Early-stage sertoliform endometrioid carcinoma of the ovary: diagnostic, molecular, and therapeutic considerations

Highlights

• •Sertoliform variant of ovarian endometrioid carcinoma is extremely rare.
• •Dual CTNNB1 and FBXW7 mutations characterize a low-grade, indolent molecular profile.
• •Accurate diagnosis requires integration of morphology, immunohistochemistry, and molecular data.
• •Endocrine therapy was used as an individualized management approach in early-stage disease.
• •Long-term remission was observed with surgical resection and close surveillance over 3 years.

Background

The sertoliform variant of ovarian endometrioid carcinoma is exceedingly rare and often mimics sex-cord stromal or Brenner tumors, creating diagnostic challenges. Case: A 72-year-old woman presented with progressive abdominal distention and pain. MRI revealed a 22.7 × 13.8 × 16 cm mixed cystic–solid pelvic mass with mild ascites and elevated tumor markers. She underwent total hysterectomy, bilateral salpingo-oophorectomy, omentectomy, and lymphadenectomy. Pathology demonstrated low-grade endometrioid carcinoma, sertoliform variant, confined to the left ovary. Immunostains were positive for ER, AE1/AE3, β-catenin (nuclear/cytoplasmic), CDX2, and EMA. Molecular profiling revealed CTNNB1 (p.S33A) and FBXW7 (p.Q624*) pathogenic variants. She received adjuvant letrozole and remains disease-free at 3 years post-surgery. Conclusion: This case highlights the diagnostic complexity of ovarian tumors with sertoliform morphology and the importance of integrating morphologic, immunohistochemical, and molecular data. When confined to the ovary, prognosis is excellent following surgical resection. Endocrine therapy may be considered on an individualized basis in hormone-responsive tumors, although its role in early-stage disease remains unproven.

1. Introduction

Endometrioid carcinoma accounts for approximately 10 % of epithelial ovarian cancers and is typically associated with low-grade histology, early-stage presentation, and favorable outcomes (Lim and Oliva, 2010, McCluggage, 2008). The sertoliform variant, first characterized by Eichhorn and Young in 2006, is extraordinarily uncommon and histologically mimics sex-cord stromal or Brenner tumors (Eichhorn and Young, 2006, Lim and Oliva, 2010). Misclassification may occur, particularly on frozen section or limited sampling (McCluggage, 2008). Reported cases describe unilateral tumors with endometrioid differentiation, strong estrogen and progesterone receptor expression, and nuclear β-catenin accumulation, consistent with low-grade molecular pathway (McConechy et al., 2014). To date, only a small number of cases have undergone comprehensive molecular profiling (D’Angelo and Prat, 2015, WHO Classification of Female Genital Tumours. 5th ed. Lyon: International Agency for Research on Cancer, 2020).

We report a case of FIGO stage IA low-grade endometrioid carcinoma, sertoliform variant, notable for its large size, prominent adenofibromatous stroma with dystrophic calcifications, and dual CTNNB1 and FBXW7 pathogenic variants. This case highlights the diagnostic complexity of this rare subtype and provides insight into its molecular landscape and clinical management.

2. Case presentation

A 72-year-old postmenopausal woman presented with several months of abdominal bloating and discomfort. A prior CT obtained for trauma had shown uterine enlargement and a small left adnexal lesion. Subsequent MRI revealed a 22.7 × 13.8 × 16 cm complex cystic–solid mass with mild ascites and elevated tumor markers (CA-125 159 U/mL, HE4 77 pmol/L, CEA 4.3 ng/mL). She underwent total hysterectomy, bilateral salpingo-oophorectomy, omentectomy, and lymphadenectomy. Grossly, the left ovary was replaced by a 22.5 cm solid, lobulated mass with fibrotic stroma and dystrophic calcifications. Microscopically, the tumor displayed infiltrating islands and ribbons of epithelial cells with occasional glandular differentiation within an adenofibromatous background (Fig. 1A–B). Immunostains demonstrated ER and EMA positivity with nuclear β-catenin accumulation (Fig. 2A–B). All lymph nodes, omentum, and peritoneal biopsies were negative for malignancy.

Fig. 1.

(A) Low-power H&E shows a solid, lobulated tumor with adenofibromatous architecture and dystrophic calcifications. (B) Medium-power H&E reveals nests and ribbons of epithelial cells with glandular differentiation in fibrotic stroma.

Fig. 2.

Immunohistochemical profile confirming endometrioid lineage. (A) High-power EMA demonstrates strong expression in glandular and sertoliform areas. (B) β-catenin shows nuclear and cytoplasmic positivity confirming CTNNB1-activated endometrioid differentiation, high power.

The final diagnosis was FIGO stage IA low-grade endometrioid carcinoma, sertoliform variant, confined to left ovary. No adjuvant chemotherapy was recommended. Given the strong hormone response expression, the patient was managed with individualized endocrine therapy using letrozole (2.5 mg daily) and close surveillance.

At 3 years following surgery, she remains clinically disease-free. Serial imaging demonstrates no evidence of recurrence, and serum tumor markers within normal limits (CA-125 19 U/mL, HE4 85 pmol/L, CEA 2 ng/mL), and circulating tumor DNA testing is negative.

3. Molecular findings

Comprehensive genomic profiling revealed ER ≥ 75 %, PR ≥ 90 %, MSI stable, TMB 4 mut/Mb, HRD-negative. Pathogenic variants were detected in CTNNB1 (p.S33A) and FBXW7 (p.Q624*). No alterations were found in BRCA1/2, KRAS, PTEN, or TP53.

4. Discussion

The sertoliform variant of ovarian endometrioid carcinoma represents a rare morphologic subtype characterized by architectural patterns resembling sex-cord stromal differentiation (Eichhorn and Young, 2006). Since its initial description, fewer than 30 well-documented cases have been reported, most presenting as unilateral, early-stage tumors with favorable outcomes following surgical resection, as summarized in Table 1 (Lim and Oliva, 2010, Matsuo et al., 2020). The prominent adenofibromatous stroma and dystrophic calcifications in the present case further contributed to diagnostic complexity and initially raised concern for a Brenner or sex-cord stromal neoplasm (McCluggage, 2008).

Table 1.

Published cases of ovarian endometrioid carcinoma, sertoliform variant.

Author (Year)	Age	Tumor Size	Stage	ER / β-catenin	Molecular Data	Treatment	Outcome / Follow-up
Eichhorn & Young (2006)	NR	NR	I	ER+, β-catenin+	Not reported	Surgery alone	NED
Lim and Oliva (2010)	NR	NR	I	ER+	Not reported	Surgery alone	NED
D’Angelo and Prat (2015)	NR	NR	I	ER+, β-catenin+	Not reported	Surgery alone	NED
Matsuo et al. (2020)	NR	NR	I	ER+	Not reported	Surgery ± adjuvant*	NED
Present case	72	22.5 cm	IA	ER+, β-catenin+	CTNNB1, FBXW7	Surgery + letrozole	NED (36 mo)

^*Treatment and follow-up details were inconsistently reported across published cases. Most reported patients were treated with surgery alone and demonstrated favorable outcomes.

Molecular profiling supported an indolent endometrioid pathway, with a pathogenic CTNNB1 exon 3 mutation resulting in constitutive Wnt/β-catenin signaling and nuclear β-catenin accumulation (McConechy et al., 2014, Morin, 1999). This alteration is characteristic of low-grade endometrioid carcinomas and is associated with hormone receptor expression and favorable prognosis. The concurrent FBXW7 mutation is notable. FBXW7 encodes a tumor suppressor involved in ubiquitin-mediated degradation of oncogenic proteins. While FBXW7 loss has been associated with aggressive behavior in certain malignancies, its role in gynecologic cancers appears context-dependent. (Davis et al., 2014). In endometrioid carcinomas, FBXW7 mutations may coexist with CTNNB1 alterations within an indolent molecular subtype. To our knowledge, this is the first reported sertoliform endometrioid ovarian carcinoma harboring an FBXW7 mutation.

For FIGO stage IA low-grade endometrioid ovarian carcinoma, NCCN guidelines recommend observation following complete surgical staging (NCCN, 2024). Large retrospective series have demonstrated excellent outcomes with surgery alone in early-stage disease (Chan et al., 2008, Matsuo et al., 2020). In this case, letrozole was selected as an individualized, non-cytotoxic option in a postmenopausal patient with diffuse ER/PR expression and β-catenin–driven tumor biology, influenced by the extreme rarity of the sertoliform variant and limited published data guiding management. This approach represents extrapolation from other low-grade Müllerian tumors within a recognized data-free zone, including low-grade serous ovarian carcinoma and recurrent endometrial carcinoma (Gershenson et al., 2012, Slomovitz et al., 2015); observation alone would have been guideline-concordant, and the favorable outcome cannot be attributed definitively to endocrine therapy.

Surveillance consisted of clinical examination and serum tumor markers every 3–6 months for two years, with periodic imaging thereafter. ctDNA testing was used only as an adjunctive, exploratory tool. There is no evidence supporting routine ctDNA monitoring in low-grade ovarian cancer, and limited tumor shedding may reduce sensitivity; ctDNA remains investigational in this setting (Pereira et al., 2021, Zhang et al., 2022).

5. Conclusion

The sertoliform variant of ovarian endometrioid carcinoma is a distinct, hormone-responsive subtype that can closely mimic sex-cord stromal tumors. Accurate diagnosis requires careful morphologic assessment, corroborated by immunohistochemistry and molecular profiling. When confined to the ovary, prognosis is excellent following surgical resection alone. Endocrine therapy may be considered on an individualized basis in highly hormone-responsive tumors, although its role in early-stage disease remains unproven. Molecular profiling enhances diagnostic confidence and provides insight into tumor biology, while molecular surveillance strategies such as ctDNA testing remain investigational in this indolent subset.

Funding statement

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Author contributions.

J.S. conceived the case report, conducted the investigation, collected data, and drafted the manuscript. NG and KBG reviewed and proofread the final draft and contributed to literature resources and manuscript refinement.

Ethical compliance

Written informed consent was obtained from the patient for publication of this case and accompanying images. Institutional review board approval was not required.

9. Patient consent

Written informed consent was obtained from the patient for publication of this case report and accompanying images. The patient has been fully anonymized in accordance with journal policy. Institutional review board approval was not required.

10. Declaration of Generative AI and AI-Assisted Technologies in the Manuscript Preparation Process

During the preparation of this work, the author used ChatGPT (OpenAI, GPT-5 model) to assist in structuring, language refinement, and formatting of the case report. After using this tool, the author thoroughly reviewed, verified, and edited all content and takes full responsibility for the accuracy and integrity of the published article.

CRediT authorship contribution statement

Janhvi Sookram: Writing – original draft, Resources, Investigation, Data curation. Nisha Garg: Writing – review & editing, Resources. Kevin B. Gilchrist: Methodology, Data curation.

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.