Low tumor cell content predicts favorable prognosis in germinoma patients

Abstract

Background Germinoma preferentially occurs in pediatric and young adult age groups. Although they are responsive to treatment with chemotherapy and radiation, the treatment may cause long-term sequelae in their later lives. Here, we searched for clinical and histopathological features to predict the prognosis of germinoma and affect treatment response. Methods A total of 114 germinoma cases were included in the analysis. We investigated the association between clinical factors, tumor cell content, and progression-free survival (PFS). Results The tumor cell content was widely distributed from <5% to 90% in the specimens, with a median value of 50%. Female patients showed higher tumor cell content in the specimens (p=0.002). Cases with lesions at atypical sites showed shorter PFS than those with lesions at other sites (p=0.03). Patients with a higher tumor cell content (≥50%) showed shorter PFS than those with a lower tumor cell content (<50 %) (p=0.03). In multivariate analysis, tumor cell content was the only statistically significant prognostic factor (p=0.04). Among the seven cases treated with local radiation and chemotherapy, all three cases that recurred (two outside of the radiation field, one unknown) had tumor cell content of ≥50% in the original specimen, whereas all four cases without recurrence had tumor cell contents of <50%. Conclusions We found that tumor cell content significantly affected the prognosis of germinomas. Although validation of these results using an independent and larger cohort is necessary, this potentially opens the possibility of leveraging this pathological factor in future clinical trials when stratifying the treatment intensity.

Biomarkers for risk-based treatment modifications for CNS germ cell tumors: Updates on biological underpinnings, clinical trials, and future directions

“…One of the novel aspects of evaluating and stratifying germinoma treatment strategies is that cases with many immune cells have shown better prognoses than those with a high tumor content in previous research ( 28 ). Moreover, this finding remained statistically significant when incorporating information on tumor location, as tumor location is another prognosis-related factor, as described previously ( 29 ). Currently, it is not standard practice to only treat germinoma with chemotherapy without radiation therapy, based on the results of previous clinical trials in which frequent relapses were observed in patients with germinoma treated with chemotherapy only ( 30 ).…”

“…Most dominant immune cells are lymphocytes (T-cell and B-cell, approximately 60-70% on average) and natural killer cells, but immune cell repertoire in germinoma also includes myeloid-derived cells such as macrophages accounting for approximately 20-30% on average ( 28 ). The ratio between germinoma cells and immune cells is known to vary substantially depending on case characteristics, with <10% to 90% of tumor cells (out of all nucleated cells in tissue specimens) observed on hematoxylin-eosin (H-E) staining ( 29 ). As germinoma cells are obviously larger than immune cells and their cell morphologies differ, it would not be very challenging to calculate the ratio of tumor cells to immune cells in daily clinical practice.…”

“…Thus, a certain proportion of germinoma cases may be cured with chemotherapy alone. Germinoma presenting with abundant immune cells may be a good candidate for reduced treatment intensity ( 29 ).…”

High endothelial venules in intracranial germinomas: Implications for lymphocytes infiltration

“…Lower tumor cell content, typical location (neurohypophysis or pineal gland), and abundant infiltrating lymphocytes are significantly associated with a better prognosis of germinoma. 2 , 27 , 28 Interestingly, in the present study (Figure 4 ), HEVs density was significantly correlated with lower tumor cell content, not to mention their relationship with the amounts of T and B cells. Furthermore, our study also showed that all the HEV‐high tumors were located in the suprasellar and pineal regions.…”

“…However, several factors have been shown to possess prognosis signi cance for germinoma in previous studies. Lower Tumor cell content, typical location (neurohypophysis or pineal gland), and abundant in ltrating lymphocytes are signi cantly associated with a better prognosis of germinoma (2,27,28). Interestingly, in the present study, HEVs density was signi cantly correlated with lower tumor cell content, not to mention their relationship with the amounts of T and B cells.…”