xRead - Nasal Obstruction (September 2024) Full Articles

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2 Histopathology Non-ITAC morphologically displays neither features of intestinal-type nor salivary-type adenocarcinoma. The his togenesis and the origin of low-grade non-ITAC are still debated. Two sites of origin of non-ITAC are proposed: the surface epithelium or the submucosal glands. 1176,1180,1181 Low-grade non-ITACs exhibit typically an exophytic or papillary growth and have tubulo-glandular, papillary, and microcystic patterns. Most of the low-grade non-ITACs are considerably less pleomorphic than ITACs. The glands are closely packed with minimal stroma and no basal layer. They are composed of cuboidal to columnar cells with only focal mild atypia. PNI and necrosis are typi cally not present. 1171,1172 This is in contrast to high-grade non-ITACs that are histologically very heterogeneous on both the architectural and cytological levels. Common fea tures of high-grade non-ITAC are cellular pleomorphism, brisk mitotic activity, necrosis, and infiltrating growth. 1171 These features are currently the most distinguishing char acteristics between high-grade and low-grade non-ITAC. However, it must be emphasized that definitive crite ria are lacking. 1156,1182 Indeed, low-grade and high-grade are diagnosed according to mitoses, necrosis, and cell pleomorphism, but no clear definitions are given in the literature. 3 IHC and molecular profiling Low-grade non-ITACs have a high expression of CK7, exhibit a focal expression of S100, DOG1, and SOX10, and can be positive for MUC1, MUC4, and MUC5ac. 1180,1183–1186 SOX-10 and DOG-1 immunoreactivity have been noted in a subset, suggesting seromucinous differentiation. 1180 Typ ically there is no expression of CK20, CDX2, MUC2, and MUC6. 1187 Due to the lack of basal cells in low-grade non ITAC, there is an absence of p63 or 34BE12 staining. 1172 Diffuse expression of CK7 is seen in 43% of high-grade non-ITACs. 1175 Rare cases express seromucinous mark ers (SOX-10, DOG1). 1180 p16 positivity has been described in the few cases associated with high-risk HPV. 1175 The absence of SATB2 in non-ITAC is able to differentiate ITAC from non-ITAC with a high specificity. 1181 A second molec ular marker differentiating non-ITAC from ITAC is OTX type 1 gene where OTX1 mRNA was identified only in non-ITAC. 1188,1189 At the time of writing, no significant data regarding molecular profiling have been published

on high-grade non-ITAC. Table XXII.B.1 summarizes the above studies and findings.

4 Renal cell-like adenocarcinoma RCLADs are rare, low-grade, malignant tumors, histologi cally composed by glandular and follicular areas in various proportion. These tumors present a female-to-male ratio of 2:1, with a wide range of age of presentation. Most tumors arise in the nasal cavity and symptoms are usually nonspecific (e.g., epistaxis, nasal obstruction). 1190 From a histological standpoint, neoplastic cells are uniform, cuboidal to polyhedral, with abundant clear to eosinophilic cytoplasm. 1191 Mitoses are rare, while necrosis and PNI are absent. There is a strong positivity for CK7, EMA, SOX10, and S100. There is absent CAIX and PAX8 immunoreac tivity. Seromucinous gland markers (SOX10 and S100) are present, and these features are shared with most cases of low-grade non-ITAC, thus justifying the inclusion of this tumor in the non-ITAC group. Typically, on MRI, these tumors enhance avidly, like renal cell carcinoma. 1192 Definitive diagnosis always requires the exclusion of a renal clear cell carcinoma, clinically and/or radiologically. 5 Role of surgery No standardized treatment or well-established guidelines concerning sinonasal non-ITAC are available throughout the literature. Endoscopic transnasal resection, especially when negative postoperative margins can be achieved, remains the treatment of choice. When it follows an opti mal preoperative imaging protocol and is carried out by an experienced surgical team, it can significantly reduce length of hospitalization. 261 Treatment modalities includ ing surgery have been associated with higher survival rates, whether followed by adjuvant RT or not. 53 Open and endoscopic approaches should not be con sidered as divergent, since regardless of the approach, negative resection margins are their common goal. Extrap olated data from studies that do not discriminate between ITAC and non-ITAC patients suggest that there is no statis tically significant difference between endoscopic and open surgical approaches in OS. 1158 CFR is indicated when endo scopic transnasal resection cannot provide adequate access to the tumor circumference; however, it may be associated with increased morbidity. 174