PD-L1 expression and CD8+ tumor-infiltrating lymphocytes are associated with ALK rearrangement and clinicopathological features in inflammatory myofibroblastic tumors.

Background: Inflammatory myofibroblastic tumors (IMTs) are rare mesenchymal neoplasms that are composed of myofibroblastic cells accompanied by inflammatory infiltrate. We investigated the immune profiles of IMTs, including PD-L1 expression and proportion of CD8+ tumor-infiltrating lymphocytes (TILs), as well as its clinicopathological characteristics according to ALK gene rearrangementstatus.

Methods: Twenty-eight IMTs from 25 patients were retrieved from our pathology files (2005-2015), and their clinicopathological parameters and outcomes were analyzed. Immunohistochemistry (IHC) was performed using whole-tissue sections to detect PD-L1 and CD8 expression, and fluorescent in situ hybridization (FISH) analysis and IHC were performed using tissue microarrays to identify rearrangements in the ALK, ROS1 , and RET genes.

Results: ALK rearrangement was observed in 11 cases (44.0%), and all cases exhibited diffuse cytoplasmic ALK expression during IHC. ROS1 or RET rearrangement was not detected using IHC or FISH. IMTs harboring ALK rearrangement ( ALK -positive) were located in the lungs ( n = 7), genitourinary tract ( n = 2), and mesentery ( n = 1). The mean patient age was 33.2 years for ALK -positive IMTs and 53.1 years for ALK -negative IMTs. All patients with ALK -positive IMTs survived without recurrence or metastasis. IMTs with metastasis and/or recurrence were ALK -negative and exhibited elevated PD-L1 expression (positive tumor cells: 70.0% vs . 21.3%, P = 0.023; H-score: 107.5 vs . 26.3, P = 0.005). In addition, ALK -negative IMTs had a more CD8+ TILs, compared to ALK -positive IMTs (23.3% vs . 8.9%, P = 0.027).

Conclusion: ALK -positive IMTs are characterized by younger age, well-defined margins, frequent involvement of the lung, and fewer CD8+ TILs. Greater PD-L1 expression was observed in IMTs with tumor necrosis and metastasis/recurrence, which were also negative for ALK rearrangement. These results suggest that immune checkpoint inhibitors may be a novel option for treating patients with advanced IMT.