Clinical and Pathological Profiles and Recurrence Risk Factors of Uterine Leiomyoma Variants：A Retrospective Cohort Study

Clinical and Pathological Profiles and Recurrence Risk Factors of Uterine Leiomyoma Variants：A Retrospective Cohort Study | Authorea try { document.documentElement.classList.add('js'); } catch (e) { } var _gaq = _gaq || []; _gaq.push(['_setAccount', 'G-8VDV14Y67G']); _gaq.push(['_trackPageview']); (function() { var ga = document.createElement('script'); ga.type = 'text/javascript'; ga.async = true; ga.src = ('https:' == document.location.protocol ? 'https://ssl' : 'http://www') + '.google-analytics.com/ga.js'; var s = document.getElementsByTagName('script')[0]; s.parentNode.insertBefore(ga, s); })(); Skip to main content Preprints Collections Wiley Open Research IET Open Research Ecological Society of Japan All Collections About About Authorea FAQs Contact Us Quick Search anywhere Search for preprint articles, keywords, etc. Search Search ADVANCED SEARCH SCROLL This is a preprint and has not been peer reviewed. Data may be preliminary. 4 March 2026 V1 Latest version Share on Clinical and Pathological Profiles and Recurrence Risk Factors of Uterine Leiomyoma Variants：A Retrospective Cohort Study Authors : Chunming Li , Wenchao Zhou , Huiyu Fan , Zheng Lou , Yizhou Huang , Linjuan Ma , and Jianhong Zhou 0000-0003-3028-9426 [email protected] Authors Info & Affiliations https://doi.org/10.22541/au.177265810.06808962/v1 187 views 92 downloads Contents Abstract Supplementary Material Information & Authors Metrics & Citations View Options References Figures Tables Media Share Abstract Objective : To evaluate the prevalence and independent risk factors for recurrence following myomectomy of leiomyoma variants. Design: Retrospective cohort study Setting : Women’s Hospital, Zhejiang University School of Medicine. Population or Sample : 723 consecutive patients with confirmed variant leiomyomas (cellular, bizarre nuclei, mitotically active, etc.) treated from January 2014 to December 2024. Among these, 443 women undergoing uterine-conserving surgery were analyzed for recurrence. Methods : Medical records were reviewed for clinicopathological characteristics, surgical approaches, and follow-up data. Risk factors were analyzed using univariate and multivariate logistic regression. Cumulative recurrence rates were calculated using Kaplan-Meier analysis. Main Outcome Measures: Recurrence rate, time to recurrence, predictive risk factors, and cumulative recurrence rates at 12, 36, and 96 months. Results: Cellular leiomyoma was the most common subtype (65.0%). Recurrence occurred in 117 patients (26.4%). Of these, 51 (43.6%) required reoperation, with 34 (66.7%) undergoing hysterectomy. Two leiomyomas with bizarre nuclei recurred as sarcomas; three cellular leiomyomas progressed to disseminated peritoneal leiomyomatosis. Independent predictors of recurrence included younger age, open myomectomy, greater number of fibroids removed, increased intraoperative blood loss, and nulliparity. Pregnancy was protective. Cumulative recurrence rates were 30.7% at 12 months, 68.7% at 36 months, and 94.9% at 96 months. Conclusion: Leiomyoma variants demonstrate high recurrence rates post-myomectomy. Younger patients, open surgical approach, multiple fibroids, and significant bleeding are associated with increased risk, while pregnancy is protective. Close long-term surveillance is essential given the potential for malignant transformation. Clinical and Pathological Profiles and Recurrence Risk Factors of Uterine Leiomyoma Variants：A Retrospective Cohort Study Chunming Li MD a , Wenchao Zhou MD b , Huiyu Fan MD a , Zheng Lou MD a , Yizhou Huang MD a , Linjuan Ma MD a , Jianhong Zhou MD a# a Women’s Reproductive Health Key Laboratory of Zhejiang Province, Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou 310006, China b Cixi People’s Hospital Medical and Health Group # Correspondence and requests for materials should be addressed to J. Z. ( [email protected] ). Women’s Reproductive Health Key Laboratory of Zhejiang Province, Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou 310006, China Running Foot Uterine Leiomyoma Variants: Clinical-Pathological Profiles and Recurrence Risks Abstract Objective : To evaluate the prevalence and independent risk factors for recurrence following myomectomy of leiomyoma variants. Design: Retrospective cohort study Setting : Women’s Hospital, Zhejiang University School of Medicine. Population or Sample : 723 consecutive patients with confirmed variant leiomyomas (cellular, bizarre nuclei, mitotically active, etc.) treated from January 2014 to December 2024. Among these, 443 women undergoing uterine-conserving surgery were analyzed for recurrence. Methods : Medical records were reviewed for clinicopathological characteristics, surgical approaches, and follow-up data. Risk factors were analyzed using univariate and multivariate logistic regression. Cumulative recurrence rates were calculated using Kaplan-Meier analysis. Main Outcome Measures: Recurrence rate, time to recurrence, predictive risk factors, and cumulative recurrence rates at 12, 36, and 96 months. Results: Cellular leiomyoma was the most common subtype (65.0%). Recurrence occurred in 117 patients (26.4%). Of these, 51 (43.6%) required reoperation, with 34 (66.7%) undergoing hysterectomy. Two leiomyomas with bizarre nuclei recurred as sarcomas; three cellular leiomyomas progressed to disseminated peritoneal leiomyomatosis. Independent predictors of recurrence included younger age, open myomectomy, greater number of fibroids removed, increased intraoperative blood loss, and nulliparity. Pregnancy was protective. Cumulative recurrence rates were 30.7% at 12 months, 68.7% at 36 months, and 94.9% at 96 months. Conclusion: Leiomyoma variants demonstrate high recurrence rates post-myomectomy. Younger patients, open surgical approach, multiple fibroids, and significant bleeding are associated with increased risk, while pregnancy is protective. Close long-term surveillance is essential given the potential for malignant transformation. Funding : This work was supported by the National Key Research and Development Program of China (2022YFC2704100), Natural Science Foundation of Zhejiang (LY24H260001). Keywords: Recurrence; leiomyoma variants; myomectomy; risk factor; uterine-conserving surgery Funding This work was supported by the National Key Research and Development Program of China (grant number 2022YFC2704100), the Natural Science Foundation of Zhejiang (grant number LY24H260001). All awarded grants underwent external peer review for scientific quality by independent expert panels. The National Key Research and Development Program of China was reviewed by a multidisciplinary committee of senior researchers and clinical experts. The Natural Science Foundation of Zhejiang employed a blinded peer review process involving domain-specific reviewers. The funders had no role in study design, data collection, data analysis, data interpretation, or writing of the manuscript. The research team had full independence in conducting the study and deciding to submit the article for publication. Introduction Uterine fibroids (UF), represent the most prevalent benign neoplasms in the female reproductive tract [1]. While most exhibit typical histological features, rare pathological variants (e.g., cellular leiomyoma, fumarate hydratase-deficient leiomyoma, et al.) identified in the 2020 World Health Organization (WHO) Classification account for approximately 10% of preoperative uterine myoma suspicions [2]. These variants share common clinical presentations include abnormal uterine bleeding, pelvic heaviness and the intraoperative management with conventional leiomyomas, but their rarity hinders epidemiologic research and evidence-based guideline development. Despite benign histopathological classification, some variants exhibit distinct pathological features, particularly in increased mitotic activity, cellular atypia and quasi-malignant phenotypes [4], with molecular studies linking certain subtypes to transcriptional profiles resembling leiomyosarcomas [5] , suggesting unique implications for patient outcomes. Myomectomy is a preferred surgical option for fertility-preserving treatment of uterine fibroids, but recurrence remains a major concern, with 10-year cumulative recurrence rates of up to 27% for conventional leiomyomas [6] . For rare variants, existing recurrence-related research is limited by mixed surgical outcome data (combining myomectomy and hysterectomy), inconsistent classification systems, and short follow-up periods, leading to unclear recurrence patterns and prognostic differences from common fibroids. This knowledge gap also lacks consensus on postoperative management, challenging clinical decision-making. This study aims to comprehensively analyze the clinical, surgical, and pathological characteristics of uterine leiomyoma variants in a large patient cohort. By identifying key recurrence risk factors, we seek to fill current knowledge deficits and provide evidence to optimize personalized management strategies for women with these unique uterine tumors. Materials and Methods This was a single-center, retrospective descriptive study conducted at Women’s Hospital, Zhejiang University (Hangzhou, China), a tertiary referral center. Consecutive case diagnosed with uterine leiomyoma variants via postoperative pathological examination between January 2014 and December 2024 were eligible for enrollment. Clinical data were retrieved retrospectively from electronic medical records and telephone-based follow-up, which included demographic characteristics, initial diagnosis, clinical manifestations, preoperative evaluations, surgical details, postoperative pathological results, clinical status at the latest follow-up, and survival outcomes. Only patients who underwent myomectomy were included. Patients received gynecological examinations and ultrasound imaging at 3 months postoperatively. At the 3-months follow-up, ultrasound imaging was used to confirm if there was no fibroid residual or a maximum diameter ≤2 cm. Inadequate tumor resection was defined as residual fibroids＞2 cm on ultrasound 3 months postoperatively. Patients with confirmed residue or incomplete follow-up were excluded. Due to the retrospective nature of the research, written consent from participants was waived. The research was conducted in compliance with the Declaration of Helsinki and received formal approval from our institutional ethics committee (protocol number: IRB-20230032-R). Statistical analyses were conducted using SPSS 26.0 (IBM Inc., Chicago, USA). Categorical variables were presented as counts and percentages, and group comparisons (recurrence vs. non-recurrence) were analyzed using Pearson’s chi-square test or Fisher’s exact test, as appropriate. The Shapiro–Wilk test was used to assess the normality of continuous variables, followed by the Mann–Whitney U-test for intergroup comparisons. Cumulative recurrence rates were analyzed using Kaplan–Meier curves. Binary logistic regression analysis was conducted, with recurrence as the dependent variable and patient characteristics as covariates; multivariable models was constructed using backward stepwise elimination. A two-sided P < 0.05 was considered statistically significant. Results A total of 723 cases of uterine leiomyoma variants were identified in our hospital over a 10-year period based on final pathological diagnoses. Cellular leiomyoma (CL) was the most common subtype, comprising 470 cases (65.0%), followed by leiomyoma with bizarre nuclei (71 cases, 9.8%), and lipoleiomyoma (69 cases, 9.5%). Fumarate hydratase-deficient leiomyoma constituted 5.3% (38 cases), and mixed variants involving two distinct pathological subtypes numbered 27 cases (3.7%). Among mixed variants, the combination of cellular and bizarre-nuclei leiomyoma was most prevalent, representing 74.1% of mixed variants and 2.8% of all cases (Table 1). Among the 723 cases, 337 (46.6%) were asymptomatic and detected during routine physical examinations, and 10 (1.4%) were incidentally identified during unrelated surgeries. Main presenting symptoms included menorrhagia (209 cases, 28.9%), followed by prolonged menstruation (101 cases, 13.9%). Other manifestations comprised dysmenorrhea (26 cases, 3.6%), chronic pelvic pain (33 cases, 4.6%), abdominal mass (8 cases, 1.1%), irregular vaginal bleeding (51cases, 7.1%), and adjacent organ compression (42 cases, 5.81%). Additionally, 12.7% (92/723) of patients had overlapping two or more symptoms, and 69 reproductive-aged women (9.5%) presented with symptomatic rapid tumor growth. Imaging evaluation was pivotal for preoperative planning of uterine leiomyomas variants. All patients underwent ultrasonography within 1 month preoperatively; additional imaging included MRI (404 cases) and CT (56 cases). Preoperative imaging frequently revealed tumor degeneration, suspected CL, or indeterminate lesions with malignant suspicion. Ultrasonography identified degeneration in 41 cases, which pathologically corresponded to 16 CL, 19 lipoleiomyoma, 4 bizarre-nuclei leiomyomas, 1 epithelioid leiomyoma, and 1 diffuse leiomyomatosis. MRI identified 52 degenerations, confirmed pathologically as 31CL, 8 lipoleiomyoma, 6 FH-deficient leiomyoma, and 5 bizarre-nuclei leiomyomas; CT indicated degeneration in 3 cases. Concordant degeneration findings on both MRI and ultrasonography were noted in 24 cases (15 CL, 5 lipoleiomyomas, 3 FH-deficient variants, 1 dissecting leiomyoma), while CT and ultrasonography showed consistent degeneration in 2 cases. For CL suspicion, preoperative ultrasonography suspected 7 cases (6 pathologically confirmed), and MRI suggested 11 cases (9 confirmed). Malignancy could not be ruled out by ultrasonography in 4 cases, MRI in 17 cases, and CT in 2 cases; postoperative pathology confirmed all these cases as benign (16 CL, 1 stroke-induced leiomyoma). Concordant malignant suspicion between ultrasonography and MRI was observed in 2 cases. Overall, preoperative imaging indicated 169 cases (23.4%) of non-simple uterine leiomyomas lesions. Of the initial 723 patients, 229 (31.7%) who underwent hysterectomy or residual mass resection and 29 myomectomy patients with follow-up failure were excluded. After further excluding 21 cases (4.3%) with residual masses post-myomectomy, the final cohort comprised 443 eligible patients who underwent myomectomy (Fig. 1). The median follow-up period was 48 months (interquartile range: 22.25-77; range: 3-187). The overall recurrence rate was 26.4% (117/443), with a time-dependent increasing trend. Recurrence was most frequent in mixed-type variants (43.8%, 6/14), followed by bizarre-nuclei leiomyoma (30.0%, 15/50), CL (26.5%, 83/313), lipoleiomyoma (19.2%, 5/26), and FH-deficient leiomyoma (10.7%, 3/28). The most common mixed subtype at recurrence was cellular-bizarre nuclei leiomyoma (5/11, 45.5%). Of the recurrent cases, 51 (43.5%) underwent reoperation, with 34 (66.6%) receiving hysterectomy. Reoperation pathology confirmed 29 variant leiomyomas, 17 conventional leiomyomas, 2 leiomyosarcomas (both initially diagnosed as bizarre-nuclei leiomyoma), and 3 cases of peritoneal disseminated leiomyomatosis (all initially diagnosed as CL). Two of the latter cases underwent secondary cytoreductive surgery. The mean interval between initial surgery and reoperation was 46.0 ± 5.24 months, with no disease-related deaths reported. Patient baseline characteristics are summarized in Table 2. The recurrence group had a significantly lower mean age (36 years) than the non-recurrence group (41 years). No intergroup differences were observed in body mass index (BMI), fibroid-related symptoms, or menarche. Patients with a history of prior myomectomy or elevated preoperative serum tumor marker CA125 were more prone to recurrence. However, a family history of fibroids in first-degree relatives or a positive family history of tumors did not increase the recurrence risk. Women in the recurrence group had significantly fewer prior pregnancies and deliveries than those in the non-recurrence group. The preoperative hemoglobin levels were found to be lower in the recurrence group compared with the non-recurrence group ( P =0.048). Detailed data on surgical procedures were collected. Of all patients, 133 (30%) underwent open myomectomy, while the majority- 310 (70%) -underwent laparoscopic myomectomy. Significantly more recurrences were observed after open myomectomy ( P <0.001). In patients with postoperative fibroid recurrence, the median number of UFs removed was 2 (1, 7.5), compared with 1 (1, 3) in the non-recurrent group. The Wilcoxon Mann-Whitney analysis showed a statistically significant difference in the number of fibroids between the recurrence and non-recurrence groups postoperatively ( P ＜0.001). Among recurrent cases, 80 patients (68.4%) had a uterine size smaller than 12 gestational weeks, while 37 patients (31.6%) had a uterine size of 12 gestational weeks or larger. Chi-square analysis demonstrated a significant association between uterine size and postoperative recurrence ( P =0.012). Overall, the mean largest dimension of fibroids was 6.49±3.06 cm; no significant difference was noted between the recurrent group (6.66±3.44 cm) and the non-recurrent group (6.23±2.83cm). The intraoperative blood loss in the postoperative recurrence group was 245.7 ± 424.93 ml, which was significantly greater than that in the non-recurrence group (112.63 ± 174.65 ml), and this difference reached statistical significance. Histopathological features were also analyzed. In terms of cytological atypia, Ki-67 value, and p16 status, no significant differences were found between patients with disease recurrence and those without. Regarding mitotic count/10 HPFs, 127 cases (92.7%) had 0-5, 8 cases (5.8%) had 6-9, and 2 cases (1.5%) had ≥10. A higher mitotic count/10 HPFs showed a significantly different distribution in relation to recurrence. Postoperative procreation was observed in 40 patients (9.0%), and neither fertility after surgery nor postoperative gonadotropin-releasing hormone agonist treatment was found to reduce the risk of recurrence. Univariate Logistic regression analysis revealed associations between several variables and disease recurrence (Table 3). Multivariate logistic regression indicated that the mitotic count per 10 high-power fields (odds ratio [OR], 1.619; 95% confidence interval [CI], 1.006–2.605; p = 0.047), age (OR, 0.442; 95% CI, 0.262–0.747; p = 0.002), delivery status (OR, 0.873; 95% CI, 0.467–1.633; p = 0.048), surgical approach (open vs. laparoscopic myomectomy; OR, 1.438; 95% CI, 0.814–2.491, p = 0.027), intraoperative blood loss (OR, 1.218; 95% CI, 0.669–2.229; p = 0.024), and the median number of uterine fibroids removed (OR, 3.035; 95% CI, 1.749–5.265; p ＜0.001) were independent predictors of recurrence. The cumulative uterine fibroid recurrence rates following myomectomy were 30.67% at 12 months postoperatively, 68.71% at 36 months postoperatively, which increased to nearly 85.6% by 60 months of follow-up. and 94.9% at 96 months postoperatively (Fig. 2). Discussion To the best of our knowledge, this is the first study investigating the incidence and recurrence of uterine leiomyoma variants following myomectomy, based on the 2020 WHO criteria. Variant leiomyomas account for 3–10% of all uterine fibroids, predominantly affecting women aged 40–50 years [7] . Yuka Oi etal retrospectively analysis 471 patients who underwent uterine leiomyoma surgery and found that the incidence of variants was significantly higher in postmenopausal patients than in premenopausal counterparts (23.3% [7/30] vs. 3.2% [14/441]), respectively [8] . Cellular leiomyoma stands out as the most common subtype (5%-10%) [9, 10] , while lipoleiomyomas comprise around 0.35–2.9 % of all uterine leiomyomas, especially postmenopausal women [8, 11, 12] , and FH-deficient leiomyomas (1.4%) are rarer with a mean diagnosis age of 30 years, approximately 10 years earlier than sporadic uterine leiomyomas [13] . Historically, numerous studies failed to classify certain subtypes, such as bizarre and mitotically active leiomyomas, as variants; instead, they grouped them under the umbrella term “atypical leiomyomas”. This inconsistent classification approach has contributed to significant variability in reported incidence rates of leiomyoma variants [14] . Our study’s sample size of 723 cases is considered sufficient to provide meaningful insights into their clinical characteristics. Clinical manifestations of variant leiomyomas-including menorrhagia, pelvic pressure, and dysmenorrhea, overlap with conventional leiomyomas [7] . However, their higher cellular density typically drives more rapid growth and larger tumor sizes, which may exacerbate symptom severity. While a substantial proportion of patients remain asymptomatic, a previous overview reported that nearly 75% of leiomyoma patients are asymptomatic [16] , whereas our cohort demonstrated a lower asymptomatic rate of 41.5%. The remaining patients exhibited one or more clinical symptoms, with menorrhagia being the most prevalent manifestation. 12.6% had multiple pre-operative symptoms, highlighting the potential for multifocal symptom burden in this population. No clinical indicators reliably distinguish leiomyoma variants from ordinary leiomyomas from or leiomyosarcomas [15]. Preoperative imaging is vital for distinguishing common fibroids from variants, though diagnostic limitations persist. Ultrasonography often identifies fibroid degeneration in variants but struggles to specify exact pathological subtypes. Our study also showed ultrasound primarily detected degenerative changes rather than definitive typing. By contrast, MRI offers superior soft-tissue contrast: CL exhibit intermediate-to-low T2-weighted signal intensity, while lipoleiomyomas show T1-hyperintensity. Among 404 preoperative MRIs in our cohort, 11 cases were suspected as CL, with 9 confirmed pathologically. Notably, literature reports varying diagnostic accuracy: one study (n=45) found MRI had 10% sensitivity but 100% specificity for CL [17] , while another highlighted MRI’s utility in identifying lipoleiomyomas via fat component visualization [11] . The rarity of variants complicates radiologic diagnosis, and no imaging technique reliably enables preoperative pathological confirmation. Recurrence remains a critical concern for fertility-preserving myomectomy. Conventional leiomyomas have 22–51% recurrence at 3–10 years post myomectomy [18] , but data on variants are scarce. A meta-analysis examining the treatment outcomes of leiomyomas with bizarre nuclei reported an overall pooled recurrence risk of 5.5%. It is important to note that this analysis included both myomectomy and hysterectomy cohorts. Since hysterectomy for benign fibroids essentially eliminates the risk of recurrence, the reported 5.5% rate likely underestimates actual recurrence potential, as evidenced by our findings [20] . Ming Y etal researched 59 patients with CL who underwent myomectomy, and found the postoperative recurrence rate was 49.2% [21] . Our large cohort identified an overall recurrence rate of 26.4%, the difference maybe our data volume is much larger than theirs. Previous studies have also explored the recurrence and reoperation rates of uterine leiomyomas. Susan D Reed’s investigation, involving 628 leiomyoma surgeries, revealed that 127 (21.8%) required secondary procedures [6] . Singh SS et al. noted post-myomectomy recurrence rates of 15–33%, with 10%-21% of patients undergoing hysterectomy within 5-10 years [22] . In contrast, our cohort exhibited a reoperation rate of 43.5%, with 34 cases (66.6%) receiving hysterectomy. This elevated rate is likely attributed to the unique pathological subtypes of the tumors, prompting clinicians to advocate for more aggressive surgical interventions, including hysterectomy, to prevent potential malignancy. Regarding the issue of tumor dissemination, the risk of peritoneal dissemination following morcellation is relatively low, with a reported 0.9% incidence in follow-up studies [7] . But previous studies have also reported that most cases of disseminated peritoneal leiomyomatosis (DPL) originate from CL [23] . In the existing literature, there is one documented case where a mitotically active leiomyoma transformed into leiomyosarcoma 7 months after hysterectomy [24] , one patient with previous pathology of CL developed high-grade endometrial stromal sacoma [21] . Damasco etal. identified 2 cases (3%) of benign myoma variants (n = 55) that exhibited metastatic behavior [25] . In our study, 2 cases initially diagnosed as bizarre nuclear leiomyoma later developed leiomyosarcoma. Additionally, 3 cases of myomatosis were identified; these were initially diagnosed as cellular leiomyoma, but the reoperation pathology indicated peritoneal disseminated leiomyomatosis. These findings suggest that in-bag morcellation could be a viable alternative to minimize the risk of tumor dissemination. No disease specific deaths were observed in our research, but previous study revealed that disease-specific deaths resulting from leiomyoma variants occurred between 6 –11 years post-diagnosis [4] . A large case series focusing on leiomyoma variants reported that women diagnosed with CL or atypical leiomyomas exhibited a quasi-malignant phenotype and ultimately succumbed to the disease [10, 26]. However, the median follow-up duration for survivors in the series by Giuntoli et al. was 15.6 years (187.2 months) —a period notably longer than that of our study cohort. This is the first large-scale study identifying recurrence risk factors for variant leiomyomas. Multivariate analysis showed the median number of resected fibroids is an independent risk factor for the recurrence of variant leiomyomas. This observation is consistent with studies demonstrating that CL patients with three or more fibroids have a higher risk of recurrence, given that CL constitute the predominant histological subtype within variant leiomyomas, these results underscore the clinical relevance of fibroid burden in predicting recurrence of variant leiomyomas [21] . Previous studies about typical leiomyoma also demonstrated that patients diagnosed with more than one leiomyoma have increased risk of recurrence [27-28] . Mitsuru Shiota et al., found that following laparoscopic myomectomy, patients in the recurrence group had significantly longer surgical times, greater blood loss, and a higher number of enucleated myomas compared to those in the non-recurrence group [29] . Candiani et al. [30] reported that post-myomectomy pregnancy (at least one pregnancy) was associated with a reduced risk of recurrence (HR 0.6, 95% CI 0.4-0.9). However, in our study, multivariate logistic regression analysis revealed no significant association (OR:1.9, 95% CI 0.898-4.021; p=0.093), this discrepancy possibly due to the relatively low post-operative pregnancy and delivery rates observed in our cohort. Notably, intraoperative blood loss was greater in cases with recurrent uncommon benign uterine tumors. This may be attributed to the higher vascularity of these lesions compared to conventional uterine fibroids, as well as the presence of multiple fibroids, which can increase surgical complexity and bleeding risk. Our research revealed that the cumulative recurrence rates of variant leiomyomas after myomectomy stood at 30.67% at 12 months postoperatively, rose to 68.71% at 36 months, further increased to nearly 85.6% by 60th month of follow-up, and reached 94.9% at 96 months postoperatively; in comparison, Yoo and colleagues documented that following laparoscopic myomectomy, the recurrence rates of myomas at 1,3,5 and 8 years were 11.7%, 36.1%, 52.9% and 84.4% respectively [31] . Radosa MP etal. demonstrated that the cumulative recurrence risk was 4.9% at 24 months and 21.4% at 60 months post-operatively [28] . While Nezhat et al. documented recurrence rates of 31.7% and 51.4% at 3 and 5 years postoperatively, and Fedele et al. noted a 51% recurrence rate at 5 years postoperatively [32, 33] ; it should be noted that due to variations in definitions of recurrence and data collection methods across different studies, the validity of comparing the findings among these studies may be restricted, and the scarcity of cases also results in insufficient experience to formulate standard follow-up guidelines. Currently, there are no official guidelines for the clinical follow-up of leiomyoma variants. A recent study [34] indicated that CLwith chromosome 1p deletions, a genetic alteration also present in leiomyosarcoma, may show more aggressive clinical behavior and thus require more intensive surveillance, so in summary, given the significant increase in recurrence rates within the first three years after surgery, and with this potential for delayed recurrence compared to uterine leiomyosarcoma (LMS), as reflected in our research and relevant studies, we should strengthen monitoring during this period. In our study, no women die of leiomyoma variants were seen, but in other research, 3 (3/20) disease-specific deaths of women with a leiomyoma variant occurred [3] . Conclusions While the majority of leiomyoma variants follow a benign clinical trajectory, they are associated with risks of recurrence and potential malignant transformation, underscoring the need for rigorous long-term follow-up in affected patients. In the future, a multi-center database can be established to verify risk factors and explore standardized operating procedures. Declaration of Interest statement The authors declare that they have no known competing financial interests or personal associations that could have appeared to impact the work demonstrated in this paper. Author contributions statement Chunming Li : Conceptualization, Funding acquisition, Methodology, Investigation, Formal analysis, Validation, Writing – original draft, Writing – review & editing. Wenchao Zhou : Investigation, Validation, Visualization. Huiyu Fan : Investigation, Formal analysis, Validation. Zheng Lou : Data curation, Writing – review & editing. Yizhou Huang : Data curation, Visualization. Linjuan Ma : Data curation, Writing – review & editing. Jianhong Zhou : Funding acquisition, Conceptualization, Methodology, Validation, Writing – review & editing. 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Gynecology and Minimally Invasive Therapy, 2012. 1(1): p. 34-36.[30]. Candiani GB, Fedele L, Parazzini F, Villa L. Risk of recurrence after myomectomy. Br J Obstet Gynaecol. 1991 Apr;98(4):385-9. [31]. Yoo EH, Lee PI, Huh CY, Kim DH, Lee BS, Lee JK,. et al., Predictors of leiomyoma recurrence after laparoscopic myomectomy. J Minim Invasive Gynecol. 2007 Nov-Dec;14(6):690-7. [32]. Nezhat FR, Roemisch M, Nezhat CH, Seidman DS, Nezhat CR. Recurrence rate after laparoscopic myomectomy. J Am Assoc Gynecol Laparosc. 1998 Aug;5(3):237-40. [33]. Fedele L, Parazzini F, Luchini L, Mezzopane R, Tozzi L, Villa L. Recurrence of fibroids after myomectomy: a transvaginal ultrasonographic study. Hum Reprod. 1995 Jul;10(7):1795-6. [34]. Hodge JC, Pearce KE, Clayton AC, Taran FA, Stewart EA. Uterine cellular leiomyomata with chromosome 1p deletions represent a distinct entity. Am J Obstet Gynecol. 2014 Jun;210(6):572.e1-7. Table 1. Distribution of uterine leiomyoma variants Table 2. Characteristics of the women who underwent myomectomy with rare variant of uterine smooth muscle tumors at women’s Hospital, School of Medicine, Zhejiang University, HangZhou, China, 2004–2014 Table 3. Univariate Logistic regression analysis revealed associations between several variables and disease recurrence Fig. 1 A flowchart of the study Fig. 2 The cumulative uterine fibroid recurrence rates following myomectomy Supplementary Material File (figure.docx) Download 48.27 KB File (tables.docx) Download 96.27 KB Information & Authors Information Version history V1 Version 1 04 March 2026 Copyright This work is licensed under a Non Exclusive No Reuse License. Keywords epidemiology: general gynaecology general gynaecology gynaecological surgery: general Authors Affiliations Chunming Li Women's Hospital School of Medicine Zhejiang University View all articles by this author Wenchao Zhou Cixi People's Hospital View all articles by this author Huiyu Fan Women's Hospital School of Medicine Zhejiang University View all articles by this author Zheng Lou Women's Hospital School of Medicine Zhejiang University View all articles by this author Yizhou Huang Women's Hospital School of Medicine Zhejiang University View all articles by this author Linjuan Ma Women's Hospital School of Medicine Zhejiang University View all articles by this author Jianhong Zhou 0000-0003-3028-9426 [email protected] Women's Hospital School of Medicine Zhejiang University View all articles by this author Metrics & Citations Metrics Article Usage 187 views 92 downloads .FvxKWukQNSOunydq8rnd { width: 100px; } Citations Download citation Chunming Li, Wenchao Zhou, Huiyu Fan, et al. 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