Diagnosis and classification of uterine fibroids

The risk of malignancy in fibroids is low and lies between 0.05%–0.81%. 51 The likelihood of malignancy varies depending on risk factors such as advanced age, postmenopausal status, African descent, prior pelvic radiation, tamoxifen, childhood retinoblastoma, and hereditary leiomyomatosis and renal cell cancer (HLRCC). 52 The index of suspicion should be higher in postmenopausal patients. 53 , 54 , 55 While some ultrasound features may be more suggestive of malignancy, uterine fibroids and leiomyosarcoma share a similar radiographic appearance, consisting of focal masses with possible central necrosis. 56 , 57 Ultimately, only a surgical specimen can provide a final diagnosis, as none of the imaging modalities, nor any tumor markers, can safely distinguish them. Smooth muscle tumors of uncertain malignant potential (STUMP) and other malignancies (cervical, endometrial) should also be included in the differential diagnosis. Other diagnostic modalities, such as endometrial and cervical biopsies, can prove extremely useful if malignancies are suspected. STUMP, however, cannot be diagnosed on imaging. 58

RL, SH, IMH, AVO, MGM, and AM contributed to conceptualization, writing, editing, and finalizing of the manuscript. All authors agreed with the final version of the manuscript and its submission to the journal.

This research received no external funding.

Abnormal uterine bleeding (AUB) is the most frequently reported symptom associated with uterine fibroids. FIGO has designed a system that allows for a five‐element categorization of nongestational AUB symptoms, referred to as the FIGO AUB System 1. 6 , 11 This system defines abnormalities regarding frequency, regularity, duration, and menstrual volume and includes assessment for intermenstrual bleeding. It is predominantly fibroids with a submucosal component that have been linked directly to heavy menstrual bleeding (HMB). While the mechanisms whereby these benign tumors cause AUB are not totally clear, it is thought to be secondary to fibroid‐related microscopic and macroscopic vascular abnormalities, impaired endometrial hemostasis, and altered molecular angiogenic factors that collectively impair local endometrial hemostasis. 12 , 13 , 14 As a result, fibroid‐related AUB typically presents as regular cycles associated with heavy or prolonged menstrual bleeding in ovulatory individuals. The probably limited role of intramural fibroids as contributors to AUB is evolving and may be related to the size, specific molecular expressions, and proximity to the endometrium. Additionally, altered uterine contractility may further exacerbate HMB. 15 , 16 These issues are discussed in detail elsewhere in this special collection. 3 Fibroid‐related AUB may coexist with other causes of AUB, and clinicians should consider endometrial sampling in women older than 40 years to rule out malignancy or hyperplasia. 17 Both infertility and recurrent early pregnancy loss are symptoms associated with fibroids. However, due to their high prevalence, uterine fibroids are frequently found in individuals with infertility and recurrent pregnancy loss. 18 One of the challenges faced by both investigators and clinicians is determining which fibroid(s) may be the infertility culprit and which may be innocent bystanders. Another critical reproductive challenge is their potential relationship with pregnancy outcomes. The pathogenesis of fibroid‐related infertility is discussed in detail elsewhere in this special collection. 3 The relationship between uterine fibroids and pregnancy outcomes is another topic addressed within this special collection. 19 All of the submucosal fibroids (FIGO Types 0, 1, 2, 3, 2–5, and 3–5) have been associated with infertility, 18 whereas the relationship with recurrent pregnancy loss is less clear. Two mechanisms have been proposed: (1) altered contractility of the inner myometrium, often associated with Type 4 or submucosal fibroids that have significant myometrial involvement; and (2) impaired endometrial receptivity, thought to result from fibroid‐associated abnormal molecular and cellular signaling in the endometrium overlying submucosal fibroids. 20 The disruption of inner myometrial contractility can adversely affect sperm transport within the endometrial cavity and proximal oviduct 21 and can potentially hinder the embryo's implantation in the decidualized endometrium. 18 Uterine fibroids that do not cause anatomical distortion of the fallopian tubes are unlikely to impact fertility, at least by altering tubal transport of sperm, oocytes, or embryos. Submucosal fibroids that produce high levels of transforming growth factor‐β3 (TGF‐β3) have been linked with a reduced expression of endometrial factors associated with endometrial receptivity, such as HOXA10 and 11, throughout the endometrium, and not only in the section overlying the fibroid. 22 Fibroids are also associated with adverse pregnancy outcomes such as preterm birth, fetal malpresentation, abruption, and labor dystocia. These risks are greater in those with multiple, large (>4–5 cm) and retroplacental fibroids. 23 Fibroids often cause bulk‐related symptoms due to their physical size and location. Patients commonly report pelvic pressure, lower back pain, abdominal discomfort, bloating, obstructive symptoms, and a sensation of pelvic fullness. Fibroids positioned anteriorly or posteriorly can compress the bladder or rectum, resulting in urinary frequency, difficulty emptying the bladder, or constipation. In severe cases, particularly large fibroids may lead to urinary obstruction or rare hydronephrosis. The extent and severity of these symptoms correlate with fibroid size, number, and anatomical placement within the uterus. 24 , 25 Symptomatic fibroids substantially diminish a patient's quality of life and productivity. The Uterine Fibroid Symptom and Health‐Related Quality of Life Questionnaire (UFS‐QoL) is a disease‐specific validated tool that effectively evaluates the impact of fibroids. 26 It comprises two parts: (1) Symptom severity score evaluating bulk and pain symptoms, menstrual bleeding, and fatigue, with a score of 0–100, where higher scores mean increased fibroid burden; and (2) Health‐related quality of life (score of 0–100) that evaluates domains such as concern, activity, energy/mood, control, self‐consciousness, and sexual function, where a higher score is indicative of a better quality of life. Patients with moderate to severe fibroid symptoms report significantly reduced quality of life, increased healthcare utilization, greater reliance on analgesics and iron supplements, and considerable loss of productivity, including frequent absence from work. Surveys demonstrate widespread impacts extending to sexual life, work performance, and relationships, highlighting the extensive socioeconomic burden posed by symptomatic uterine fibroids. 27 The racial and other environmental contributors to the development and growth of uterine fibroids are discussed in detail elsewhere in this special collection. 3 However, substantial disparities exist in the prevalence and symptom severity of fibroids among various ethnic groups. Compared to white women, black women experience earlier onset, larger fibroid volume, longer symptom duration, and a higher incidence of anemia. 28 , 29 Unsurprisingly, the disparities extend beyond the disease prevalence and severity as they also impact access to quality and patient‐centered care. Compared to white women, black, Latina and Asian women are less likely to access minimally invasive surgical care for fibroid management, and they tend to experience more postoperative complications. 29 , 30 Similarly, East Asian women present at a younger age, exhibit prolonged symptom duration, and face significant fibroid‐related burdens, although with a lower reported severity of symptoms. South and Southeast Asian populations also demonstrate higher rates of fibroid diagnoses compared to white populations, underscoring the importance of recognizing ethnic variations in clinical presentations. 31 These disparities may reflect differences in genetic susceptibility, environmental exposures, healthcare access, and sociocultural factors influencing disease perception and management preferences. Recognition of ethnic disparities is critical for personalized patient care and optimized clinical outcomes as the structural determinants driving disease burden disparities potentially lie at the center of care access and outcome inequities. 29 , 32 , 33

The diagnosis of uterine fibroids may occur during the assessment for symptoms such as AUB, infertility, or bulk symptoms, or incidentally after imaging, including the uterus. As discussed above, uterine fibroids typically cause HMB, and such bleeding is generally cyclical and predictable among ovulatory individuals. The location, volume, and number of tumors are key elements in determining the relationship between the fibroids and the symptoms at hand, especially HMB, infertility, and recurrent pregnancy loss. As a result, a thorough menstrual history, including all the elements of FIGO's AUB System 1, is critical to the establishment of an individualized differential diagnosis. 24 Although possibly palpable, manual examination of the uterus may also be limited by the patient's body habitus or by the inability to perform vaginal examination. On occasion, speculum examination may reveal a fibroid in the cervical canal, or in the vagina if complete prolapse has occurred. Regardless, the diagnosis and phenotypic categorization of uterine fibroids rely primarily on imaging with ultrasound or MRI to guide subsequent clinical management. 24 Challenges in diagnosis mainly relate to the standardization and quality of imaging reports. A study evaluating 1500 imaging reports for fibroids across 19 Canadian centers found that only 23% of ultrasound reports met all quality criteria, as recommended by the MUSA guidelines, 10 , 34 with considerable interinstitutional variation in report quality. Ultrasound reports frequently fall below internally endorsed quality standards, leading to potential misdiagnosis and suboptimal patient management. Adherence to standardized structured reporting is critical, regardless of imaging modality, as accurate fibroid characterization directly impacts treatment decisions and outcomes. 35 , 36 Enhanced adherence to structured imaging guidelines is essential to improve diagnostic accuracy, differentiate fibroids from conditions such as adenomyosis or malignancies, predict therapeutic responses, and plan surgical interventions. Clinicians caring for patients with uterine fibroids are encouraged to develop skills in image interpretation and ultrasound performance. While it has limitations, ultrasonography is the first‐line modality due to its availability, ease of use, absence of radiation exposure, and relatively low cost. 10 , 37 Transabdominal and especially transvaginal ultrasonography effectively identify fibroids with sensitivity rates ranging from 90%–99%. 24 It also provides invaluable information regarding the presence of adnexal structural pathology. Furthermore, its dynamic nature helps to map and classify the type of fibroids using FIGO's leiomyoma classification system. As outlined by MUSA criteria, 9 , 10 fibroids typically present with a regular or lobulated uterine contour, well‐defined margins, and asymmetric uterine walls. They are smooth, round, or oval, often with edge shadowing and homogeneous echogenicity. Vascular features include circumferential blood flow and a nonthickened junctional zone. Evaluation of the endometrial cavity for a submucosal fibroid component can be performed by sonohysterography, utilizing contrast‐infused saline or gel, which increases diagnostic accuracy. Both two‐ and three‐dimensional sonohysterography achieve near‐perfect sensitivity and specificity (98%–100%) for diagnosing submucosal fibroids and may be an alternative to hysteroscopy in clinical practice. 38 , 39 , 40 However, the accuracy of ultrasound is limited by large body habitus, enlarged uterus, and shadowing with multifibroid uteri. Furthermore, ultrasound cannot reliably assess the blood supply of fibroids, which is necessary to predict the success of uterine artery embolization. 24 Although significantly more expensive, MRI remains the most accurate diagnostic modality for detecting fibroids, with a reported sensitivity of 99%, providing superior soft tissue contrast and a large field‐of‐view (Figure  2 ). 41 It is especially valuable for fibroid mapping in preparation for surgery or minimally invasive treatments 42 and distinguishing among FIGO types, such as Type 3 from 4, or deep Type 2 from 2 to 5. 43 It also provides critical information regarding their perfusion, the presence of tissue degeneration, and the presence of features that distinguish fibroids from adenomyosis or adenomyomas. 42 An additional advantage of MRI is its ability to detect features that are concerning for leiomyosarcoma, with a pooled sensitivity of 90% and specificity of 96%. 44 Finally, magnetic resonance‐guided high‐intensity focused ultrasound (MRgHIFU) is a minimally invasive treatment option for reducing the volume of fibroids, in which MRI plays an integral role. 45 FIGO classification of fibroids on sagittal (a–h, j, l) and axial (i, k) T2‐weighted MRI (arrows). (a) Normal zonal uterine anatomy with hyperintense endometrium, hypointense junctional zone, and intermediate signal myometrium. (b) Pedunculated, submucous intracavitary Type 0 leiomyoma of the uterine anterior wall (arrow), attached to the endometrium by a narrow stalk (≤10% of the mean of three diameters of the leiomyoma). (c) Submucous Type 1 leiomyoma has an intramural portion that is less than 50% of the mean diameter of the leiomyoma. (d) Submucous Type 2 leiomyoma has an intramural portion, with more than 50% of the mean diameter of the leiomyoma. (e) Type 3 leiomyoma is located completely intramurally but abuts the endometrium without distortion. (f) Intramural Type 4 leiomyomas with no contact to the endometrium or to the serosa. (g) Subserous Type 5 leiomyoma with an intramural portion, with more than 50% of the mean diameter. (h) Subserous Type 6 leiomyoma with an intramural portion of less than 50% of the mean diameter. (i) Pedunculated subserous Type 7 leiomyoma, attached to the serosa by a narrow stalk (≤10% of the mean of three diameters of the leiomyoma). (j) Type 8 cervical leiomyoma. This category includes leiomyomas without relation to the myometrium, cervical leiomyomas, and leiomyomas of the round or broad ligaments without direct attachment to the uterus. (k) Submucous and subserous, intramural hybrid‐type 2–5 leiomyoma of the uterine posterior wall. (l) Intramural hybrid Type 3–5 leiomyoma of the anterior uterine fundus with <1 mm distance between the leiomyoma and the endometrium (without distortion) and with <1 mm distance between the leiomyoma and the serosa. In addition, further leiomyomas of the uterine fundus and posterior wall are shown. The European Society of Urogenital Radiology (ESUR) has published guidelines for magnetic resonance work‐up in patients with known or suspected uterine fibroids, aiming to standardize imaging practices and provide a reporting template. 46 The basic protocol comprises T2‐weighted (axial and sagittal) and T1‐weighted sequences (axial). In certain situations, advanced techniques are considered: dynamic contrast‐enhanced imaging (DCE) for indeterminate adnexal masses; DCE and optionally diffusion‐weighted imaging (DWI) for rapidly growing uterine masses and fibroids with intermediate to high signal on T2‐weighted sequences; and magnetic resonance angiography/DCE and DWI for pre‐ and postembolization assessment. 46 Fibroids typically have circumscribed margins on MRI and appear homogeneously hypointense on T2‐weighted sequences and iso‐ or hypointense to normal myometrium on T1‐weighted sequences. 44 We recommend reporting the width of the inner free margin (IFM) for Types 4 and 5 fibroids and the outer free margin (OFM) for Types 2, 3, and 4 fibroids due to the impact on technique and the risk of surgical and ablative procedures. Atypical signal patterns on MRI are possible; for example, in cellular fibroids (T2‐hyperintense) as well as in degenerated fibroids, depending on the type of degeneration (hyaline, cystic/hydropic, red/hemorrhagic/carneous, apoplectic, myxoid, fatty). In contrast to fibroids, the most specific criteria for adenomyosis diagnosis include an irregular appearance of the junctional zone, the presence of myometrial cysts, and adenomyomas. 47 Adenomyomas are ill‐defined myometrial lesions that commonly exhibit tiny cystic components or hemorrhagic components. 48 Leiomyosarcoma typically presents with irregular margins, moderate to high T2 signal intensity, variable T1 signal intensity, diffusion restriction, and central nonenhancing areas. 44 Limitations of MRI are the additional costs, restricted availability, particularly in low‐income countries, and difficulties and/or increased risks in patients with claustrophobia or implants. Hysteroscopy can contribute to the diagnosis and categorization of fibroids despite several limitations. First, access to diagnostic hysteroscopy may be limited, especially if regional or general anesthesia is required. Second, although usually accurate in categorizing Type 0 and 1 tumors, diagnostic hysteroscopy remains limited in distinguishing Type 2 from Type 2–5 fibroids, given the restricted assessment of size and depth of myometrial involvement. 6 Nonetheless, such an approach is more invasive than sonohysterography. Furthermore, hysteroscopy has no role in the diagnosis of Type 4 and greater lesions. While traditional imaging modalities such as ultrasound and MRI remain central in fibroid diagnosis, emerging modalities show promise in advanced fibroid diagnosis. Contrast‐enhanced ultrasound (CEUS) uses intravenously injected microbubbles to enhance the vascularity of the myometrium. This technique can allow for evaluation of fibroid vascular patterns that can help distinguish sarcomas. 49 Ultrasound‐based elastography techniques, such as strain elastography and shear wave elastography, can evaluate fibroid stiffness in relation to the surrounding myometrium. This experimental technique may assist with the diagnosis of adenomyosis and have the potential to guide and monitor treatment. 49 , 50

Uterine fibroids, also referred to as leiomyomas, are benign uterine tumors with a lifetime prevalence of approximately 75% depending on race, age, and a variety of genetic and environmental factors 1 , 2 (although the terms can be used interchangeably, uterine fibroids/fibroids will be used across this article for consistency). While many individuals remain asymptomatic, approximately 30% of those affected experience symptoms that impact their overall quality of life. 1 Furthermore, when symptoms occur, they may not be related to the fibroids since abnormal uterine bleeding (AUB), infertility, recurrent pregnancy loss, pressure, pain, urinary frequency, or gastrointestinal dysfunction may be present with a variety of otherwise unrelated conditions. The epidemiology and pathogenesis of uterine fibroids have been discussed elsewhere in this special collection. 3 In this article we explore their classification, symptomatology, and diagnosis. First, we discuss the origins of classification systems designed to aid basic and clinical research, as well as education and clinical care.

None to declare.

The phenotype of a uterus affected by fibroids varies considerably depending on their size and number, their myometrial involvement, and their relationship to the endometrium and uterine serosa. The FIGO classification system for uterine fibroids, first published in 2011 (Figure  1 ), was an expansion of the system reported by Wamsteker over 30 years ago. 4 The goal was to provide a standardized method for describing the relationship of a given fibroid to the endometrium, myometrium, and uterine serosa. 5 , 6 This system was developed to enhance consistency in clinical management, improve communication among healthcare providers, and inform the design of basic, translational, epidemiological, and clinical research to facilitate the process of meta‐analyses. While its origins were from FIGO's Committee on Menstrual Disorders and Related Health Impacts (MDRHI), as but one of the potential causes of AUB, the system can be applied to infertility, recurrent pregnancy loss, and other symptoms that patients might experience. FIGO leiomyoma subclassification system. 5 The system comprises a three‐level hierarchy that, at its simplest level, is binary, reflecting the presence (or absence) of uterine fibroids (or leiomyomas) by classifying leiomyoma‐associated AUB as “AUB‐L” regardless of a suspected causal relationship. The secondary system distinguishes a spectrum of submucosal fibroid phenotypes with varying degrees of endometrium contact by categorizing them as AUB‐L SM . Leiomyomas without endometrial contact are categorized as AUB‐L o for “other” or outside the endometrium. The tertiary system further subclassifies fibroids based on their relationship to the endometrium and/or serosa. For a submucosal fibroid, the categorization is based upon the proportion of the tumor that is within the myometrium. Accordingly, a fibroid that is entirely (100%) within the endometrial cavity and connected to the endometrium by a stalk, effectively without any myometrial involvement, is designated as a “Type 0”. If there is myometrial involvement that is less than half the mean diameter of the tumor (<50%), it is categorized as Type 1. A Type 2 fibroid focally distorts the endometrial cavity but with ≥50% (and <100%) of its mean diameter located within the myometrium. Type 3 fibroids abut the endometrium to variable degrees without focally distorting the endometrial cavity. Intramural fibroids are entirely surrounded by myometrium and are classified as Type 4 tumors. The subserosal fibroid classification mirrors the submucosal classification including Type 5 (≥50% of the mean myoma diameter within the myometrium), Type 6 (<50% of the mean diameter in the myometrium), and Type 7 (attached to the serosa with a stalk while being 100% external to the myometrium). Type 8 tumors typically depict fibroids that are entirely cervical in location but also include those “parasitic” tumors that are detached from the uterus. The transmural or “hybrid” category represents tumors that are in contact with both the endometrium and the uterine serosa; for example, a “2–5” fibroid would indicate a fibroid with a submucous and a subserous component, with more than half its mean diameter within the myometrium. Another hybrid commonly seen is the Type 3–5, while Types 2–6, 3–6, and 1–5 are possible but uncommon. The 2018 FIGO MDRHI Committee issued a revised system that suggested refinements to the classification system 6 to improve specificity and clinical applicability. It defined pedunculated fibroids (i.e. submucous Type 0 and subserosal Type 7) by the presence of a narrow stalk defined as ≤10% of the mean fibroid diameter. In this iteration, Type 3 fibroids were formally distinguished from Type 2 fibroids exclusively through hysteroscopy with minimal intrauterine pressure for clear visualization. The revision also provided enhanced guidance for clinical and research settings, recommending a minimum dataset that includes uterine volume and fibroid count obtained through imaging techniques such as transvaginal ultrasonography or magnetic resonance imaging (MRI). Additionally, fibroid location (anterior, posterior, lateral, or central) and position within the vertical uterine plane (upper half, lower half, or both) were standardized. Another uterine fibroid classification system, compatible with the FIGO system, has been published to provide more granularity for submucous fibroids, particularly oriented to the hysteroscopic surgeon. 7 This system has been evaluated to determine the prognosis for a hysteroscopic myomectomy of Types 0, 1, and 2 myomas according to the type, myometrial location, size, and mapping within the endometrial cavity. To date, the system has not been revised to consider FIGO Type 3 tumors. Despite the availability of these classification systems for well over a decade, challenges remain. There is still significant interobserver variability when classifying fibroids using the FIGO system, highlighting the need for increased reproducibility and refinement to better standardize nomenclature and inform clinical decision‐making. 8 Furthermore, the FIGO classification system alone may not comprehensively describe the clinical implications of uterine fibroids. Clinicians may require additional details about fibroid location and characteristics that have important clinical implications, such as distance from the fibroid to the serosa or endometrium and fibroid vascularity. These additional characteristics may be assessed by complementary data points using other systems such as the Morphological Uterus Sonographic Assessment (MUSA) criteria. 9 , 10