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Background: The clinical significance of tertiary lymphoid structures (TLSs) is not well-documented in early oral tongue squamous cell carcinoma (OTSCC).Methods: A total of 310 cases of early (cT1-2N0) OTSCC were included in this multicenter study. Assessment of TLSs was conducted on hematoxylin and eosin-stained sections. TLSs were assessed both in the central part of the tumor and at the invasive front area.Results: The presence of TLSs associated with improved survival of early OTSCC as presented by Kaplan-Meier survival analyses for disease-specific survival (P = 0.01) and overall survival (P = 0.006). In multivariable analyses, which included conventional prognostic factors, the absence of TLSs associated with worse disease-specific survival with a hazard ratio (HR) of 1.96 (95% CI 1.09-3.54; P = 0.025) and poor overall survival (HR 1.66, 95% CI 1.11-2.48; P = 0.014).Conclusion: Histological evaluation of TLSs predicts survival in early OTSCC. TLSs showed superior prognostic power independent of routine WHO grading and TNM staging system. [ABSTRACT FROM AUTHOR]

Little is known about the histopathological characteristics that may differentiate early oral tongue cancer (OTSCC) between young and older patients. From a total of 311 cases diagnosed with clinically early‐stage OTSCC at 6 institutions, only 42 patients were young patients were aged ≤45 years. For comparison, 42 patients >60 years old were matched for center of management, clinical stage and gender. We compared epithelial and stromal histopathologic parameters between the two groups. Most of the parameters were similar between the two groups, although the young patients appeared to have marginally higher intensity of tumor budding, histologic risk score, infiltrative pattern of invasion and tumor‐stroma ratio. However, none of the factors showed significant difference when comparing the two groups. The histological parameters reflect mechanisms of invasive growth and tissue response to invasive growth, but not the etiological difference in OTSCC between young and older patients. Further investigations are necessary to compare the genetic background of early OTSCC in the two groups. [ABSTRACT FROM AUTHOR]

The proliferation marker, securin, is involved in the progression of many carcinomas. However, its expression in oral tongue squamous cell carcinoma (OTSCC) has not been previously studied. We examined securin expression by immunohistochemistry in OTSCC. A total of 93 cases treated for OTSCC were included in this study. Expression of securin in OTSCC was studied by immunohistochemistry of tissue microarrays (52 cases) and routine tumor sections (41 cases). Securin overexpression is significantly associated with higher tumor grade ( P = 0.03). Overexpression of securin was observed more frequently in advanced stages of OTSCC than in earlier stages but the difference was not statistically significant. These findings suggest that overexpression of securin in OTSCC may be important during progression of this cancer. No significant association was found between securin expression and the prognosis of OTSCC. [ABSTRACT FROM AUTHOR]

Background: Cell-in-cell structures (caused by cell cannibalistic activity) have been related to prognosis of many cancers. This is the first multi-institutional study to assess the prognostic impact of cell-in-cell structures in a large cohort of early oral tongue squamous cell carcinomas (OTSCC).Methods: A total of 308 cases from five Finnish University Hospitals and from the A.C. Camargo Cancer Center, São Paulo, Brazil, were included in this study. Cell-in-cell structures were evaluated on surgical postoperative sections that stained with hematoxylin and eosin staining.Results: We found that cell-in-cell structures associated with cancer-related mortality in univariable analysis with a hazard ratio (HR) of 2.99 (95%CI 1.52-5.88; P = 0.001). This association was confirmed in multivariable analysis (HR 2.22, 95%CI 1.12-4.44; P = 0.024). In addition, statistically significant associations were observed between the cell-in-cell structures and other adverse histopathologic characteristics including deep invasion (P <  0.001), high index of tumor budding (P = 0.007), worst pattern of invasion (P <  0.001), perineural invasion (P = 0.01), and stroma-rich pattern (P = 0.001).Conclusions: Our findings demonstrate a significant relationship between cell-in-cell formation and aggressive characteristics of early OTSCC. Cell-in-cell structures have a distinct impact as a novel prognostic indicator in early OTSCC and they can be easily assessed during routine pathology practice. [ABSTRACT FROM AUTHOR]

Summary: Mobile tongue squamous cell carcinoma (MTSCC) is known for its strong propensity for regional metastasis and poor patient survival despite aggressive treatment, thus calling for new and reliable markers for predicting prognosis and guiding therapeutic management. Towards this end, three classes of markers were investigated: cancer-associated fibroblasts (CAFs; α-SMA positivity) as a representative of the tumor microenvironment, maspin (mammary serine protease inhibitor) as a tumor marker likely to be modulated by factors within the tumor microenvironment, and DNA content and Ki-67 labeling index as inbuilt tumor markers in 128 cases of MTSCC using immunohistochemistry and image cytometry. Of these markers, only CAF density was independently and relatively strongly associated with elevated mortality from MTSCC. The hazard ratio in the CAF-rich type of tumor microenvironment was 4.85 (95% CI 1.41–16.6, versus the CAF-poor) when adjusted by proportional hazards modeling for the center where the patient was managed, gender, tumor stage, presence of neck metastasis and age at diagnosis. CAF density was unrelated to non-MTSSC mortality. Given the strong association between increased CAF density and higher mortality in MTSCC, routine assessment of CAF density for disease course prognosis and inclusion as an integral part of treatment protocols are recommended. [ABSTRACT FROM AUTHOR]