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Beyond the uterus: Metastatic leiomyoma
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Received: ,
Accepted: ,
How to cite this article: Koetter BM, Adcock CS, Vento F, Paolini BM. Beyond the uterus: Metastatic leiomyoma. J Clin Imaging Sci. 2026;16:20. doi: 10.25259/JCIS_231_2025
Abstract
Uterine leiomyomas are common benign smooth muscle tumors typically confined to the uterus and hormonally responsive to estrogen and progesterone, typically regressing after menopause. Rarely, they demonstrate metastatic behavior despite benign histology, a condition known as benign metastasizing leiomyoma (BML). BML is exceedingly rare and can mimic malignancy, posing diagnostic challenges. We report a rare case of a 53-year-old woman with a history of hysterectomy for leiomyomas who presented with dyspnea and chest pain. Imaging revealed numerous bilateral pulmonary nodules, later confirmed to be smooth muscle tumors. After being lost to follow-up, she returned 2 years later with new breast and forearm masses. Imaging and biopsy confirmed metastatic smooth muscle tumors consistent with BML. Breast lesions mimicked benign cysts on ultrasound, underscoring the importance of clinical and histological correlation. The patient responded well to treatment with symptom improvement. This case highlights the rare phenomenon of BML metastasizing to multiple extrauterine sites, including the breast and soft tissues, locations infrequently reported. Imaging findings, particularly in the breast, can mimic benign lesions such as simple cysts, underscoring the need for biopsy and correlation with clinical history. BML should be considered in women with a history of uterine fibroids and indolent-appearing metastases without fludeoxyglucose uptake on positron emission tomography, computed tomography, and cystic appearance on ultrasound of breast lesions. Early recognition is crucial to avoid misclassification as malignancy and to guide effective hormonal treatment.
Keywords
Breast ultrasound
Case report
Leiomyomas Metastasizing leiomyoma
INTRODUCTION
Uterine leiomyomas, commonly known as fibroids, are the most prevalent benign tumors of the female reproductive system. Leiomyomas originate from smooth muscle cells of the myometrium of the uterus and are hormonally responsive to estrogen and progesterone. They typically occur in reproductive-aged individuals and often regress post-menopause. In rare cases, a perplexing condition known as benign metastasizing leiomyoma (BML) can arise, wherein histologically benign smooth muscle tumors, identical in appearance to uterine leiomyomas, are found in extrauterine sites.[1-3] BML often occurs after primary gynecological surgery.[4]
BML poses unique clinical challenges as its multiplicity and multi-organ metastases can mimic malignant behavior, leading to potential misdiagnosis and, consequently, inappropriate or overly aggressive management.[3,5] Imaging plays an indispensable role in identifying and differentiating BML from other neoplasms and characterizing the extent of disease.
We present a case of delayed diagnosis of rare BML in a 53-year-old woman with biopsy-proven metastases to the breast, lung, and soft tissues of the forearm. The primary objective is to highlight the unique imaging characteristics observed, particularly the unusual anechoic ultrasound appearance of the breast metastases which mimicked benign cystic lesions.
CASE REPORT
A 53-year-old woman presented to the emergency department with complaints of chest pain and one month of dyspnea. She had a history of a supracervical hysterectomy 10 years earlier for a leiomyomatous uterus causing menorrhagia. Chest radiograph and chest computed tomography (CT) revealed innumerable bilateral well-circumscribed, solid pulmonary nodules [Figure 1]. No pleural effusions or lymphadenopathy were present. In addition, multiple thyroid nodules were incidentally noted.
Initial diagnostic workup included a transbronchial biopsy with bronchoalveolar lavage and fine-needle aspiration (FNA) of level VII lymph nodes, both of which were negative for malignancy and infectious etiology. Subsequently, positron emission tomography (PET) CT was performed, which demonstrated no notable uptake in the pulmonary nodules. Consultation with cardiothoracic surgery recommended a video-assisted thoracic surgery (VATS) wedge biopsy for definitive diagnosis; although, the procedure was initially deferred.
Concurrently, the thyroid nodules were further evaluated with FNA, revealing atypia of undetermined significance. The patient underwent an elective thyroidectomy, with pathology confirming an oncocytic adenoma. In addition, at the time of the surgery, thyroglobulin levels were normal, indicating that the pulmonary nodules were unlikely to originate from the thyroid.
Eventually, the patient underwent a VATS wedge resection of the left upper lobe. Pathology revealed a metastatic smooth muscle neoplasm with estrogen receptor (ER) and progesterone receptor (PR) positivity. The lung biopsy sample was desmin positive, smooth muscle actin (SMA) positive, and Ki-67 highlighted only approximately 2% of the tumor nuclei. She was referred to gynecologic oncology for further evaluation. A follow-up body CT was recommended to evaluate the extent of disease to guide management decisions; however, the patient was lost to follow-up.
Two years later, the patient presented with a worsening cough. A repeat chest CT demonstrated a similar extent of bilateral pulmonary nodules, no lymphadenopathy, and a new left breast mass. A CT of the abdomen and pelvis showed a mass in the mesentery and multiple enhancing masses within the body wall. The case was reviewed by the gynecologic oncology tumor board, which recommended a biopsy of the body wall mass and initiation of letrozole while awaiting pathology results.
Mammographic workup of the breasts demonstrated two solid, high-density, oval shaped masses with circumscribed margins in the left breast measuring 1.1 cm and 0.6 cm [Figure 2]. Ultrasound showed corresponding oval-shaped predominantly anechoic masses with circumscribed margins and posterior acoustic enhancement. There was adjacent but not internal vascularity [Figures 3 and 4]. Despite the lesions’ cystic appearance, ultrasound-guided biopsy was recommended given the patient’s history and the fact that these masses were new and appeared solid on CT and high-density on the mammogram. Ultrasound-guided biopsy was performed, at which time the masses were confirmed to be solid. The biopsy pathology was consistent with BML.
In addition, a soft-tissue mass on the right forearm, which had been growing for 1 year, was biopsied. Pathology of these lesions revealed a low-grade smooth muscle tumor consistent with metastasizing leiomyoma. The forearm mass [Figure 5] on ultrasound was oval in shape with circumscribed margins, similar to the breast mass; however, the mass was hypoechoic in echogenicity and slightly heterogeneous, unlike the anechoic breast lesions.
Laboratory workup before medication induction demonstrated perimenopausal levels of follicle-stimulating hormone (FSH) and estradiol (estradiol 43.2, FSH 20.9, and CA-125 5.5). The patient began treatment with a gonadotropin-releasing hormone (GnRH) agonist and letrozole to control disease progression. Following treatment, the patient reported a reduction in the size of the forearm mass, and imaging confirmed decreased size of other masses [Figure 6]. Her respiratory symptoms also improved.
DISCUSSION
BML is a rare condition which affects women of middle-age with a history of uterine leiomyomas and often presents with multiple metastatic lesions.
Pathogenesis
The precise pathological mechanisms driving BML are unknown, with the most common theory being that leiomyoma tissue spreads hematological after uterine surgery. An alternative theory is the metaplastic transformation of coelomic tissue.[6]
The hormonal responsiveness of BML is well-established, and metastatic lesions often express estrogen and progesterone receptors. The disease fluctuates based on hormonal fluctuations, with progression occurring during pregnancy or exogenous hormonal use and regression observed with menopause.[5,7]
Imaging findings
Lungs are the most common site of metastasis.[5] Characteristically, pleural effusions and mediastinal/hilar lymphadenopathy are absent which can serve as a clue against other lung metastases. Lung tissue also contains both estrogen and progesterone receptors.[8] A key imaging characteristic that aids in differentiating BML from malignant metastases is no or minimal FDG activity on FDG-PET/CT as in the presented case.[9] The lack of hypermetabolism is a significant diagnostic pointer toward BML in the correct clinical context. It is crucial to recognize that there is documented variability in FDG uptake in BML. While most cases do have a no to low FDG uptake, some described moderate and even high FDG uptake. Importantly, the FDG update has not been shown to correlate with clinical aggressiveness or Ki-67 proliferation index.[9]
BML can also metastasize to other tissues that express hormone receptors, such as the breast, as observed in this case. However, only one additional case demonstrated breast metastases in BML, which also described metastases to soft tissue, lung, and breast. In this other case, the breast metastases were described as “enhancing masses” seen on CT.[7] In our patient, ultrasonography of the breast masses demonstrated anechoic masses with posterior acoustic enhancement, a finding mimicking simple cystic lesions. The anechoic appearance observed in our patient’s breast BML is a notable deviation from the typical hypoechoic appearance of most solid metastases. The anechoic appearance in solid smooth-muscle tumors may be secondary to homogenous cellularity or minimal internal interfaces. This “red herring” presentation underscores a potential diagnostic pitfall. While posterior acoustic enhancement can be seen with certain high-grade solid lesions or lesions with fluid content, a predominantly anechoic appearance for a solid tumor is unusual.[10] This finding suggests that BML may exhibit a broader spectrum of imaging appearances including a “cyst-like” anechoic breast lesion. Radiologists should be aware of this potential pitfall and should have a degree of suspicion for an anechoic mass if it is new or growing and the patient has a history of uterine leiomyomas and/or multiple metastatic-appearing lesions.
While imaging findings can help suggest a BML diagnosis, definitive diagnosis hinges on biopsy of an extrauterine lesion demonstrating bland-appearing smooth muscle cells often demonstrating ER and PR positivity. Classically, these tumors will also stain positive for desmin and SMA positive as in the present case, reflecting the smooth muscle origin of these lesions. Importantly, BML usually demonstrates a low Ki-67 proliferation index, as in the presented case, whereas uterine leiomyosarcomas will often have an elevated Ki-67 index suggestive of cellular proliferation.[9,11]
Management
Treatment strategies often involve hormone therapy aimed at reducing estrogen exposure, such as with GnRH agonists or aromatase inhibitors. Hormonal suppression has been shown to stabilize or shrink lesions in many patients.[3] Depending on the extent and location of the disease, reports have even demonstrated complete tumor regression following definitive oophorectomy.[12]
The management of BML often depends on the extent of metastasis and the patient’s symptoms. Surgical resection may be considered for isolated lesions, and systemic hormone therapy is used for widespread or unresectable disease.[3,12]The patient in this case demonstrated a positive response to GnRH agonist and letrozole therapy, with a reduction in mass size and improvement in respiratory symptoms. This outcome underscores the importance of hormone therapy in controlling disease progression in patients with BML. Early recognition of this rare condition is paramount as it affords appropriate management strategies which can lessen the patient’s tumor burden and symptomatology.
CONCLUSION
Radiologists should recognize BML which often is seen in reproductive-aged woman with a history of leiomyomas and multiple metastatic-appearing lesions. It is hormonally responsive and often metastasizes to tissues which express ER and PR receptors (i.e., lungs and breasts). In breast imaging,BML lesions can present on ultrasound as nearly anechoic masses with posterior acoustic enhancement, mimicking other benign conditions such as a simple cyst. Proper and timely diagnosis of BML requires correlation with the patient’s imaging findings, clinical history, and hormonal status. Early recognition affords timely treatment.
Ethical approval:
The Institutional Review Board approval is not required.
Declaration of patient consent:
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patienthas given consent for their images and other clinical information to bereported in the journal. The patient understand that the patient’s namesand initials will not be published and due efforts will be made toconceal their identity, but anonymity cannot be guaranteed.
Conflicts of interest:
There are no conflicts of interest.
Use of artificial intelligence (AI)-assisted technology for manuscript preparation:
The authors confirm that there was use of artificial intelligence (AI)-assisted technology for assisting in the initial idea generation, literature searching, and image resizing.
Financial support and sponsorship: Nil.
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