xRead - Nasal Obstruction (September 2024) Full Articles

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sex in most studies. 48,1349,1417,1460–1463 Previous irradiation (e.g., for NPC) has been suggested as an important risk factor. 1464 Alos et al. described positivity for p16 in 14 of 19 SNEC cases. However, HPV DNA could not be detected, so a larger scale HPV association seems unlikely. 1465 2 Molecular profiling, histologic subtypes, and impact of grade By definition, sinonasal ScNEC and LcNEC are poorly differentiated, high-grade malignancies, with its specific histological features being identical to their more com mon pulmonary counterparts. The tumors typically show nests of uniform round cells that infiltrate surrounding tissue, with an immunohistochemical positivity for cytok eratin (e.g., CKAE1/AE3, CK8) and neuroendocrine cell markers such as synaptophysin or chromogranin, while S100 and TTF-1 are negative. 1171,1349 PNI and lymphovascu lar invasion are infrequently observed. The differentiation between LcNEC and ScNEC is mostly performed based on the variation in mean cellular sizes, but in ScNEC, the nucleoli are typically absent or inconspicuous, whereas in LcNEC, they are more irregular and prominent. 1171 LcNEC can be differentiated from SNUC as the latter shows a neuroendocrine differentiation only on an immunohis tochemical or ultrastructural level, whereas the former also features morphologic (i.e., light microscopy) charac teristics of neuroendocrine differentiation. 1171,1459 Arecent study on molecular profiling of poorly differentiated neu roendocrine carcinoma of the head and neck region (including five sinonasal ScNECs and seven sinonasal LcNECs) has revealed—for the sinonasal cases—a high Ki-67 index of > 60% in all cases, universal loss of Rb, an overexpression of p53 in 90% of cases, and an infrequent occurrence of various potentially targetable mutations. 1466 Yet, none of the sinonasal cases in the mentioned study showed a mutational burden high enough for indicating immunotherapy ( > 10 mutations/mutational burden), so a strong role for immunotherapy seems unlikely. Ulti mately, utmost care in the determination of the right histopathological diagnosis seems warranted as treatment recommendations and prognosis depend accordingly. 1467 3 Workup and staging The staging classification of the AJCC 8th edition has most commonly been used. There seem to be no spe cific imaging features with regard to LcNEC or ScNEC (such as intratumoral calcifications that can be found in olfactory neuroblastoma), so a combination of CT and MRI is advisable for local tumor assessment. 1461,1462 Felix-

median OS of 12 months and 12%–30% survival at 1–2 years for patients with SMARCB1 -deficient carcinoma. 1431,1439 The only reported outcome for SMARCA4 -deficient sinonasal carcinoma is 66% disease-related mortality (median 3 months). 1433 Treatment typically includes a combination of surgery and adjuvant RT with or without chemotherapy, although this recommendation is extrapolated from studies of SNUC. It is unknown whether SMARCB1 -deficient carci noma responds to IC similarly to SNUCs, but SMARCB1 deficient carcinoma was not explicitly excluded from the aforementioned study of IC in SNUC. 1403,1431,1440 The SWI / SNF complex and suppression of cyclin D1 transcrip tion may be future therapeutic targets. 1432,1438 C Neuroendocrine carcinoma According to the 5th edition of the WHO classification of head and neck tumors, large-cell neuroendocrine carcino mas (LcNEC) and small-cell neuroendocrine carcinomas (ScNEC, sometimes SmCC) are poorly differentiated, high grade representatives of sinonasal tumors with neuroen docrine differentiation (STND) that are of epithelial origin (sinonasal neuroendocrine carcinomas, or SNEC). 17,1459 As sinonasal ScNEC and LcNEC are rare tumors that have been only recently clearly classified, the existing litera ture that specifically addresses these entities (and that does not combine different sinonasal tumors into one group) is clearly limited. This section serves as an update to the complementary ICSB 2019 document (Section VIII.C). 5 specific risk factors Similar to other SNM, ScNEC and LcNEC usually present with nonspecific symptoms such as nasal obstruction, epis taxis, rhinorrhea, exophthalmos, and headache. 1460–1462 As ectopic hormone production (e.g., ACTH, beta-MSH, cal citonin, serotonin, or ADH) may be present in only 1% of cases, corresponding symptoms are not a reliable indica tor of disease. 1404 In an extensive retrospective study by Patel et al., the incidence of SNECs (with a large propor tion of LcNEC and ScNEC) is reported to be as low as 0.015 cases per 100.000 and shows a marked (yet nonspecific) increase in incidence over time. 48 In a smaller case series, however, Sjöstedt et al. described a 10% increase in diagno sis of SNEC over a 34-year period. 52 This finding most likely supports improved methods in diagnosis with various ancillary techniques. The mean age of the affected patients is between 49.2 and 62.5 years. 1349,1404,1417,1460,1461,1463 There seems to be a slight to marked predominance of the male 1 Clinical presentation, epidemiology, and