Diverse Presentations of Extrauterine Leiomyomas in the Female Urogenital Tract: A Retrospective Series of 51 Cases

ABSTRACT

Background:

Extrauterine leiomyomas (EULs) are rare benign smooth muscle tumors that arise outside the uterus, often leading to diagnostic challenges.

Objective:

To evaluate the clinical and pathological characteristics of EULs and their management in a tertiary care setting.

Methods:

This retrospective study reviewed 51 cases of EULs over a 5.5-year period. Data on demographics, clinical presentation, tumor location, histology, and treatment were analyzed.

Results:

The mean patient age was 41.6 years, with 41.2% aged 40–50 and 15.7% post-menopausal. Abnormal uterine bleeding (AUB) was the most common symptom (66.7%). Tumors were most frequently located in the cervix (72.5%), followed by the broad ligament (11.8%) and ovaries (7.8%). Histologically, EULs resembled uterine leiomyomas, showing spindle-shaped cells and low mitotic activity. Surgical excision was the primary treatment.

Conclusion:

EULs, though uncommon, should be considered in differential diagnoses of pelvic masses. Accurate histopathological evaluation is essential to avoid misdiagnosis and unnecessary intervention. This study enhances current understanding of EUL presentation and management.

INTRODUCTION

Extrauterine leiomyomas (EULs) are rare, benign smooth muscle tumors that develop outside the uterus. While uterine leiomyomas are common, occurring in up to 70%–80% of women, their extrauterine counterparts are significantly less frequent.[1] EULs may present in many locations, including the vulva, ovaries, urethra, kidneys, urinary bladder, and other parts of the genitourinary tract, and can also occur in other parts of the body including the lungs, retroperitoneum, or lymph nodes.[2] Although the exact cause remains unknown, these tumors often arise in women with a history of uterine leiomyomas, especially after myomectomy or hysterectomy, suggesting a possible hematogenous or lymphatic spread of benign smooth muscle cells from the uterus.[3,4]

Diagnosing EULs is challenging due to their varied presentations and the lack of specific symptoms. Many patients remain asymptomatic, with the tumors discovered incidentally during imaging for other conditions.[2,3] Imaging modalities can aid in detection, but the definitive diagnosis often relies on histopathological examination, showing characteristics similar to uterine leiomyomas.[5] Differentiating EULs from malignant counterparts such as leiomyosarcomas is crucial, as the latter requires more aggressive treatment.[6,7]

Given the rarity and potential for misdiagnosis, awareness of EULs is essential for gynecologists, radiologists, and pathologists. Recognizing this benign condition helps avoid unnecessary aggressive treatments and highlights the importance of long-term monitoring, particularly in women with a history of uterine fibroids.[8,9]

Considering these diagnostic challenges and the rarity of EULs, we conducted a retrospective analysis at our institution to examine the incidence, clinical presentations, and common locations of EULs, aiming to improve the understanding of their occurrence and management.

MATERIALS AND METHODS

A retrospective search was conducted over a period of 5.5 years (January 2019–July 2024) in a tertiary healthcare referral center. Case records and slides were re-evaluated by two histopathologists. Clinical details including age, clinical complaints, location of the tumor, radiological findings, and clinical differential diagnosis were recorded. All hematoxylin- and eosin-stained and immunohistochemistry (IHC) slides were re-evaluated for the presence of leiomyoma. Additional features such as the presence of a histological subtype, infarct type necrosis, hyalinization, calcification, and cystic change were also noted. The presence of additional leiomyomas at other sites was also documented.

The data were tabulated and analyzed using SPSSv23 software (IBM SPSS Statistics for Windows, Version 23, IBM Corp., Armonk, NY). Categorical variables were expressed as percentages. Normally distributed quantitative variables were expressed as mean ± standard deviation (SD) and nonnormally distributed ones as intervals.

RESULTS

A total of 51 cases of EULs were found after retrospective analysis. The mean age (SD) of the patients was 41.6 (10.4). Age of the patients ranged from 16 to 75 years. The majority of women (21, 41.2%) belonged to the age group of 40–50 years. Only 8 cases (15.7%) were postmenopausal. Out of 51 women, 34 complained of abnormal uterine bleeding (AUB). The other presenting complaints included discharge, menorrhagia, and difficulty in urination (in two cases of urethral and paraurethral locations of the tumor). The various differentials considered clinically were site-specific and ranged from a polyp, fibroid to neoplasm for the cervix, endometrial hyperplasia, and fibroid for broad ligament and carcinoma in the case of ovarian masses.

The most common site for extrauterine leiomyoma was the cervix (37), followed by broad ligament (6) and ovary (5) [Table 1]. Of the 37 cases with cervical leiomyoma, 6 cases also had additional intrauterine leiomyomas. Microscopically, 2 cases showed surface ulceration, 1 was a cellular leiomyoma and another showed myxoid degeneration. Among the cases of broad ligament leiomyoma [Figure 1], 1 had additional intrauterine leiomyomas and another had intrauterine leiomyoma with adenomyosis. Of the 5 ovarian cases, one case had bilateral involvement with the presence of additional parametrial [Figure 2] and intrauterine leiomyomas and adenomyosis as well, one had an intrauterine angioleiomyoma, and another had intravenous leiomyoma with cardiac extension. A single case of urethral leiomyoma was found, which showed features of hyalinization. The sole case of renal leiomyoma found was seen in a 39-year-old female with a horseshoe kidney and renal calculi. Table 1 summarizes the cases based on their sites.

Table 1.

Details of extrauterine leiomyoma cases based on their location

Location	n (%)
Cervix	37 (72.54)
Broad ligament	6 (11.76)
Ovary	4 (7.84)
Urethra	1 (1.96)
Ovary, parametrium	1 (1.96)
Renal	1 (1.96)
Paraurethral	1 (1.96)

Figure 1.

Gross specimen of a case of renal isthmic cyst leiomyoma (a). Photomicrographs of the renal isthmic cyst leiomyoma showing interlacing fascicles spindle cells with indistinct borders and eosinophilic cytoplasm, cigar-shaped nuclei and small nucleoli (b: H and E, ×200 and c: ×400). Photomicrograph of leiomyomas in the broad ligament (d: H and E, ×400), paraurethral region (e: H and E, ×100), and urethra (f: H and E, ×400)

Figure 2.

Photomicrographs of a patient with leiomyomas in the ovary (a: H and E, ×200) as well as the parametrium (b: H and E, ×100 and c: ×400)

DISCUSSION

EULs are rare benign tumors that originate from smooth muscle cells but develop outside the uterus. Although the exact mechanisms behind their occurrence remain speculative, it is widely believed that these tumors may result from the spread of benign smooth muscle cells through the hematogenous or lymphatic routes.[1,6] This phenomenon is particularly observed in women with a history of uterine leiomyomas, especially following surgeries such as myomectomy or hysterectomy, where benign smooth muscle fragments might disseminate to other parts of the body. An alternative hypothesis involves metaplasia of coelomic mesenchymal cells, but evidence remains inconclusive.[3]

The incidence of EULs is notably lower than that of uterine leiomyomas. They have been found in a wide range of anatomical sites, including the ovaries, broad ligament, retroperitoneum, urethra, and even distant organs such as the lungs.[2] Clinically, these tumors often remain asymptomatic and are detected incidentally through imaging studies. Histopathological evaluation is crucial for confirming the diagnosis, as EULs share morphological characteristics with uterine leiomyomas.[10] Microscopically, these tumors are composed of spindle-shaped cells with elongated, cigar-like nuclei, arranged in interlacing fascicles. They have minimal mitotic activity and a low Ki-67 proliferation index, which helps differentiate them from malignant tumors such as leiomyosarcomas. IHC often shows positivity for estrogen and progesterone receptors, further supporting their uterine origin.[7]

Unlike EULs, leiomyosarcomas demonstrate higher mitotic activity (usually >10 mitoses per 10 high-power fields), cellular atypia, and coagulative tumor cell necrosis. Leiomyosarcomas are aggressive malignant tumors with a much higher recurrence rate and poorer prognosis.[4] While benign metastasizing leiomyoma (BML) and EULs share histological features, BML is unique in its tendency to metastasize, most commonly to the lungs. They can be distinguished by their occurrence in multiple distant sites and corresponding clinical presentation.[3] Low-grade endometrial stromal sarcoma (LGESS) can mimic the appearance of smooth muscle tumors but differs in that it originates from endometrial stromal cells. LGESS tends to infiltrate surrounding tissues, unlike the well-circumscribed nature of EULs.[4]

Our study found the mean age of patients to be 41.6 years, with most cases (41.2%) falling within the 40–50-year age group. This is consistent with other studies, which report a similar age distribution for EULs.[2] Interestingly, only 15.7% of our cases were postmenopausal, a figure slightly lower than those reported in other case series. The literature suggests that a significant number of EULs occur in postmenopausal women, likely due to the delayed presentation of these tumors.[3,11]

The clinical presentation of EULs in our study varied, with 34 out of 51 women reporting AUB, a common presenting symptom for leiomyomas in general. Other complaints included menorrhagia and, in cases involving the urethra and paraurethral areas, difficulty in urination. This variety in symptoms has also been reported in existing literature and highlights the importance of considering EULs in the differential diagnosis of any pelvic mass.[1]

The sites of EULs in our study were consistent with previously reported cases, although with some variation in frequency. The most common site of occurrence in our patients was the cervix (72.5% of cases), followed by the broad ligament (11.8%) and ovary (7.8%). This high incidence of cervical leiomyomas is comparable with some reports that emphasize the cervix as a frequent location for EULs, particularly among women with a history of uterine leiomyomas.[1] In contrast, other studies have highlighted different sites as more prevalent, such as the retroperitoneum and lungs, particularly in cases of BML.[2,4] The broad ligament and ovaries are recognized as potential sites for smooth muscle cell implantation.[3] However, the presence of bilateral ovarian involvement and coexisting intrauterine leiomyomas, as seen in one of our patients, is relatively uncommon.[11] Less common sites in our study included the urethra, renal isthmic area, and paraurethral region, each represented by a single case. Previous literature has reported similar unusual sites but these are rare.[2] Studies have also reported vulvar leiomyomas; however, no such case was found in our patient group.[8,12] These findings underscore the diverse anatomical distribution of EULs and emphasize the need for comprehensive diagnostic evaluation to distinguish them from malignancies in various locations.

Treatment of EULs, as with uterine leiomyomas, primarily involves surgical resection. Although these tumors are benign, their size and location can cause significant symptoms, necessitating removal. In cases where multiple leiomyomas are present, the risk of recurrence or development of additional tumors is low but warrants long-term follow-up. Surgical resection not only provides symptom relief but also allows for definitive histopathological diagnosis, excluding malignancy.[3,4]

CONCLUSIONS

EULs, though rare, remain an important entity for clinicians to recognize due to their potential for misdiagnosis. Awareness among gynecologists, radiologists, and pathologists is critical to avoid overtreatment and ensure appropriate management. Our study adds to the growing body of literature on EULs, highlighting the cervix, broad ligament, and ovaries as the most common sites, and emphasizing the importance of histopathological evaluation in differentiating these benign tumors from more aggressive malignancies.

Conflicts of interest

There are no conflicts of interest.

Funding Statement

Nil.