Imaging in Uncommon Uterine Malignancies

Keywords

uterus - MRI - sarcoma - mesenchymal - malignancy - leiomyosarcoma - leiomyomas - endometrial stromal sarcoma - carcinosarcoma - STUMP

Introduction

Uterine malignancies are rising globally, with both incidence and mortality rates showing a steady increase over the past decade.[1] Despite their prevalence, uncommon uterine malignancies present significant diagnostic and therapeutic challenges due to their rarity and frequently nonspecific imaging features.

While definitive diagnosis typically relies upon histopathology, certain imaging features may aid in narrowing the differential diagnosis and suggesting a likely diagnosis. As multidisciplinary care becomes increasingly central to oncology, radiologists play a pivotal role in disease evaluation and guiding subsequent clinical management. This review highlights the key imaging features of uncommon uterine malignancies, emphasizing magnetic resonance imaging (MRI) features. Relevant sections of the latest fifth edition of the World Health Organization (WHO) classification of female genital tumors are also discussed.

Classification

According to the WHO classification (2020), uterine malignancies are classified into three main categories: epithelial, mesenchymal (sarcomas), and mixed epithelial and mesenchymal tumors. The epithelial category is the most prevalent, primarily comprising endometrial carcinoma, which itself includes several subtypes, such as endometroid, serous, clear cell, squamous cell, and other rare variants. Mesenchymal tumors represent the second most common category of uterine malignancies and arise from the stromal or mesenchymal uterine tissue, and are often referred to as sarcomas. Uterine sarcomas account for 8% of all uterine malignancies,[2] and are further classified into two groups: nonepithelial and mixed epithelial–nonepithelial, based on the type of cancerous cell and presumed tissue of origin.[3] Smooth muscle tumors are the most common subtype within this mesenchymal category. Notably, in the previous WHO classification, carcinosarcoma was considered a mixed epithelial and mesenchymal tumor; however, in the current classification, it is categorized as an endometrial carcinoma. The classification of uterine malignancies into common and uncommon types is illustrated in [Fig. 1], while the classification of uterine sarcomas is detailed in [Fig. 2].

Fig. 1 Flowchart depicting the classification of uterine malignancies into common and uncommon types (after modification of the fifth edition of WHO classification of tumors of female genital tract).

Fig. 2 Classification of uterine sarcomas.

Imaging Techniques

A brief overview of the various imaging modalities used for uterine malignancies is described.

Ultrasound

Ultrasound is the initial imaging modality for evaluating the female pelvis. The assessment typically begins with a trans-abdominal scan using a low-frequency curvilinear probe, performed with a distended urinary bladder to serve as an acoustic window. Subsequently, a transvaginal scan can be performed to better assess the uterus and the endometrium, after emptying the urinary bladder. Doppler can be performed to assess the vascularity of the mass. However, ultrasound offers limited soft tissue characterization and is less useful in differentiating benign from malignant uterine lesions, though it can detect ascites and large peritoneal metastases.

Computed Tomography

Computed tomography (CT) is primarily utilized for staging purposes, to detect loco-regional and distant metastases. A contrast-enhanced CT of the chest, abdomen, and pelvis is usually performed. Positive oral contrast can be given to better detect peritoneal deposits, but it can obscure calcified peritoneal deposits. CT has no role in the characterization of uterine masses, due to its limited soft tissue resolution.

Magnetic Resonance Imaging

MRI provides the highest accuracy in characterization of uterine masses,[4] in view of the high soft tissue contrast resolution, availability of diffusion sequences, and multiplanar imaging. It can also better localize the position of the lesion within the uterus. The patient should undergo 4 to 6 hours of fasting prior to MRI to reduce artefacts from bowel peristalsis. The urinary bladder should be emptied prior to the scan, as a full bladder can produce motion artefacts. Vaginal gel opacification may be considered if vaginal infiltration is suspected.

The algorithmic approach to imaging uncommon uterine malignancies on MRI is provided in [Table 1].

Table 1 Stepwise evaluation of atypical uterine masses on MRI to diagnose malignant etiology

Steps	Evaluation on MRI
1.	Assess for extrauterine disease. Presence of nodal metastases/peritoneal implants/significantly elevated tumor markers suggests malignancy
2.	Identify any solid-enhancing component on the post-contrast sequences
3.	Assess the T2 signal intensity of the solid-enhancing component. Intermediate to high signal intensity suggests malignancy
4.	Evaluate the DWI signal on the high b-value image. Intermediate to high signal (to endometrium/lymph node) favors malignancy
5.	Measure the ADC value. If <0.9 × 10−3 mm2/s, it is highly suspicious for malignancy

Abbreviations: ADC, apparent diffusion coefficient; DWI, diffusion weighted imaging; MRI, magnetic resonance imaging.

Positron Emission Tomography/CT

Positron Emission Tomography (PET) uses 18-flouro-deoxy-glucose (18F-FDG) to detect metabolically active tumor cells, and is combined with CT to provide anatomical localization of tracer uptake. Patients should fast for at least 6 hours prior to the scan, and the bladder should be emptied to reduce artefacts in the pelvis as 18F-FDG is excreted by the kidneys. Physiological FDG uptake may be seen in the endometrium, ovarian follicles, and corpus luteum. PET/CT is particularly helpful in cases of suspected recurrence and advanced uterine malignancies.

Key Features of Uncommon Uterine Malignancies

Leiomyosarcoma

Uterine leiomyosarcoma (LMS) is a rare but aggressive, malignant mesenchymal tumor originating from the myometrial smooth muscle, accounting for 1% of all uterine malignancies.[5] It is the most common subtype of uterine sarcoma, comprising about 70% of cases.[6] Due to overlapping clinical and imaging features with benign leiomyomas (including various forms of degeneration), LMS can be challenging to diagnose preoperatively. Notably, up to 0.28% of surgically resected presumed benign leiomyomas are diagnosed as LMS after pathologic analysis.[7] LMSs are characterized by an aggressive behavior (even when confined to the uterus), with a 5-year-survival rate of 25 to 76%, reducing to 10 to 15% in patients with metastatic disease at presentation.[8] It most commonly occurs in women aged >40 years with a median age of 60 years, and carries a high postoperative recurrence rate of 45 to 73%.[2] Similar to benign leiomyomas, the most common site involved is the uterine corpus, and the lesions can be intramural, submucosal, or subserosal, with intramural being the most common.

Known risk factors include obesity, diabetes, long-term tamoxifen usage, and pelvic irradiation, with the incidence being higher among the black race and postmenopausal women. The majority of cases of LMS arise de novo; however, in 0.2% it arises from sarcomatous transformation of a pre-existing benign leiomyoma.[9] Therefore, a postmenopausal women presenting with a new or an enlarging uterine mass should raise the suspicion of uterine LMS. Clinical presentation often mirrors that of benign leiomyomas and may include abnormal uterine bleeding (in 56%), palpable lower abdominal mass (in 54%), and pelvic pain (in 22%). Rarely, LMS can present with hemoperitoneum due to tumor rupture into the peritoneal cavity, or with clinical features secondary to extra-uterine invasion or distant metastases.

LMS can be differentiated from benign leiomyomas on histopathological examination, on the basis of ≥10 mitoses per 10 high-power (400 × ) fields, moderate to severe cytological atypia, and coagulative tumor cell necrosis, with two out of three needed to establish a diagnosis of LMS. Some smooth muscle tumors are extremely difficult to classify as benign or malignant, and are labelled as smooth muscle tumor of uncertain malignant potential (STUMP). There are three pathological subtypes of LMS: conventional (spindle cell) LMS, epithelioid LMS, and myxoid LMS.

Imaging Features

On ultrasound, certain features may raise suspicion for LMS over benign leiomyomas, which include irregular borders, large size (>8 cm), areas of cystic degeneration/necrosis, higher peak systolic velocity and lower resistive index, and an increase in central vascularity (leiomyomas usually show peripheral vascularity, while LMSs show central and peripheral vascularity). However, ultrasound has limited specificity, and there is substantial overlap in features with atypical or degenerating leiomyomas.[10]

CT plays a limited role in local evaluation, but is useful in detecting distant metastases. 18F-FDG PET may aid in identifying hypermetabolic lesions, with LMS usually showing moderate to intense uptake (mean standardized uptake value [SUV] of 6.4), while leiomyomas usually show mild uptake with a mean SUV of 1.74.[11] However, occasionally leiomyomas can show intense uptake in premenopausal women, which can produce diagnostic uncertainty.[11]

On MRI, LMS usually presents as a new or enlarging infiltrative myometrial mass, with irregular borders and areas of internal hemorrhage and necrosis and resultant early heterogeneous contrast enhancement ([Figs. 3] and [4]). On T2-weighted imaging (WI), the solid enhancing components have intermediate to high signal intensity. The solid enhancing areas also show high signal intensity on high b-value diffusion weighted imaging (DWI) with corresponding low signal intensity on apparent diffusion coefficient (ADC) maps. On T1 WI, it shows focal hyperintense areas (secondary to hemorrhage). Peritoneal implants and enlarged lymph nodes can also be seen in advanced disease. A cut-off of 0.9 × 10⁻³ mm²/s is used for the ADC map, with low values predicting a higher chance of malignancy.[12] But there can be considerable overlap in ADC values of benign and malignant uterine lesions, and therefore, they should always be interpreted in conjunction with other imaging findings. In a study by Tamai et al,[13] significant differences were observed between LMS and degenerating fibroids (which can have high signal intensity on T2 WI). Furthermore, Thomassin-Naggara et al reported that by combining the analysis of b1000 DWI image, ADC map, and T2 WI, MRI achieved an accuracy of 92.4% in distinguishing benign and uncertain/malignant myometrial lesions.[14] Differentiating features between LMS and leiomyoma are tabulated in [Table 2].

Table 2 Highlighting the differentiating features of leiomyosarcoma and leiomyoma (and its variants)

	Leiomyosarcoma	Leiomyoma (and variants)
General features • Age • Size • Growth • Margins	• Peri/post-menopausal • Larger • Rapid • Irregular	• Pre-menopausal • Smaller • Stable/slow • Circumscribed
Ultrasound • Heterogeneity • Echogenicity • Vascularity • Peak systolic velocity[10] • Resistive index[10]	• More heterogeneous • Variable • Central and peripheral • Higher (>41 cm/s) • <0.4	• Less heterogeneous • Usually hypoechoic • Usually peripheral • Lower (<41 cm/s) • >0.4
CT • Nodal and distant metastases	• Common	• Extremely uncommon   (maybe seen in benign metastasizing leiomyoma and intravenous leiomyomatosis)
MRI • T2 WI	• Solid areas are intermediate to hyperintense	• Usually hypointense (however, leiomyomas with cystic and myxoid degeneration are hyperintense)
• T1 WI	• Multiple hyperintense areas due to hemorrhage	• Usually, intermediate to hypointense • Can show diffuse hyperintensity in lipoleiomyoma and diffuse/peripheral hyperintensity in red degeneration
• Diffusion restriction	• Present	• Absent • Seen in cellular leiomyomas • Seen in red degeneration (hemorrhage can restrict diffusion)
• b1000 DWI	• High signal	• Low signal (T2 blackout effect) • Can be high in cellular leiomyoma
• ADC map	• Corresponding low signal: usually ≤0.9 × 10−3	• In cellular leiomyoma: corresponding low signal but >0.9 × 10−3
• Enhancement	• Early heterogeneous, with nonenhancing necrotic areas	• Variable • Cellular leiomyoma shows intense homogeneous enhancement
• Endometrial interface	• Disrupted, with thickened endometrium[15]	• Might be displaced or compressed; but preserved with no endometrial thickening
PET • Standardized uptake value (SUV) • Distant metastases	• Moderate to intense uptake (mean SUV ∼6.4) • Can be seen	• Mild uptake (mean SUV ∼1.74) (occasionally intense in pre-menopausal women and cellular leiomyomas) • Extremely uncommon

Abbreviations: ADC, apparent diffusion coefficient; CT, computed tomography; DWI, diffusion weighted imaging; MRI, magnetic resonance imaging; PET, positron emission tomography; WI, weighted imaging.

Fig 3. (A–F) Pathologically proven case of epithelioid leiomyosarcoma. Sagittal T2 WI image (A) depicting a circumscribed large mass located intramurally in the fundus of uterus (asterisk). It shows heterogeneous signal intensity on T2 WI. Axial T1 FS image (B) showing hyperintense areas within suggestive of hemorrhage (arrow). Axial T2 WI (C) showing the heterogeneous signal intensity (asterisk). Axial post-contrast image (D) showing the lesion has heterogeneous enhancement (plus symbol). On axial DWI image (E), it shows heterogeneously high signal intensity (dashed arrow), with the corresponding areas exhibiting signal drop (dashed arrow) on apparent diffusion coefficient (ADC) map (F) with a mean value of 0.6599. DWI, diffusion weighted imaging; FS, fat saturated; WI, weighted imaging.

Fig. 4 (A–F) Pathologically proven case of leiomyosarcoma. Axial (A) and coronal (B) contrast-enhanced CT images depicting a large ill-defined irregular mass involving the uterus (asterisk) with infiltration into adjoining pelvic structures. Sagittal T2 WI (C) and axial T2 WI (D) depicting a large irregular shaped uterine mass with heterogeneous signal intensity, with predominantly central hyperintense areas due to necrosis (white arrow). On axial T1 FS image (E), it is predominantly isointense with few hyperintense areas suggestive of hemorrhage (black arrow). On axial T1 FS post-contrast image (F), it shows heterogeneous predominantly peripheral enhancement (white arrow), due to central necrosis. CT, computed tomography; FS, fat-saturated; WI, weighted imaging.

Endometrial Stromal Sarcoma

Endometrial stromal sarcoma (ESS) is a rare uterine malignancy, accounting for 0.2% of all malignant uterine tumors, and is the second most common uterine sarcoma, comprising 10 to 15% of all uterine sarcomas.[16]

According to the WHO classification (2020), it can be classified into low-grade and high-grade ESS. Low-grade ESS is composed of tumor cells resembling proliferative-phase endometrial stroma, permeating the myometrium with or without lymphovascular invasion (sometimes prominent). High-grade ESS is composed of uniform high-grade round and/or spindle cells with extensive lymphovascular invasion, brisk mitotic activity, and necrosis.

Low-grade ESS is usually seen in younger women (average age ∼39 years) with a favorable prognosis, while high-grade ESS is usually seen in postmenopausal women (mean age ∼61 years) with a worse prognosis. Long-term tamoxifen usage and pelvic irradiation are risk factors for developing ESS. Patients usually present with abnormal uterine bleeding, pelvic pain, and dysmenorrhea.

Imaging Features

ESS most commonly presents as a mass epicentered at the endometrium, or a polypoidal mass within the endometrial cavity. However, it may also appear as a purely myometrial-based mass, in which case it can be difficult to distinguish from a degenerating leiomyoma.[17]

On MRI, ESS typically demonstrates heterogeneous signal intensity, showing T1 WI hypointensity and T2 WI hyperintensity. A hallmark imaging feature is the presence of lymphatic and vascular invasion, producing serpiginous bands of T2 hyperintense tumor extending into the myometrium, compressing the adjacent smooth muscle fibers (which show a normal T2 hypointense signal), creating a characteristic “bag of worms” appearance. Internal necrosis, hemorrhage, and diffusion restriction can also be seen (similar to other uterine sarcomas). It shows heterogeneous post-contrast enhancement ([Fig. 5]), being intermediate to hyper-enhancing as compared to myometrium: this helps to differentiate it from endometrial carcinoma, which is hypo-enhancing as compared to myometrium (another differentiating imaging feature of ESS and endometrial carcinoma is that ESS shows more irregular borders with marginal nodularity due to tumor extension along vessels and lymphatics[3]).

Fig. 5 (A–E) Pathologically proven case of endometrial stromal sarcoma: sagittal T2 (A) and axial T2 (B) images depicting a mass in the posterior myometrium (white arrow), with an exophytic component with rectal invasion (dashed arrow). On axial post-contrast image (C), the mass shows heterogeneous enhancement with rectal invasion (dashed arrow). On DWI image (D) and the corresponding ADC image (E), the tumoral component shows diffusion restriction with low ADC values (double arrows). ADC, apparent diffusion coefficient; DWI, diffusion weighted imaging.

High-grade ESS in comparison with low-grade ESS is larger, shows more internal hemorrhage, and appears more heterogeneous with marked vascular and lymphatic invasion, with a characteristic finding of feather-like enhancement.[18]

ESS presenting as a myometrial mass can mimic an atypical or degenerating fibroid. There are some imaging features that can help differentiate between the two. A peripheral low signal intensity rim on T2 WI (due to surrounding fibrous rim),[19] irregular margins, and the solid component appearing homogeneous are features suggestive of ESS. However, a peripheral rim of T2 hyperintensity (due to surrounding edema)[15] and smooth margins with the solid component showing a speckled appearance[20] go in favor of leiomyoma.

Smooth Muscle Tumor of Uncertain Malignant Potential

STUMP is a histopathological diagnosis applied to a heterogeneous group of uterine smooth muscle tumors that have features suspicious but insufficient for LMS diagnosis. These tumors exceed the histological thresholds for benign leiomyomas and their variants, but remain insufficient for a definitive diagnosis of LMS. STUMP accounts for 0.01% of all surgically treated uterine smooth muscle tumors.[21] The mean age of diagnosis is 43 years, which is a decade earlier than that of patients with LMS.[22] The overall 5-year survival rate ranges from 92 to 100%.[23]

For tumors unexpectedly diagnosed as STUMP on histopathology, patients who underwent myomectomy rather than hysterectomy should be kept on imaging surveillance, as 5 to 30% of these tumors may metastasize ([Fig. 6]), recur aggressively at the local site, or progress to LMS.[22] Unlike LMS, STUMP takes a longer time to recur, and patients can survive for a long time even after recurrence; therefore, long-term surveillance even after hysterectomy is recommended.[24]

Fig. 6 (A–D) Pathologically proven case of STUMP. Axial (A), coronal (B), and sagittal (C) contrast-enhanced CT image depicts a large ill-defined mass involving the fundus and body of uterus, extending into the abdomino-pelvic cavity. No obvious invasion into the surrounding structures noted. Two years after hysterectomy, the patient developed lung metastases: axial lung window CT chest image (D). CT, computed tomography; STUMP, smooth muscle tumor of uncertain malignant potential.

Imaging Features

Due to overlapping pathological appearance, the imaging appearance of leiomyoma variants, STUMP and LMS, can be similar and very hard to differentiate ([Fig. 7]). There is limited description of STUMP based on a few case series, which describe them as large heterogeneous masses on T1 WI and T2 WI with early heterogeneous enhancement with the solid component showing diffusion restriction (in view of high cellularity).[25] [26]

Fig. 7 (A–C) Pathologically proven case of smooth muscle tumor of uncertain malignant potential (STUMP). Contrast-enhanced CT sagittal (A), axial (B), and coronal (C) images depicting a large ill-defined heterogeneously enhancing mass in the uterus, extending up to the serosa with nonenhancing necrotic areas within. CT, computed tomography.

Carcinosarcoma

Carcinosarcoma is a biphasic malignancy composed of both high-grade carcinomatous and sarcomatous elements. Although it was historically classified as a uterine sarcoma and referred to as a malignant mixed Müllerian tumor, this terminology is no longer in use. According to the current WHO classification, carcinosarcoma is now recognized as a dedifferentiated variant of endometrial carcinoma, rather than a true sarcoma.[27] It represents the rarest, yet most aggressive subtype of endometrial carcinoma.[28] Carcinosarcoma accounts for approximately 5% of all uterine malignancies, yet it is responsible for around 15% deaths related to uterine cancer,[29] highlighting its aggressive behavior. In addition, 60% of patients have extra-uterine disease at the time of diagnosis[30]; and over 50% patients develop recurrent disease despite surgery and adjuvant therapy.[31] Carcinosarcoma exhibits a high metastatic potential, with a particularly elevated incidence of spread to the lymph nodes and lungs, in addition to other distant metastatic sites. It typically occurs in postmenopausal women in the 6th to 7th decade with similar risk factors as in endometrial carcinoma, with postmenopausal bleeding being the most common symptom.

Histologically, carcinosarcoma is characterized by the presence of both carcinomatous (epithelial) and sarcomatous (mesenchymal) components, which are usually intimately admixed, at least focally. The carcinomatous component most often shows endometroid or serous differentiation, while the sarcomatous component is typically homologous (i.e., containing mesenchymal components normally found within the uterus), but it can have heterologous elements (including chondrosarcoma, rhabdomyosarcoma, or rarely osteosarcoma). Histologic diagnosis relies on thorough morphologic evaluation and comprehensive sampling to detect both the components, as one may predominate.

Imaging Features

Carcinosarcoma commonly presents as a large polypoidal mass that distends the endometrial cavity ([Fig. 8]). In some cases, the tumor may prolapse through the cervix, and rarely, fundal lesions have been associated with uterine inversion. Imaging features are nonspecific and frequently overlap with those of endometrial carcinoma. [Table 3] presents a comparative overview of the MRI features of carcinosarcoma and endometrial carcinoma, with particular emphasis on their key differentiating characteristics.

Table 3 Differentiating MRI features of carcinosarcoma and endometrial carcinoma[32]

MRI features	Carcinosarcoma	Endometrial carcinoma
T1 WI	Isointense to myometrium Can have hyperintense areas due to hemorrhage	Isointense to myometrium
T2 WI	Heterogeneous Hyperintense to myometrium Iso to hypointense to endometrium	Similar to carcinosarcoma
Dynamic contrast enhancement (DCE)	Early, avid, and persistent enhancement, which is equal to or more than myometrium	Hypo-enhancing compared to myometrium
Cervical stromal invasion	More common	Less common
Pelvic lymphadenopathy	More common	Less common
Craniocaudal tumor dimension	Larger	Lesser
ADC map	Low signal More heterogeneous signal due to sarcomatous component	Low signal

Abbreviation: ADC, apparent diffusion coefficient.

Fig. 8 (A–D) Pathologically proven case of carcinosarcoma. Axial T1 (A), axial T2 (B), sagittal T2 (C), and coronal T2 (D) images depicting a large mass lesion (asterisk) which is isointense on T1 WI and intermediate signal intensity on T2 WI. It is predominantly lying within the endometrial cavity with myometrial extension along the anterior and left lateral myometrium (dashed arrow). The mass is seen to bulge into the cervical canal. Note is made of an anterior myometrial fibroid (white arrow), which is hypointense on T1 and T2 with mild enhancement. WI, weighted imaging.

Adenosarcoma

Adenosarcoma is a rare biphasic neoplasm, composed of benign epithelial components and a malignant stromal component. According to the latest WHO classification, it is categorized as a mixed epithelial and mesenchymal tumor. This is a rare neoplasm, accounting for 0.5% of all uterine neoplasms and 8% of uterine sarcomas.[3] Adenosarcoma is usually located within the uterus; however, rarely it can arise from the cervix, vagina, and extrauterine pelvic tissues (secondary to endometriosis[33]). It most commonly occurs in postmenopausal women; however, younger patients including adolescent girls can be affected. It typically presents as a large polypoidal mass within the endometrial cavity, commonly prolapsing into the cervix and vagina. It has a favorable prognosis, as compared to the other uterine sarcomas.

Pathologically, it is composed of proliferating malignant stroma, with non-neoplastic Müllerian epithelium, forming broad leaf-like structures projecting into the mucosal surface. The sarcomatous component is usually homologous; however, rarely it may be heterologous, showing rhabdomyosarcomatous or sex-cord differentiation.[34] In cases where the sarcomatous component constitutes >25% of the tumor, it is referred to as sarcomatous overgrowth[35] and is associated with a worse prognosis.

Imaging Features

It most commonly presents as a large, well-defined polypoidal lesion in the endometrial cavity, commonly prolapsing into the cervical canal or vagina. Internal cystic areas and hemorrhage are very common, with heterogeneous enhancement in the post-contrast sequence. A multi-septated multi-cystic or a “lattice-like” appearance is characteristic (due to intervening septa), but uncommon.[36]

On T1 WI, hyperintense areas are seen due to internal hemorrhage. This is very common, seen in 84.6% cases,[36] helping to differentiate from other polypoidal lesions such as endometrial polyps and a prolapsed submucosal leiomyoma, in which hemorrhage is less commonly encountered. On T2 WI, it is heterogeneously markedly hyperintense, which is a characteristic feature.[37] In the post-contrast phase, it shows heterogeneous enhancement due to the varied tumor composition of cellular areas, necrosis, and cystic areas. There is lower diffusion restriction in adenosarcoma, due to its lower grade as compared to other sarcomas.[38]

It is difficult to differentiate from other polypoidal lesions, such as endometrial carcinoma and carcinosarcoma, with overlapping imaging features.

Perivascular Epithelioid Cell Tumor

Perivascular epithelioid cell tumor (PEComa) is a rare subtype of mesenchymal tumors, which are composed of perivascular epithelioid cells (PECs) that express melanocytic and smooth muscle markers. The majority of the cases are sporadic; however, 10% can be associated with tuberous sclerosis.[39] PEComas can have an overlapping clinical, pathological, and radiological appearance with leiomyomas and leiomyosarcomas, and can be difficult to diagnose.

Pathologically, it consists of epithelioid cells arranged in dyscohesive nests, with thin-walled vessels surrounding the tumor cells, suggesting its perivascular location. Tumor cells express human melanoma black (HMB) 45 or melan-A, along with at least one myoid marker.

Imaging Features

Preoperative diagnosis is extremely rare, and diagnosis is usually established at pathological examination, with no definitive radiological imaging features, and very limited cases have been reported in the literature to date.

In a study by Tirumani et al,[40] commonly seen imaging findings are: large, well-circumscribed masses, homogeneous enhancement, T1 iso- to hypointense to myometrium, and heterogeneously hyperintense on T2. The imaging appearance can radiologically mimic leiomyomas and leiomyosarcoma ([Fig. 9]). Hematogenous metastases are commonly seen, with the lung being the most common site, followed by the liver.[40]

Fig. 9 (A–D) Pathologically proven case of perivascular epithelioid cell tumor (PEComa). Axial T1 WI (A) and coronal T2 WI (B) reveal a large, well-defined, heterogeneous intramural uterine lesion (asterisk). The lesion is mildly hyperintense on T1 WI and predominantly hyperintense, with few intermediate signal intensity areas on T2 WI, suggestive of hemorrhagic and cystic components. Bilateral ovaries are normal (dashed arrow). Sagittal T2 WI (C) and post-gadolinium T1 WI (D) show that the lesion is predominantly in the posterior myometrium. It is heterogeneously enhancing with a large central necrotic/cystic component (white arrow). WI, weighted imaging.

Uterine Tumors Resembling Ovarian Sex-Cord Tumors

Uterine tumors resembling ovarian sex-cord tumors (UTROSCTs) are a uterine neoplasm that morphologically resemble ovarian sex-cord tumors, without any recognizable component of endometrial stroma. They account for <0.5% of all uterine malignancies and 10 to 15% of mesenchymal uterine malignancies.[41] They usually arise from the uterus; however, can occasionally arise from the cervix. UTROSCT typically occurs in peri-menopausal or postmenopausal women, with abnormal uterine bleeding being the most common symptom. Occasionally, it can be asymptomatic, detected incidentally. It is usually benign, but can develop local recurrence and distant metastases, necessitating close follow-up after conservative surgery. These can be either submucosal or intramural in location.

Imaging Features

Given the rarity and nonspecific appearance, the diagnosis is usually established via histopathology. There are no established characteristic imaging findings of this tumor. The commonly described findings through various case reports and case series include[42] [43] [44]: intermediate to hypointense on T1 WI and intermediate to hyperintense on T2 WI with variable enhancement and diffusion restriction ([Fig. 10]). Because of these features, it can mimic cellular leiomyoma and LMS.

Fig. 10 (A–D) Pathologically proven case of uterine tumors resembling ovarian sex-cord tumor (UTROSCT). Sagittal (A) and coronal (B) T2 WI showing a well-defined predominantly hyperintense mass in the sub-endometrial location in the lower uterine segment (white arrow). Bilateral ovaries are normal (dashed arrow). Axial pre- (C) and post-contrast (D) T1 WI showing that the mass is predominantly isointense on T1 WI (white arrow) and shows intense heterogeneous post-contrast enhancement with few necrotic areas (white arrow). WI, weighted imaging.

The summary of the characteristic imaging features of various uncommon uterine malignancies described in this review is tabulated in [Table 4].

Table 4 Summarizing the characteristic imaging features and close imaging differentials of various uncommon uterine malignancies

Uncommon uterine malignancy	WHO classification	Incidence (% of all uterine malignancies)	Characteristic imaging features	Close imaging differential
LMS	Mesenchymal tumor	1% (most common uterine sarcoma)	Solid-enhancing components show: • High signal on T2 WI • High signal on b1000 DWI image • Corresponding low signal on ADC map	Leiomyoma variants STUMP
ESS	Mesenchymal tumor	0.2%	Commonly presents as a polypoidal mass in the endometrial cavity T2 WI: “bag of worms” appearance High-grade ESS: feather-like enhancement	Leiomyoma variant (when ESS is intramural in location)
STUMP [Pathological diagnosis]	Mesenchymal tumor	0.02%	None	Leiomyoma variants LMS
Carcinosarcoma [old terminology: malignant mixed Müllerian tumor]	Epithelial tumor (variant of endometrial carcinoma)	5%	Commonly presents as a polypoidal mass in the endometrial cavity Prolapse into cervix/vagina Early, avid, and persistent enhancement Very large craniocaudal tumor extent High incidence of nodal and lung metastases	Endometrial carcinoma
Adenosarcoma	Mixed epithelial and mesenchymal tumor	0.5%	Polypoidal lesion in endometrial cavity Commonly prolapse into the cervix/vagina T2 WI markedly hyperintense: “Lattice-like” appearance Internal hemorrhage common	Endometrial Polyp Carcinosarcoma
PEComas (benign or malignant)	Mesenchymal tumor	Not available (<100 cases reported in literature[45])	Large Circumscribed Homogeneous enhancement Hematogenous metastases	Leiomyoma Leiomyosarcoma
UTROSCT (usually benign; can be malignant)	Mesenchymal tumor	<0.5%	Nonspecific appearance	Cellular leiomyoma Leiomyosarcoma

Abbreviations: ESS, endometrial stromal sarcoma; LMS, leiomyosarcoma; PEComas, perivascular epithelioid cell tumor; STUMP, smooth muscle tumor of uncertain malignant potential; UTROSCT, uterine tumors resembling ovarian sex-cord tumor; WHO, World Health Organization; WI, weighted imaging.

Conclusion

In uncommon uterine malignancies, an accurate pretreatment diagnosis based on imaging features alone may be difficult to achieve, as the radiological findings can often be overlapping. Ultrasound has a limited role in characterization, and contrast-enhanced CT and 18F-FDG PET/CT can be used to detect lymphadenopathy and distant metastatic disease. MRI remains the imaging modality of choice for local staging and assessment of disease extent. Despite the lack of pathognomonic findings, certain MRI features can help narrow the differential diagnosis and guide appropriate management. In the context of multidisciplinary care, imaging plays a pivotal role in optimizing treatment planning, surveillance, and overall patient outcomes.

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