Tertiary Lymphoid Structures in Sinonasal Squamous Cell Carcinoma

Introduction: Sinonasal squamous cell carcinoma (SNSCC) has no reliable biomarkers for prognosis. Tertiary lymphoid structures (TLS) are ectopic lymphoid formations found in the microenvironment of tissues with chronic inflammation, and their presence/maturity level has been demonstrated to be predictive of improved survival and response to therapy in multiple cancers.

Methods: The OHSU sinonasal malignancy database was queried for diagnoses between 1996 and 2017. A random sample of 56 were selected (28 with recurrences, 28 without recurrences). Multiplex immunohistochemistry was performed on a single tissue section from each tumor with a panel of 9 markers for various cell types found within TLS. A machine-learning platform was utilized for image processing. Cytometry analysis was then performed to identify cell types based on their signal pattern. Tissue sections were then classified by level of TLS maturity based on the presence of the various components of mature TLS (T-cells, dendritic cells, high endothelial venules).

Results: Demographic data of the patients selected showed no significant differences in gender, age, or T-stage between those with recurrences and those without. Initial CD20 staining revealed that 11 tumors had no appreciable B-cell clusters. For these, a subsequent tissue section at least 12 µm away from the original section was stained for CD20. A total of 6 had B-cell clusters while 5 did not. The remainder of the staining panel was carried out for the 51 tumors with B-cell clusters. After classifying the tumors by level of TLS maturity, survival analysis was carried out. For tumors with either intermediate or mature TLS, median overall survival was 5.79 years compared with 2.38 years for those without (p = 0.055). Median disease-free survival was 5.849 years for those with intermediate or mature TLS compared with 2.38 for those without (p = 0.872).

Conclusions: TLS may be predictive of improved overall survival among patients with SNSCC, however there does not appear to be a correlation with recurrences. Further investigation is warranted.