Uterine sarcomas constitute <10% of all uterine malignancies, and the majority are either ULMS or ESS [1]. ULMS, a rare and aggressive cancer with poor prognosis, accounts for 1% of all uterine malignancies and is the most common subtype of uterine sarcoma, with an annual incidence of 0.64/100,000 [2]. The age of onset is usually 50-55 years [2]. ULMS is associated with an increased mortality rate owing to frequent recurrence and distant metastasis, with 5-year survival rates of 57% and 16% for stages I and IV, respectively [4]. Leiomyosarcoma can occur anywhere in the pelvis, including the cervix, urinary bladder, or uterus, with the most common location being the uterus, as observed in this patient [5]. ULMS can present with abnormal vaginal bleeding (56%), a palpable pelvic mass (54%), and pelvic pain (22%) [6]. As these symptoms mimic other benign uterine tumors, they often cause a delayed diagnosis. This patient had persistent pelvic pain and abnormal uterine bleeding for 4 months, which led to further diagnostic workup for uterine malignancy. Laboratory and imaging studies cannot reliably diagnose ULMS. Although uterine fibroids usually do not develop into ULMS, they may coexist, as found in this patient [7]. In a few patients, lactate dehydrogenase or CA-125 levels, which are non-specific findings and unreliable predictors of ULMS, were elevated. MRI is a reliable method for the preliminary diagnosis of uterine tumors [8]. All patients should undergo imaging studies such as MRI to rule out metastatic ULMS. MRI resonance imaging did not reveal any metastatic disease. The absence of metastatic disease aids in staging the disease and directing appropriate treatment. There are different modalities for diagnosing uterine mesenchymal sarcomas, such as histological examination, immunohistochemistry (IHC), and/or molecular studies. ULMS is histologically composed of spindle cells with a blunt terminal nucleus and an active mitotic activity of 10 mitoses per 10 high-power fields, which corresponds to the histological findings in this patient.
Histologically distinguishing ULMS from other uterine mesenchymal neoplasms (such as ESS) often presents a diagnostic complexity. In cases with equivalent features, the IHC panel was used as an adjunct to morphology. The following IHC panel is routinely used to differentiate ULMS from ESS: estrogen receptor (ER), progesterone receptor (PR), desmin, smooth muscle actin (SMA), h-caldesmon, and CD10 [9,10,11,12]. However, no immunomarker is sensitive or specific enough to diagnose and distinguish these neoplasms; therefore, an IHC panel of markers was performed. We performed IHC in this patient because the histologic features were inconclusive. While IHC helped us identify this case as high-grade uterine sarcoma, we still could not conclude a confirmatory diagnosis due to the overlapping IHC features between ULMS and ESS. It is important to distinguish between them, since both have a different clinical course and management. For example, ESS has an indolent disease course that responds to hormonal treatment due to ER and PR expression [13]. In contrast, ULMS has a clinically aggressive course, with high mortality rates. [13].
There is an extensive morphological and immunophenotypic overlap between various uterine mesenchymal neoplasms. The use of novel antibodies, such as GEM and transgelin, to distinguish tumors has been discussed in the medical literature to distinguish the tumors [13]. A growing body of evidence suggests the use of novel gene expression signatures to differentiate between ESS and ULMS. For example, the following genes are only overexpressed in ULMS such as SLCA7A10/ASC1, EFNB3, CCND2, ECEL1, ITM2A, NPW, PLAG1, and GCGR [13]. PLAG-1 rearrangement can distinguish ULMS from ESS [14]. It has been shown that ~25% of the uterine myxoid leiomyosarcomas harbor TRPS1-PLAG1 and RAD51B-PLAG1 gene fusions [3]. These gene rearrangements can be detected by FISH or sequencing of fusion transcripts [3]. Targeted RNA sequencing methods used in this patient can detect both known and novel fusions and thus significantly improve analytical sensitivity [3].
In this patient, A RAB2A-PLAG1 gene fusion was identified, which confirmed the diagnosis of ULMS. The RAB2A-PLAG1 gene fusion has not been previously reported in the English literature.