Answer: SMARCB1 (INI-1) deficient sinonasal carcinoma

Histology: The tumor consisted of expanding nests of cells in the sinonasal mucosa. No areas of dysplasia or carcinoma in situ were seen in the surface epithelium. The tumor was highly infiltrative, with areas of perineural and bone invasion. Tumor necrosis was evident, and the mitotic rate was high. The tumor nuclei were uniformly round, with open chromatin a single prominent nucleolus. The tumor cells contained abundant eosinophilic cytoplasm that was often eccentrically located, imparting a “rhabdoid” appearance to the cells. There were no areas of clear-cut squamous or glandular differentiation in the tumor. Immunohistochemical studies showed that the tumor was diffusely positive for pan-cytokeratin and p63, and negative for synaptophysin, chromogranin, NUT-1, actin, desmin, and S-100. Finally, SMARCB1 (INI-1) immunostaining revealed a complete lack of expression in the tumor cells; staining in the background stromal and inflammatory cells was intact. Taken together, the findings were consistent with what has recently been described as SMARCB1 (INI-1)-deficient carcinoma of the sinonasal tract.

Discussion: SMARCB1 (INI-1) is a tumor suppressor gene located on chromosome 22q11.2. Its gene product is ubiquitously expressed in nuclei of all normal tissues. SMARCB1 gene inactivation has been implicated in the pathogenesis of a diverse group of malignant neoplasms that tend to share “rhabdoid” cytomorphology. Recently, we and Agaimy, et al. independently introduced a new member of the SMARCB1 (INI-1) deficient tumor family: SMARCB1 (INI-1) deficient sinonasal carcinoma.

Twelve SMARCB1 (INI-1) deficient sinonasal carcinomas have been described to date. These carcinomas tend to grow as epithelioid nests in the sinonasal submucosa, architecturally mimicking the much more common squamous cell carcinoma. These tumors are usually highly infiltrative, with frequent bone invasion. At the cellular level, each SMARCB1 (INI-1) deficient sinonasal carcinoma contained some cells that are recognizable as rhabdoid or plasmacytoid, but the number of these cells is variable. In some cases, like the one presented here, they predominate and are very noticeable, while in other examples they are singly dispersed among more basaloid tumor cells. While the tumor cell cytoplasm is variable in quality, the tumor nuclei of these carcinomas tend to be uniformly round with open chromatin and a prominent nucleolus. Nuclear pleomorphism is not typical. None of the SMARCB1 (INI-1) deficient sinonasal carcinomas has shown overt squamous or glandular differentiation, but most of the cases we reported exhibited psuedovascular spaces that in one case led to a diagnosis of non-intestinal adenocarcinoma.

The consistent immunophenotypic features of SMARCB1 (INI-1) deficient carcinoma are strong, diffuse cytokeratin expression along with a complete absence of SMARCB1 (INI-1) immunostaining. Five of 11 cases were focally positive for synaptophysin, 4 of 9 were positive for p63 and p40 (with diffuse expression in 3 of 4 positive cases). In the 8 cases were SMARCB1 (INI-1) FISH was successfully performed, 6 showed SMARCB1 copy number alterations. Five cases showed homozygous deletion of SMARCB1, while an additional case showed a heterozygous deletion pattern. ).

SMARCB1 (INI-1) deficient sinonasal carcinomas present with non-specific signs and symptoms like pain, eye symptoms, and obstruction. Many cases have shown aggressive behavior in the form of local invasion into the brain and/or skull base. of 11 patients experienced local recurrence, 5 of 11 had regional or distant metastasis, and 5 of 11 patients up have died of their disease.

Reference(s):
– Bishop, et al. AJSP 2014; 38:1282-9.
– Agaimy, et al. AJSP 2014; 38: 1274-81.