral nasal polyposis, histologically diagnosed as Inverted sinonasal papilloma, which is a rare entity.

MON-260 Sinonasal Papilloma Masquerading as a Pituitary Macroadenoma

Background: Sinonasal tumors are rare, with annual worldwide incidence of approximately 1 in 100,000, and are not commonly considered in the differential diagnosis of pituitary tumors (1). Sinonasal tumors are well known for their invasiveness, tendency to recur and association with malignancy. We present a case of sinonasal papilloma presenting as a large suprasellar mass. Clinical Case: A 61 year-old male with a past medical history including type 2 diabetes mellitus presented with chief complaints of headaches and visual disturbances over the past 6 months. Prior to admission he experienced episodes of left eye midline deviation associated with diplopia. New onset dysphagia associated with leftward tongue deviation prompted him to seek medical attention. The social history was notable for chemical exposures in his work at a hair salon; he is sexually active with his husband. He has had no sexually transmitted infections and has been vaccinated against human papilloma virus (HPV). CT of the brain showed a large sellar mass. A subsequent MRI of the pituitary demonstrated a large destructive mass centered on the clivus elevating the pituitary gland into the suprasellar cistern. The mass measured 6 cm x 4.5 cm in the axial plane with displacement without invasion of the cavernous sinuses. The mass extended anteriorly into the ethmoid sinuses and extended posteriorly into the prepontine cistern displacing the basilar artery. Pituitary hormonal analysis included a 250 mcg Cosyntropin stimulation test resulting with a random cortisol of <1.0 ug/dl rising to 17.7 ug/dl following Cosyntropin administration. Additional anterior pituitary results included FSH of 3.8 mIU/ml (1.5-14 mIU/ml), LH of 1.3 mIU/ml (1.4-7.7 mIU/ml), total testosterone of 230 ng/dl (300-700 ng/dl), and prolactin 11.1 ng/ml (2.6-13 ng/ml). Ophthalmology was consulted for visual field testing which proved normal, however a partial left cranial nerve VI palsy was noted likely secondary to cavernous sinus involvement. A biopsy of the sellar mass was obtained by bedside nasal endoscopy. The initial biopsy was consistent with a non-dysplastic, inverted sinonasal papilloma with negative HPV and P16 serologies. The patient underwent resection of the pituitary mass, with surgical pathology showing superficially invasive squamous cell carcinoma arising from sinonasal papilloma. Conclusion: This is one of the very few cases reported in the literature of a sinonasal papilloma masquerading as a pituitary mass. Sinonasal papilloma should be considered when evaluating large destructive suprasellar tumors. Although a benign tumor, the local aggressiveness of sinonasal papilloma and the potential to give rise to squamous cell carcinoma highlights the significance of identifying this lesion.