Sinonasal Undifferentiated Carcinoma

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Article initiated by:

Ellen Ingram, John Thompson, MD

All contributors:

Ellen Ingram, Nagham Al-Zubidi, MD, Michael T Yen, MD, Joseph Giacometti, MD, John Thompson, MD

Assigned editor:

Joseph Giacometti, MD, Noor Laylani, MD

Review:

Assigned status Up to Date

 by Noor Laylani, MD on November 26, 2024.

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Disease Entity

Disease

Sinonasal undifferentiated carcinoma (SNUC) is an extremely rare and highly aggressive malignant neoplasm of the nasal cavity and/or paranasal sinuses. It was first described in 1986. It often presents as a large neoplasm (> 4 cm) at an advanced stage with a poor prognosis. The lesion grows rapidly and invades nearby structures, often resulting in bony destruction. Symptoms can include nasal obstruction, epistaxis, headache, facial pain, visual impairment, proptosis, and cranial nerve palsies. SNUC is clinicopathologically distinctive from other tumors but is difficult to study due to its low incidence, which is estimated to be 0.02 per 100,000.

Etiology

While its histogenesis is uncertain, SNUC is believed to originate from ectodermally-derived Schneiderian epithelium. SNUC was histologically defined by Frierson et. al to be without squamous or glandular differentiation. However, a proposed expansion of the definition includes tumors with focal squamous differentiation so long as the lesion presents clinically as SNUC, and most cells are undifferentiated and pleomorphic.

In a Swedish survey, SNUC comprised 5.8% of sinonasal tumors. The most common areas of origin appear to be the nasal cavity and the ethmoid and maxillary sinuses.

Epidemiology

In a study by Chambers et al. with 318 cases of SNUC in the United States, the majority of patients were male (62%) and identified as white (82.7%). Patients most frequently presented in their fifth decade of life. The age-adjusted incidence rate was estimated to be 0.02 per 100,000. There are no clear risk factors.

Diagnosis

Signs and Symptoms

SNUC commonly presents as nasal obstruction, epistaxis, headache, and facial pain; however, visual impairment, proptosis, and cranial nerve palsies can also occur. Rapid progression of symptoms over weeks to months is characteristic. The neoplasm typically presents with locally extensive disease involving the orbital and/or cranial bones; the lesion may also extend intracranially.

Visual impairment is generally from compression of the intra-orbital optic nerve; however, there has been a report of extension of the tumor through the anterior cranial fossa with compression of the optic tracts.

Clinical diagnosis

Diagnosis is often delayed until disease has reached an advanced stage. The delay is multifactorial, but early benign presentation and unimpeded growth within the sinus cavities are potential contributors.

The Kadish staging is commonly used in this disease. It was originally described for olfactory neuroblastoma in 1976. Group A involves tumor confined to the nasal cavity, B involves the nasal cavity and the paranasal sinuses, and C has tumor spread beyond these structures. A modified stage D has either cervical lymph node or distant metastasis. Higher Kadish stage has been associated with a poorer prognosis.

Diagnostic procedures

Radiography typically shows a locoregionally advanced lesion invading nearby cranial bones, such as those that make up the orbit. Other adjacent compartments and structures can be involved, and intracranial extension is possible. Phillips et al. first described the MR (Table 1) and CT imaging findings. Imaging alone is not enough to differentiate most sinonasal tumors.

CT imaging generally shows non-calcified masses with sinus obstruction. Adjacent bony destruction or remodeling is common. Non-contrast CT shows soft tissue attenuation, and contrast imaging shows variable enhancement.

Table 1. MR imaging sequence findings for sinonasal undifferentiated carcinoma.

Imaging Sequence	Findings
T1 without contrast	Homogeneous mass, isointense to skeletal muscle
T2	Hyperintense to skeletal muscle
DWI	Hyperintense to skeletal muscle
T1 with contrast	Heterogeneous enhancement

In-depth pathologic descriptions can be found in a 2005 review by Ejaz et al. and is summarized as follows. SNUC typically is a large, fungating tumor with poorly defined margins. Light microscopy shows hypercellular proliferation and various growth patterns with extensive necrosis. Most cells must, by definition, be undifferentiated and pleomorphic. Thus, immunohistochemistry (IHC) is important for diagnosis. SNUC stains positively for cytokeratin (CK) 7, CK8, and CK9 and is diffusely reactive to pankeratins; however, SNUC does not stain positively for CK4, CK5/CK6, or CK14. Other IHC markers demonstrate variable results.

Differential diagnosis

•Squamous cell carcinoma

•Olfactory neuroblastoma

•Small-cell undifferentiated neuroendocrine carcinoma

•Lymphoepithelial carcinoma of the sinonasal tract

•Mucosal malignant melanoma

•Hematolymphoid malignancies

•Rhabdomyosarcoma

Management

General treatment and prognosis

SNUC typically carries a poor prognosis, as it most often presents at an advanced stage. Different combinations of chemotherapy, radiotherapy, and surgical resection have been used and there is not a universal treatment strategy. The following is an analysis of recent retrospective studies.

A study performed by Khan et al. with 460 patients found an overall 5-year survival of 42.2%. Surgical resection combined with adjuvant chemoradiotherapy increased 5-year survival relative to chemoradiotherapy alone (55.8% versus 42.6%, respectively). Negative margins at time of surgery further increased the rate of survival (75.3%). However, patients with late-stage tumors displayed no difference in survival between the two treatment groups. The study suggested surgical resection be part of the treatment plan when negative margins are deemed feasible. All patients who underwent surgery and found to have positive margins were dead by year 5.

Gamez et al., in a 40-patient series, found triple modal treatment of radiation, chemotherapy, and surgical resection to have a 5-year survival of 51% versus 38% in those who underwent different management. Patients who underwent intensity-modulated radiotherapy (IMRT), an advanced form of 3-D conformal radiotherapy, as opposed to other radiotherapy, had increased survival (59% versus 16%), as did those who received radiation doses ≥ 60 Gy to the primary site (73% versus 23%). They found that only patients who underwent non-IMRT radiation treatments developed retinal or optic neuropathy toxicity (5.0% overall).

De Bonnecaze et al. also found IMRT to be superior to conventional radiotherapy for 2-year recurrence free survival (73.8% versus 39.7%) in a study of 54 patients. Patients who underwent induction chemotherapy also had improved survival rates (73.2% versus 40%). Interestingly, neither patients who had skull base involvement nor those with orbital invasion had worse survival than those who did not. A separate study by Kuo et al., however, did not find an improved survival with induction versus adjuvant chemotherapy.

Metastatic disease was a poor prognostic indicator in the Khan study. 60.2% of patients with known staging presented with advanced tumors (American Joint Committee on Cancer [AJCC] stage 3 or 4), and the overall 5-year survival rate was 42.2%. However, patients with metastatic disease had a 5-year survival rate of 18.6%.