Molecular Biomarkers in Sinonasal Cancers: New Frontiers in Diagnosis and Treatment

Purpose of Review: Sinonasal tumors are rare and heterogeneous diseases which pose challenges in diagnosis and treatment. Despite significant progress made in surgical, oncological, and radiotherapy fields, their prognosis still remains poor. Therefore, alternative strategies should be studied in order to refine diagnosis and improve patient care. Recent Findings: In recent years, in-depth molecular studies have identified new biological markers, such as genetic abnormalities and epigenetic variations, which have allowed to refine diagnosis and predict prognosis. As a consequence, new histological entities have been described and specific subgroup stratifications within the well-known histotypes have been made possible. These discoveries have expanded indications for immunotherapy and targeted therapies in order to reduce tumor spread, thus representing a valuable implementation of standard treatments. Summary: Recent findings in molecular biology have paved the way for better understanding and managing such rare and aggressive tumors. Although further efforts need to be made in this direction, expectations are promising

Sinonasal mucosal melanoma: Molecular profile and therapeutic implications from a series of 32 cases

BACKGROUND: Primary sinonasal mucosal melanomas are aggressive tumors with a poor clinical control by current treatments, raising the urgent need of novel strategies. METHODS: By fluorescence in situ hybridization (FISH), direct sequencing, and immunohistochemistry, we investigate the spectrum of molecular abnormalities in a cohort of 32 cases of primary sinonasal mucosal melanomas. RESULTS: We found that all primary sinonasal mucosal melanomas lack BRAF V600E mutation; in addition, they are characterized by somatic mutations of NRAS (22%) and KIT (12.5%), together with amplification of RREB1 (100%) and loss of MYB (76%). The large majority of cases showed KIT protein expression (96.9%). Among tumor suppressor genes, primary sinonasal mucosal melanomas showed loss of PTEN (48.1%) and p16/INK4a (55.2%). All tested cases showed expression of pAkt and pErk, suggesting a combined activation of PI3K/Akt and RAS-mitogen-activated protein kinase (MAPK) pathways. CONCLUSIONS: This molecular fingerprint strongly argues against the clinical efficacy of BRAF-inhibitors, but could candidate primary sinonasal mucosal melanomas to therapeutic strategies targeting RAS and KIT mutations or inhibiting PI3K-Akt-mTOR pathway

A 3-dimensional transnasal endoscopic journey through the paranasal sinuses and adjacent skull base: a practical and surgery-oriented perspective

An endoscopic approach through the transnasal corridor is currently the treatment of choice in the management of benign sinonasal tumors, cerebrospinal fluid leaks, and pituitary lesions. Moreover, this approach can be considered a valid option in the management of selected sinonasal malignancies extending to the skull base, midline meningiomas, parasellar lesions such as craniopharyngioma and Rathke cleft cyst, and clival lesions such as chordoma and ecchordosis. Over the past decade, strict cooperation between otorhinolaryngologists and neurosurgeons and acquired surgical skills, together with high-definition cameras, dedicated instrumentation, and navigation systems, have made it possible to broaden the indications of endoscopic surgery. Despite these improvements, depth perception, as provided by the use of a microscope, was still lacking with this technology. The aim of the present project is to reveal new perspectives in the endoscopic perception of the sinonasal complex and skull base thanks to 3-dimensional endoscopes, which are well suited to access and explore the endonasal corridor. In the anatomic dissection herein, this innovative device came across with sophisticated and long-established fresh cadaver preparation provided by one of the most prestigious universities of Europe. The final product is a 3-dimensional journey starting from the nasal cavity, reaching the anterior, middle, and posterior cranial fossae, passing through the ethmoidal complex, paranasal sinuses, and skull base. Anatomic landmarks, critical areas, and tips and tricks to safely dissect delicate anatomic structures are addressed through audio comments, figures, and their captions

Typical and Atypical Symptoms of Petrous Apex Cholesterol Granuloma: Association with Radiological Findings

Objective: Petrous apex cholesterol granuloma (PACG) is a lesion that can give rise to different symptoms, and correlations with etiopathology are ambiguous. The aim of this study is to analyze the association between PACG symptoms and radiological findings at presentation, in order to establish a reproduceable pre-operative radiological evaluation and guide the surgical indication. Methods: PACG patients were collected in two tertiary care hospitals. All cases underwent CT/MRI to evaluate the cyst localization and erosion of surrounding structures. Typical and atypical symptoms were then analyzed and compared to radiologic findings established in accordance with the literature. Results: Twenty-nine patients were recruited; the most common symptoms were headache (69%), diplopia (20.7%) and fainting (24.1%), an atypical clinical manifestation related to jugular tubercle involvement. Significant associations between symptoms and radiologic findings were noted in terms of headache and temporal lobe compression (p = 0.04), fainting and jugular tubercle erosion (p < 0.001), vestibular symptoms and internal auditory canal erosion (p = 0.02), facial paresthesia and Meckel’s cave compression (p = 0.03), diplopia and Dorello canal involvement (p = 0.001), and tinnitus and cochlear basal turn erosion (p < 0.001). All patients were treated via an endoscopic–endonasal approach, in which extension was tailored to each case. At a median follow-up of 46 months, 93.1% of patients experienced resolution of symptoms. Conclusions: This clinico-radiological series demonstrates associations between symptoms and anatomical subsites involved with PACG. Hence, it may guide the surgeon at the time of surgical decision, since it asserts that typical and atypical symptoms are actually related to PACG

Surgical approaches for possible positions of an olfactory implant to stimulate the olfactory bulb

Introduction: Current scientific developments seem to allow for an "olfactory implant"in analogy to cochlear implants. However, the position and surgical approaches for electrical stimulation of the olfactory system are unclear. Methods: In a human anatomic cadaver study, we investigated different endoscopic approaches to electrically stimulate the olfactory bulb (OB) based on the following considerations: (1) the stimulating electrode should be close to the OB. (2) The surgical procedure should be as non-invasive and safe as possible and (3) as easy as possible for an experienced ENT surgeon. Results: In summary, the endoscopic intracranial positioning of the electrode via a widened ostium of the fila olfactoria or a frontal sinus surgery like a Draf IIb procedure is a good option in terms of patients' risk, degree of difficulty for ENT surgeons, and position to the OB. Endoscopic intranasal positioning appeared to be the best option in terms of patient risk and the degree of difficulty for ENT surgeons. Although a bigger approach to the OB using a drill and the combined intranasal endoscopic and external approach enabled a close placement of the electrode to the OB, they do not seem relevant in practice due to their higher invasiveness. Conclusion: The study suggested that an intranasal positioning of a stimulating electrode is possible, with placements beneath the cribriform plate, extra- or intracranially, applying elegant surgical techniques with low or medium risk to the patient and a close placement to OB