Digestive system neuroendocrine carcinomas (NECs) are rare neoplasms originating from neuroendocrine cells with a poor prognosis and limited effective treatments. Programmed cell death protein 1/ligand 1 (PD-1/PD-L1) blockade has been used in the management of more than 10 solid tumors and has achieved promising clinical outcomes. PD-L1 expression, immune cell infiltration, tumor mutational burden (TMB), and microsatellite instability (MSI) are all verified biomarkers that can predict the response to anti-PD-1/PD-L1 therapy. Here, we investigated PD-L1 expression and immune cell infiltration density by immunohistochemical (IHC) staining of tumor samples from 33 patients with digestive system NECs. Tumor and paratumor normal samples from 31 of these patients underwent whole-exome sequencing to evaluate TMB and the MSI-high (MSI-H) status. In total, 29.0% of digestive system NECs had positive PD-L1 expression according to the tumor proportion score (TPS). Infiltration of CD3 + , CD8 + , and CD68 + cells was observed in 69.7, 27.3, and 54.5% of patients, respectively. The TMB value for patients sequenced ranged from 0.57 to 11.75 mutations/Mb, with a median of 5.68 mutations/Mb. mSINGS, MSIsensor, and MSIseq were used to analyze the MSI status according to the sequencing data, and in our evaluation, no MSI-H status was detected. Our data might indicate a limited potential of anti-PD-1/PD-L1 monotherapy in digestive system NECs, although clinical trials are warranted.

Rationale: Carotid body tumors (CBTs) are head and neck paragangliomas (PGLs) with a low incidence of distant metastasis. To date, only a few metastatic cases treated with detailed systemic therapy are reported and effective management is still inconclusive. Herein, we reported a metastatic CBT case with systemic therapy and reviewed the reported systemic treatment. Patient concerns: A 56-year-old man noticed multiple painless nodules on the right side of the neck and developed debilitating chest and back pain 7 years after the CBT resection. Diagnoses: Widespread bone and lymph nodes CBT metastases. Interventions: Biopsies of the enlarged lymph nodes confirmed the diagnosis of metastatic CBT and 18F-FDG PET-CT detected multiple right cervical lymph nodes and bone metastases. 24 cycles of cyclophosphamide, vincristine and dacarbazine (CVD) chemotherapy were given since May 2016 to Jul 2018 and dacarbazine maintenance therapy was given in the next 15 months follow-up period. Outcomes: Partial remission was achieved according to the Response Evaluation in Criteria in Solid Tumors 1.1 criteria. A prominent control in the metastatic lesions were also observed in 18F-FDG PET-CT scan. Lessons: Evidence for systemic management of metastatic CBTs is mainly based on studies of PGLs and pheochromocytoma. According to our review on metastatic CBT cases treated with systemic therapy from 1981 to 2018, chemotherapy, especially the CVD regimen, was a common reported management. In SDHB mutated patients, sunitinib and temozolomide could also be considered.