Invasive Stratified Mucin-producing Carcinoma (ISMC) of the Uterine Cervix: Clinicopathological and Molecular Characteristics With Special Emphasis on the First Description of Consistent Programmed Death-ligand 1 (PD-L1) Over-expression

Background/Aim: Invasive stratified mucin-producing carcinoma (ISMC) of the uterine cervix has been reported to be more aggressive than other subtypes of endocervical adenocarcinoma. We investigated the clinicopathological and molecular characteristics of eight ISMCs. Patients and Methods: We reviewed the electronic medical records and pathology slides of eight patients with ISMC and conducted programmed death-ligand 1 (PD-L1) immunostaining and targeted sequencing. Results: The patients were between 31 and 54 years. Six tumors were pure ISMCs, and two showed co-existing squamous cell carcinoma and usual-type endocervical adenocarcinoma. Lymph node metastases were detected in three cases. Three patients developed distant metastases to the adnexa, lungs, inguinal lymph nodes, and small intestine. Two patients experienced disease progression, and three developed postoperative local recurrences. All tumors showed PD-L1 over-expression, with a mean combined positive score of 73.8 (range=30-100). One tumor harbored erb-b2 receptor tyrosine kinase 2 amplification. Conclusion: ISMC of the uterine cervix exhibits a high risk of recurrence, metastasis, and resistance to chemoradiation therapy. PD-L1 overexpression was consistently observed in all ISMCs. This finding raises the possibility that patients with ISMC may benefit from PD-L1 immunotherapy.