Seven-year sonographic evolution from a simple vaginal wall cyst to hepatoid adenocarcinoma of the urethrovaginal septum

Introduction

Hepatoid adenocarcinoma (HAC) is a rare extrahepatic malignancy characterized by hepatocyte-like differentiation and elevated serum alpha-fetoprotein (AFP) levels, occurring most frequently in the stomach and other digestive organs (1). HAC of the female genital tract is exceedingly uncommon, and primary involvement of the urethrovaginal septum has rarely been described (2). We report a case in which ultrasound documented the seven-year transformation of an apparently benign cystic lesion in the urethrovaginal septum into an AFP-secreting HAC, illustrating the diagnostic value of long-term serial sonographic surveillance.

Case presentation

A 48-year-old woman presented with a three-week history of hematuria. Seven years earlier, during a routine health examination, a gynecologist palpated a suspected vaginal cyst, prompting a transvaginal ultrasound examination, which incidentally revealed a well-defined, anechoic cystic lesion (measuring approximately 3.0 cm) adjacent to the urethra in the anterior vaginal wall, with no internal vascularity. The findings were considered consistent with a benign Skene’s or Gartner’s duct cyst (Figure 1A). No follow-up was scheduled.

Figure 1 Serial transvaginal ultrasound images of the urethrovaginal septal lesion over seven years. (A) Seven years prior: color Doppler image showing a well-defined anechoic cystic mass (~3.0 cm) in the anterior vaginal wall adjacent to the urethra, with no detectable blood flow, consistent with a benign cyst. (B) Current presentation: two-dimensional transvaginal ultrasound showing a markedly enlarged cystic-solid mass (6.0 cm × 5.0 cm × 5.0 cm) at the same location, with solid components exceeding 50% of the lesion volume. (C) Color Doppler image demonstrating rich vascularity within the solid component. (D) Pulsed-wave Doppler spectral image from the solid component showing high-resistance arterial flow (resistive index, 0.81). (E) Sagittal T2-weighted MRI showing a heterogeneous cystic-solid mass with a low T2 signal mural lesion. MRI, magnetic resonance imaging.

At the current presentation, repeat transvaginal ultrasound revealed a markedly enlarged cystic-solid mass measuring 6.0 cm × 5.0 cm × 5.0 cm at the same location. The solid component accounted for more than 50% of the lesion volume and showed rich internal vascularity on color Doppler imaging (resistive index, 0.81), indicating malignant transformation (Figures 1B-1D). The patient’s serum AFP levels were elevated (222.63–273.8 ng/mL), while the liver appeared normal on ultrasonography. Magnetic resonance imaging (MRI) confirmed a heterogeneous cystic-solid mass with ill-defined margins abutting the anterior cervical lip and posterior bladder wall (Figure 1E). Positron emission tomography-computed tomography demonstrated avid tracer uptake. Based on the elevated AFP levels and the imaging findings, a yolk sac tumor was initially suspected.

The patient underwent combined transabdominal and transvaginal resection of the urethrovaginal septal tumor with total hysterectomy and bilateral salpingo-oophorectomy. The lesion was completely resected intraoperatively, and pathological examination confirmed no tumor involvement of the uterus, bilateral adnexa, or pelvic sidewall margins. Intraoperative frozen section analysis indicated a poorly differentiated malignant neoplasm.

Final histopathological examination confirmed the diagnosis of HAC: the tumor cells were large with abundant eosinophilic cytoplasm and prominent nucleoli, resembling hepatocytes. No adenomatous changes or adenocarcinomatous components were observed in the cyst wall. Immunostaining was positive for AFP (+++), hepatocyte paraffin 1 (Hepar-1) (+), glypican-3 (GPC3) (+++), cytokeratin 18 (CK18) (+++), and epithelial membrane antigen (EMA) (+++), with a Ki-67 proliferation index of approximately 70%. Markers associated with germ cell tumors [octamer-binding transcription factor 3/4 (OCT3/4), spalt like transcription factor 4 (SALL4) (focal), cluster of differentiation 30 (CD30), and human chorionic gonadotropin (HCG)], neuroendocrine differentiation, and gynecologic origin [estrogen receptor (ER), progesterone receptor (PR), and Wilms tumor 1 (WT 1)] were negative (3). Serum AFP levels decreased to 78.5 ng/mL at two weeks post-operatively and normalized thereafter. Adjuvant chemoradiotherapy was administered. At approximately three years of follow-up, the patient remains disease-free.

All procedures described in this study were performed in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Declaration of Helsinki and its subsequent amendments. Written informed consent was obtained from the patient for the publication of this article and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Discussion

This case makes two notable contributions. First, it provides direct serial ultrasound evidence of HAC arising—or initially presenting—as a purely cystic lesion before evolving into a predominantly solid mass over seven years. Whether this represents true cyst-to-carcinoma transformation or reflects an initially microscopic solid component below the resolution of ultrasound cannot be determined with certainty. Nevertheless, the anatomical depth of the urethrovaginal septum can limit visualization, and multi-planar and multi-angle scanning is essential to avoid missing early solid elements in this region (4). Second, this case highlights the diagnostic challenge posed by HAC at an unusual site. The differential diagnosis included Skene’s duct cyst, Gartner’s duct cyst, urethral diverticulum, and germ cell tumors. Moderately elevated AFP levels (approximately 300 ng/mL), combined with positive Hepar-1 and GPC3 immunostaining, supported the diagnosis of HAC and helped distinguish it from yolk sac tumor (which typically shows diffuse SALL4 positivity) and hepatocellular carcinoma (3). In contrast to gastric or other digestive tract HACs, which frequently show markedly elevated AFP levels (>1,000 ng/mL) and have a poor prognosis (median survival <2 years; 5-year survival <10%), our patient’s mildly elevated AFP levels, complete surgical resection, and adjuvant therapy appear to have contributed to her favorable three-year disease-free outcome (5).

In perimenopausal women with a cystic lesion in the urethrovaginal septum, if imaging follow-up demonstrates an increased proportion of solid components within the cyst or the appearance of abundant vascularity, AFP evaluation should be considered. The combination of these findings may raise suspicion for HAC of the urethrovaginal septum, prompting early surgical intervention to optimize outcomes.

Acknowledgments

The authors thank Lei Li, MD, Department of Pathology, West China Second University Hospital of Sichuan University, for providing the pathology images.

Footnote

Funding: This work was supported by the National Key Research and Development Program of China (No. 2017YFC0113905).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-2026-0850/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures described in this study were performed in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Declaration of Helsinki and its subsequent amendments. Written informed consent was obtained from the patient for the publication of this article and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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