Uterine Myomas and Sarcomas - Clinical and Ultrasound Characteristics and Differential Diagnosis Using Pulsed and Color Doppler Techniques.

Doppler ultrasonography can visualize an irregular distribution of vessels in the tumor; they are thin, randomly scattered or dilated, with multiple interconnections. The vessels may be located in the marginal and central areas of the tumor, with the mean resistance index (RI) values of 0.37 ± 0.03. Analyzing the vascularization pattern of lesions arising from the myometrium, it should be noted that low resistance to blood flow in the tumor vessels (RI <0.5) occurs in 9% of premenopausal and 4% of postmenopausal women ( 29 , 33 ) . Sarcoma-like lesions are characterized by MUSA grade 3 or 4 vascularization ( 39 ) . Pathologic vascularization is found in 100% of sarcomas. Peak systolic velocity (PSV) may be an additional parameter allowing for more precise diagnosis. PSV was found to be higher in uterine sarcomas than in myomas (mean: 71 cm/s vs 22.5 cm/s, respectively). PSV assessment may be a helpful indicator in differentiating between malignant and nonmalignant tumors of the uterine body. The vascularization of angiosarcomas is irregular, centrally and peripherally localized. Blood flow indices in the tumor are low.

Ultrasonography (US; including sonohysterography with saline infusion) and magnetic resonance imaging (MRI) are considered the most effective tools for the diagnosis of uterine myomas in terms of number, echostructure, volume, or location in the uterine muscle. These modalities allow precise tracing of tumor vascularization and facilitate differentiation between benign, i.e. adenomyosis, and malignant lesions ( 26 ) . Simplicity, low cost, wide availability and, most importantly, non-invasiveness are great advantages of ultrasound in gynecology. The Doppler technique enables assessment of hemodynamic changes in lower pelvic vessels, characteristic of both physiological and pathological states. Characteristics of vascular flow is possible owing to the use of parameters enabling its qualitative and quantitative assessment. These include resistance index (RI), pulsality index ( PI) and systolic-diastolic ratio ( S/D) ( 27 ) . Transabdominal imaging offers a wide field of view, high signal penetration, and the ability to examine adjacent organs beyond the pelvis minor. It is therefore more effective for visualization of large tumors, submucosal or parasitic myomas penetrating deep into the abdominal cavity. Imaging is hampered by retroverted uterus, scarring, and excessive fatty tissue. Transvaginal ultrasound (TVS) allows for detailed imaging as the transducer is placed adjacent to the tumor, which means that a high-frequency ultrasound wave can be used. It is now a routine examination in gynecology. The combination of transabdominal and endocavitary ultrasound is the most commonly used technique for detecting, mapping, and evaluating myomas ( 28 ) . Ultrasonography combined with sonoangiography allows detection of vessels as small as 100–200 μ m in diameter. Using color Doppler technique, it is possible to visualize the ascending branch of the uterine artery. Using low pulse repetition frequency (PRF) filters in the range of 600–800 Hz and wall motion filters (WMF) in the range of 50–100 Hz, arch vessels at the border of the outer and middle myometrial layers can be visualized ( 22 , 23 , 24 ) . Based on uterine arterial blood flow analysis by color Doppler, steroid sex hormones were found to be the major regulators of uterine perfusion. Estrogen and progesterone receptors are present in the uterine arteries and myometrium. Cyclic changes in the number of these receptors alter uterine blood flow. Estrogen acts as a vasodilator, increasing uterine perfusion, therefore it is more intense in premenopausal women. Progesterone has the opposite effect, decreasing uterine blood flow ( 29 ) . Based on a feedback from a panel of clinicians (Morphological Uterus Sonographic Assessment, MUSA), a common classification was proposed to describe ultrasonographic blood flow characteristics in myometrial pathology ( 26 ) . The MUSA scale is interpreted as follows: 1 – no flow; 2 – minimum flow; 3 – moderate flow; 4 – strong flow. It should be noted that myomas are usually sparsely vascularized. Color Doppler or power Doppler imaging shows myomas as structures with abundant peripheral vascularization or with poorly visible circular vascularization pattern, whereas central flow is rarely observed. The afferent branches reach the center of the tumor through peripheral arteries. The peripheral flow in the tumor is slightly more increased compared to normal myometrium and the central portion of the myoma. Doppler techniques make it easier to distinguish an endometrial polyp with a single feeding vessel from a myoma and adenomyosis, where vascularization is much more diffuse ( 30 , 31 , 32 ) . Vascular myomas are rare. They are characterized by the presence of multiple thick-walled and dilated venous and lymphatic vessels, which increase in diameter along with the tumor growth. There are no structural differences in the vasculature of sparsely and richly vascularized myomas. According to the majority of authors, resistance and pulsation indices in myoma vessels are useless, as both low- and high-resistive flow can be observed. Such a mixed type of vascularization is found mainly in pedunculated myomas. The ranges of values for resistance and pulsatility indices in the vessels of myomas are RI = 0.4–0.6 and PI = 0.7–0.9, respectively. Flow cytometry showed an inverse correlation between RI (0.27–0.73, median 0.44) and myoma volume. The Doppler flow waveform in the vessels of myomas is similar to that observed in the uterine arteries. In most cases, it is possible to visualize the diastolic flow. The lack of early diastolic notch seen in high-resistance vessels is a hallmark. High amplitude of systolic and diastolic flow velocity may occur in submucosal myometrial vessels, in which pathological vessels mimicking those found in malignant neoplasms may form ( 22 ) . The phase of the menstrual cycle and the duration of menopause do not affect the profile of blood flow in myometrial vessels, hence it is believed that there are different mechanisms regulating flow in the uterine arteries and myomal vessels. However, the influence of patient’s hormonal status on this profile is noticeable. Resistance indices in premenopausal women are lower than in menopausal patients, regardless of tumor size. Literature reports suggest the impact of lesion location and size on the Doppler blood flow profile. Larger and peripherally located myomas with features of degenerative changes are characterized by higher diastolic blood flow velocity and lower resistance index in the tumor vessels. Some authors note that an increase in lesion diameter in both pre- and postmenopausal women improves blood flow visualization regardless of tumor location, whereas a decrease in RI is seen only in the vessels of submucosal and subserosal lesions. This effect was not observed in the case of intramural myomas. Such observations are attributed to a different physiology of the surrounding tissues (endometrium, uterus) and their direct influence on myomas (pressure exerted by the myometrium) as well as their distance from the larger branches of the uterine arteries. Large myomas, characterized by central foci of necrosis, show moderate RI in peripheral vessels on Doppler, a nd low R I in vessels inside the tumor, due to vasoactive factors released in this region ( 33 ) . In 1992, Kurjak compared blood flow profiles in the uterine arteries of healthy patients and those diagnosed with uterine myomas ( 33 ) . The measurements of blood flow parameters in uterine arteries revealed lower resistance and pulsation indices and higher blood flow velocities in patients with uterine myomas. The study demonstrated that myomas alter uterine blood flow regardless of their size or the presence of clinical symptoms. The assessment of blood flow parameters in the uterine arteries and in the vessels of myomas, which are increasingly easy to visualize due to advances in imaging techniques and the sensitivity of ultrasound equipment, is extremely important to attempt differentiation from malignant lesions arising from the myometrium. Diagnostic difficulties may be encountered in the evaluation of interligamentous myomas. Ambrosio et al. showed that acoustic shadowing was present in 89% of these myomas (63% of interstitial myomas, of which 100% had shadowing within the lesion, which was the most characteristic feature of this group of tumors). Up to 89% of these myomas showed increased flow within the tumor (MUSA grade 3 or 4), compared with the control group. Interligamentous myomas were solid in 84% of cases ( 34 ) .

Nonepithelial neoplasms of the uterine corpus are rare, accounting for approximately 1% of female genital malignancies and less than 5–10% of uterine malignancies ( 35 ) . Sarcomas occur in older women (age at diagnosis is usually 62–67 years). The risk is twofold higher in black women compared to white women ( 36 ) . The prognosis for patients diagnosed with uterine sarcoma depends on tumor size and stage. Five-year survival rates for women are less than 10% except when the tumor is confined to the uterus (then it is 50%). The prognosis for uterine sarcomas is much worse than for endometrial cancer. This is due to the more rapid formation of both local and distant metastases ( 3 , 37 ) . Sarcomas are tumors composed of mesenchymal tissue. Simple (homogenous) and complex sarcomas, including homologous (derived from uterine tissue), heterologous (containing tissue not normally found in the uterus), and mixed forms (composed of a squamous or glandular, benign or malignant epithelial component and a mesenchymal component – always malignant) have been distinguished. Similar risk factors may promote the development of sarcoma or uterine cancer. Both cancers are associated with obesity, nulliparity, and excess endogenous and exogeneous estrogen ( 36 ) . Pelvic exposure to direct radiation, especially during radiation therapy, is now a significant risk factor of uterine sarcomas. So far, the etiopathogenesis and molecular abnormalities underlying these tumors have not been fully understood. The World Health Organization (WHO) classification of endometrial s arcomas distinguishes leiomyosarcoma (LMS – 40% of endometrial sarcomas, as well as non-infiltrating and infiltrating low-grade (LG ESS – 10–15% of sarcomas) and high-grade (HG ESS) endometrial stromal sarcoma (ESS). Other soft tissue sarcomas, including striated cell sarcoma and undifferentiated types characterized by nuclear pleomorphism, very rarely occur in the uterine body. Smooth muscle tumors of uncertain malignant potential (STUMP) include LMS of uncertain malignant potential, usually with good prognosis ( 38 ) . Leiomyosarcomas accounts for approximately 1.3% of malignant uterine tumors and ¼–1/3 of uterine sarcomas. The mean age of incidence is 52 years. Five-year survival rates for LMS range from 19–65%. Metastases most often occur in the lungs ( 37 ) . Poorly differentiated invasive sarcoma has an incidence of 1.8 per 1,000,000 women in the general population. The mean age at onset is 52 years. The characteristic feature of this tumor is infiltration of myometrial vessels in the form of finger-like microextensions. It is a hormone-dependent sarcoma. More than 80% of ESS have receptors for estrogen, progesterone or gonadolyserine. These receptors may be responsible for autocrine tumor growth. ESS cells express aromatase ( 1 ) . Five-year survival rates for ESS range from 50–65% ( 37 ) . Undifferentiated uterine sarcoma (UUS) is a tumor with no differentiated cells in the stroma. It is a highly malignant tumor that infiltrates the myometrium. It has a poor prognosis. Uterine sarcomas usually remain asymptomatic for a long time. Accurate diagnosis is delayed when other myometrial lesions coexist (adenomyosis, myomas) and is usually made during histopathological evaluation after hysterectomy for other indications. Abnormal, usually heavy, uterine bleeding is one of the most frequently observed symptoms, occurring in 70–90% of patients. Uterine enlargement can be found in 20–30% of patients. Lower abdominal pain occurs when the uterus is significantly enlarged or when the tumor is locally advanced. Sarcomas metastasize mainly through the bloodstream. Lymphatic spread is rare. In the case of dissemination, the symptoms depend on the location and size of the metastases ( 1 , 29 , 35 ) . The rare occurrence and histopathologic heterogeneity of endometrial sarcomas mean that the knowledge of them comes mainly from retrospective studies.

Leiomyosarcomas are usually described on ultrasonography as solid, oval tumors with heterogeneous internal echoes, containing areas of mixed and low echogenicity. Uterine sarcomas are shown in Fig. 7 and Fig. 8 . The diagnosis was confirmed by postoperative histopathological examination. Sarcoma. Mixed echogenicity, richly vascularized, grade 4 color Doppler lesion Mixed echogenicity sarcoma lesion The endometrium is usually thin, atrophic, with mucosal pattern depending on the phase of the cycle in young women. Retrograde changes in the form of centrally localized necrosis are very common. On the other hand, the hypoechogenic areas in sarcomas due to the presence of focal necrosis are also found in myomas. Therefore, myomas and sarcomas are often difficult to differentiate on ultrasound. The size of the tumor is very important. Rapid growth of the tumor (doubling of the lesion diameter within 6 months may raise suspicion of sarcoma) may be one of the most important alarming symptoms. The lack of calcifications inside the tumor and the absence of acoustic shadowing is the most characteristic US feature of sarcomas, although definitive diagnosis cannot be based on US image. On ultrasound, endometrial stromal sarcoma appears as a polypoid, hypoechoic, pronounced tumor of the uterine cavity originating from the endometrium, enlarging the uterine cavity and the entire uterine body. The tumor usually does not involve the entire mucosa and may infiltrate the myometrium at the base, which is also seen on ultrasound.

Differentiation between myomas and uterine sarcomas is difficult and not always possible. Ultrasonography and magnetic resonance imaging are the gold standard for the diagnosis of uterine tumors. It can be generally accepted that the finding of a large inhomogeneous uterine tumor on ultrasound in a post-menopausal patient should raise the suspicion of sarcoma even when the sparse vascularization of the lesion is shown in imaging ( 21 , 37 ) . It is now known that neither RI nor PI analysis can clearly distinguish between myomas and uterine sarcomas. It is estimated that RI is not significantly different between myomas and leiomyosarcomas (mean: 0.49 ± 0.18) ( 31 ) . The diagnosis of uterine tumors is actually limited to transabdominal and transvaginal ultrasound. Both methods are widely used and readily available. To distinguish whether the lesion is benign or malignant, in case of diagnostic difficulties, Doppler imaging should be used, following the rule that benign lesions are usually hyperechoic, less vascularized – most often in the periphery (MUSA grade 1). Since sarcomas are usually single, large tumors, often rapidly growing, the recommended ultrasound follow-up of suspicious lesions should be performed after 3 months. Virtually all sarcomas have increased vascular flow (MUSA grade 3 or 4) and cystic degeneration is found within the tumor in half of the cases. Women under the age of 40 years are at a low risk of sarcomas. Ultrasonography using color Doppler appears to be a sensitive and specific method in experienced hands. However, further studies are needed to introduce sonographic terminology and methodology to the study of the uterine muscle and to clarify the imaging parameters that differentiate typical myomas from smooth muscle tumors of unknown malignant potential (STUMP) and leiomyosarcomas. The above literature review and our own experience have shown that the flow velocity is higher in uterine sarcomas than in myomas, but no unambiguous norms or values of flow parameters have been developed so far. This topic requires further studies and larger groups of women undergoing diagnosis.