Smooth muscle tumours of the uterus: MR imaging malignant predictive features-a 12-year analysis in a referral hospital in Portugal.

PURPOSE: To evaluate the magnetic resonance imaging (MRI) features that may help distinguish leiomyosarcomas from atypical leiomyomas (those presenting hyperintensity on T2-W images equal or superior to 50% compared to the myometrium). MATERIALS AND METHODS: The authors conducted a retrospective single-centre study that included a total of 57 women diagnosed with smooth muscle tumour of the uterus, who were evaluated with pelvic MRI, between January 2009 and March 2020. All cases had a histologically proven diagnosis (31 Atypical Leiomyomas-ALM; 26 Leiomyosarcomas-LMS). The MRI features evaluated in this study included: age at presentation, dimension, contours, intra-tumoral haemorrhagic areas, T2-WI heterogeneity, T2-WI dark areas, flow voids, cyst areas, necrosis, restriction on diffusion-weighted imaging (DWI), apparent diffusion coefficient (ADC) values, signal intensity and heterogeneity after contrast administration in T1-WI, presence and location of unenhanced areas. The association between the MRI characteristics and the histological subtype was evaluated using Chi-Square and ANOVA tests. RESULTS: The MRI parameters that showed a statistically significance correlation with malignant histology and thus most strongly associated with LMS were found to be: irregular contours (p < 0.001), intra-tumoral haemorrhagic areas (p = 0.028), T2-WI dark areas (p = 0.016), high signal intensity after contrast administration (p = 0.005), necrosis (p = 0.001), central location for unenhanced areas (p = 0.026), and ADC value lower than 0.88 × 10-3 mm2/s (p = 0.002). CONCLUSION: With our work, we demonstrate the presence of seven MRI features that are statistically significant in differentiating between LMS and ALM.

Uterine tumours with myogenic differentiation harbouring SRF::RELA fusions.

AIMS: In 2017, a subset of cellular variants of myofibroma and myopericytoma with a smooth muscle-like immunophenotype and harbouring recurrent SRF::RELA gene fusions was reported. Although the anatomical distribution was found to be quite broad, no tumours with these gene fusions in the female reproductive system have been illustrated to date. METHODS AND RESULTS: Herein, we report the histological and immunophenotypical features of three uterine tumours with SRF::RELA gene fusions. Microscopically, all three tumours were composed of cellular oval to spindle cells arranged in intersecting fascicles with variable amounts of collagen and a rich capillary network. Mitotic figures were scant. Regarding immunohistochemistry, diffuse staining for desmin, oestrogen receptor and progesterone receptor was observed in all three cases. The first case exhibited focal staining for h-caldesmon, whereas the latter two cases had diffuse staining. Furthermore, SRF::RELA rearrangement was observed in all three cases by using next-generation sequencing (NGS). Follow-up, ranging from 11 to 15 months, was available for these three patients, all of whom were well without evidence of disease. CONCLUSIONS: In conclusion, we reported a special group of uterine neoplasms with myogenic differentiation harbouring SRF::RELA rearrangement. Although the follow-up time was limited, morphological characteristics and other studies with follow-up data supported that this type of uterine neoplasm appeared to behave in a benign manner. Further studies with longer follow-up are needed to clarify the biological nature of this particular type of uterine tumour.

Uterine mesenchymal tumours: recent advances.

Almost all uterine mesenchymal tumours have been historically classified as either smooth muscle or endometrial stromal neoplasms. Recent application of molecular techniques has identified numerous lesions with distinctive genetic abnormalities and clinicopathological characteristics. Newly discovered uterine sarcoma subtypes include high-grade endometrial stromal sarcomas with BCOR genetic abnormalities, fibrosarcoma-like uterine sarcomas with NTRK rearrangements and COL1A-PDGFRB fusions, as well as undifferentiated uterine sarcomas with SMARCA4 mutations. Novel PLAG1 and PGR fusions have been identified in subsets of myxoid and epithelioid leiomyosarcomas. Some uterine tumours resembling ovarian sex-cord tumour harbour GREB1 and ESR1 rearrangements. Histological and immunophenotypical features as well as underlying genetic abnormalities defining these lesions are discussed.

Uterine tumour resembling ovarian sex cord tumour: first report of a large series with follow-up.

AIMS: Uterine tumour resembling ovarian sex cord tumour (UTROSCT) is an uncommon mesenchymal neoplasm of uncertain histogenesis. While it is considered a neoplasm of uncertain but low malignant potential, there is limited evidence for this as there are no large studies with follow-up. We aimed to determine the clinical behaviour of this uncommon neoplasm and investigate clinicopathological parameters which predict behaviour. METHODS AND RESULTS: From a series of 34 cases of UTROSCT, mainly from consultation practice, we obtained follow-up information which was obtained by contacting referring pathologists and clinicians. The follow-up periods ranged from 6 to 135 months (mean 39 months). Eight of 34 patients (23.5%) developed extrauterine metastasis to a variety of sites, including pelvic and abdominal peritoneum, ovary, lymph nodes, bone, liver and lung, and three patients (8.8%) died of tumour. Those neoplasms which exhibited malignant behaviour occurred on average in older patients, and were larger and more likely to exhibit necrosis, lymphovascular invasion, cervical involvement, significant nuclear atypia and significant mitotic activity. However, only the presence of necrosis and significant mitotic activity was statistically significant. CONCLUSIONS: While our figure of 23.5% of cases exhibiting malignant behaviour may reflect some bias related to consultation practice our results show that, not uncommonly, these neoplasms have an aggressive clinical course with extrauterine metastasis. Given the overlap in pathological parameters between clinically benign and malignant neoplasms, UTROSCTs are all best regarded as potentially malignant.

Submucous uterine adenosarcoma-minimally invasive treatment.

BACKGROUND: Uterine adenosarcomas are rare malignant gynaecological tumours. Due to its submucous localization, they can be easily confound with benign tumours like endometrial polyps or submucous myomas. However, the treatment of uterine adenosarcomas requires an oncologic surgical approach. CASE PRESENTATION: In the following case report, we present the minimally invasive treatment of a uterine adenosarcoma by hysteroscopy and laparoscopy in a 37-year-old patient and discuss the special role of hysteroscopy in such cases. CONCLUSIONS: In case of unknown or suspect intrauterine tumours, a diagnostic and operative hysteroscopy with biopsy could be realized prior to laparoscopic hysterectomy especially when the use of a laparoscopic electric morcellation is planned. Thus, a correct oncologic approach can be guaranteed if an adenosarcoma is diagnosed. TRIAL REGISTRATION: ISRCTN.

Highly malignant endometrial stromal sarcoma in a cat.

An 11-year-old female Persian cat underwent ovariohysterectomy due to dilation of the uterine cavity with irregular thickening of the wall. Macroscopically, the middle and distal regions of the left uterine horn were swollen and the uterine wall was irregularly thickened due to the development of multiple coalescent, variably sized nodules. Microscopically, the nodules had originated in the endometrium and were composed of round to polygonal neoplastic cells arranged in dense sheets or ill-defined fascicles. The neoplastic cells had locally invaded the myometrium and reached the subserosa, with lymphovascular invasion. Immunohistochemically, the neoplastic cell population was partially positive for CD10, an established marker of endometrial stromal sarcoma (ESS) in humans, with focal and diffuse nuclear immunopositivity for oestrogen and progesterone receptors and immunonegativity for desmin and α-smooth muscle actin. Based on these findings, the uterine tumour was diagnosed as ESS and was considered to correspond morphologically to high-grade ESS in humans.

Comprehensive exploration unveiling the sonography and histopathology of uterine leiomyoma in a cow.

Genital tumours are rare among cattle, largely due to their relatively short lifespans. Leio-myoma, a smooth muscle tumour being more prevalent in dogs, appears only at a rate of 1.00 - 2.00% in cattle, affecting reproductive efficiency in cases of complete uterine obstruction. This case report involves an 8-year-old cow with repeated insemination attempts unveiled 5.00 cm intra-luminal uterine mass, obstructing the right uterine horn. Transrectal sonography (TRUS) revealed a highly vascularized mass with normal ovarian function. Confirmation of clinical condition, i.e., uterine leiomyoma, via uterine biopsy concluded the presence of neoplastic smooth muscle cells arranged in interlacing bundles showing mild pleomorphism, and special staining using Masson's trichrome revealed an unappreciable amount of connective tissue; subsequently right flank celiotomy was performed to remove the benign tumour. Forty-five days after celiotomy, TRUS examination confirmed an unobstructed uterine horn, and bilateral oviduct patency was adjudged with 2.50% methylene blue. Following treatment for chronic endometritis, artificial insemination led to conception nearly 90 days post-procedure. The TRUS aids preliminary diagnosis, while definitive identification demands necropsy and surgical methods. This case underscores the diagnostic significance of TRUS, histopathology and celiotomy for identifying and managing uterine leiomyoma in cattle.

Therapeutic management of uterine tumours resembling ovarian sex cord tumours including a focus on fertility: A systematic review.

OBJECTIVE: Uterine tumours resembling ovarian sex cord tumours (UTROSCTs) are extremely rare. To date, most patients with UTROSCTs have undergone hysterectomy and had a benign clinical course. Fertility-preserving surgery should be considered because some patients with UTROSCTs are aged < 40 years. This paper reviews the treatment and prognosis for patients with UTROSCTs, with a focus on fertility. METHODS: PubMed, MEDLINE and Scopus were searched systematically for case reports and case series of UTROSCTs published in English from inception to December 2022, and initial treatment and recurrence rates were compared. The following data were extracted: age; symptoms; initial therapy; metastasis at diagnosis; disease-free survival (DFS); and recurrence. RESULTS: In total, 147 patients (72 studies) reporting the clinical course of UTROSCTs were analysed. The median age at diagnosis was 50 years, and 28 (19.0 %) patients were aged < 40 years. Most patients (n = 125, 85.0 %) underwent hysterectomy as the initial surgery, with a recurrence rate of 17.6 % (n = 22). The recurrence rate was 30 % (n = 6) in patients who underwent mass resection (n = 20). Among the 15 patients who underwent mass resection aged < 40 years, seven went on to achieve pregnancy (46.7 %) and six had successful deliveries (40.0 %). No significant differences in 5- and 10-year DFS were found between the hysterectomy and mass resection groups (p = 0.123 and 0.0612, respectively). Bilateral salpingo-oophorectomy in addition to hysterectomy was not significantly associated with 10-year DFS (p = 0.548). CONCLUSION: While total hysterectomy is the recommended treatment for UTROSCTs based on recurrence rates, mass resection is an acceptable treatment option for patients who wish to retain their childbearing potential. It is recommended that these women should plan for pregnancy and delivery as soon as possible after mass resection, and should undergo hysterectomy within 5 years.

Uterine sarcoma: a clinical case and a literature review.

BACKGROUND: Uterine sarcomas are rare gynaecologic tumours representing 3-7% of all uterine malignancies. The aetiology of sarcomas is still unclear: it is thought, that chromosomal translocations have influence on wide histological variety of sarcomas. Presenting symptoms are vague and nonspecific. Usually sarcoma causes abnormal vaginal bleeding, can cause abdominal or pelvic pain, or manifests as a rapidly growing uterine tumour. The diagnosis of sarcoma is often made retrospectively after surgical removal of a presumed benign uterine neoplasm, because imaging modalities such as ultrasound, computed tomography, or magnetic resonance imaging cannot yet accurately and reliably distinguish between benign leiomyoma and malignant pathology. If there are certain clinical features that raise a suspicion of malignancy in the uterus, it is recommended to avoid the use of power morcellation through laparoscopic surgery in order to prevent disease dissemination. MATERIALS AND METHODS: We present a clinical case of a 64-year-old patient, who was referred to hospital due to abdominal pain and tenesmus that lasted for two days. From a past medical history it was known that previously the patient had been diagnosed with uterine myoma. Transvaginal ultrasonography showed a 10.4 cm × 9.8 cm uterine tumour of nonhomogeneous structure with signs of necrosis and good vascularization. The patient refused urgent hysterectomy, that was advised to her. The patient was operated on one month later and total hysterectomy with bilateral salpingooforectomy was performed. Postoperative histological evaluation showed undifferentiated sarcoma uterus pT1b L/V0. Imaging modalities were made to evaluate possible dissemination of the disease. In the absence of signs of disease progression, the patient received radiotherapy and brachytherapy and was followed-up by doctors. RESULTS AND CONCLUSIONS: Uterine sarcomas are highly malignant tumours that originate from smooth muscles and connective tissue elements of the uterus and make up 1% of all malignant gynaecological tumours and about 3-7% of all malignant uterine tumours. Imaging modalities cannot yet reliably distinguish benign myomas from malignant sarcomas. It is important not to damage the wholeness of uterus during operation in order to prevent dissemination of the disease in the abdominal cavity. The low-grade endometrial stromal sarcoma has the best survival prognosis, while carcinosarcoma and undifferentiated uterine sarcoma have the lowest survival rates.

Chemoresistant gestational trophoblastic neoplasia: a case report.

Gestational trophoblastic neoplasia (GTN) is a disease of women in reproductive age. It is one of the most chemotherapy responsive and highly curable cancer. It is diagnosed when there is clinical, radiologic, pathologic, and/or hormonal evidence of persistent or relapsed gestational trophoblastic disease. In most instances, it is cured by surgical evacuation of the uterus. If persistent, it is treated with chemotherapy which provides response in >90% of the cases. In the unresponsive persistent cases and if the women has completed her child bearing, hysterectomy is generally recommended. Here, we report a rare case of chemoresistant GTN which was confirmed to be placental-site trophoblastic tumour (PSTT) on biopsy.

Tumor uterino que recuerda a los tumores de los cordones sexuales del ovario (UTROSCT): un caso clinicopatológico / Uterine tumour resembling ovarian sex cord tumours (UTROSCT): A clinicopathological case

Introducción: El tumor uterino que recuerda al tumor de los cordones sexuales del ovario (UTROSCT) es un tumor muy infrecuente de histogénesis incierta, incluido en la actual clasificación de tumores del estroma endometrial de la Organización Mundial de la Salud. Principales síntomas y/o hallazgos clínicos: Mujer de 48 años, sin antecedentes de interés, acudió a consulta por hipermenorreas en los últimos ciclos. La exploración ginecológica era normal. Diagnósticos principales, intervenciones terapéuticas y resultados: El estudio ecográfico mostró una lesión nodular submucosa de 26×21mm. Se le realizó histeroscopia diagnóstica, identificándose un mioma submucoso no accesible para extirpación ambulatoria. Se llevó a cabo histeroscopia quirúrgica procediéndose a miomectomía con asa de diatermia. Histológicamente se observó tejido muscular liso masivamente infiltrado por células de poco citoplasma con diferenciación glandular positivas con citoqueratinas, interpretándose como fragmentos de pared miometrial infiltrados por carcinoma. Se le realizó estudio de extensión e histerectomía. En la pieza quirúrgica no se identificó neoplasia residual. Se revaluó la biopsia previa y se amplió el estudio inmunohistoquímico, observándose positividad para marcadores de los cordones sexuales, epiteliales y musculares lisos. Ante estos hallazgos, el diagnóstico definitivo fue UTROSCT. Conclusión: El UTROSCT muestra generalmente un comportamiento benigno. Sin embargo, se considera de potencial maligno incierto, debido a que presenta una baja tasa de recurrencias y metástasis excepcionales. Desde el punto de vista histopatológico es importante reconocer esta entidad, ya que su histológica es variada imitando una amplia gama de tumores tanto benignos como malignos, por lo que es necesario realizar estudio inmunohistoquímico para su correcto diagnóstico.(AU)

Introduction: Uterine tumour resembling ovarian sex cord tumour (UTROSCT) is a very rare tumour of uncertain histogenesis, included in the current classification of endometrial stromal tumours of the World Health Organization. Main symptoms and/or clinical findings: 48-year-old woman with no history of interest, consulted for hypermenorrhoea in recent cycles. The gynaecological examination was normal. Main diagnoses, therapeutic interventions, and results: The ultrasound study showed a submucosal nodular lesion of 26×21mm. A diagnostic hysteroscopy was performed, identifying a submucosal myoma not accessible for outpatient removal. Surgical hysteroscopy was performed, proceeding to myomectomy with loop diathermy. Histologically, smooth muscle tissue was observed massively infiltrated by cells with scant cytoplasm and positive glandular differentiation for cytokeratins, interpreted as fragments of the myometrial wall infiltrated by carcinoma. An extension study and hysterectomy were performed. No residual neoplasia was identified in the surgical piece. A previous biopsy was re-evaluated and an immunohistochemical study was extended, showing positivity for sexual cord, epithelial, and smooth muscle markers. Given these findings, the definitive diagnosis was UTROSCT. Conclusion: UTROSCT generally shows benign behaviour. However, it is considered to be of uncertain malignant potential, due to its low rate of recurrence and rare metastases. From the histopathological point of view, it is important to recognize this entity, since its histology is varied, mimicking a wide range of tumours, both benign and malignant, making it necessary to perform an immunohistochemical study for its correct diagnosis.(AU)

Vaginal leiomyoma.

Leiomyomas are common benign tumors in the uterus. However, vaginal leiomyomas remain an uncommon entity with only about 300 reported cases. Here, we report a case of a 38-year-old multigravida who presented with lower abdominal pain and vaginal bleeding. A physical examination and ultrasonography were performed, and a diagnosis of cervical fibroid was made. Pervaginal removal of the tumor was performed and subsequent histopathology revealed a vaginal leiomyoma. Although a rare tumor, vaginal leiomyomas may present with a variety of clinical features and may be mistaken preoperatively for cervical fibroid. Removal of tumor by vaginal route, wherever possible, with subsequent histopathological examination appears to be the optimum management plan.

Wilms' Tumour gene 1 (WT1) as an immunotherapeutic target.

High grade uterine sarcoma and recurrent endometrial carcinoma are aggressive cancers with limited treatment options, resulting in a poor prognosis. In this research we focused in the first place on the detection of a highly immunogenic tumour-associated antigen Wilms' tumour gene 1 (WT1) in uterine tumours. We were able to reveal its overexpression in the tumour cells of high grade sarcomas and carcinosarcomas . Moreover, patients with WT1 positive tumours had a significantly worse prognosis than patients who were WT1 negative. For carcinomas, WT1 was present in only a minority of tumour cells, but in the majority of intratumoural blood vessels. Small blood vessels in the normal tissue surrounding the carcinoma were also WT1 positive, suggesting a role for WT1 in angiogenesis. WT1 was hardly expressed or absent in the non-tumour or benign tumoural uterus (myoma, polyp). The next step was to develop a targeted treatment against WT1. We opted for dendritic cell (DC) based immunotherapy. Nevertheless a basal expression of WT1 in monocytes and in vitro cultured unloaded DC was observed, the electroporation of in vitro cultured DC with WT1-mRNA resulted in a higher expression of WT1 by the DC. WT1-mRNA loaded DC were used for in vivo stimulations of T cells, resulting in the rise of WT1-specific T cells and a transient molecular response (decrease of CA125) in an end stage endometrial carcinoma patient. No toxic side effects were reported. Future in vivo research, carried out in a phase I clinical trial in our center, will reveal the ability of this new therapy to induce an immunological and possible clinical response in WT1 positive uterine cancer patients.

Uterine Sex Cord Tumour- Management Dilemma

Uterine sex cord tumour is a very rare tumour with uncertain management strategies and prognosis. A 61-year-old, nulliparous, who was not on hormone replacement therapy, presented with first episode of postmenopausal bleeding. A transvaginal scan revealed an enlarged uterus with thick endometrial lining and features of multiple degenerated fibroid. Endometrial biopsy was negative for malignancy. Computed tomography of the abdomen and pelvis confirmed the mass, with atrophic ovaries and incidental finding of bilateral hydronephrosis requiring stentings. Otherwise, there were no pelvic lymph nodes enlargement. Our impression was a uterine sarcoma and we decided for total abdominal hysterectomy with bilateral salpingooophorectomy. Surprisingly, the histology report confirmed uterine sex cord tumour. There are less cases of recurrence and there is no general consensus on the management. However, we decided for adjuvant chemotherapy (BEP regime) as the malignant cells infiltrated more than half of myometrial thickness, with good outcome.