xRead - Nasal Obstruction (September 2024) Full Articles

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ICAR SINONASAL TUMORS

distant metastatic disease. 1146 With such a surveillance protocol, earlier detection of recurrences increases the pos sibility to cure patients who experience relapses. 1144,1154 Globally, the recurrence rate after definitive treatment ranges from 17.6% to 49.6%. 1155 The largest cohort stud ies on sinonasal ITAC have found that this cancer tends to recur mainly at the primary site (12%–16%), which is generally treatable by means of revision surgery and/or stereotactic radiosurgery. Regional recurrences to neck nodes are rare (1%), while distant metastases can occur in a nonnegligible proportion of cases (6%–10%) with limited possibility to cure patients despite using different protocols of chemotherapy and/or immunotherapy. 1146 Oncologic outcomes are impacted by several factors, including patient characteristics, stage at presentation, and biological features of the tumor. Age > 54 years; cer tain histology subtypes (mucinous signet-ring vs. solid or mucinous alveolar goblet vs. papillary, colonic, or mixed); positive surgical margins; and advanced pT clas sification at presentation with invasion of the lateral or posterior wall of the sphenoid sinus, orbit, dura, and brain have been identified as negative prognostic factors. 104,293,1155,1156 High proliferation index and poor grade of differentiation are significantly associated with worse prognosis. 104,293,1144,1151,1155,1156 In the largest Euro pean published series, 5-year OS, DSS, and DFS are 72.7% (67.3%–78.5%), 80.0% (75.1%–85.2%), and 73.2% (68.1%– 78.6%), respectively. 293,1155,1157 Further improvements in survival rates might be obtained only by deciphering the genetic profile and the molecular landscape of such a rare cancer, in order to bet ter stratify patients according to prognosis and discover potential new drug targets for precision medicine. 1158,1159 Data available to date show that there is a low incidence of EGFR , K-RAS , and BRAF mutations and a high rate of increase in the number of EGFR copies. This genetic fingerprint seems to support the potential for anti- EGFR drugs. 1145,1154 Current evidence for use of anti- EGFR drugs is limited, but several clinical trials are ongoing for patients with metastatic disease. 1157,1160 Similarly, the high MET mutation rate (64%) suggests a possible role for the MET signaling pathway in the oncogenesis of ITAC and sup ports the possible use of MET inhibitors as an alternative option. 1161 Moreover, ITACs with HRAS mutation have a worse prognosis and might benefit from administration of inhibitors of the MAPK / ERK pathway, possibly in com bination with cyclin-dependent kinase-4/6 inhibitors. 1162 Limited evidence based on in vitro studies is currently available in this regard and further studies will be needed to explore the real benefit of these drugs in the clinical setting.

C Nonintestinal-type adenocarcinoma Non-ITACs are nonsalivary adenocarcinomas of the sinonasal area. The WHO has defined non-ITAC as an adenocarcinoma that arises in the sinonasal tract and does not show features of salivary gland neoplasia and does not have an intestinal phenotype—essentially a diagnosis of exclusion. 17,1167 Nonintestinal-type ITACs are further classified into low-grade and high-grade non-ITACs. Low-grade non-ITACs must be classified separately from other nonsalivary adenocarcinomas because of their favorable prognosis. Low-grade non-ITAC was described more than 30 years ago, and in the litera ture several synonyms have been used such as terminal tubulus adenocarcinoma, sinonasal tract seromucous adenocarcinoma, and sinonasal tubulopapillary low-grade adenocarcinoma. 1168–1170 Rare cases may histologically resemble metastatic renal carcinoma and these cases are designated as sinonasal renal cell-like adenocarcinoma (RCLAD). 1171 As a matter of fact, under the umbrella of non-ITAC several different histotypes are included. Some reports also make the association between low grade non-ITAC and REAH leading to controversy in the dividing line between reactive glandular lesions and adenocarcinomas. 1172 In one study, 33% of low-grade tubular sinonasal adenocarcinomas were found in asso ciation with REAHs. 1173 Similarly, high-grade non-ITAC probably does not represent a single distinct entity but is rather a collection of several different adenocarcinoma types. 1171 factors In low-grade non-ITAC, males and females are equally affected. 1174 The average age at diagnosis is 48 years but with a wide range from childhood until elderly. 1172,1175 Patients with high-grade adenocarcinoma are more likely to be older and male than those with low-grade tumors. 1176,1177 Low-grade non-ITACs have a predilec tion for the nasal cavity (38.2%), but also occur in the maxillary (30.5%) and ethmoid sinuses (18.9%). 1172,1178 In high-grade non-ITAC, approximately one third involve the nasal cavity only and often these tumors present at advanced stages, so it is not possible to identify a clear site of origin. 1175 In contrast to ITAC, there are no established risk factors for the development of low grade and high-grade non-ITAC. 1172 Only rarely have high-grade non-ITACs been associated with high-risk HPV. 1179 1 Clinical presentation, epidemiology, risk