Case Report HRAS and PIK3CA Mutations in Sinonasal Oncocytoma: Case Report
by Sánchez-Fernández P1*, Riobello C2, Cubides MC1, Cabal VN2, Suárez- Fernández L2, Vivanco B3, Hermsen M2, Llorente JL1
1Department of Otolaryngology, Hospital Universitario Central de Asturias, 33011 Oviedo, Spain.
2Department of Head and Neck Oncology, Instituto de Investigación Sanitaria del Principado de Asturias, 33011 Oviedo, Spain.
3Department Pathology, Hospital Universitario Central de Asturias, 33011 Oviedo, Spain.
*Corresponding Author: Paula Sánchez Fernández, Department of Otolaryngology, Hospital Universitario Central de Asturias, 33011 Oviedo, Spain.
Received Date: 22 July 2023
Accepted Date: 26 July 2023
Published Date: 28 July 2023
Citation: P Sánchez-Fernández, C Riobello, MC Cubides, VN Cabal, L Suárez-Fernández, et al. (2023) HRAS and PIK3CA Mutations in Sinonasal Oncocytoma: Case Report. Ann Case Report 8: 1381. https://doi.org/10.29011/2574-7754.101381
Abstract
Purpose: Oncocytomas are benign or malignant neoplasms that can occur in any organ, but in the paranasal sinuses they are rare and are usually malignant. Histologically, they are characterized by the accumulation of defective mitochondria due to mitochondrial dysfunction and an imbalance between mitochondrial biogenesis and mitophagy. Mainly alterations occur in Mitochondrial DNA (mtDNA), without the role of other oncogenes or tumor suppressor genes in the maintenance of the oncocytic phenotype being clearly known. Methods: We present a case of a 65-year-old man with a benign sinonasal oncocytoma that presented as a slow-growing sinonasal tumor that affected the lacrimal sac. Complete surgical removal of the tumor was performed without recurrence after four years of follow-up. We performed NGS by analyzing a panel of 131 genes from cancerrelated tumors and matching germline DNA (blood sample) to search for somatic mutations and copy number abnormalities. Results: NGS revealed two non-synonymous point somatic changes affecting HRAS (p.Gln61Arg) in 48% of the tumor reads and PIK3CA (p.Glu545Lys) in 36%. HRAS is involved in MAPK and AMPK signaling and PIK3CA mutation is related to activation of PI3K-AKT-mTOR pathway signaling. Both pathways have been related to mitochondrial biogenesis and mitophagy and they are the most frequently altered in oncocytomas of other locations. We found no significant copy number gains or losses. Conclusion: Gene mutations in a case of benign sinonasal oncocytoma are similar to oncocytomas in other locations and may be used to better understand its pathogenesis and promote the development of future therapies.
Keywords: Benign Oncocytoma; Gene Mutations; Next Generation Sequencing; Signaling Pathways; Sinonasal Oncocytoma
Introduction
Oncocytomas are rare neoplasms characterized by epithelial cells with abundant cytoplasmic eosinophilic granules (oncocytes) because of the accumulation of defective mitochondria [1,2]. These tumors are also called oxyphilic, oncocytic, eosinophilic, or, in the case of thyroid tumors, Hürthle cell tumors in the literature. They can arise in any organ, but they exhibit a particularly high incidence in endocrine organs. Thyroid, parathyroid, adrenal gland, pituitary gland, kidney, salivary gland (mainly parotid), breast and lung are the organs in which oncocytomas are most frequently observed. In the head and neck area, they represent less than 1% of epithelial tumors of the major salivary glands. More infrequently they may arise from the minor salivary glands and from the Schneider respiratory epithelium. This results in oncocytic tumors in the paranasal sinuses, nasal cavity, and nasolacrimal duct [3,4].
The peculiar phenotype of oncocytomas makes them a suitable and appropriate model for studies aiming to better understand the role of the mitochondria and metabolism in carcinogenesis. A full understanding of the mechanisms involved in the formation and maintenance of the oncocytic phenotype is still needed but the existence of mitochondrial dysfunction and imbalance between mitochondrial biogenesis and mitophagy is known, mainly due to alterations in mitochondrial DNA (mtDNA), and an additional contribution of oncogene/tumor suppressor gene alterations in nuclear DNA (nDNA) [5].
Oncocytomas are typically benign tumors and usually present low proliferation rates but when they arise in minor salivary glands, sinonasal cavity or thyroid they tend to be more locally invasive and have a greater malignant potential [1]. Currently, surgery is the treatment of choice for these neoplasms. Radiotherapy is not indicated because oncocytes are considered radioresistant [6]. In sinonasal oncocytomas, in general, an endoscopic approach is performed, but sometimes open or combined approaches are required to ensure complete removal. Recurrence is rare but can occur due to occult multifocality [3]. Local and/or lymph node recurrences may appear several years after surgery in patients with malignant oncocytoma [7].
We present clinical, histopathological and genetic details of a case of a sinonasal oncocytoma involving the lacrimal sac that was surgically removed using an open approach.
Case Report
A 65-year-old man presented with progressive painless enlargement of the left lacrimal tract accompanied by nasal respiratory failure and ipsilateral purulent rhinorrhea. He had no history of exposure to radiation, metals or wood or asbestos dust. The patient had already been referred to our otorhinolaryngology service 9 years before due to suspicion of a nasal tumor. However, the patient did not come to the consultations until he began with evident clinical changes.
Physical examination revealed a 3x3 cm left paranasal tumor completely occupying the left nostril and lacrimal sac with intact skin and displacing the eyeball upwards without affecting ocular mobility.
A facial Computed Tomography (CT) was performed, revealing a large mass that partially occupied the left orbit, the nasolacrimal duct, and the left nostril with an expansive appearance and bone infiltration (Figure 1: a,b,c)
Figure 1: Preoperative (a,b,c) and postoperative (d,e,f) CT images are shown in axial (a,b,d,e) and coronal (c,f) slices of the patient
An endoscopic biopsy of the nasal tumor was performed. Pathological examination showed an encapsulated lesion with nests of cells with extensive granular and eosinophilic cytoplasm, with occasional glandular lights, but no trace of atypia or lymphovascular or perineural invasion (Figure 2). Immunohistochemical staining showed that cells retained myoepithelial lining with calponin, CK34β12, and p63. Variable positivity was observed with CD10 and CK8. CK7 was focal positive. Neuroendocrine differentiation markers synaptophysin and chromogranin were negative. CDK20, CDX2, S100 and C117 were also negative, and the Ki 67 index was 5%. Also, RCC (“Renal Cell Carcinoma Marker”) was negative. The most relevant immunohistochemical results are shown in Figure 3.
Figure 2: A representative histological image of the oncocytoma with hematoxylin and eosin staining is shown. Magnification 20