When Benign Masquerades as Malignant: A Case of Expansively Growing Ovarian Leiomyoma Challenging Preoperative and Intraoperative Diagnosis.

This case report describes a 22‐year‐old female who presented with one month of irregular vaginal bleeding. She had a prior abdominal operation for “small intestinal ptosis,” a history of vulvar fibrous polyp excision, and a history of breast fibroadenoma surgery. She is unmarried and reports no history of sexual activity. Abdominal palpation revealed a pelvic mass measuring approximately 10 cm × 9 cm. The mass was firm, had limited mobility, and lacked tenderness or rebound tenderness. Imaging findings: Transabdominal and transrectal ultrasound showed an anteverted uterus of normal size and shape with an endometrial thickness of 8 mm. A hypoechoic mass on the left uterine side measured 108 mm × 86 mm × 65 mm, had clear margins, an irregular shape, heterogeneous internal echoes, and visible linear blood‐flow signals. A separate cystic mass in the left adnexal region measured 25 mm × 19 mm. Pelvic fluid accumulated to a depth of 31 mm. Contrast‐enhanced pelvic MRI demonstrated marked T2 hypointensity with strong contrast enhancement of the left adnexal mass, findings highly suggestive of an adnexal tumor. Differential diagnoses included fibrofollicular carcinoma, cystic adenofibroma, and Brenner tumor. Laboratory tests: Tumor markers were as follows: CA125 37.70 U/mL, HE4 22.90 pmol/L, and premenopausal ROMA score 1.31%. Testosterone was mildly elevated at 0.86 ng/mL. Complete blood count, liver and kidney function tests, and coagulation parameters showed no significant abnormalities. After thorough preoperative preparation and discussion with the patient's family, laparoscopic exploration was performed. Intraoperative findings: Approximately 100 mL of pale‐yellow ascites were present. Two firm masses protruded from the uterine fundus, measuring approximately 1.5–3.5 cm in diameter. The left ovary was completely distorted and replaced by multiple fused, grayish‐white, firm masses with overall dimensions of approximately 11 cm × 10 cm × 9 cm; intraoperative observation revealed that there was an absence of macroscopically identifiable normal ovarian tissue in the left ovary. The tumor had substantially replaced the ovary. The masses were densely adherent to the left uterine horn and involved the left ovarian ligament, broad ligament, and round ligament. The right adnexa appeared normal. See Figure  1 for details. Intraoperative diagnosis: Multiple tumors of the left ovary, broad ligament mass, and uterine mass. Given the extensive lesion and uncertain pathology, and with family consent, a single‐port laparoscopic–assisted small‐incision left adnexal and mass resection plus uterine mass resection was performed. Utilizing laparoendoscopic single‐site (LESS) surgery with a minor auxiliary incision in the left lower abdomen, we successfully executed en bloc resection of the left adnexa and the associated uterine ligaments, encompassing the broad, round, and proper ovarian ligaments. Concurrently, uterine fibroids were also removed. The specimen was extracted directly through the single‐port platform, thus obviating the need for abdominal extension or morcellation. Intraoperative frozen section of the left adnexa suggested a theca‐stromal tumor, with leiomyoma not excluded; final diagnosis awaited routine paraffin section and immunohistochemistry. See Figure  2 . The procedure was uneventful. Intraoperative laparoscopic views. (A) Overall view. (B) Left uterine round ligament leiomyoma view. (C) Right adnexal region view. (D) Left adnexal region view. ●: Normal anatomical structure. ▲: Leiomyoma. Intraoperative frozen section pathology image. The specimen consists of a grayish‐white, slightly yellowish, fragmented mass measuring 15 cm × 14 cm × 2 cm. The cut surface is grayish‐white with a faint yellow tinge and shows focal hemorrhage. Small cystic spaces containing pale yellow fluid are present on some cut surfaces. A fallopian tube with its fimbrial end is included, measuring 4.5 cm in length and 0.7 cm in diameter. Routine sections: Hematoxylin and eosin staining, together with immunohistochemistry, were consistent with leiomyoma in the left adnexal mass. Microscopic examination revealed only scant residual normal ovarian tissue adjacent to the leiomyoma, with the majority of the ovary replaced by the tumor. The left fallopian tube showed no significant abnormalities. See Figure  3 . Routine histopathology section image. Immunohistochemistry showed CK‐Pan (−), CD34 (−), Desmin (+), SMA (+), Caldesmon (+), ER (+), α‐Inhibin (−), CR (−), CD99 (+), CD10 (−), STAT‐6 (−), β‐Catenin (cytoplasmic +), and a Ki67 index of 5%. Ascites cytology detected no malignant tumor cells.

Xi Luo: conceptualization, data curation, funding acquisition, methodology, visualization, writing – original draft, writing – review and editing. Neng Jing Yin: data curation, methodology, supervision, writing – review and editing. Xiao Ying Fan: conceptualization. Ling Li Zhang: data curation, funding acquisition, methodology, project administration, resources. Li Sha Zou: data curation, funding acquisition, investigation, methodology, supervision, writing – review and editing.

Ethical review and approval were waived for this study due to the fact that it is a retrospective case report based on data collected during routine clinical care. Noexperimental procedures were performed, and all patient data were fully anonymized. Retrospective analyses of this nature do not require formal ethical approval. The patient provided written informed consent for both treatment and publication.

Hunan Provincial Department of Education Scientific Research Project, 25C1398. Huzhou City Social Funding Program, 2023‐81. Hunan Administration of Traditional Chinese Medicine Research Project, 20240413. Hunan University of Chinese Medicine Joint University‐Hospital Fund Project, 2024XYLH180.

Postoperatively, the patient recovered well. Testosterone decreased to 0.38 ng/mL, and the patient was discharged in remission. Discharge management and follow‐up: The patient received 3.75 mg of leuprolide acetate subcutaneously for 6 cycles after discharge. Post‐treatment gynecological color Doppler ultrasound showed an anteverted uterus with uterine body dimensions of approximately 41 mm × 38 mm × 30 mm and a cervical length of 28 mm. Borders were clear. Endometrial thickness was 3 mm with uniform echogenicity, and no significant intramyometrial mass echogenicity was detected. After left adnexal resection, the right ovary measured approximately 26 mm × 14 mm, with no significant mass echogenicity in the right adnexal region. No notable fluid‐filled hypoechoic areas were observed in the pelvis. Diagnosis: Post‐left adnexal resection, no significant abnormalities were noted elsewhere.

Ovarian leiomyoma (OL) is a rare benign tumor that arises from the smooth muscle component of ovarian tissue. Although leiomyomas most commonly occur in the uterus (uterine fibroids), they can rarely develop in the ovaries and are difficult to diagnose preoperatively. OL presents with diverse but typically nonspecific symptoms, which complicates preoperative identification. Systematic research on OL has been scarce; most publications are case reports or small retrospective series. Collectively, these reports indicate that OL usually presents as a unilateral, small (typically < 3 cm in diameter), asymptomatic incidental lesion. Bilateral occurrences have been reported, primarily in younger women [ 11 ] (around 20 years old [ 12 , 13 , 14 ]). Most cases were asymptomatic (approximately 69.2%) [ 4 ] and were often discovered incidentally during surgery as small tumors [ 1 ]. The most commonly affected age group is perimenopausal women [ 15 ], whereas postmenopausal tumors tended to be larger. Symptoms of ovarian leiomyomas were generally nonspecific. Most reported tumors were small (mean diameter ~3.7 cm) and produced no subjective symptoms; as tumors enlarged, chronic or persistent lower abdominal pain developed [ 5 ]. Torsion caused acute abdominal pain in some cases [ 16 ]. Abdominal mass or distension occurred when tumors were large—for example, tumors exceeding 10 cm produced palpable abdominal masses or progressive distension [ 17 ]. Additional reported symptoms included heavy menstrual bleeding, intermenstrual bleeding [ 15 ], or postmenopausal bleeding [ 17 ]. OL is a benign smooth muscle tumor, histologically similar to uterine leiomyoma, but originating within ovarian tissue [ 3 ]. Previous reports state that primary OL typically presents as a well‐defined, small, solitary tumor, unilateral in most cases and bilateral only rarely in young women [ 15 ], contrasting markedly with malignant leiomyosarcoma. However, this case is the first reported pathologically confirmed benign OL that showed an invasive, disseminated, multifocal fusion pattern of local growth at surgery. We performed single‐port laparoscopic surgery and found the left ovary completely deformed and replaced by multiple fused grayish‐white hard masses measuring approximately 11 cm × 10 cm × 9 cm in total. Minimal residual normal ovarian tissue remained and was nearly negligible. The mass was densely adherent to the left uterine horn, and the left ovarian ligament, broad ligament, and round ligament contained multiple disseminated lesions. The precise mechanism responsible for the dense adhesion between the tumor and the left uterine horn remains uncertain. However, intraoperative observations suggest a potential association with the rare multifocal fused or dissemination/implantation‐like growth pattern occasionally exhibited by ovarian leiomyomas. Two firm masses, 1.5 cm and 3.5 cm in diameter, protruded from the uterine fundus and appeared disseminated across the uterine surface. The right adnexa showed no external abnormalities. This pattern represents the extremely rare “invasive localized growth variant,” a phenotype that displays growth characteristics similar to malignant tumors. Crucially, such growth patterns complicate surgeons' initial intraoperative decision‐making, particularly for young women who wish to preserve fertility. Previously, no reports described this extremely rare “aggressive localized growth variant” pattern in OL. Because malignant or borderline tumors were initially suspected, unilateral adnexal resection with frozen section analysis was the prudent choice. This study documents this exceptionally rare “aggressive localized growth variant,” improving understanding of the pattern and prompting further consideration of whether tumor excision alone is feasible. Ovarian leiomyoma (OL) is extremely rare and is seldom considered a primary clinical differential diagnosis. Imaging studies and intraoperative biopsies present substantial diagnostic challenges. Definitive diagnosis requires immunohistochemical analysis of routine histopathology specimens. Clinically, the main differential diagnosis is ovarian fibroma; in the present case, the intraoperative frozen section was interpreted as an ovarian theca‐stromal tumor. OL resembles uterine leiomyoma, consisting of well‐differentiated smooth muscle cells arranged in bundles or whorls. The nuclei are spindle‐shaped with minimal atypia and mitotic figures are rare. Immunohistochemistry shows positivity for smooth muscle actin (SMA), desmin, and caldesmon [ 18 ]. Sex cord–stromal tumors (e.g., granulosa cell tumors) are distinguished by expression of sex hormone markers such as inhibin and calretinin. Immunohistochemical negativity for inhibin‐α is the gold standard for excluding fibromas and theca cell tumors. Ovarian fibromas can appear morphologically similar but lack smooth muscle differentiation markers, for example they are desmin‐negative [ 19 ]. Elevated serum testosterone in this case suggests a sex cord–stromal tumor. Ultrasound showing ascites and a solid adnexal mass primarily indicates malignant ovarian carcinoma, although benign lesions such as Meigs syndrome or ovarian fibromas can also produce ascites. Mechanisms include tumor compression of blood vessels or lymphatics, stimulation of peritoneal fluid production, or hormone‐mediated effects. Its rapid growth and extensive involvement raised concern for leiomyosarcoma. The absence of cellular atypia, a high mitotic rate, and tumor necrosis on pathology is the gold standard for distinguishing sarcomas. In diagnosing primary ovarian leiomyomas, our case emphasizes the importance of microscopic features to differentiate them from ovarian fibromas, leiomyosarcomas, and stromal tumors. The cystic–solid appearance of OL significantly complicates preoperative diagnosis. As OL enlarges, portions of the tissue undergo infarction and liquefaction, producing cystic changes on imaging. This mixed appearance displays features that mimic malignancy both radiologically and clinically [ 17 ]. The underlying mechanism may involve cystic degeneration of leiomyomas related to ischemia, necrosis, or mucoid degeneration. Studies indicate that uterine leiomyomas selectively proliferate under hypoxic conditions via activation of factors such as VEGF through the HIF‐1α pathway, which can lead to local ischemic necrosis and cystic degeneration [ 19 ]. On ultrasound, OL can appear as a well‐defined cystic–solid mass: the solid component shows heterogeneous echogenicity, whereas the cystic areas reflect degeneration or necrosis. Sixty‐four point 4% of ovarian carcinosarcomas present as “solid tumors with cystic areas,” with the solid tissue showing a “cooked appearance” [ 20 ]. Although that description refers to malignant tumors, it highlights the diagnostic importance of cystic–solid morphology [ 21 ]. On MRI, OL may present as a layered core on T2‐weighted images, clearly showing cystic–solid mixing; the solid portions typically have low to moderate signal intensity (similar to uterine leiomyomas), while the cystic regions show high signal intensity. Care is warranted regarding imaging overlap with degenerative changes in uterine leiomyomas (e.g., mucoid degeneration or necrosis) [ 22 ]. PET/CT findings have occasionally shown ovarian leiomyomas with high FDG uptake, potentially leading to misdiagnosis as malignant ovarian tumors [ 23 ]. However, the literature has also noted that benign metastatic leiomyomas (BML) may demonstrate lower FDG uptake, and FAPI (fibroblast activation protein inhibitor) PET/CT may offer greater sensitivity [ 23 ]. Most ovarian leiomyomas (OLs) are unilateral, well circumscribed, and solitary. In contrast, this case presented multiple, disseminated, and invasive features: numerous smooth muscle tumors involved the ovarian surface, uterine surface, left ovarian ligament, broad ligament, and round ligament. The tumors were confluent, retained clear boundaries, and showed irregular shapes. The contralateral fallopian tube and ovary were not involved. This unilateral distribution supports the “local origin” hypothesis (ovarian hilum vascular smooth muscle). Although leiomyomas typically arise from uterine smooth muscle cells [ 22 ], the presence of vascular smooth muscle in the ovarian hilum (the muscular layers of the ovarian artery and vein) provides histological support for a local origin of primary ovarian leiomyomas. Ovarian portal vascular smooth muscle may serve as the cellular source of OL [ 24 ]. Multiple studies emphasize the role of angiogenesis in leiomyoma development. The ovarian vasculature undergoes continuous remodeling during the ovulatory cycle, and active angiogenesis occurs within leiomyomas. Abnormal vascular remodeling of ovarian portal vascular smooth muscle may therefore initiate tumor formation, consistent with the unilateral presentation of OL [ 25 ]. Mutations in genes such as MED12 and HMGA2, which have been identified in uterine leiomyomas, may likewise arise in ovarian portal vascular smooth muscle [ 14 ]. Clonal analyses confirm that multiple leiomyomas can originate from a single precursor cell, supporting the hypothesis that OL may arise from clonal expansion of locally mutated cells a hormone‐sensitive constitution [ 26 ]. Ovarian steroid hormones (estradiol, progesterone) regulate smooth muscle cells [ 27 ]. The vascular smooth muscle of the ovarian hilum is directly exposed to the ovary's locally concentrated hormonal environment, which may promote unilateral tumorigenesis via hormone receptor pathways [ 28 ]. Multifocal or ligament involvement can be explained by either a “multicentric origin” or direct contiguous spread along ipsilateral ligament structures. The patient had concurrent uterine fibroids, which may suggest a potential role for hormonal factors in the development of both tumors, although the exact pathogenesis of multifocal OL remains unclear and requires further investigation. Therefore, we administered 6 months of gonadotropin‐releasing hormone analogue (GnRH‐a) therapy postoperatively to assess its potential to reduce recurrence rates. However, in most postmenopausal patients with large symptomatic OL, the markedly low estrogen levels after menopause may render OL hormone‐insensitive. OL are rare in clinical practice, so primary care physicians may encounter them only infrequently, and intraoperative frozen‐section pathology often fails to deliver a rapid, definitive diagnosis. When surgeons encounter large, irregularly shaped tumors with multiple fusions that mimic malignant growth patterns, widening the surgical field (e.g., adnexal resection) is a reasonable and prudent choice. Improved recognition of this condition has allowed intraoperative identification of benign features that enable maximal preservation of ovarian tissue—a consideration especially important for young women who desire fertility. Current literature on the direct impact of OL on fertility is limited. In this case, the tumor occupied the vast majority of the ovary, leaving minimal residual ovarian tissue. Potential mechanisms by which fertility may be impaired include: (1) mechanical interference—compression of the ovarian cortex or fallopian tube that affects follicular development or oocyte transport; (2) altered local microenvironment—local inflammation or disrupted blood flow that compromises oocyte quality or embryo implantation [ 29 ]; and (3) endocrine disruption—secretion of bioactive substances by the lesion that perturbs ovarian hormone balance [ 30 ]. Existing evidence indirectly suggests that ovarian leiomyomas may impair fertility through mechanical compression or local microenvironmental changes, particularly when lesions are multiple or large. However, targeted studies are needed to clarify their independent effect on fertility. Management should be individualized, with priority given to preserving ovarian function [ 31 ]. The role of multidisciplinary teams (MDTs) in preoperative planning and intraoperative emergency decision‐making is emphasized, as is the essential role of comprehensive pathological assessment in preventing overtreatment. This single‐center case report warrants cautious extrapolation of its conclusions. Its simulation of malignant tumor growth patterns serves as a valuable teaching case. Although OL is benign, it can present with an alarmingly invasive appearance. OL should be included in the differential diagnosis of complex solid adnexal tumors in young women. Diagnosing OL requires comprehensive histopathological and immunohistochemical analysis, which is essential for tailoring treatment, particularly fertility‐sparing approaches.

Written informed consent has been obtained from the patient to publish this paper, including any potentially identifiable data or images. We declare that the patient has been informed and agrees to publish identifiable information in open access journals.

Histological classification of ovarian tumors includes epithelial tumors, germ cell tumors, sex cord–stromal tumors, other types, and metastatic tumors. Solid or predominantly solid lesions encompass ovarian carcinoma, fibrofolliculoma, granulosa cell tumor, Brenner tumor, and others. Consequently, preoperative imaging and ancillary tests often fail to distinguish OL from these entities. OL is often misdiagnosed as ovarian carcinoma or as other solid ovarian spindle cell tumors, such as ovarian fibromas, stromal tumors, or leiomyosarcomas [ 10 ]. Immunohistochemistry effectively excludes malignancy and remains the gold standard for confirming an OL diagnosis [ 7 ].

Ovarian leiomyoma (OL) is a mesenchymal tumor that originates in the ovary. Although its precise tissue origin remains unclear, most researchers propose that it arises from vascular smooth muscle at the ovarian hilum. OL may also develop from the ovarian cortex or stroma, from smooth muscle of the broad ligament, or through ovarian endometriosis. Currently, no established diagnostic criteria exist for OL. Its histological features closely resemble those of uterine leiomyomas, and pathology is the diagnostic gold standard. Confirmation is achieved by immunohistochemical staining, which typically shows positive expression of smooth muscle actin and desmin [ 1 ]. Sangalli first described OL in 1862 [ 2 ], classifying them as rare benign ovarian tumors that represent 0.5% to 1% of all benign ovarian neoplasms [ 3 ]. To date, approximately 100 cases have been reported worldwide [ 4 ]. Most OL are asymptomatic or produce only mild symptoms and are often found incidentally during examinations or surgery. As the tumor grows, it can compress surrounding organs and cause abdominal pain or distension [ 5 ], palpable abdominal masses [ 6 ], and abnormal uterine bleeding, which may result from coexisting uterine fibroids or tumor‐induced endocrine disturbances [ 7 ]. The age distribution is concentrated mainly between 20 and 65 years, with most cases occurring in premenopausal women [ 8 ]. Incidence peaks between ages 39 and 45 [ 9 ]. Typically, the lesion is unilateral, although bilateral cases have been reported. Tumor diameters range from 1.2 to 7.0 cm, with a mean of 3.7 cm. Larger masses—reported to reach 25 cm—have produced progressive abdominal distension [ 4 ]. The biological behavior of OL is comparable to that of benign uterine leiomyomas and is characterized by well‐defined tissue margins. Although occasional atypical cases have been reported in the literature, none have demonstrated the extensive involvement that mimicked malignant tumor characteristics as observed in this case. This extreme example necessitated a re‐evaluation of the clinicopathological spectrum of OL, explored the root causes of diagnostic confusion, and had profound implications for treatment decisions in young patients.

The authors declare no conflicts of interest.