The Deceptive Signal: p16 Positivity Suggestive of Human Papilloma Virus Infection Masking a Second Primary...

Synchronous primary malignancies of the female genital tract are rare, comprising a small subset of gynecologic cancers. The concurrent presence of endometrioid endometrial adenocarcinoma and Squamous Cell Carcinoma (SCC) of the cervix is exceptionally rare. It accounts for less than 1% of reported cases.

A 75-year-old postmenopausal woman presented with intermittent vaginal bleeding. Imaging studies revealed a bulky uterus with an endometrial lesion suspicious for malignancy. An initial cervical biopsy identified high-grade papillary SCC of the ectocervix with diffuse p16 positivity. However, the MRI revealed a large endometrial mass that invaded more than 50% of the myometrium. The patient underwent a staging laparotomy with a radical hysterectomy. Histopathological evaluation confirmed two distinct malignancies: a moderately differentiated endometrioid endometrial adenocarcinoma (FIGO Stage IB) with squamous morules and a small, completely excised cervical SCC. No nodal or peritoneal metastases were identified. Postoperatively, the patient received adjuvant external beam radiotherapy and vaginal brachytherapy.

This case underscores the importance of a multidisciplinary approach, including immunohistochemistry and imaging, in diagnosing synchronous gynecological malignancies. Recognizing the coexistence of distinct tumors is essential for accurate staging and tailored treatment planning to improve patient outcomes.