Beware of a multi‐fibroid uterus: The importance of ultrasound reporting in the early detection of uterine sarcomas

Abstract

Primary uterine malignancy masquerading as a benign leiomyoma is a rare yet devastating condition if missed on ultrasound. Although there are no current guidelines to aide in early ultrasound identification of these high‐risk patients prior to histological analysis, certain imaging characteristics may heighten the suspicion of malignancy. Unfortunately, these atypical features are often not included in ultrasonographic reports resulting in delayed treatment and catastrophic consequences. We present a case of a uterine Ewing's sarcoma (ES), which was diagnosed as a multi‐fibroid uterus on initial ultrasound. The lack of clinical suspicion resulted in a delay to definitive diagnosis and a sub‐optimal surgical resection. We compare this to a standard case of a multi‐fibroid uterus in order to highlight the differences in ultrasonographic appearance. This case delineates the importance of accurate identification and open reporting of suspicious features in order to assist ultrasonographers and specialist gynaecologists in creating a differential diagnosis of an otherwise common condition. A high index of suspicion of atypical lesions may lead to early life‐saving interventions and careful tissue control during surgery, resulting in improved patient outcomes.

Introduction

Primary uterine malignancy has a reported incidence of up to 1 in every 350 cases of suspected uterine leiomyoma. Of the lesions that are non‐endometrial in origin, sarcomas are by far the most common.1 One subset of these is Ewing's sarcoma (ES), a primitive neuroectodermal tumour of primary uterine origin which has been sparingly described in the literature.2 ES are quite aggressive and require an early diagnosis, appropriate surgical management and combined chemo/radiation therapy for optimal long‐term survival.3 These lesions may be misdiagnosed as benign leiomyomas, a mistake that may prove to be fatal, as in our case. Careful analysis and reporting of ultrasound imaging is vital in the consideration of malignancy as an early differential diagnosis.4 Although no guidelines currently exist to help sonographers or clinicians differentiate malignant from benign myometrial lesions, certain patterns of haemorrhage, degeneration and blood flow may be described as atypical and may indicate an increase in the likelihood of malignancy. However, unless these and other suspicious features are communicated to treating physicians, management of these high‐risk patients may be delayed. To date, only two cases of the ultrasonographic appearance of ES have been described in the literature.2, 4 We present a case of uterine ES reported as a benign leiomyoma on ultrasound and compare it to a patient with a benign multi‐fibroid uterus (Figures 1, 2, 3).

Figure 1.

Trans‐vaginal and trans‐abdominal ultrasound scan images suggestive of a benign‐appearing fibroid.

Figure 2.

Colour Doppler image of a benign appearing fibroid.

Figure 3.

Macroscopic appearance of the benign fibroid visualised in Figure 9.

Case presentation

A 34‐year‐old woman gravida 2, parity 2 presented to the emergency department (ED) with a recent episode of moderate vaginal bleeding, a negative pregnancy test and a palpable 18‐week gestation size uterine mass. An ultrasound scan (USS) (Figures 4, 5, 6) described a 90‐mm exophytic mass lesion suggestive of a leiomyoma arising from the posterior lower uterine segment. Another smaller lesion was identified in the left side of the uterus measuring 28 mm. Unfortunately, the suspicious multi‐cystic appearance, with areas of haemorrhage, necrosis and increased vascularity of the larger mass were not included in the report and a conclusion of a multi‐fibroid uterus was made.

Figure 4.

Trans‐vaginal ultrasound scan of the pelvis demonstrating a large heterogeneous, multi‐cystic uterine lesion with areas suggestive of haemorrhage and necrosis.

Figure 5.

Trans‐vaginal ultrasound scan showing a suspicious looking posteriorly placed exophytic mass lesion (A) and a concentric heterogeneous mass with edge shadowing suggesting of a fibroid (B).

Figure 6.

Trans‐vaginal colour Doppler image of the uterine lesion showing increased vascularity.

Approximately, 7 months after a failed course of medical management, an urgent hysterectomy was organised. During this procedure, it was noted that there was a large fluid‐filled inferio‐posterior lesion involving the uterosacral ligaments. This lesion appeared degenerative with significant external vascularity. Unfortunately during the surgical procedure, the mass was resected in vivo. Strict tissue care was not adhered to as the surgeons were unaware of the potential malignant nature of the lesion. Large amounts of necrotic debris spilled into the abdominal cavity. The lesion appeared to include the cervix and the outer half of the myometrium (Figure 7). The liver was smooth and regular with no clear nodules, and lymph nodes felt unremarkable. The patient made an uneventful post‐operative recovery and was discharged home. Unfortunately, she returned after 8 weeks with a post‐coital vaginal vault dehiscence, which required surgical management.

Figure 7.

Specimen post hysterectomy. The body of the uterus can be seen on the left, with the large necrotic sarcoma localised in the posterior wall in the lower segment and cervix.

Histopathology, immunological and genetic screening were consistent with an atypical ES. The final histological diagnosis was made based on microscopic features and positive results of several immunological cell markers. Fluorescence in situ hybridisation, a genetic analysis, returned an atypical, but positive result for the EWSR1 gene, consistent with ES. Histopahtology images from our case demonstrating malignant cells, invading and pushing smooth muscle, have been compared with a high‐power view of a benign leiomyoma showing fascicles of smooth muscle cells (Figures 8, 9).

Figure 8.

Necrotic mass in the posterior cervix and lower uterine segment showing sheets of round malignant cells invading and pushing smooth muscle.

Figure 9.

High‐power view of leiomyoma showing fascicles of smooth muscle cells.

Tumour staging was performed and a computed tomography and positron emission tomography (CT PET) scan identified extensive metastatic disease with several sub‐pleural and pelvic nodules, as well as vertebral deposits (Figure 10).

Figure 10.

PET scan showing lung metastasis with a 13‐mm ill‐defined parenchymal opacity within the superior segment of the left lower lobe.

The patient was commenced on a combined chemotherapy treatment regime. Six‐month follow‐up imaging found a reduction in peripheral metastatic deposits but new local recurrence at the vaginal vault was identified. Although her prognosis was initially described as approximately 30% survival in 5 years, she unfortunately recently succumbed to the disease.

Discussion

Uterine fibroids place a significant financial strain on health systems as a major cause of morbidity in women worldwide. The reported incidence of symptomatic fibroids is reported to be between 3% and 27% of the general population, although this may be >40% in certain ethnic groups.5, 6 These numbers are likely inaccurate, as majority of women with fibroids are asymptomatic and the diagnosis is often incidental. The severity of symptoms is often thought to be dependent on the location, size and number of fibroids.7 The most common, and often only, and significant symptom is heavy bleeding with periods. This is a result of both proximal myometrial and endometrial vasculature congestion, as well as increased endometrial surface area.8 Treatment options range from observational and medical, to surgical, depending on the impact on each individuals quality of life. When medical management fails, surgical options include uterine artery embolisation, myomectomy or the gold standard, hysterectomy. In the United States, 33.5% of the 600,000 hysterectomies performed each year are for fibroids.8

To date, there are no reliable clinical or radiological methods to accurately differentiate malignant from benign lesions prior to histological analysis.9 Occasionally, attempted hormonal or radiological therapy for symptomatic fibroids may delay a histological diagnosis of uterine malignancy. The importance of differentiating malignant lesions from benign fibroids has become ever important with an increase in medical management options and uterine sparing surgery. There is concern that new minimally invasive surgical techniques may have the potential to worsen long‐term outcomes for these patients. Laparoscopic power morcellation of fibroids for symptomatic bleeding has gained significant negative press lately. In 2014, the United States of America Food and Drug Administration warned against the use of power morcellation for suspected leiomyoma due to a 1 in 350 risk of malignancy and the potential risk of dissemination.10 However, this risk appears to be over‐estimated, with a more recent publication stating the overall risk of malignancy to be 1 in 1,124.11 In addition, several recent retrospective studies, although small, have shown an increased risk of local recurrence and lower survival rates in these missed cases and highlight the importance of a pre‐procedure diagnosis.12

Primary non‐endometrial uterine malignancy is rare and is potentially catastrophic if missed. Malignant myometrial tumours are often of mesenchymal origin, although they may be mixed with epithelial cell lines. Mesenchymal primary uterine sarcomas account for up to 9% of uterine myometrial malignancies, however this prevalence is dependent on racial groups.1 Of these rare uterine sarcomas, ES belong to a group collectively known as primitive neuroectodermal tumours and may present anywhere in the body. Primary uterine origin tumours are extremely rare with only 48 cases published in the literature to date.2 Mittal et al.13 noted that the main presenting complaint for these patients was abnormal uterine bleeding. Definitive diagnosis is often difficult in cases of advanced disease with poorly differentiated cells. Immunochemistry and genetic analysis are implemented in cases with atypical histology, though our case emphasises that not all tumours fit into specific patterns. Management usually includes surgical resection of the disease followed by chemotherapy and radiotherapy. Staging of the disease is important for prognosis, though the small number of reported cases mean limited accuracy when predicting long‐term survival. However, disseminated disease is the most powerful marker for prognosis.14 Case studies similar to ours have noted that patients with limited, or undetectable, metastatic disease on regular imaging modalities may progress to develop significant disease. Although there is no data on survival rates of primary uterine ES, Baldini et al.15 found a 5‐year survival rate of 38% for the composite of extra‐skeletal primary ES.

Ultrasound remains the gold standard for diagnosing fibroids. Due to their remarkably variable nature, location and size, images of appropriate quality are paramount. The Morphological Uterus Sonographic Assessment group describes a fibroid as a well‐defined and round lesion with some relation to the myometrium. Shadowing at the edges and internal fan‐shaped shadowing are common, with Doppler assessment often eliciting circumferential flow.16 The echogenicity of a fibroid is most dependent on the relative ratio of smooth muscle to fibrous tissue, however, in most cases it is similar of that of the myometrium.17 In addition, acoustic shadowing arises from the muscle and connective tissue interphases.16, 18 In cases where there is mixed echogenicity, histology often reveals haemorrhage and oedema. Myxoid degeneration may be seen in cases with hypoechoic cystic structures and fluid. Van Den Bosch et al.16 suggest that fibroids with this type of appearance be labelled as atypical. Other pathology that may mimic these atypical appearances include endometriomas, degenerating fibroids, adenomyotic cysts, lipoleiomyoma and rarely, uterine sarcomas.19, 20

The current ultrasonographic description of uterine malignancy is based around a small group of case series.16 Although many authors agree that there are no clear differentiating features16, 21, sonographers and clinicians should be suspicious of fibroids exhibiting rapid growth and areas of haemorrhage.16, 22 Unfortunately, even these have shown to be non‐specific.22 In these circumstances, it would be prudent to consider further radiological imaging with MRI to evaluate the risk of malignancy.20, 23 Exacoustos et al.24 concluded that leiomyosarcomas usually appeared as single intramyometrial tumours, 50% of which had features of cystic degeneration. The group followed on from several studies by looking at the peripheral and central vascular flow of leiomyosarcomas.21, 25 These studies describe an increased irregularity in the disbursement of vessels in malignant tumours compared to benign leiomyomas. Other studies have looked at intramural Doppler indices to define the risk of malignancy; however, none have been able to replicate substantial enough sensitivities to be of any clinical significance.25, 26 The ultrasound appearance of ES has been described in two case reports. Tepper et al.2 made the diagnosis retrospectively and unfortunately, as in our case, described a case where a missed diagnosis resulted in poor tissue control at surgery. The appearance at ultrasound found two irregular components: an area of echogenic solid‐appearing tissue and an area of multiple small cysts. Loverro et al.2 noted a highly suspicious appearing uterine tumour with complex echogenicity on ultrasound prior to surgery. Intraoperative histology revealed a soft tissue neoplasm with malignant features. The tumour was able to be removed en‐bloc and the patient had progressed disease free for 2 years following a course of chemotherapy and radiotherapy. The cystic nature of both lesions was highlighted by the authors and may be an important finding to include when describing uterine lesions.

One major issue in the analysis of myometrial lesions is the significant lack of standardisation in description and reporting. The Morphological Uterus Sonographic Assessment (MUSA) statement published in 2015 aims to standardise the process of reporting sonographic features of the myometrium.16 Until there is a wider clinical uptake of standardisation by both sonographers and clinicians, a detailed description of all myometrial lesions should be routinely included in ultrasound reports. Medical practitioners often use ultrasound as an important tool to support clinical decisions yet are insufficiently trained to individually interpret ultrasound images, heavily relying on highly skilled sonographic and radiological conclusions. Thus, the detail contained within reports has a vital role in determining patient outcomes.

Conclusion

Ultrasonographers are perfectly positioned to have a significant impact on clinical outcomes by ensuring appropriate reporting of imaging findings.18 When atypical‐appearing leiomyomas are noted at ultrasound, an accurate and detailed description of the lesion may prompt the treating team to consider rarer conditions such as ES. This would allow the opportunity to request further radiological imaging with MRI and appropriate subspecialty referral. This in turn may also prompt adequate tissue control at surgery offering the patient the most optimal chance of survival.

Consent

Verbal consent was obtained from the patient for publication of this case report and the accompanying images. Unfortunately, the patient passed away recently.

Competing interests

The authors declare that they have no competing interests.

Author contributions

AK, MM and BH compiled and approved the final manuscript. AK contributed to the interpretation of ultrasound scans.