PSP, a type of lung tumor, exhibits a low lymph node metastasis rate of 2–4% [4], with distant metastases being exceedingly rare. Metastatic PSP is rare and few case reports have documented distant metastases [5, 8]. This case report documents the first PSP case with multiple distant metastases that responded to treatment with ipilimumab and nivolumab following the failure of repeated local treatments.

In this case, the PSP was TTF-1 positive, indicating its origin from type 2 alveolar epithelial cells [3]. Thoracic tumors, including non-small cell lung cancer (NSCLC), generally respond well to immunotherapy; however, the efficacy of immune checkpoint inhibitors in patients with PSP has rarely been reported. A previous study demonstrated the efficacy of pembrolizumab in metastatic PSP, although it was not evaluated in combination with apatinib and PD-L1 [8]. The 5-year CheckMate227 Part 1 results indicated that ipilimumab and nivolumab improved overall survival (OS) compared to chemotherapy in patients with metastatic NSCLC, particularly those without PD-L1 expression in the tumor [9]. Hence, ipilimumab and nivolumab were chosen to treat this metastatic PSP case based on the absence of PD-L1 expression.

The AKT signaling pathway is critical for tumor growth, particularly the AKT1 E17K mutation, which is found in 1.2% of all cancers. The NCI-MATCH study indicated that capivasertib, an AKT inhibitor, may be effective for E17K-mutated tumors with a 28.6% response rate [7]. AKT1 E17K has also been reported in PSP [8], as demonstrated in this case. However, another study suggested that the AKT1 E17K mutation alone does not exhibit malignant behavior and that combining AKT1 mutations with other oncogenes could accelerate the malignant progression of benign PSPs [8]. Thus, the targeted inhibition of AKT alone may be insufficient.

This study has certain limitations. As PSP is a low-grade tumor, it is questionable whether a 7-month treatment duration is sufficient to assess the efficacy of ipilimumab and nivolumab. Additionally, the small size of the mammary biopsy sample precluded genomic or PD-L1 evaluation. Despite these limitations, our findings hold significance for oncologists in similar scenarios.