Squamous cell carcinoma arising from ovarian mature cystic teratoma with concurrent cervical high-risk HPV infection and low-grade squamous intraepithelial lesion: a case report

Abstract

Objective

Malignant transformation of ovarian mature cystic teratoma (MCT) is uncommon, with squamous cell carcinoma (SCC) being the predominant type. Its pathogenesis remains poorly understood, and the potential role of human papillomavirus (HPV) infection is controversial.

Case report

A 58-year-old postmenopausal woman presented with a huge complex cystic-solid pelvic mass. The elevated Serum SCC antigen revealed potential malignant transformation. Intraoperative frozen section revealed squamous cell carcinoma arising from mature cystic teratoma, and comprehensive staging surgery was performed. Histopathological examination confirmed the International Federation of Gynecology and Obstetrics (FIGO) stage IA SCC arising from MCT. The patient achieved complete remission after surgery and four cycles of adjuvant carboplatin/paclitaxel chemotherapy, with no recurrence at 24-month follow-up. Notably, this case was found to have the HPV infection and a low-grade squamous intraepithelial lesion. The cervical lesion was HPV positive with P16 expression, while the ovarian tumor demonstrated HPV negative with P16 negativity and P53 positivity.

Conclusion

For patients with ovarian teratoma, it is necessary to be vigilant about the malignant transformation when the patients are elderly with a large mass and elevated tumor biomarkers. However, it is not clear whether the role of the gene mutation-driven mechanism is in the pathogenesis of this case, since substantive evidence based on genomic sequencing is lacking.

Introduction

Ovarian mature cystic teratoma (MCT) is the most common ovarian germ cell tumor, accounting for approximately 10%-20% of ovarian tumors [1, 2]. Although MCT is generally benign, malignant transformation occurs rarely, with a reported incidence of approximately 0.17%-2.0%; squamous cell carcinoma (SCC) is the most frequent malignant histological subtype [2, 3]. Because the clinical manifestations and imaging appearances are often nonspecific, malignant transformation is frequently diagnosed only by intraoperative frozen section or postoperative histopathological examination [1, 2, 4].

No standardized management strategy has been established for SCC arising from MCT because of its rarity. Current treatment approaches are largely derived from retrospective studies and systematic reviews, and generally emphasize complete surgical resection, comprehensive staging or cytoreduction when appropriate, and individualized consideration of platinum-based chemotherapy [1, 2, 5–7]. The pathogenesis of SCC arising from MCT remains heterogeneous and poorly understood. Persistent high-risk human papillomavirus (HPV) infection is a well-established driver of cervical squamous lesions [8], and several reports have suggested that HPV infection may contribute to malignant transformation of MCT in selected cases [9–11]. However, molecular evidence supporting a universal HPV-driven pathway in SCC-MCT remains limited [12].

Here, we report a case of ovarian SCC arising from MCT in a postmenopausal woman with concurrent cervical high-risk HPV infection and low-grade squamous intraepithelial lesion (LSIL). This case contributes to the limited literature on SCC-MCT by offering a detailed clinicopathological observation and provides an opportunity to investigate the etiological relationship between HPV and ovarian SCC.

Case presentation

A 58-year-old postmenopausal woman presented to The Second Affiliated Hospital of Shandong First Medical University for evaluation of thyroid nodules. She had experienced lower abdominal pain for approximately two months, without abnormal vaginal bleeding or gastrointestinal symptoms such as nausea or vomiting. A pelvic mass was incidentally detected on ultrasonography, leading to referral to the gynecology department.

Serum tumor markers were elevated, suggesting potential malignant transformation: SCC antigen (SCC-Ag), 15.985 ng/mL; CA19-9, 104.63 U/mL; and CA242, 89.444 U/mL. CA125 was within the normal range. Pelvic magnetic resonance imaging (MRI) demonstrated a large complex cystic-solid mass in the left adnexal area, approximately 130 × 119 × 144 mm, containing fat components and calcifications, with restricted diffusion in the solid portion (Fig. 1).

Fig. 1.

Magnetic resonance imaging findings in patients with SCC-MCT. Note: A large and complex cystic-solid mass in the left adnexal area, approximately 130 × 119 × 144 mm, containing fat components and calcifications, with restricted diffusion in the solid portion. Abbreviation: MCT, Mature Cystic Teratoma; SCC, squamous cell carcinoma

Laparoscopic exploration was performed. Intraoperatively, the left ovary was markedly enlarged and contained sebaceous material, hair, and solid nodules within the cyst. No ascites was present, and no abnormalities were observed in the uterus, right ovary, omentum, or peritoneum. Intraoperative frozen section suggested SCC arising from MCT. Therefore, comprehensive staging surgery was completed, including total hysterectomy with bilateral salpingo-oophorectomy, omentectomy, and systematic lymphadenectomy.

Postoperative histopathological examination confirmed stage IA ovarian SCC arising from MCT according to the 2014 International Federation of Gynecology and Obstetrics (FIGO) staging system (Fig. 2). The tumor demonstrated typical SCC morphology, including infiltrative growth, intercellular bridges, and keratin pearl formation. Critically, the SCC component was identified in continuity with benign teratomatous elements, supporting its origin from MCT (Fig. 2). Peritoneal washing cytology was negative, and no metastasis was found in any of the resected lymph nodes (0/25). Serum tumor markers normalized promptly after surgery. The patient achieved complete remission after surgery and four cycles of adjuvant chemotherapy with paclitaxel plus carboplatin. Close follow-up showed no evidence of recurrence as of June 2026, 24 months after surgery.

Fig. 2.

Pathological findings. Note: (A) Benign components of the MCT, including bone, adipose tissue, and epithelium (H&E staining, 100×); (B) Invasive squamous cell carcinoma component within the MCT, showing severe atypia with intercellular bridges and keratin pearls (H&E staining, 100×). MCT, Mature Cystic Teratoma

Notably, preoperative cervical screening revealed high-risk HPV types 39/51 positivity and atypical squamous cells of undetermined significance. Colposcopy with cervical biopsy and postoperative histopathological examination demonstrated LSIL, without evidence of invasive cervical carcinoma (Fig. 3). HPV genotyping was performed on cervical samples and formalin-fixed paraffin-embedded ovarian tumor tissue using polymerase chain reaction. The cervical lesion was positive for high-risk HPV types 39 and 51 and showed p16 block positivity. In contrast, the ovarian SCC component was negative for HPV-DNA and P16, while showing P53 positivity (Fig. 4). The absence of invasive cervical carcinoma, together with the histological continuity between the ovarian SCC component and benign teratomatous elements, supported malignant transformation from MCT rather than metastatic cervical SCC.

Fig. 3.

Cervical intraepithelial neoplasia (grade 1). Note: Focal squamous epithelial hyperplasia with mild atypia

Fig. 4.

Immunohistochemical analysis of ovarian-like cell carcinoma. Note: (A) Ki67 immunohistochemical staining was shown (200 × magnification); (B) P53 immunohistochemical staining was shown (200 × magnification). P53 positive in the ovarian SCC part is confirmed; (C) CK56 immunohistochemical staining was shown (200 × magnification); (D) P40 immunohistochemical staining was shown (200 × magnification). Note: SCC, squamous cell carcinoma

Discussion

SCC arising from ovarian MCT is an uncommon but clinically important malignancy. In the present case, the patient was a 58-year-old postmenopausal woman with a large cystic-solid adnexal mass, markedly elevated serum SCC-Ag, and restricted diffusion in the solid component on pelvic MRI. These findings were consistent with previously reported warning signs for malignant transformation, including older age, postmenopausal status, large tumor size, solid components within a teratoma, and elevated tumor markers [13–17]. Although most MCTs are benign, malignant transformation should be considered when these features are present, particularly in postmenopausal patients.

Preoperative diagnosis of SCC arising from MCT remains difficult because clinical symptoms and imaging findings are often nonspecific. In many reported cases, the diagnosis is made only during intraoperative frozen section or postoperative pathological examination [2–4, 18]. In this patient, intraoperative frozen section played an important role in guiding surgical decision-making. Once SCC arising from MCT was suspected, comprehensive staging surgery was performed. The final diagnosis was supported by the presence of invasive SCC in continuity with benign teratomatous components. This histological continuity is essential for distinguishing malignant transformation within MCT from metastatic SCC involving the ovary. In addition, no invasive cervical carcinoma was identified on cervical biopsy or the hysterectomy specimen, further supporting a primary ovarian origin rather than metastasis from the cervix.

The most distinctive feature of this case is the coexistence of cervical high-risk HPV infection and LSIL with ovarian SCC arising from MCT. The pathogenesis of ovarian SCC remains controversial, with particular debate surrounding whether HPV infection plays a causative role. HPV is a double-stranded DNA virus that most commonly infects the cervical transformation zone. It can integrate into the host genome and disrupt normal cell cycle regulation through multiple mechanisms, ultimately leading to carcinogenesis. Persistent infection with high-risk HPV types is established as the primary cause of squamous cell carcinoma of the cervix, vagina, and vulva. The role of HPV in the malignant transformation of MCT remains controversial. Some case reports have detected HPV DNA in ovarian SCC arising from MCT and have suggested that HPV infection may contribute to malignant transformation in selected cases [9–11]. However, this mechanism is not consistently supported by molecular studies. Cooke et al. reported that all 25 ovarian SCC-MCT samples in their cohort were HPV-negative and instead demonstrated a mutation-associated landscape characterized by frequent alterations in TP53, CDKN2A, and PIK3CA [12].

To explore the potential link between HPV infection and malignant transformation of MCT, we performed HPV DNA testing using PCR and immunohistochemical analyses specifically on the ovarian malignant component. Our results demonstrated that the ovarian SCC lesion was HPV-DNA negative and p16 negative, with concurrent P53 positivity. This discordant molecular phenotype suggests that the ovarian SCC in this case is etiologically independent of the cervical HPV infection, and that an HPV-independent pathway was likely involved in the malignant transformation of the ovarian teratoma. Notably, previous genomic profiling studies have reported frequent TP53 mutations in SCC-MCT. We speculate that a gene mutation-driven mechanism may have been primarily responsible, although this hypothesis remains unverified. We acknowledge that P53 expression should not be equated with a confirmed TP53 mutation. Since genomic sequencing was not performed in this case, the precise molecular drivers underlying the pathogenesis remain unclear.

There is currently no standardized treatment strategy for SCC arising from MCT because of its rarity. Complete surgical resection remains the cornerstone of management, and FIGO stage is one of the most important prognostic factors [1–3, 5–7]. Adjuvant chemotherapy for SCC-MCT remains controversial, and no consensus has been established. Currently, platinum-based chemotherapy is the main regimen, and it has been shown to improve survival for advanced-stage patients. Some studies suggest that observation alone may be sufficient for patients with FIGO stage IA disease after comprehensive surgical staging. In the present case, considering the extremely large tumor size and the patient’s limited access to close postoperative surveillance, four cycles of adjuvant chemotherapy with paclitaxel and carboplatin were performed. The patient achieved complete remission, and at the last follow-up in June 2026 (24 months post-surgery), no evidence of recurrence was observed.

This case has several limitations. First, genomic sequencing was not performed; therefore, the proposed HPV-independent and possible mutation-associated pathway remains inferential. Second, this is a single case report, and no causal relationship can be established between the observed immunohistochemical profile and tumorigenesis. Third, the follow-up period of 24 months is still relatively short for evaluating long-term recurrence risk. Despite these limitations, this case provides a useful pathological reminder: synchronous cervical HPV infection does not necessarily indicate an HPV-driven etiology for ovarian SCC arising from MCT. Careful pathological examination, HPV testing, and immunohistochemical comparison between synchronous lesions may help clarify tumor origin and avoid overinterpretation of cervical HPV positivity.

Conclusion

We reported a case of FIGO stage IA ovarian SCC arising from MCT in a postmenopausal woman with concurrent cervical high-risk HPV infection and LSIL. Malignant transformation should be suspected in postmenopausal women with large ovarian MCTs and elevated SCC-Ag, and intraoperative pathological examination is important for timely diagnosis and appropriate surgical management. Further molecular studies, including genomic sequencing, are needed to clarify the mechanisms underlying the malignant transformation of MCT.

Abbreviations

MCT

Mature cystic teratoma

SCC

Squamous cell carcinoma

SCC-Ag

SCC antigen

SCC-MCT

SCC arising in MCT

MRI

Magnetic resonance imaging

FIGO

International Federation of Gynecology and Obstetrics

HPV

Human papillomaviru

ASC-US

Atypical squamous cells of undetermined significance

LSIL

Low-grade squamous intraepithelial lesion

CT

Computerized tomography

Authors’ contributions

Wenna Zhao: Investigation, Writing–original draft preparation, Writing–review and editing. Yaxuan Sun: Investigation, Resources, Data curation, Writing–original draft preparation. Masmuha Marshed Al Ramadhany : Resources, Writing–original draft preparation. Ruochen Wu: Resources. Yifang Zhang: Conceptualization, Supervision, Data curation, Writing–review and editing.All authors reviewed the manuscript.

Funding

The authors indicated that there was no external funding for this study.

Data availability

The data supporting the findings of this case report are included in the published article. Additional clinical and pathological information is not publicly available because of patient privacy considerations but may be obtained from the corresponding author on reasonable request, subject to appropriate ethical and privacy restrictions.

Declarations

Ethics approval and consent to participate

Not applicable.

Consent for publication

The authors have obtained written informed consent from the patient to publish this case report and any accompanying images.

Competing interests

The authors declare no competing interests.