Olfactory neuroblastoma associated with extensive “in situ” lesion and aberrant glandular and rhabdomyosarcomatous differentiation

Abstract

A case of olfactory neuroblastoma (ONB) associated with extensive intraepithelial neoplastic proliferation, evidenced by an "in situ" lesion, in the overlying olfactory epithelium and aberrant glandular and rhabdomyosarcomatous differentiation is reported. The tumor was a polypoid lesion that involved the upper nasal cavity and ethmoid sinus of a 63-year-old woman and consisted of an ONB surrounded by and mixed with a proliferative lesion of rhabdomyoblastic cells, consistent with an embryonal rhabdomyosarcoma. A few small foci of tubular glands with mucus-producing cells were also observed. In the olfactory epithelium covering the polypoid lesion, a nested or band-like arrangement of primitive-appearing small cells was found, and the tumor cells were immunoreactive for epithelial cell adhesion molecule (detected with Ber-EP4) and low-molecular weight cytokeratin (detected with CAM5.2) but not for synaptophysin or calretinin. The intraepithelial lesion was contiguous with the subepithelial cell nests of ONB and appeared to invade the subjacent stroma and show transition to ONB, and some tumor cell nests of ONB also contained small aggregates of similar primitiveappearing cells. The intraepithelial growth was considered to represent a preinvasive precursor lesion of ONB. Previous descriptions of an "in situ" lesion in ONB are limited.The aberrant glandular and rhabdomyosarcomatous differentiation noted in this case is also an exceptionally rare phenomenon of ONB.

Sinonasal Tumors With Neuroepithelial Differentiation (Olfactory Carcinoma)

“…Nevertheless, 48% of patients developed rapidly progressive disease, and, in limited follow-up, 28% died of disease. These clinical characteristics also closely parallel those previously reported in similar tumors under assorted names 12,13,24,26–40. Of course, this aggressive behavior is not unexpected given the high histologic grade of most of these tumors and by itself does not confirm the presence of a unique category or differentiate these neuroepithelial neoplasms from other high-grade sinonasal tumor types.…”

“…The majority of cases in this series displayed several key histologic and immunohistochemical characteristics: (1) a mix of nested, lobulated, and solid architecture, (2) overt neural differentiation in the form of rosette formation, neurofibrillary stroma, and occasional ganglion-like cells, (3) cytologically high-grade neuroendocrine cells with enlarged and hyperchromatic nuclei, (4) intermixed complex, often ciliated glands with eosinophilic cytoplasm, (5) nonfocal pancytokeratin expression that is strongest in the glandular component, ( 6) at least focal positivity for neuroendocrine markers, and (7) variable S100 protein-positive sustentacular cells. Although previous reports of tumors with overlapping features of ONB and epithelial differentiation were described using a diverse range of names, 12,13,24,[26][27][28][29][30][31][32][33][34][35][36][37][38][39][40] rereview of histologic descriptions and photomicrographs of these published cases suggests that most also share similar features to those in our series regardless of original neuroepithelial differentiation does comprise a recognizable histologic and immunohistochemical pattern in the sinonasal tract. Moreover, although this phenotype has never been systematically characterized in the literature, the consistent findings across a large number of cases in this series suggest that neuroepithelial differentiation is a recurrent phenomenon worthy of formal recognition rather than a rare aberration.…”

“…These clinical characteristics also closely parallel those previously reported in similar tumors under assorted names. 12,13,24,[26][27][28][29][30][31][32][33][34][35][36][37][38][39][40] Of course, this aggressive behavior is not unexpected given the high histologic grade of most of these tumors and by itself does not confirm the presence of a unique category or differentiate these neuroepithelial neoplasms from other high-grade sinonasal tumor types. However, these findings do confirm that these neuroepithelial neoplasms have a recurrent clinical as well as histologic phenotype.…”

“…The name olfactory carcinoma has previously been proposed for such tumors to reflect their overlapping neuroepithelial elements. 24,25 However, the lack of any meaningful consensus regarding the nature of these tumors is reflected in a plethora of alternative designations, including ONB with divergent epithelial differentiation, 13,[26][27][28][29] mixed ONB and carcinoma, [30][31][32][33] olfactory neuroepithelioma, 12,[34][35][36][37] mixedlineage ONB, 24 and blastomatous variant of high-grade sinonasal adenocarcinoma. 38 This taxonomic hodgepodge is almost entirely informed by isolated case reports or small series.…”