Entirely Exophytic HPV-associated Endocervical Adenocarcinoma: A Rare But Potentially Aggressive Neoplastic Phenomenon

A subset of human papillomavirus (HPV)-associated endocervical adenocarcinoma (EA) displays exclusively exophytic growth, with or without a classic villoglandular appearance. Given that increased depth and extent of destructive stromal invasion are associated with poorer prognosis for HPV-associated EA, it is believed that exclusively exophytic tumors are associated with a relatively indolent clinical course. There is, however, a paucity of data regarding the behavior of these neoplasms. We assembled a cohort of 73 patients with entirely resected cervix-confined HPV-associated EA treated with primary operative therapy. The tumors were classified based on architecture and presence/extent of stromal invasion, and histopathologic parameters, including the International Federation of Gynecology and Obstetrics (FIGO) 2018 substage and lymphovascular invasion (LVI). Clinical outcomes including local recurrence, metastasis, and death were evaluated. Of 73 tumors, 4 (6%) demonstrated exclusively exophytic growth (0.4-2.2 cm in maximal dimension). All lacked LVI as well as nodal involvement. None of the 4 patients with exclusively exophytic tumors received adjuvant therapy. Two of the 4 (50%), however, experienced recurrence and both patients eventually died of causes related to EA. Of the remaining 69 cases with a component of nonexophytic growth, <6% of patients experienced tumor recurrence. Our study has found that, in at least a subset of cases, exclusively exophytic HPV-associated EA is associated with adverse outcomes. Additional studies are needed to substantiate these findings and to identify additional features (pathologic, molecular, etc.) that may aid in identifying those patients who could benefit from more aggressive treatment.