June 2021 – Gynecological Pathology

The correct answer is: High-grade neuroendocrine carcinoma, large cell type.

Neuroendocrine carcinoma (NEC) is a rarely encountered entity in the cervix, comprising less than 5 percent of diagnosed cervical cancer. Like the more commonly seen cervical squamous cell carcinoma and adenocarcinoma, most of these tumors are driven by human papillomavirus (HPV), particularly HPV18. However, NEC carries a much poorer prognosis due to its aggressive behavior and propensity for metastatic spread. Because NEC is uncommon and has no specific morphologic features to suggest the site of origin, it can be misdiagnosed as metastatic carcinoma, leading to an unnecessary work up in search of the primary site. In this case the endometrial metastases can erroneously point to an endometrial cancer with involvement of the cervix. As a surrogate marker for an HPV-mediated process, P16 immunohistochemical stain can aid in making the correct diagnosis, which can then be confirmed by in situ hybridization. Although NEC has no precursor lesion that would allow diagnosis of preinvasive disease during screening procedures, HPV-driven NEC can be prevented with the available vaccine. 

References

1. Castle PE, Pierz A, Stoler MH. A systematic review and meta-analysis on the attribution of human papillomavirus (HPV) in neuroendocrine cancers of the cervix. Gynecol Oncol. 2018 Feb;148(2):422-429. 
2. Alejo M, et al; RIS HPV TT study group. Contribution of Human papillomavirus in neuroendocrine tumors from a series of 10,575 invasive cervical cancer cases. Papillomavirus Res. 2018 Jun;5:134-142.