What DDx panel is appropriate to distinguish HPV-related cervical adenocarcinoma vs low-grade endometrial endometrioid adenocarcinoma?

• A. ER, vimentin, CEA, & p16
• B. ER, PR, HER2, & GATA3
• C. p53, p16, vimentin, & PAX8
• D. pancytokeratin, p63, ER, & CK20

Answer: (A)

The key idea is using an immunohistochemical panel that captures both HPV-driven changes and endometrial differentiation.

p16 is a strong surrogate marker for HPV-related carcinomas. When HPV drives a cervical adenocarcinoma, p16 shows diffuse, block-like staining. In contrast, endometrial endometrioid adenocarcinomas typically do not show this diffuse p16 pattern; their p16 staining is usually weaker or focal.

Estrogen receptor status helps indicate tissue origin. Endometrial endometrioid adenocarcinomas commonly express ER, reflecting hormone sensitivity, whereas HPV-related cervical adenocarcinomas are usually ER-negative.

Vimentin tends to be expressed in endometrial tumors, helping indicate endometrial lineage, while cervical HPV-related tumors are less consistently positive for vimentin.

Carcinoembryonic antigen (CEA) expression is more characteristic of endometrial adenocarcinomas in this context and can support endometrial origin when aligned with the other markers.

Putting it together, a pattern of p16 positivity with ER negativity, coupled with vimentin positivity and CEA expression, supports HPV-related cervical adenocarcinoma; a pattern of ER positivity, vimentin positivity, and CEA expression with weaker or absent p16 supports endometrial endometrioid adenocarcinoma. This combination provides the clearest distinction between the two entities.