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Diagnostic evaluation of uterine myomas
G Model EURO 11202 No. of Pages 8
European Journal of Obstetrics & Gynecology and Reproductive Biology xxx (2019) xxx–xxx
Contents lists available at ScienceDirect
European Journal of Obstetrics & Gynecology and Reproductive Biology journal homepage: www.elsevier.com/locate/ejogrb
Full length article
Diagnostic evaluation of uterine myomas Sofia Olallaa , Javier Monleonb , Ignacio Cristóbala,* , María Luisa Cañetec a
Ginecologia y Obstetricia, Hospital Clínico San Carlos, Madrid, Spain Ginecologia y Obstetricia, Hosptal La Fe, Valencia, Spain c Unidad de Miomas, Clínica Santa Elena, Madrid, Spain b
A R T I C L E I N F O
A B S T R A C T
Article history: Received 6 November 2019 Received in revised form 8 February 2020 Accepted 13 February 2020 Available online xxx
The optimal selection of patients for medical therapy, noninvasive procedures, or surgery depends on an accurate assessment of the size, number, and position of myomas. Imaging techniques available for confirming the diagnosis of myomas include sonography, hysteroscopy, and MRI. © 2020 Published by Elsevier B.V.
Keywords: Uterine myoma Fibroids Ultrasound Elastrography MRI
Introduction First step in evaluating a woman with clinical suspicion of leiomyomas is to look into typical symptoms such as heavy or prolonged menstrual bleeding, bulk related symptoms (pelvic pressure or pain, constipation, and dyspareunia) or reproductive dysfunction. Fibroids are sometimes found in asymptomatic women during routine pelvic examination or incidentally during imaging. The clinician should also perform a precise physical examination comprising of abdominal and pelvic examination. The abdominal examination should include palpation for a pelvic or abdominal mass and the uterine fundus should be noted. The pelvic examination should consist of a thorough bimanual pelvic examination evaluating the size, contour and mobility of the uterus. Findings consistent with a leiomyomatous uterus are a mobile and enlarged uterus with irregular contour. The clinical diagnosis of uterine leiomyomas is based upon pelvic imaging, with pelvic ultrasound being the study of choice. The ultrasonographic evaluation of fibroids is currently considered an easy, cost effective and accurate method. It can be performed using the transvaginal or the transabdominal probe, depending on whether the fibroid is of pelvic or abdominal location. MRI offers a better visualization of each individual fibroid providing more information about the size and location, however due to the cost of
* Corresponding author. E-mail address: [email protected] (I. Cristóbal).
this modality, it is best reserved for diagnostic doubts or challenging cases. Another diagnostic method is the direct visualization of the uterine cavity via hysteroscopy. With this technique it is possible to evaluate submucosal and protruding myometrial leiomyomas and characterize the extend of protrusion. Typical fibroid Leiomyomas are typically seen as well-defined and rounded lesions, surrounded or attached to the myometrium with circumferential vascularity and edge or internal fan- shaped shadowing. The ultrasonographic appearance of the fibroid is related to the amount of muscle cells and fibrous stroma present in the lesion. However, there are many forms in which a fibroid can be seen on the US without this typical feature, calling this kind of lesions atypical leiomyomas [1]. The serosal contour of a uterus in the presence of fibroids can be lobulated or regular depending on the location of the lesions. The myometrial walls are then often asymmetrical. The number and location of the fibroids should be evaluated using the FIGO classification and size of each lesion should be estimated measuring the three largest diameters. Fibroids usually have a rounded shape, however they may also be oval or lobulated. They can have hyperechogenic or hypoechogenic rim with smooth contour. Acoustic shadowing is common in this kind of lesion, most frequently edge shadowing or internal fan-shaped shadowing. The echogenicity of the lesion should be described with it being uniform (hyper-, iso- or hypoechogenic) or with mixed echogenicity if degeneration is
https://doi.org/10.1016/j.ejogrb.2020.02.023 0301-2115/© 2020 Published by Elsevier B.V.
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present. The junctional zone is usually preserved, unless there are FIGO type 1–3 lesions that may interrupt or overstretch it. It is important to note the myoma’s vascular pattern, which may be circumferential, intralesional or both. It is also key to evaluate the degree of vascularization with the color score explained upwards. Generally, fibroids show peripheral high vascularization with low internal vascularity. Pelvic ultrasound and doppler Ultrasonography is the first stage technique for assessing the myometrium. As fibroids are the most common pathology of the myometrium, pelvic ultrasound is the first study line and should be performed on all women. Musa terminology On 2015 the MUSA (Morphological Uterus Sonographic Assessment) statement paper was published. It is a consensus statement on terms, definitions and measurements that can be used to describe and report myometrial findings [2]. This allows to have standardized terms and a common terminology to report outcomes consistently as well as reduce intra- and interobserver variability. Ultrasound examination of the uterus may be performed using both the transabdominal (TAS) and the transvaginal (TVS) approach. TSV is preferred as it delivers a more detailed vision yet with limited depth of view. The TAS approach should be utilized to evaluate images beyond the small pelvis due to its wide vision but its resolution is limited by abdominal adiposity, scars or the presence of a retroflexed uterus. Therefore, they are complementary approaches. Using MUSA terminology, first step is to evaluate the uterine morphology. Uterine length can be measured adding the sum of the fundal length and the cavity length to the cervix length. Other measurements to be noted are the longest anteroposterior diameter of the uterus in the sagittal plane and the longest transverse diameter in the transverse plane. The complete volume of the uterus can be calculated if necessary. The serosal contour of the uterus should be described as either regular or lobulated. Myometrial wall symmetry should either be evaluated subjectively or objectively measuring both anterior and posterior myometrial walls in the sagittal plane from the external uterine serosa to the internal endometrial contour including the junctional zone and calculating the ratio. The junctional zone, which should be analyzed. If the results are normal, it should be reported as visible and regular. In the case they are not, it may be described as irregular, interrupted, not visible or not assessable. Any alteration should be described as well as the magnitude, the location and the extent of this finding. The second step is the description of any myometrial pathology. Myometrial overall echogenicity should be evaluated as either homogeneous or heterogenous. If any heterogenicity is found, its characteristics should be specified as follows. Any myomethrial pathology can be localized in one or more lesions or diffuse. The definition of the lesion should be determined as ill-defined or welldefined. All well-defined lesions should be described according to its location, size and site with the FIGO classification of fibroids [3]. This classification takes several items into account comprising of the relationship of the leiomyoma to the endometrium and the serosa, the uterine location of the fibroid (upper segment, lower segment; cervix, anterior, posterior, lateral) as well as the size and the number of lesions. Classification numbers range from 0 to 8. Submucosal fibroids (Fig. 1) are classified ranging from number 0–2, being 0 intracavitary lesions attached to the myometrium by a
Fig. 1. Submucosal Myoma type 0 (A) and type 2 (B) and HD live.
narrow stalk, whereas number 1 and 2 require a portion of the lesion to be intramural, with number 1 being less than 50 % and 2 at least 50 %. Type 3 are intramural fibroids in contact with the endometrium, whilst type 4 are entirely within the myometrium with no extension to the endometrium or the serosa (Fig. 2). Subserosal fibroids are classified from number 5–7, representing the mirror image of submucosal leiomyomas, with type 5 being at least 50 % and type 6 less than 50 % intramural. Number 7 are fibroids which are completely extramural and attached to the serosa by a stalk. Other kind of fibroids that do not relate with the myometrium at all are classified under type 8. Well-defined lesions
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Fig. 2. Polyp and Myoma type 4, in this photo you can see de different ecogenicity).
should be described with its penetration which is defined as the ratio between the maximum thickness of the lesion and the total uterine wall thickness. As well as the myometrium itself, the echogenicity of the myometrial lesions should be described as homogeneous or heterogeneous and as hypo-, iso-, or hyperechogenic compared to that of the adjacent myometrium. Other characteristics of the lesion such as the echogenicity of the rim and the shape of the lesion (round, oval, lobulated or irregular) should also be defined. Ultrasound examination is very useful too to achieve the volume of the myoma, which is very important if we consider a conservative management of it. If we consider more than one diameter, a 7 cm myoma may have twice the volumen than 7 cm in diameter as well (Fig. 3). Another key item to be determined is the presence of shadowing produced by the lesion. Shadowing can be seen as edge shadows or internal shadows and with different degrees from slight to strong. There can be a special kind of shadowing called fan-shaped shadowing which consists of alternate hyperechogenic with hypoechogenic stripes. Other myometrial pathologies that should be reported are myometrial cysts and their content, hyperechogenic islands and the presence of hyperechogenic subendometrial lines or buds that disrupt the junctional zone. Third step in evaluating the myometrium should is to study the uterine vascularization using color or power Doppler. The vascular pattern of the whole uterus should be evaluated either as uniform or not. If there is a myometrial lesion, the vascular pattern within the lesion should also be described. Lesions can have circumferential, intralesional or translesional vascularity, defined by vessels that cross the lesion perpendicular to the uterine cavity. It is also useful to describe the morphology, number and the direction of the vessels. Not only the type of vascularization but also the degree should be reported. This can be done using a subjective color score that describes the amount of color in a lesion. Color score 1 is a lesion with no color, 2 with minimal amount of color, 3 with moderate color and 4 with abundant color.
Elastography Elastography is an ultrasound tool that measures the elastic features of tissues. It quantifies the stiffness and illustrates the information as a color map above the usual US image. It also allows the assessment of myometrial pathology such as myoma or adenomyosis through the different elastic characteristics of the lesions. Myoma have proven to be stiffer than healthy uterine tissue whilst adenomyosis is softer. Elastography could therefore help in identifying focal myometrial lesions, providing information about exact location and extent as well as support in the differential diagnosis of both focal findings [4]. MRI Magnetic resonance imaging is an accurate technique for imaging uterine myomas mostly in cases when US is proving limited. This occurs when the patient has a high body-massindex, when the myoma coexists with other pelvic or another uterine pathology or when there are numerous lesions. Because of its soft tissue characterization and multiplanar imaging MRI offers excellent morphologic details giving accurate information about number, size and location of the lesions as well as the presence of degeneration. It also correctly detects other pelvic pathologies such as adenomyosis. T1 weighted images provide a good discrimination between the lesion and the adjacent adipose tissue, whilst the T2 weighted image delivers one between the lesion and the normal myometrium or endometrium. Therefore, T1 is best when evaluating subserosal fibroids and T2 when evaluating submucous or intramural fibroids. The typical MRI features of fibroids have been described as well-circumscribed lesions with low signal intensity on T2 weighted images (Figs. 4 and 5). If degeneration and necrosis is present, it may show variable appearance with high-signal intensity on T1 and heterogenous on T2 weighted images (Fig. 6) [5–7].
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Fig. 3. Volume is very important if we consider a conservative management of it. If we consider more than one diameter, a 7 cm myoma may have twice the volumen than 7 cm in diameter as well. A Myoma 7 cm. diameter, volume 68 cm2. B Myoma 7 cm. diameter, but volume 153 cm2.
Hysteroscopy In women with suspected submucous fibroids, it is useful to perform a hysteroscopy in order to visualize the uterine cavity and diagnose protruding myometrial lesions. With this technique we can characterize the extend of protrusion and perform hysteroscopic procedures such as resection or morcellation. Submucosal fibroids are classified according to the European Society for
Gynecological Endoscopy (ESGE) considering the degree of penetration of the submucous myoma in the myometrium, with type 0 classification being fibroids that are entirely in the endometrial cavity without any myometrial extension (pedunculated), type 1 being fibroids with less than 50 % myometrial extension, and type 2 having 50 % or more myometrial extension. The STEP-W classification (Lasmar's Classification) was developed in order to predict the difficulty and complexity of
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Fig. 4. Uterus with multiple myomas. MRI, axial view (4A, 4C and 4D) and a sagittal view (4B) with many myomas in an infertile patient. Endometrium normal (4C). Big myoma in the uterine fundus (4D).
hysteroscopic myomectomy. This classification takes not only the penetration into account but also other parameters like the extension of the base of the nodule with respect of the wall of the uterus as well as the size and topography. This has proven to have a higher correlation with the technical difficulty in performing the procedure than the ESGE Classification. A score is calculated for each of these parameters and each fibroid has its own final score. Patients are classified into three groups depending on the surgical prognosis taking the myoma with the highest score into account. Group I is considered a low complexity procedure, group II a complex myomectomy and in patients under in group III it is advisable to suggest an alternative non hysteroscopic technique [8,9].
Differential diagnosis Leiomyoma may result in some diagnostical doubts and differential diagnosis should be done with other pathologies that cause similar clinical manifestations such as abnormal uterine bleeding or uterine enlargement. The differential diagnosis includes three main conditions: adenomyosis, uterine sarcoma and ovary mass. Adenomyosis consists of the presence of endometrial glands and stroma inside the myometrium. It is common to find an enlarged uterus clinically. Ultrasonographically it appears as
ill-defined lesions, usually involving most of the uterus and dispersed within the myometrium. In some cases it can form a confined lesion called adenomyoma which can closely resemble leiomyomas on imaging. Other ultrasound features typical of adenomyosis are myometrial wall asymmetry, poorly defined junctional zone, presence of myometrial cyst or areas with mixed echogenicity. As we told before, hence the importance of having described well the junctional zone, which is well defined in cases of myomas, but no so well clearly defined in adenomyosis.The vascularity of the lesions is typically translesional rather than circumferential. Nevertheless, adenomyosis may be difficult to diagnose with ultrasound [10]. Uterine sarcomas are malignant tumors that arise from the smooth muscle or connective uterine tissue cells. The diagnosis is based upon histologic examination, usually following surgery for presumed leiomyomas. Nevertheless, it is important to correctly suspect malignancy in any uterine lesion because misclassifying a uterine sarcoma as a benign myoma may result in a poorer prognosis for the patient. However up until now it remains a real challenge as it is an area that is poorly covered in the literature. The symptomatology and signs are very similar to those caused by fibroids, so preoperative differential diagnosis is difficult. Suspicion of sarcoma may increase based upon presence of risk factors such as premenopausal status, long-term use of tamoxifen or history of pelvic irradiation. With pelvic US examination, uterine sarcomas are
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Fig. 5. Same patient after treatment with ulipristal acetate. We can see the volume decrease of the myomas and the effect on endometrium (PAEC) (5A and 5C).
Fig. 6. Red necrosis in myoma (MRI) (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article).
usually seen as large and isolated solid masses with mixed echogenicity. They may contain irregular cystic areas due to necrosis. The presence of shadowing or calcification is not common and tumor borders are irregular in most cases. They
usually have moderate to rich vascularization with irregular vessel distribution. If a malignant lesion is suspected, studies have found that it could be useful to take endometrial sampling that can lead to preoperative diagnosis.
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Smooth muscle tumors of uncertain malignant potential (STUMPs) have similar US appearance as myomas and may therefore be indistinguishable preoperatively [11]. Assessment of the potencial myoma growth Uterine myomas usually grow during fertile age, and this must not be seen as a hint of malignancy. Moreover, knowing the growth rhythm and its normal physiopathology is key issue. Being able to determine the potential growth in a single exploration is a main objective if we want to establish a long term plan of treatment. Myomas characteristics in the first diagnosis are related to the probability of needing a treatment in the future [12]. When high growth potential is suspected, we may plan some surgical or medical treatment in order to slow down its progression, before the myoma would affect patients quality of life. There are not many studies focused on myomas growth and its risk factors [13]. We may asume that growth rate is independent for each myoma, even in the same woman [14]. And there is also good evidence that between 7 and 20 % of the fibroids may shrink even dissapear. Mean growth (in volume) has been estimated in 9% per 6 month. While in women under 35 the rate is similar between black and white etnicity, the growth seems to decrease only in whites after this age [15]. As a thumb rule, approximately one third of the myomas will grew some one third of their volume, in a period between six months and a year [14–16]. Literature is not conclusive regarding predictor factors. Location, parity and BMI seem not to affect the growth and there are not many data regarding family influence [15]. Size role at the moment of diagnosis is controversial. While some studies report that initial size is proportional to the future myoma growth [17], others show that smaller myomas have more increment [3]. Some papers refer that initial size is not related to the growth [15]. Even some authors report that lonely myomas had been reported to grew faster [14]. Although it is not clear how predictor factors may influence, the methods based on 3D power Doppler Ultrasound are being studied to predict growth, by measuring Vascular Index (VI) in the myoma vascularization. In a prospective 12 month follow up of 66 women diagnosed with a maximum of two fibroids with expectant management, growth mean of 9% was observed. In those myomas with higher VI, growth was jncreased also (10,5%), while in the group with lower VI, decreased (8 %). An increase of 1% in VI at the baseline meant an increase of volume of 7.00 cm [3] at twelve months [18]. Discussion When we evaluate a patient with uterine fibroids, we must consider a whole set of aspects related with the disease. We believe it is important to say that we are evaluating women with myomas, not an isolated myoma. Good communication with patients is essential. This will provide precise knowledge of the situation but also will allow to expose the perception of the woman about the illness. It is also crucial to find out the preferences and desires of our patient. Ultrasound and image proofs are the main pillar in diagnose, but we have to be able correlate them with the symptoms and possible surgical accesses. Thus it is very advisable that the gynecologist who is treating the patient, whether medically or surgically, is the same who performs and interprets ultrasound. If specific doubts arise a more specialized exam is recommended to clarify these aspects.
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Once we have collected all data we must try to consider an accurate diagnosis and prognosis. According to the type of myomas, symptomatology, and the woman characteristics and preferences we must have in mind the present needs but also the lapse of time until menopause arrives. Our aim should achieve the best possible quality of life, with the less treatment burden. Thus, we have to balance the possible necessity of a medical or surgical treatment along those years based on the present diagnosis to avoid overtreatment and also the delay of necessary interventions [19]. Present symptomatology, evolutionary prognosis and patient desires in terms of pregnancy desire, treatment preferences must be carefully recorded in the clinical history. Uterine Fibroid Sympton-QoL (UFS_QoL) has been designed to evaluate accurately the symptoms and their effect on the patient. It consider several issues such as concern, control, activities, sexual function, energy and mood and self conscience of the patient. They are checked through individual items designed to measure each aspect and then combined to get a final score [20]. Although the physician intuitive process to summarize the clinical picture is suitable for day practice, it is necessary to obtain numerical values when we want to compare precisely. It is becoming mandatory in investigation terms and it is recommended in particular clinical cases. Declaration of Competing Interest The authors confirm that there are no known conflict of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome. References [1] Alcázar J, Pascual M, Guerriero S. Ultrasound of pelvic pain in the non-pregnant female. 1st ed 6000 Broken Sound Parkway NW, Suite 300 Boca Raton, FL: CRC Press; 2019. p. 82–95 33487-2742. [2] Van den Bosch T, Dueholm M, Leone F, Valentin L, Rasmussen C, Votino A, et al. Terms, definitions and measurements to describe sonographic features of myometrium and uterine masses: a consensus opinion from the Morphological Uterus Sonographic Assessment (MUSA) group. Ultrasound Obstet Gynecol 2015;46(3):284–98. [3] Munro M, Critchley H, Broder M, Fraser I. FIGO classification system (PALMCOEIN) for causes of abnormal uterine bleeding in nongravid women of reproductive age. Int J Gynecol Obstet 2011;113(1):3–13. [4] Frank M, Schäfer S, Möllers M, Falkenberg M, Braun J, Möllmann U, et al. Importance of transvaginal elastography in the diagnosis of uterine fibroids and adenomyosis. Ultraschall Der Med 2015;37(4):373–8. [5] Omary R, Vasireddy S, Chrisman H, Ryu R, Pereles F, Carr J, et al. The effect of pelvic MR imaging on the diagnosis and treatment of women with presumed symptomatic uterine fibroids. J Vasc Interv Radiol 2002;13(11):1149–53. [6] Hricak H, Tscholakoff D, Heinrichs L, Fisher M, Dooms G, Reinhold C, et al. Uterine leiomyomas: correlation of MR, histopathologic findings, and symptoms. Radiology 1986;158(2):385–91. [7] Kido A, Togashi K, Koyama T, Yamaoka T, Fujiwara T, Fujii S. Diffusely enlarged uterus: evaluation with MR imaging. Radiographics 2003;23(6):1423–39. [8] Lasmar R, Barrozo P, Dias R, de Oliveira M. Submucous myomas: a new presurgical classification to evaluate the viability of hysteroscopic surgical treatment—preliminary report. J Minim Invasive Gynecol 2005;12(4):308–11. [9] Lasmar R, Lasmar B, Celeste R, da Rosa D, Depes D, Lopes R. A new system to classify submucous myomas: a brazilian multicenter study. J Minim Invasive Gynecol 2012;19(5):575–80. [10] Van den Bosch T, Coosemans A, Morina M, Timmerman D, Amant F. Screening for uterine tumours. Best Pract Res Clin Obstet Gynaecol 2012;26(2):257–66. [11] Ludovisi M, Moro F, Pasciuto T, Di Noi S, Giunchi S, Savelli L, et al. Imaging in gynecological disease (15): clinical and ultrasound characteristics of uterine sarcoma. Ultrasound Obstet Gynecol 2019. [12] Baird DD, Saldana TM, Shore DL, Hill MC, Schectman JM. A single baseline ultrasound assessment of fibroid presence and size is strongly predictive of future uterine procedure: 8-year follow-up of randomly sampled premenopausal women aged 35–49 years. Hum Reprod 2015;30(12):2936–44. [13] Armbrust R, Klaus-Dieter W, Sehouli J, Matthias D. The growth of uterine myomas in untreated women: influence factors and ultrasound monitoring (Jan 2018). Arch Gynecol Obstet; Heidelberg Tomo 2018;297(1):131–7, doi: http://dx.doi.org/10.1007/s00404-017-4568-5).
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[14] Baird DD, Garrett TA, Laughlin SK, Davis B, Semelka RC, Ped- dada SD. Shortterm change in growth of uterine leiomy- oma: tumor growth spurts. Fertil Steril 2011;95:242–6. [15] Peddada SD, Laughlin SK, Miner K, Guyon JP, Haneke K, Vah- dat HL, et al. Growth of uterine leiomyomata among pre- menopausal black and white women. Proc Natl Acad Sci U S A 2008;105:19887–92. [16] Brölmann H, Tanos V, Grimbizis G, Ind T, Philips K, van den Bosch T, et al. Options on fibroid morcellation: a literature review. Gynecol Surg 2015;12:3–15. [17] Mavrelos D, Ben-Nagi J, Holland T, Hoo W, Naftalin J, Jurko- vic D. The natural history of fibroids. Ultrasound Obstet Gynecol 2010;35:238–42.
[18] Nieuwenhuis LL, Keizer AL, Stoelinga B, Twisk JWR, Hehenkamp WJK, Brölmann HAM. JAF Huirnea Fibroid vascularisation assessed with threedimensional power Doppler ultrasound is a predictor for uterine fibroid growth: a prospective cohort study. BJOG 2018;125(April (5)):577–84. [19] Mas A, Tarazona M, Dasí Carrasco J, Estaca G, Cristóbal I, Monleón J. Updated approaches for management of uterine fibroids. Int J Womens Health 2017;9:607–17 Sep 5. [20] Spies JB, Coyne K, Guaou NG. The UFS QOL, a new disease specific symptom and health related quality of life questionnaire for leiomyomata. Obstet Gynecol 2002;99:290 –30.
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European Journal of Obstetrics & Gynecology and Reproductive Biology xxx (2019) xxx–xxx
Contents lists available at ScienceDirect
European Journal of Obstetrics & Gynecology and Reproductive Biology journal homepage: www.elsevier.com/locate/ejogrb
Full length article
Diagnostic evaluation of uterine myomas Sofia Olallaa , Javier Monleonb , Ignacio Cristóbala,* , María Luisa Cañetec a
Ginecologia y Obstetricia, Hospital Clínico San Carlos, Madrid, Spain Ginecologia y Obstetricia, Hosptal La Fe, Valencia, Spain c Unidad de Miomas, Clínica Santa Elena, Madrid, Spain b
A R T I C L E I N F O
A B S T R A C T
Article history: Received 6 November 2019 Received in revised form 8 February 2020 Accepted 13 February 2020 Available online xxx
The optimal selection of patients for medical therapy, noninvasive procedures, or surgery depends on an accurate assessment of the size, number, and position of myomas. Imaging techniques available for confirming the diagnosis of myomas include sonography, hysteroscopy, and MRI. © 2020 Published by Elsevier B.V.
Keywords: Uterine myoma Fibroids Ultrasound Elastrography MRI
Introduction First step in evaluating a woman with clinical suspicion of leiomyomas is to look into typical symptoms such as heavy or prolonged menstrual bleeding, bulk related symptoms (pelvic pressure or pain, constipation, and dyspareunia) or reproductive dysfunction. Fibroids are sometimes found in asymptomatic women during routine pelvic examination or incidentally during imaging. The clinician should also perform a precise physical examination comprising of abdominal and pelvic examination. The abdominal examination should include palpation for a pelvic or abdominal mass and the uterine fundus should be noted. The pelvic examination should consist of a thorough bimanual pelvic examination evaluating the size, contour and mobility of the uterus. Findings consistent with a leiomyomatous uterus are a mobile and enlarged uterus with irregular contour. The clinical diagnosis of uterine leiomyomas is based upon pelvic imaging, with pelvic ultrasound being the study of choice. The ultrasonographic evaluation of fibroids is currently considered an easy, cost effective and accurate method. It can be performed using the transvaginal or the transabdominal probe, depending on whether the fibroid is of pelvic or abdominal location. MRI offers a better visualization of each individual fibroid providing more information about the size and location, however due to the cost of
* Corresponding author. E-mail address: [email protected] (I. Cristóbal).
this modality, it is best reserved for diagnostic doubts or challenging cases. Another diagnostic method is the direct visualization of the uterine cavity via hysteroscopy. With this technique it is possible to evaluate submucosal and protruding myometrial leiomyomas and characterize the extend of protrusion. Typical fibroid Leiomyomas are typically seen as well-defined and rounded lesions, surrounded or attached to the myometrium with circumferential vascularity and edge or internal fan- shaped shadowing. The ultrasonographic appearance of the fibroid is related to the amount of muscle cells and fibrous stroma present in the lesion. However, there are many forms in which a fibroid can be seen on the US without this typical feature, calling this kind of lesions atypical leiomyomas [1]. The serosal contour of a uterus in the presence of fibroids can be lobulated or regular depending on the location of the lesions. The myometrial walls are then often asymmetrical. The number and location of the fibroids should be evaluated using the FIGO classification and size of each lesion should be estimated measuring the three largest diameters. Fibroids usually have a rounded shape, however they may also be oval or lobulated. They can have hyperechogenic or hypoechogenic rim with smooth contour. Acoustic shadowing is common in this kind of lesion, most frequently edge shadowing or internal fan-shaped shadowing. The echogenicity of the lesion should be described with it being uniform (hyper-, iso- or hypoechogenic) or with mixed echogenicity if degeneration is
https://doi.org/10.1016/j.ejogrb.2020.02.023 0301-2115/© 2020 Published by Elsevier B.V.
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present. The junctional zone is usually preserved, unless there are FIGO type 1–3 lesions that may interrupt or overstretch it. It is important to note the myoma’s vascular pattern, which may be circumferential, intralesional or both. It is also key to evaluate the degree of vascularization with the color score explained upwards. Generally, fibroids show peripheral high vascularization with low internal vascularity. Pelvic ultrasound and doppler Ultrasonography is the first stage technique for assessing the myometrium. As fibroids are the most common pathology of the myometrium, pelvic ultrasound is the first study line and should be performed on all women. Musa terminology On 2015 the MUSA (Morphological Uterus Sonographic Assessment) statement paper was published. It is a consensus statement on terms, definitions and measurements that can be used to describe and report myometrial findings [2]. This allows to have standardized terms and a common terminology to report outcomes consistently as well as reduce intra- and interobserver variability. Ultrasound examination of the uterus may be performed using both the transabdominal (TAS) and the transvaginal (TVS) approach. TSV is preferred as it delivers a more detailed vision yet with limited depth of view. The TAS approach should be utilized to evaluate images beyond the small pelvis due to its wide vision but its resolution is limited by abdominal adiposity, scars or the presence of a retroflexed uterus. Therefore, they are complementary approaches. Using MUSA terminology, first step is to evaluate the uterine morphology. Uterine length can be measured adding the sum of the fundal length and the cavity length to the cervix length. Other measurements to be noted are the longest anteroposterior diameter of the uterus in the sagittal plane and the longest transverse diameter in the transverse plane. The complete volume of the uterus can be calculated if necessary. The serosal contour of the uterus should be described as either regular or lobulated. Myometrial wall symmetry should either be evaluated subjectively or objectively measuring both anterior and posterior myometrial walls in the sagittal plane from the external uterine serosa to the internal endometrial contour including the junctional zone and calculating the ratio. The junctional zone, which should be analyzed. If the results are normal, it should be reported as visible and regular. In the case they are not, it may be described as irregular, interrupted, not visible or not assessable. Any alteration should be described as well as the magnitude, the location and the extent of this finding. The second step is the description of any myometrial pathology. Myometrial overall echogenicity should be evaluated as either homogeneous or heterogenous. If any heterogenicity is found, its characteristics should be specified as follows. Any myomethrial pathology can be localized in one or more lesions or diffuse. The definition of the lesion should be determined as ill-defined or welldefined. All well-defined lesions should be described according to its location, size and site with the FIGO classification of fibroids [3]. This classification takes several items into account comprising of the relationship of the leiomyoma to the endometrium and the serosa, the uterine location of the fibroid (upper segment, lower segment; cervix, anterior, posterior, lateral) as well as the size and the number of lesions. Classification numbers range from 0 to 8. Submucosal fibroids (Fig. 1) are classified ranging from number 0–2, being 0 intracavitary lesions attached to the myometrium by a
Fig. 1. Submucosal Myoma type 0 (A) and type 2 (B) and HD live.
narrow stalk, whereas number 1 and 2 require a portion of the lesion to be intramural, with number 1 being less than 50 % and 2 at least 50 %. Type 3 are intramural fibroids in contact with the endometrium, whilst type 4 are entirely within the myometrium with no extension to the endometrium or the serosa (Fig. 2). Subserosal fibroids are classified from number 5–7, representing the mirror image of submucosal leiomyomas, with type 5 being at least 50 % and type 6 less than 50 % intramural. Number 7 are fibroids which are completely extramural and attached to the serosa by a stalk. Other kind of fibroids that do not relate with the myometrium at all are classified under type 8. Well-defined lesions
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Fig. 2. Polyp and Myoma type 4, in this photo you can see de different ecogenicity).
should be described with its penetration which is defined as the ratio between the maximum thickness of the lesion and the total uterine wall thickness. As well as the myometrium itself, the echogenicity of the myometrial lesions should be described as homogeneous or heterogeneous and as hypo-, iso-, or hyperechogenic compared to that of the adjacent myometrium. Other characteristics of the lesion such as the echogenicity of the rim and the shape of the lesion (round, oval, lobulated or irregular) should also be defined. Ultrasound examination is very useful too to achieve the volume of the myoma, which is very important if we consider a conservative management of it. If we consider more than one diameter, a 7 cm myoma may have twice the volumen than 7 cm in diameter as well (Fig. 3). Another key item to be determined is the presence of shadowing produced by the lesion. Shadowing can be seen as edge shadows or internal shadows and with different degrees from slight to strong. There can be a special kind of shadowing called fan-shaped shadowing which consists of alternate hyperechogenic with hypoechogenic stripes. Other myometrial pathologies that should be reported are myometrial cysts and their content, hyperechogenic islands and the presence of hyperechogenic subendometrial lines or buds that disrupt the junctional zone. Third step in evaluating the myometrium should is to study the uterine vascularization using color or power Doppler. The vascular pattern of the whole uterus should be evaluated either as uniform or not. If there is a myometrial lesion, the vascular pattern within the lesion should also be described. Lesions can have circumferential, intralesional or translesional vascularity, defined by vessels that cross the lesion perpendicular to the uterine cavity. It is also useful to describe the morphology, number and the direction of the vessels. Not only the type of vascularization but also the degree should be reported. This can be done using a subjective color score that describes the amount of color in a lesion. Color score 1 is a lesion with no color, 2 with minimal amount of color, 3 with moderate color and 4 with abundant color.
Elastography Elastography is an ultrasound tool that measures the elastic features of tissues. It quantifies the stiffness and illustrates the information as a color map above the usual US image. It also allows the assessment of myometrial pathology such as myoma or adenomyosis through the different elastic characteristics of the lesions. Myoma have proven to be stiffer than healthy uterine tissue whilst adenomyosis is softer. Elastography could therefore help in identifying focal myometrial lesions, providing information about exact location and extent as well as support in the differential diagnosis of both focal findings [4]. MRI Magnetic resonance imaging is an accurate technique for imaging uterine myomas mostly in cases when US is proving limited. This occurs when the patient has a high body-massindex, when the myoma coexists with other pelvic or another uterine pathology or when there are numerous lesions. Because of its soft tissue characterization and multiplanar imaging MRI offers excellent morphologic details giving accurate information about number, size and location of the lesions as well as the presence of degeneration. It also correctly detects other pelvic pathologies such as adenomyosis. T1 weighted images provide a good discrimination between the lesion and the adjacent adipose tissue, whilst the T2 weighted image delivers one between the lesion and the normal myometrium or endometrium. Therefore, T1 is best when evaluating subserosal fibroids and T2 when evaluating submucous or intramural fibroids. The typical MRI features of fibroids have been described as well-circumscribed lesions with low signal intensity on T2 weighted images (Figs. 4 and 5). If degeneration and necrosis is present, it may show variable appearance with high-signal intensity on T1 and heterogenous on T2 weighted images (Fig. 6) [5–7].
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Fig. 3. Volume is very important if we consider a conservative management of it. If we consider more than one diameter, a 7 cm myoma may have twice the volumen than 7 cm in diameter as well. A Myoma 7 cm. diameter, volume 68 cm2. B Myoma 7 cm. diameter, but volume 153 cm2.
Hysteroscopy In women with suspected submucous fibroids, it is useful to perform a hysteroscopy in order to visualize the uterine cavity and diagnose protruding myometrial lesions. With this technique we can characterize the extend of protrusion and perform hysteroscopic procedures such as resection or morcellation. Submucosal fibroids are classified according to the European Society for
Gynecological Endoscopy (ESGE) considering the degree of penetration of the submucous myoma in the myometrium, with type 0 classification being fibroids that are entirely in the endometrial cavity without any myometrial extension (pedunculated), type 1 being fibroids with less than 50 % myometrial extension, and type 2 having 50 % or more myometrial extension. The STEP-W classification (Lasmar's Classification) was developed in order to predict the difficulty and complexity of
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Fig. 4. Uterus with multiple myomas. MRI, axial view (4A, 4C and 4D) and a sagittal view (4B) with many myomas in an infertile patient. Endometrium normal (4C). Big myoma in the uterine fundus (4D).
hysteroscopic myomectomy. This classification takes not only the penetration into account but also other parameters like the extension of the base of the nodule with respect of the wall of the uterus as well as the size and topography. This has proven to have a higher correlation with the technical difficulty in performing the procedure than the ESGE Classification. A score is calculated for each of these parameters and each fibroid has its own final score. Patients are classified into three groups depending on the surgical prognosis taking the myoma with the highest score into account. Group I is considered a low complexity procedure, group II a complex myomectomy and in patients under in group III it is advisable to suggest an alternative non hysteroscopic technique [8,9].
Differential diagnosis Leiomyoma may result in some diagnostical doubts and differential diagnosis should be done with other pathologies that cause similar clinical manifestations such as abnormal uterine bleeding or uterine enlargement. The differential diagnosis includes three main conditions: adenomyosis, uterine sarcoma and ovary mass. Adenomyosis consists of the presence of endometrial glands and stroma inside the myometrium. It is common to find an enlarged uterus clinically. Ultrasonographically it appears as
ill-defined lesions, usually involving most of the uterus and dispersed within the myometrium. In some cases it can form a confined lesion called adenomyoma which can closely resemble leiomyomas on imaging. Other ultrasound features typical of adenomyosis are myometrial wall asymmetry, poorly defined junctional zone, presence of myometrial cyst or areas with mixed echogenicity. As we told before, hence the importance of having described well the junctional zone, which is well defined in cases of myomas, but no so well clearly defined in adenomyosis.The vascularity of the lesions is typically translesional rather than circumferential. Nevertheless, adenomyosis may be difficult to diagnose with ultrasound [10]. Uterine sarcomas are malignant tumors that arise from the smooth muscle or connective uterine tissue cells. The diagnosis is based upon histologic examination, usually following surgery for presumed leiomyomas. Nevertheless, it is important to correctly suspect malignancy in any uterine lesion because misclassifying a uterine sarcoma as a benign myoma may result in a poorer prognosis for the patient. However up until now it remains a real challenge as it is an area that is poorly covered in the literature. The symptomatology and signs are very similar to those caused by fibroids, so preoperative differential diagnosis is difficult. Suspicion of sarcoma may increase based upon presence of risk factors such as premenopausal status, long-term use of tamoxifen or history of pelvic irradiation. With pelvic US examination, uterine sarcomas are
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Fig. 5. Same patient after treatment with ulipristal acetate. We can see the volume decrease of the myomas and the effect on endometrium (PAEC) (5A and 5C).
Fig. 6. Red necrosis in myoma (MRI) (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article).
usually seen as large and isolated solid masses with mixed echogenicity. They may contain irregular cystic areas due to necrosis. The presence of shadowing or calcification is not common and tumor borders are irregular in most cases. They
usually have moderate to rich vascularization with irregular vessel distribution. If a malignant lesion is suspected, studies have found that it could be useful to take endometrial sampling that can lead to preoperative diagnosis.
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Smooth muscle tumors of uncertain malignant potential (STUMPs) have similar US appearance as myomas and may therefore be indistinguishable preoperatively [11]. Assessment of the potencial myoma growth Uterine myomas usually grow during fertile age, and this must not be seen as a hint of malignancy. Moreover, knowing the growth rhythm and its normal physiopathology is key issue. Being able to determine the potential growth in a single exploration is a main objective if we want to establish a long term plan of treatment. Myomas characteristics in the first diagnosis are related to the probability of needing a treatment in the future [12]. When high growth potential is suspected, we may plan some surgical or medical treatment in order to slow down its progression, before the myoma would affect patients quality of life. There are not many studies focused on myomas growth and its risk factors [13]. We may asume that growth rate is independent for each myoma, even in the same woman [14]. And there is also good evidence that between 7 and 20 % of the fibroids may shrink even dissapear. Mean growth (in volume) has been estimated in 9% per 6 month. While in women under 35 the rate is similar between black and white etnicity, the growth seems to decrease only in whites after this age [15]. As a thumb rule, approximately one third of the myomas will grew some one third of their volume, in a period between six months and a year [14–16]. Literature is not conclusive regarding predictor factors. Location, parity and BMI seem not to affect the growth and there are not many data regarding family influence [15]. Size role at the moment of diagnosis is controversial. While some studies report that initial size is proportional to the future myoma growth [17], others show that smaller myomas have more increment [3]. Some papers refer that initial size is not related to the growth [15]. Even some authors report that lonely myomas had been reported to grew faster [14]. Although it is not clear how predictor factors may influence, the methods based on 3D power Doppler Ultrasound are being studied to predict growth, by measuring Vascular Index (VI) in the myoma vascularization. In a prospective 12 month follow up of 66 women diagnosed with a maximum of two fibroids with expectant management, growth mean of 9% was observed. In those myomas with higher VI, growth was jncreased also (10,5%), while in the group with lower VI, decreased (8 %). An increase of 1% in VI at the baseline meant an increase of volume of 7.00 cm [3] at twelve months [18]. Discussion When we evaluate a patient with uterine fibroids, we must consider a whole set of aspects related with the disease. We believe it is important to say that we are evaluating women with myomas, not an isolated myoma. Good communication with patients is essential. This will provide precise knowledge of the situation but also will allow to expose the perception of the woman about the illness. It is also crucial to find out the preferences and desires of our patient. Ultrasound and image proofs are the main pillar in diagnose, but we have to be able correlate them with the symptoms and possible surgical accesses. Thus it is very advisable that the gynecologist who is treating the patient, whether medically or surgically, is the same who performs and interprets ultrasound. If specific doubts arise a more specialized exam is recommended to clarify these aspects.
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Once we have collected all data we must try to consider an accurate diagnosis and prognosis. According to the type of myomas, symptomatology, and the woman characteristics and preferences we must have in mind the present needs but also the lapse of time until menopause arrives. Our aim should achieve the best possible quality of life, with the less treatment burden. Thus, we have to balance the possible necessity of a medical or surgical treatment along those years based on the present diagnosis to avoid overtreatment and also the delay of necessary interventions [19]. Present symptomatology, evolutionary prognosis and patient desires in terms of pregnancy desire, treatment preferences must be carefully recorded in the clinical history. Uterine Fibroid Sympton-QoL (UFS_QoL) has been designed to evaluate accurately the symptoms and their effect on the patient. It consider several issues such as concern, control, activities, sexual function, energy and mood and self conscience of the patient. They are checked through individual items designed to measure each aspect and then combined to get a final score [20]. Although the physician intuitive process to summarize the clinical picture is suitable for day practice, it is necessary to obtain numerical values when we want to compare precisely. It is becoming mandatory in investigation terms and it is recommended in particular clinical cases. Declaration of Competing Interest The authors confirm that there are no known conflict of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome. References [1] Alcázar J, Pascual M, Guerriero S. Ultrasound of pelvic pain in the non-pregnant female. 1st ed 6000 Broken Sound Parkway NW, Suite 300 Boca Raton, FL: CRC Press; 2019. p. 82–95 33487-2742. [2] Van den Bosch T, Dueholm M, Leone F, Valentin L, Rasmussen C, Votino A, et al. Terms, definitions and measurements to describe sonographic features of myometrium and uterine masses: a consensus opinion from the Morphological Uterus Sonographic Assessment (MUSA) group. Ultrasound Obstet Gynecol 2015;46(3):284–98. [3] Munro M, Critchley H, Broder M, Fraser I. FIGO classification system (PALMCOEIN) for causes of abnormal uterine bleeding in nongravid women of reproductive age. Int J Gynecol Obstet 2011;113(1):3–13. [4] Frank M, Schäfer S, Möllers M, Falkenberg M, Braun J, Möllmann U, et al. Importance of transvaginal elastography in the diagnosis of uterine fibroids and adenomyosis. Ultraschall Der Med 2015;37(4):373–8. [5] Omary R, Vasireddy S, Chrisman H, Ryu R, Pereles F, Carr J, et al. The effect of pelvic MR imaging on the diagnosis and treatment of women with presumed symptomatic uterine fibroids. J Vasc Interv Radiol 2002;13(11):1149–53. [6] Hricak H, Tscholakoff D, Heinrichs L, Fisher M, Dooms G, Reinhold C, et al. Uterine leiomyomas: correlation of MR, histopathologic findings, and symptoms. Radiology 1986;158(2):385–91. [7] Kido A, Togashi K, Koyama T, Yamaoka T, Fujiwara T, Fujii S. Diffusely enlarged uterus: evaluation with MR imaging. Radiographics 2003;23(6):1423–39. [8] Lasmar R, Barrozo P, Dias R, de Oliveira M. Submucous myomas: a new presurgical classification to evaluate the viability of hysteroscopic surgical treatment—preliminary report. J Minim Invasive Gynecol 2005;12(4):308–11. [9] Lasmar R, Lasmar B, Celeste R, da Rosa D, Depes D, Lopes R. A new system to classify submucous myomas: a brazilian multicenter study. J Minim Invasive Gynecol 2012;19(5):575–80. [10] Van den Bosch T, Coosemans A, Morina M, Timmerman D, Amant F. Screening for uterine tumours. Best Pract Res Clin Obstet Gynaecol 2012;26(2):257–66. [11] Ludovisi M, Moro F, Pasciuto T, Di Noi S, Giunchi S, Savelli L, et al. Imaging in gynecological disease (15): clinical and ultrasound characteristics of uterine sarcoma. Ultrasound Obstet Gynecol 2019. [12] Baird DD, Saldana TM, Shore DL, Hill MC, Schectman JM. A single baseline ultrasound assessment of fibroid presence and size is strongly predictive of future uterine procedure: 8-year follow-up of randomly sampled premenopausal women aged 35–49 years. Hum Reprod 2015;30(12):2936–44. [13] Armbrust R, Klaus-Dieter W, Sehouli J, Matthias D. The growth of uterine myomas in untreated women: influence factors and ultrasound monitoring (Jan 2018). Arch Gynecol Obstet; Heidelberg Tomo 2018;297(1):131–7, doi: http://dx.doi.org/10.1007/s00404-017-4568-5).
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[18] Nieuwenhuis LL, Keizer AL, Stoelinga B, Twisk JWR, Hehenkamp WJK, Brölmann HAM. JAF Huirnea Fibroid vascularisation assessed with threedimensional power Doppler ultrasound is a predictor for uterine fibroid growth: a prospective cohort study. BJOG 2018;125(April (5)):577–84. [19] Mas A, Tarazona M, Dasí Carrasco J, Estaca G, Cristóbal I, Monleón J. Updated approaches for management of uterine fibroids. Int J Womens Health 2017;9:607–17 Sep 5. [20] Spies JB, Coyne K, Guaou NG. The UFS QOL, a new disease specific symptom and health related quality of life questionnaire for leiomyomata. Obstet Gynecol 2002;99:290 –30.
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