Endocervical adenocarcinoma with a micropapillary component: a clinicopathologic analysis in the setting of current WHO classification

Abstract

Our study aimed to investigate the clinicopathologic and molecular features of endocervical adenocarcinoma with a micropapillary component (EAC-MP) in the setting of current classification schema. We investigated 26 EAC-MP from consecutive 511 adenocarcinomas. HER2 status was analyzed by immunohistochemistry and fluorescence in situ hybridization. Four cases were performed with targeted next-generation sequencing (NGS). We found that HPV-associated adenocarcinomas (HPVA) with a micropapillary component (HPVA-MP) (n = 12) had a higher frequency of large tumor size (> 2 cm), Silva pattern C (12/12, 100%), invasion of the deep cervical wall (> 2/3) (8/12, 66.7%), lymphovascular space invasion (LVSI) (11/12, 91.7%), lymph node metastasis (4/11, 36.4%), FIGO stage III/IV (4/12, 33.3%), and HER2 amplification (3/12, 25%, P = 0.015), compared to those without (HPVA-NMP (all P < 0.05). HPV-independent adenocarcinomas (HPVI) with a micropapillary component (HPVI-MP) (n = 14) had LVSI more commonly than those without (HPVI-NMP) (P = 0.033). Survival analysis indicated that HPVA-MP was associated with worse overall survival and recurrence-free survival than HPVA-NMP (P < 0.01). Particularly, in patients with Silva pattern C, HPVA-MP appeared to have more adverse clinical outcomes (P < 0.01). No survival differences were found in HPVI-MP versus HPVI-NMP (P > 0.05). NGS identified significant mutations in STK11, TERT, ERBB2, TP53, PIK3CA, ARID1A, and NTRK2. We conclude that the micropapillary structure is an indicator for unfavorable clinical outcomes in HPVA, and can aid in the prognostic stratification of Silva pattern C EAC. The presence of HER2 amplification and specific gene mutations raise the possibility for targeted therapy in the future.

Keywords: Endocervical adenocarcinoma; HER2; Human papillomavirus (HPV); Micropapillary; Mutation; Prognosis.