A 62‐Year‐Old Female With an Intranasal Mass Extending into the Lamina Cribrosa

Clinical History

A 62‐year‐old female patient presented with constricted nasal breathing on the right side, disorder of smell and anosmia for the past six months. She had no epistaxis, rhinorrhea or loss of sensitivity in the face. Three months before presentation she suffered from a cold with swelling of the right eyelid that improved under conservative therapy. Physical examination revealed a glazed, bleeding tumor occupying the complete right nasal cavity and right nasopharynx and extending to the opposite site (Figure 1A).

Figure 1.

 

CT showed a tumor of the right sinuses with destruction of the right Lamina papyracea and the posterior wall of the right frontal sinus. MRT revealed a not clearly demarcated process of 5 × 5 × 4 cm of the right main nasal cavity that was of intermediate density on T1 weighted (Figure 1B) and inhomogeneous hyperintensity on T2 weighted images (Figure 1C). The process infiltrated the lamina cribrosa, right sphenoidal sinus, both frontal and ethmoidal sinuses causing dislocation of the right medial orbital wall but without infiltration of structures of the orbit. The process showed a close relationship to frontal central nervous system structures with potential infiltration of the meninges (Figure 1B).

To obtain a diagnosis a rhinoscopy was performed and a reddish, partly soft, partly firm piece of tissue measuring 1.3 × 0.8 × 0.3 cm was sent to the Department of Neuropathology. Two weeks later tumor resection via a combined bifrontal transcranial skull base and endonasal approach was performed and multiple small tissue fragments measuring in total more than 8 × 6 × 2 cm were sent for pathological evaluation.

Microscopic Pathology

Rhinoscopy biopsy

Paraffin sections showed a cellular tumor forming compact nests surrounded by fibrous tissue containing leukocytes (Figure 2). The tumor cells were moderately polymorphic and had a scant eosinophilic cytoplasm. Many nuclei contained prominent nucleoli (Figure 3A) and occasional mitotic figures and numerous apoptotic cells were seen. Immunohistochemistry was positive for NCAM (CD56, Figure 3B) and synaptophysin but negative for chromogranin. Some tumor cells expressed cytokeratin and weakly S100 protein (Figure 3C). No expression of these markers was observed in most tumor cells and surrounding S100‐positive sustentacular cells could not be identified (Figure 3C). The Ki‐67 labeling index was focally more than 30% (Figure 3D). The specimen also included some local connective tissue and glands that appeared inconspicuous.

Figure 2.

  

Figure 3.

   

Tumor resection

Light microscopy showed a cellular, lobulated tumor with intervening connective tissue identical to that observed in the initial sample. In addition the specimens contained local mucosa and glands. Comparable to the material from the first procedure, most glands had a regular architecture (Figure 4, right half). However, some glands had an atypical configuration but still discernible glandular structures and an intact appearing basal lamina (Figure 4, left half, and Figure 5, arrows). Here, the epithelium was multi‐layered and cells had enlarged nuclei and prominent nucleoli resembling the tumor cells (Figures 5 and 6, arrows). In contrast to the normal appearing glandular cells (Figure 7, asterisks), the atypical cells expressed NCAM (Figure 7, arrows) but not cytokeratin.

Figure 4.

    

Figure 5.

   

Figure 6.

   

Figure 7.

    

Diagnosis

Sinonasal undifferentiated carcinoma (SNUC).

Discussion

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 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, 6, 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 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.

Abstract

Malignant tumors with neuroendocrine differentiation of the nasal cavity include neuroendocrine carcinoma, small cell undifferentiated carcinoma, olfactory neuroblastoma (esthesioneuroblastoma), and sinonasal undifferentiated carcinoma (SNUC). The rarity of these tumors and overlapping clinical, histological and immunohistochemical findings make the correct diagnosis difficult. However accurate diagnosis is critical for therapy and the outcome differs significantly between these entities. Here we describe the case of a 62‐year‐old woman with an intranasal tumor extending into the adjacent anatomical compartments and with infiltration of the meninges. The suspected preoperative diagnosis was olfactory neuroblastoma. Histological and immunohistochemical analysis showed a lobulated tumor with neuroendocrine differentiation and we ultimately diagnosed the process as a SNUC. In this report, we discuss the differential diagnosis at hand and present histological findings found in the specimen indicating that the process originated from local glands present in the nasal mucosa.