Sinonasal undifferentiated carcinoma (SNUC).
Two aspects make this case of significant interest. Firstly, the differential diagnosis of tumors like the one presented here often poses a challenge to the (neuro-)pathologist. This is because it includes several entities that can display neuroendocrine differentiation (9): neuroendocrine carcinoma (NEC) including the small cell undifferentiated carcinoma (SCUNC), olfactory neuroblastoma (ON, esthesioneuroblastoma), and sinonasal undifferentiated carcinoma (SNUC). Secondly, the second specimen contained local glands with intermingled glands of atypical architecture providing an indication to the origin of the tumor at hand. It might also help to establish the origin of SNUCs which still remains uncertain (5, 7).
Malignant tumors of the nasal cavity and sinuses are rare and are most often squamous cell carcinomas and adenocarcinomas (2). Tumors with neuroendocrine differentiation are exceptions and include NEC, ON, and SNUC. Depending on the degree of differentiation the three entities can share similar histological features including a lobular architecture, nuclear polymorphism, necrosis and neuroendocrine differentiation with expression of synaptophysin, chromogranin, neuron specific enolase (NSE) and NCAM (CD56). In the head and neck NECs are uncommon with SCUNC being the most frequent (1, 3). In SCUNCs cells are small, polymorph and contain hyperchromatic nuclei without prominent nucleoli and scant cytoplasm. Areas of squamous cell differentiation and rarely gland like structures or rosettes may be present. In addition to neuroendocrine markers tumor cells variably express cytokeratins and S100 protein. The ON arises in the superior nasal cavity and peak incidences in young adults and in later adult life are observed (4). Lobulated pattern and Homer Wright rosettes characteristic for low-grade ONs are absent in higher-grade tumors (Hyams °III and °IV). Importantly, some authors doubt the existence of Hyams °III and °IV ONs and classify these tumor as SNUCs (5-7). A defining feature of ONs is the presence of S100-positive sustentacular cells surrounding nests of tumor cells (4). The SNUC is a high-grade tumor that like the NEC or ON may grow in lobules, ribbons or sheets (3, 5). Unlike the other two entities it lacks by definition specific growth patterns such as glandular structures or rosettes. The cytoplasm of tumor cells may be scant and cell borders are discernible. Large nuclei with prominent nucleoli are often observed. On the whole, the differential diagnosis between these tumors requires the careful examination of histological and immunohistochemical features. In our case, the presence of large nuclei with prominent nucleoli, absence of growth patterns, rosettes and sustentacular cells led us to classify the tumor as a SNUC. This diagnosis was further confirmed by the German reference center for brain tumors in Düsseldorf.
The histogenesis of SNUC is unclear. However, the presence of atypically configured glands next to inconspicuous glands in the case presented here might give an indication as to the origin of these tumors. The atypical glands still had a discernible glandular architecture, a basal lamina which appeared intact and cells that were morphologically identical to cells found in other areas of the tumor. In contrast to the normal glandular cells, the atypical cells exhibited signs of neuroendocrine differentiation such as expression of NCAM (CD56). Together, these features indicate a tumor in statu nascendi and argue against an infiltration or dissemination of the SNUC into local structures. This is supported by the observation that distant metastasis of SNUCs at time of presentation is uncommon (8). In our opinion it is more likely that the atypical glands represent the origin of the tumor at hand. This is in line with previous reports suggesting that the SNUC might originate from cells of the sinonasal mucosa (3, 5).
In summary, the presented case highlights the difficult differential diagnosis of nasal tumors with neuroendocrine differentiation but also supports the assumption that the SNUC originates from resident cells of the sinonasal mucosa.
Contributed by Markus J. Hofer MD, Jochen Rohlfs MD, Afshin Teymoortash MD, Axel Pagenstecher MD