Primary Mesonephric-Like Adenocarcinoma of the Ovary: A Case Report and Literature Review.

A 67‐year‐old postmenopausal woman (13 years since menopause) presented to the urology department with a 2‐week history of gross hematuria. The ultrasound examination of the urinary system revealed mild hydronephrosis of the right kidney, dilatation of the right mid‐to‐upper ureter with indistinct visualization of the distal segment, and a heterogeneous pelvic mass measuring 13.5 × 9.5 cm in the lower abdomen. Then, computed tomography urography (CTU) examination suggested a 15 × 10 × 12 cm cystic solid right adnexal mass causing extrinsic compression and stenosis of the right ureter at the iliac vessel crossing, accompanied by proximal ureteral dilatation. The patient was subsequently referred for gynecological evaluation. Notably, she reported no postmenopausal bleeding or abdominal pain. Her medical history included right calf muscular venous thrombosis treated with rivaroxaban (15 mg daily) for 5 months, with no bleeding complications. Physical and diagnostic findings: (1) Pelvic examination: atrophic cervix with mild hyperemia, and a firm, nontender pelvic mass (approximately the size of a fetal head) palpated posterior to the uterus. (2) Serum tumor markers: CA125, CA19‐9, CEA and AFP levels within normal limits. (3) Transvaginal ultrasound: The uterine morphology is normal, and a 0.7 × 0.5 × 0.4 cm hyperechoic lesion was found in the lower anterior wall, with uneven echo and small fluid‐filled areas inside the endometrium. A nonpurely cystic hypoechoic area measuring 12.5 × 14.0 × 9.3 cm was observed in the pelvic cavity, with a slight blood flow signal detected in the periphery (Figure  1 ). The bilateral ovaries were not visualized. (4) Pelvic magnetic resonance imaging (MRI): A massive cystic lesion was found in the pelvic cavity, measuring approximately 10.1 × 15.2 cm, with enhanced nodules observed along its periphery and inner wall (Figure  2 ). The solid components demonstrated iso‐hypointense on T1‐weighted images (T1WI), low signal intensity on T2‐weighted images (T2WI), and the signal was uneven on diffusion‐weighted imaging (DWI) with an apparent diffusion coefficient (ADC) value of 1.0 × 10 −3  mm 2 /s. The boundary between the lesion and the right adnexa was unclear, suggesting possible cystadenocarcinoma. A small amount of fluid was present in the pelvic cavity. No enlarged lymph nodes in the pelvic cavity were identified. Based on the patient's medical history and examination results, the preliminary diagnoses were ovarian cystadenocarcinoma (high suspicion) and right calf muscular venous thrombosis (stable on rivaroxaban). Transvaginal ultrasound image of adnexa. The pelvic magnetic resonance imaging (MRI) findings.

Na Zuo: formal analysis, writing – original draft, writing – review and editing. Li Peng: formal analysis, writing – review and editing. Di Wu: visualization. Gang Lv: conceptualization, supervision, writing – review and editing. Lu Yang: formal analysis, funding acquisition, supervision, writing – review and editing.

The research does not require the approval of the ethics committee. Written informed consent was obtained from the patient for the publication of anonymized data and accompanying images.

The final histopathological evaluation confirmed MLA involving the right ovary (Figure  3 ), coexisting with endometrial cysts. The right fallopian tube demonstrated no neoplastic involvement on microscopic examination. Immunohistochemical staining of the tumor cells revealed positive expression of PAX8 and GATA3, partially positive for CD10 at the lumen edges, and wild‐type for P53 expression. Notably, the tumor showed complete negativity for estrogen receptor (ER), progesterone receptor (PR), and TTF‐1 (Figure  4 ). All surgical margins (left adnexa, uterine corpus/cervix, omentum, and appendix) were free of malignancy. Microscopic examination of the preoperative peritoneal lavage fluid revealed mesothelial cells and a small number of inflammatory cells, but no tumor cells were identified. The final postoperative diagnosis was stage IIB MLA of the ovary, endometrial cyst, and intramuscular vein thrombosis in the lower extremities. Histological images of the ovarian masses. Immunohistochemical staining of the tumor cells. Following surgery, the patient underwent adjuvant chemotherapy consisting of 8 cycles of liposomal paclitaxel (150 mg/m 2 ) and carboplatin (AUC 5 mg/mL·min). After the completion of 2 cycles, the pelvic MRI showed a nodular lesion in the pelvic area (left of the rectum), measuring approximately 13 × 11 mm, with restricted diffusion and annular enhancement on DWI, suggestive of a metastatic tumor. The patient continued chemotherapy for two additional cycles, and a subsequent follow‐up MRI demonstrated a significant reduction in the size of the nodular lesion (approximately 8 × 8 mm). Then, after another 2 cycles of chemotherapy, a pelvic MRI showed no evidence of the nodular lesion in the pelvic area. Subsequently, the patient received 2 cycles of consolidation chemotherapy and successfully completed the treatment regimen. Thereafter, the patient has continued to receive oral apatinib as maintenance therapy up to the present date. After a 25‐month follow‐up, there is no evidence of recurrence, and the patient continues to be monitored. It is notable that the patient's tumor markers remained within the normal range throughout the perioperative period, including before surgery, after surgery, and during chemotherapy.

A laparotomy was performed on May 10, 2023. During the operation, a small amount of pelvic fluid was noted, but no significant abnormalities were observed in the left adnexal region. However, the right ovary was markedly enlarged, measuring about 10 × 15 cm, and appeared as a solid cystic mass. No abnormalities were found in the omentum and appendix. The right ovarian mass was densely adherent to the posterior uterine wall and adjacent intestines. The mass demonstrated high tension, and the cystic fluid appeared brown. A total of approximately 1100 mL of the fluid was aspirated. The right adnexa, along with the mass, was resected and sent for intraoperative frozen section examination, which reported a provisional diagnosis of an epithelial‐derived borderline ovarian tumor. A definitive diagnosis was deferred pending routine pathological results. Given the patient's age and preoperative conversation, a total hysterectomy with bilateral adnexectomy, omentectomy, and appendectomy was performed. However, due to the adhesion of the mass to the anterior rectal wall, residual tumor tissue was noted postoperatively on the anterior rectal wall, measuring approximately 1.5 cm in diameter with ill‐defined borders.

Mesonephric‐like adenocarcinoma (MLA) of the ovary is a rare malignant ovarian neoplasm, accounting for less than 1% of all ovarian tumors [ 2 ]. There are theories suggesting that this tumor may originate from the Müllerian duct and mainly present as mesonephric differentiation. Although the MLA of the ovary shares histological and immunophenotypic similarities with mesonephric adenocarcinomas, some reports suggest a coexistence of MLA with endometriosis, seromucinous borderline tumor, endometrioid adenocarcinoma, and low‐grade serous carcinoma that seem to support the theory that ovarian MLA originates from the Müllerian duct [ 3 , 4 , 5 ]. The coexistence of ovarian MLA with an endometriotic cyst in this case may further support its origin from Müllerian duct epithelium. The clinical characteristics, diagnostic criteria, and therapeutic approaches for this tumor remain to be further standardized. Based on a reported case of stage IIB ovarian MLA presenting with hematuria as the initial symptom, along with an extensive review of existing literature, the following critical issues were systematically analyzed and discussed. Although ovarian MLA is extremely rare, these tumors share clinical characteristics with other types of ovarian cancer. A multicenter study reported that the average age at diagnosis for ovarian MLA is 61 years, with pelvic pain (43%) being the most common symptom [ 6 ]. Additional symptoms may include abnormal uterine bleeding/postmenopausal bleeding (17%) and abdominal distension (17%). Notably, approximately 20% of patients are asymptomatic at presentation. In this case, the patient's initial clinical manifestation was gross hematuria, which resulted from ureteral stenosis due to compression by the pelvic mass. This presentation is also frequently observed in other forms of ovarian cancer. Therefore, the clinical manifestations of ovarian MLA are highly variable, and the early presentation of nongynecological symptoms indicates that clinicians should consider MLA in the differential diagnosis for pelvic space‐occupying lesions. Currently, the definitive diagnosis of ovarian MLA relies solely on a comprehensive integration of histopathological and immunohistochemical analysis. Pathologically, mesonephric‐like carcinomas can exhibit a diverse array of histologic patterns, including tubular, ductal, reticular, papillary, corded, glandular, glomerular, spindle‐shaped structures, as well as sieve‐like formations and their combinations [ 7 ]. Immunohistochemically, MLA resembles mesonephric adenocarcinomas (MA), with most cases showing positivity for GATA3, PAX8, TTF‐1, and calretinin [ 8 ]. CD10 staining is observed within the lumens, while WT‐1 and estrogen and progesterone receptors are negative [ 7 , 9 ]. Occasionally, there are reports of focal ER positivity, and P53 can also be positive in some cases [ 9 , 10 ]. In this case, the characteristic immunohistochemical profile (PAX8+/GATA3+/ER–/TTF‐1–) confirmed the diagnosis. Nearly all cases of MLA (92%) exhibit TTF‐1 positivity [ 11 ]. However, TTF‐1 expression was negative in the present case. Additionally, it may be advisable to screen for potential metastases or thyroid carcinoma involvement. At the molecular level, ovarian MLA is characterized by KRAS mutations, but lacks PTEN mutations/loss or microsatellite instability and gains of chromosome 1q [ 10 , 11 , 12 ]. Currently, there is no specific imaging feature for ovarian MLA, which may present as cystic‐solid mixed masses or purely solid masses [ 8 ]. Available case reports suggest its solid components typically appear hypointense signals on T2WI and heterogeneous hyperintense signals on DWI with low ADC values [ 13 , 14 , 15 ]. In a case of coexisting endometrial MLA and low‐grade endometrioid carcinoma, following 6 months of high‐dose megestrol acetate treatment, only the MLA lesion recurred after 6 years, with imaging showing complete low signal intensity on T2WI compared to partial low signal intensity observed at the initial diagnosis [ 5 ]. In the present case, the solid components exhibited low signal intensity on T2WI and heterogeneous signal intensity on DWI with low ADC values, which may correlate closely with the underlying pathological microstructure. According to the reports, the solid regions of MLA likely contained abundant fibrotic tissue, which could lead to decreased signal on T2WI [ 15 ]. Due to the high cellular density of the solid components and the tightly arranged glandular structures in MLA, water molecule diffusion is restricted, leading to heterogeneous DWI signals and low ADC values. This diffusion restriction is consistent with the imaging characteristics of highly aggressive malignancies. Notably, the imaging features of MLA are not specific and may overlap with other epithelial ovarian malignancies. However, in this case, the hypointense T2WI signal of the solid components, along with the heterogeneous DWI signal and low ADC values, provides valuable imaging‐pathological correlations. Further accumulation of cases is crucial to refine the imaging‐pathological associations and improve the preoperative assessment of this rare tumor. The limitations of serum tumor biomarkers in MLA management are strikingly evident in this case. Preoperative diagnosis of ovarian epithelial tumors is often supported by elevated serum CA125 levels [ 16 ]. Research indicates that CA125 levels are generally elevated in advanced‐stage ovarian MLA, though in the early stages, they may remain within the normal range [ 12 ]. In this case, CA125 levels remained normal throughout the clinical course. Human epididymis protein 4 (HE4) has demonstrated superior sensitivity and specificity for diagnosing and monitoring ovarian epithelial tumors [ 17 ], especially in distinguishing malignant ovarian tumors from benign conditions such as endometriosis and ovarian cysts, where CA125 levels are often falsely elevated. However, the patient's HE4 levels remained below 140 pmol/L (reference range: premenopausal < 70 pmol/L, postmenopausal < 140 pmol/L) throughout the treatment period. This demonstrated that the role of HE4 in MLA monitoring remains undefined, in contrast to its well‐established use in epithelial ovarian malignancies. Regarding therapeutic strategies, the management of ovarian MLA remains undefined due to its rarity, and existing strategies are primarily adapted from epithelial ovarian cancer (EOC) guidelines. Studies have shown that 39% of ovarian MLA patients present with advanced stage (FIGO II–IV), and 43% of patients have lymph node metastasis [ 6 ]. The absence of systematic lymphadenectomy in this case, with staging based solely on pelvic metastasis (IIB), may lead to potential understaging. Emerging evidence underscores the necessity of adjuvant chemotherapy, as exemplified by a case series demonstrating aggressive behavior in untreated early‐stage disease: A stage IA patient developed multiorgan metastases (peritoneal, pulmonary, hepatic) within 13 months postoperatively [ 8 ]. In the present case, complete resolution of a rectal‐adjacent metastatic lesion was achieved after 6 cycles of liposomal paclitaxel‐carboplatin. This is consistent with the literature, which indicates that response rates to first‐line platinum‐doublet chemotherapy for metastatic disease may be higher than initially anticipated [ 18 ]. Given the residual micro‐metastasis risk evidenced by initial treatment, two additional consolidation cycles were administered. This chemotherapy outcome suggests the potential sensitivity of ovarian MLA to platinum‐based chemotherapy regimens, warranting further investigation into its clinical implications. Currently, the primary maintenance treatment options for advanced ovarian cancer include PARP inhibitors and bevacizumab. Apatinib is an oral tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor‐2 (VEGFR‐2). A patient diagnosed with stage IVb high‐grade serous carcinoma (HGSC) achieved a progression‐free survival of 54 months following treatment with off‐label apatinib [ 19 ]. The introduction of apatinib supports further exploration in the maintenance therapy of MLA. The patient's prolonged remission (lasting 25 months) indicates that anti‐angiogenic therapies may effectively suppress microscopic residual disease in highly vascularized tumors. Follow‐up reports from multicenter studies demonstrated a 5‐year progression‐free survival (PFS) rate of 68% and a 5‐year overall survival (OS) or disease‐specific survival (DSS) rate of 71% among patients with ovarian MLA [ 6 ]. In this case, the favorable oncologic outcome (25‐month recurrence‐free survival) may be attributed to relatively early‐stage detection and achievement of complete clinical response following platinum‐based chemotherapy. However, this case quintessentially illustrates the surveillance dilemma in biomarker‐negative populations: the absence of serologic markers renders conventional CA125‐dependent surveillance protocols ineffective, necessitating paradigm shifts toward imaging‐centric monitoring frameworks. In this case, we utilized MRI to monitor the patient's condition based on the recognition of residual metastatic lesions during chemotherapy. Notably, the diagnostic efficacy of positron emission tomography‐computed tomography (PET‐CT) in detecting subclinical residual disease remains unvalidated in MLA, which may require more comprehensive and detailed investigations. Based on this case and literature synthesis, we propose the following clinical recommendations: Firstly, MLA should be considered in postmenopausal women with pelvic masses and urinary obstruction, even with normal biomarkers. Secondly, MRI may replace CA125 as the cornerstone for monitoring, given its superior sensitivity for small‐volume disease. Thirdly, early‐stage MLA may be managed with comprehensive staging surgery and platinum‐based chemotherapy, while advanced cases may benefit from anti‐angiogenic agents. Future studies may focus on molecular subtyping of MLA to identify potential therapeutic targets and establish international criteria for refining diagnostic and therapeutic protocols.

We report a case of ovarian MLA combined with an endometriosis cyst. This case illustrates the diagnostic complexity and therapeutic potential of MLA. The integration of radical surgery, post‐operation chemotherapy, and anti‐angiogenic maintenance therapy underscores the importance of personalized strategies for ovarian MLA. While long‐term survival in this patient is encouraging, more clinical and basic research is needed for a better understanding of this disease and for establishing international criteria for refining diagnostic and therapeutic protocols and developing prognostic models.

Mesonephric‐like adenocarcinoma (MLA), first identified as a novel classification of primary ovarian cancer in the 2020 World Health Organization classification of female genital tumors [ 1 ], presents diagnostic and therapeutic challenges due to its nonspecific clinical presentation, which overlaps with other ovarian carcinomas. We report a detailed clinicopathological case of a 67‐year‐old patient with ovarian MLA coexisting with endometriotic cysts, encompassing diagnostic procedures, therapeutic interventions, and follow‐up outcomes. Through a systematic literature review, we synthesize current evidence on MLA's clinical and pathological patterns, immunoprofile, radiological imaging presentations, treatment, and clinical outcomes. This study provides actionable insights to refine diagnostic accuracy and guide evidence‐based management of this emerging tumor.

The authors declare no conflicts of interest.