Assuntos
Neoplasias do Endométrio , Músculo Liso , Sarcoma do Estroma Endometrial , Humanos , Feminino , Neoplasias do Endométrio/patologia , Sarcoma do Estroma Endometrial/patologia , Sarcoma do Estroma Endometrial/diagnóstico , Diagnóstico Diferencial , Músculo Liso/patologia , Diferenciação Celular , Vimentina/metabolismo , Adulto , Leiomioma/patologia , Tumores do Estroma Gonadal e dos Cordões Sexuais/patologia , Tumores do Estroma Gonadal e dos Cordões Sexuais/diagnóstico , Tumores do Estroma Endometrial/patologia , Tumores do Estroma Endometrial/diagnóstico , Actinas/metabolismoRESUMO
Uterine spindle cell lesions share a dilemmatic overlapped features that needed to be addressed by the pathologist to reach a conclusive accurate diagnosis for its prognostic value and different management decisions. Usage of combined IHC panel can be an aiding guiding tool in this context. The aim of this study is to evaluate the diagnostic value of combined BCOR, Cyclin D1, and CD10 IHC panel in differentiating endometrial stromal sarcoma from other uterine spindle cell lesions. This study included 60 cases categorized into endometrial stromal sarcoma group (ESS) (12 cases high-grade endometrial stromal sarcoma [HGESS] and 18 cases low-grade endometrial stromal sarcoma [LGESS]), malignant uterine spindle cell lesions group (5 cases adenosarcoma [AS], 6 cases leiomyosarcoma [LS], 4 cases carcinosarcoma [CS]), and benign uterine lesions group (5 cases endometrial stromal nodule [ESN], 5 cases leiomyoma, and 5 cases adenomyosis). IHC staining procedure and evaluation for BCOR, Cyclin D1, and CD10 was performed on all studied cases. BCOR IHC staining was positive in all HGESS (12/12) of ESS group cases, with diffuse pattern in 75% of cases. BCOR-diffuse staining pattern was not recorded in any of LGESS (0/18), malignant mesenchymal lesions group (0/15), and also benign lesions group (0/15). Cyclin D1 positivity was observed only in HGESS cases, in parallel with positive-BCOR expression. On the contrary, CD10 was negatively expressed in all HGESS and positive in all LGESS, ESN, and adenomyosis cases. A specificity of 100% and sensitivity of 75% were recorded in differentiating HGESS from malignant mesenchymal lesions (including LMS, AS, and CS) and also HGESS from LGESS when using the combined panel BCOR +ve D /Cyclin D1 +ve / CD10 -ve , considering only the BCOR-diffuse staining pattern. In conclusion, BCOR +ve D /Cyclin D1 +ve /CD10 -ve as a combined panel is 100% specific and with lesser sensitivity in diagnosing HGESS as well as differentiating it from LGESS and other malignant uterine spindle cell lesions.
Assuntos
Ciclina D1 , Neprilisina , Proteínas Proto-Oncogênicas , Proteínas Repressoras , Sarcoma do Estroma Endometrial , Humanos , Feminino , Neprilisina/metabolismo , Sarcoma do Estroma Endometrial/diagnóstico , Sarcoma do Estroma Endometrial/metabolismo , Sarcoma do Estroma Endometrial/patologia , Proteínas Repressoras/metabolismo , Ciclina D1/metabolismo , Diagnóstico Diferencial , Pessoa de Meia-Idade , Adulto , Proteínas Proto-Oncogênicas/metabolismo , Neoplasias do Endométrio/diagnóstico , Neoplasias do Endométrio/metabolismo , Neoplasias do Endométrio/patologia , Imuno-Histoquímica , Biomarcadores Tumorais/metabolismo , Idoso , Neoplasias Uterinas/diagnóstico , Neoplasias Uterinas/metabolismo , Neoplasias Uterinas/patologiaRESUMO
BACKGROUND: High-grade endometrial stromal sarcoma (HG-ESS) is a rare malignant tumor with poor prognosis. To overcome the limitations of current treatment for advanced patients, the intervention of targeted drug therapy is urgently needed. CASE PRESENTATION: A 74-year-old married woman who presented with abdominal distension and lower abdominal pain was admitted to Hebei General Hospital. After surgery, immunohistochemical staining revealed a malignant tumor which was consistent with HG-ESS. Tumor recurrence occurred 2 months after surgery. Then the patient underwent chemotherapy with two courses but responded poorly. Subsequently we observed ATM, BLM, and CDH1 co-mutations by Next Generation Sequencing (NGS). Then the patient received pamiparib, which resulted in a 10-month progression-free survival (PFS) and is now stable with the administration of sintilimab in combination with pamiparib and anlotinib. CONCLUSIONS: Due to the successful use of poly ADP-ribose polymerase inhibitor (PARPi) on HG-ESS, we suggest that the selection of effective targeted drugs combined with anti- programmed death-1 (PD-1) drug therapy based on genetic testing may become a new option for the treatment of homologous repair deficient (HR-deficient) HG-ESS.
Assuntos
Proteínas Mutadas de Ataxia Telangiectasia , Caderinas , Neoplasias do Endométrio , RecQ Helicases , Sarcoma do Estroma Endometrial , Humanos , Feminino , Idoso , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/tratamento farmacológico , Neoplasias do Endométrio/patologia , Sarcoma do Estroma Endometrial/genética , Sarcoma do Estroma Endometrial/tratamento farmacológico , Sarcoma do Estroma Endometrial/diagnóstico , Proteínas Mutadas de Ataxia Telangiectasia/genética , RecQ Helicases/genética , Caderinas/genética , Antígenos CD/genética , MutaçãoRESUMO
Low-grade endometrial stromal sarcoma (LG-ESS) is a rare uterine neoplasm. Computed tomography (CT) revealed the presence of multiple small bilateral pulmonary nodules in a 58-year-old woman 1 year after surgery for LG-ESS; the clinical diagnosis was pulmonary metastasis. Hormone therapy with progesterone was initiated, after which most of the solid nodules disappeared and some transformed into cystic lesions. Seven years after hormone therapy, the patient experienced repeated pneumothorax. The cause of the pneumothorax was perforation of a metastatic focus within the wall of a small subpleural cyst that was not evident on CT images.
Assuntos
Neoplasias do Endométrio , Pneumotórax , Sarcoma do Estroma Endometrial , Neoplasias Uterinas , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias do Endométrio/patologia , Sarcoma do Estroma Endometrial/cirurgia , Sarcoma do Estroma Endometrial/diagnóstico , Sarcoma do Estroma Endometrial/patologia , Pneumotórax/diagnóstico por imagem , Pneumotórax/etiologia , HormôniosRESUMO
BACKGROUND: Endometrial stromal tumors (ESTs) are rare subset of mesenchymal uterine neoplasms. There are heterogeneous morphological, immunohistochemical, and genetic features. Approximately 50% of ESTs occur in perimenopausal women. In 2020, WHO sub-categorized ESTs into four groups: endometrial stromal nodule (ESN), low-grade endometrial stromal sarcoma (LGESS), high-grade endometrial stromal sarcoma (HGESS), and undifferentiated uterine sarcoma (UUS). OBJECTIVE: To review the morphological spectrum of endometrial stromal tumors. METHOD: This retrospective study reviewed the histomorphological features of 15 endometrial stromal tumors with respect to atypia, necrosis, mitosis, collagen bands, whorling around vessels, myometrial invasion, and inflammatory cells. Immunohistochemistry markers (CD10, SMA, and ER) along with special stains (Masson's trichrome, toluidine blue) were also studied. RESULTS: The age of the patients ranged from 32 to 60 years. Three patients were postmenopausal. The most common presenting symptom was vaginal bleeding. Five patients were operated with a clinical diagnosis of uterine fibroid. One patient presented with prolapse with no other complaint. All the 15 patients had total abdominal hysterectomy and salpingo-oophorectomy. One case showed necrosis, eight cases showed collagen bands, all the 15 cases showed whorling around vessels, one case showed vascular emboli, and seven cases showed inflammatory cells. In low-grade cases, one case showed focal atypia and one case showed focal coagulative necrosis indicating infarction. Thirteen cases were LGESS, and one case of ESN and HGESS. All cases were positive for ER and CD10. CONCLUSION: Endometrial stromal tumors demonstrate extensive permeation of the myometrium as irregular islands with frequent vascular invasion, whorling around vessels, collagen bands, and inflammatory cells. All these features should be observed thoroughly on microscopy by pathologists to clearly differentiate the low-grade and high-grade endometrial stromal tumors, and to understand the overlapping gray areas morphologically as it affects the prognosis of the patient.
Assuntos
Neoplasias do Endométrio , Tumores do Estroma Endometrial , Sarcoma do Estroma Endometrial , Neoplasias Uterinas , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Tumores do Estroma Endometrial/diagnóstico , Tumores do Estroma Endometrial/patologia , Sarcoma do Estroma Endometrial/diagnóstico , Sarcoma do Estroma Endometrial/cirurgia , Neoplasias do Endométrio/diagnóstico , Neoplasias do Endométrio/cirurgia , Neoplasias do Endométrio/genética , Estudos Retrospectivos , Colágeno , NecroseRESUMO
OBJECTIVE: Little is known about the survival differences between uterine and extrauterine low-grade endometrial stromal sarcoma (LGESS). Survival outcomes, consisting of disease-free survivals and overall survivals (OS), were compared in these two entities. METHODS: From February 2012 to June 2019, all primary LGESS cases and LGESS cases with first recurrence in the study center were reviewed. The clinicopathological characteristics and survival outcomes of extrauterine and uterine LGESS patients were compared for both primary and recurrent diseases. RESULTS: During the study period, 143 patients with primary LGESS and 56 patients with recurrent LGESS were included and followed up to 1 June 2020, among whom 8 (5.6%) and 10 (17.8%) patients were identified as having extrauterine LGESS. Patients with primary and recurrent extrauterine LGESS had similar clinicopathological characteristics to those of patients with uterine LGESS. In primary or in recurrent LGESS cases, in univariate analysis, patients with uterine and extrauterine LGESS had similar disease-free intervals after the last treatment, and they also had similar OSs after the diagnosis. Ovarian preservation led to significantly increased recurrence for primary LGESS [hazard ratio (HR) 4.9, 95% CI: 2.3-10.1, P <0.001) and repeated recurrence for recurrent LGESS (HR 3.1, 95% CI: 1.3-7.3, P =0.009). Surgical treatment for recurrent LGESS decreased repeated recurrence after the first recurrence (HR 0.2, 95% CI: 0.1-0.7, P =0.006). No factors were found to be associated with the OS of primary or recurrent LGESS. CONCLUSION: The clinical characteristics and survival outcomes of extrauterine LGESS are similar to those of uterine LGESS. Surgery is the treatment of choice for recurrent LGESS. Ovarian preservation is detrimental to disease-free survival but not to OS in both uterine and extrauterine LGESS.
Assuntos
Neoplasias do Endométrio , Recidiva Local de Neoplasia , Sarcoma do Estroma Endometrial , Humanos , Feminino , Sarcoma do Estroma Endometrial/patologia , Sarcoma do Estroma Endometrial/mortalidade , Sarcoma do Estroma Endometrial/cirurgia , Sarcoma do Estroma Endometrial/terapia , Sarcoma do Estroma Endometrial/diagnóstico , Pessoa de Meia-Idade , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/mortalidade , Neoplasias do Endométrio/terapia , Neoplasias do Endométrio/cirurgia , Neoplasias do Endométrio/diagnóstico , Adulto , Prognóstico , Estudos Retrospectivos , Estudos de Coortes , Intervalo Livre de Doença , IdosoRESUMO
Diagnosing low-grade and high-grade endometrial stromal sarcoma (LG-ESS and HG-ESS) is a challenge. This study aimed to identify biomarkers. 22 ESS cases were analyzed using Illumina microarrays. Differentially expressed genes (DEGs) were identified via Limma. DEGs were analyzed with String and Cytoscape. Core genes were enriched with GO and KEGG, their pan-cancer implications and immune aspects were studied. 413 DEGs were found by exome sequencing, 2174 by GSE85383 microarray. 36 common genes were identified by Venn analysis, and 10 core genes including RBFOX1, PCDH7, FAT1 were selected. Core gene GO enrichment included cell adhesion, T cell proliferation, and KEGG focused on related pathways. Expression was evaluated across 34 cancers, identifying immune DEGs IGF1 and AVPR1A. Identifying the DEGs not only helps improve our understanding of LG-ESS, HG-ESS but also promises to be potential biomarkers for differential diagnosis between LG-ESS and HG-ESS and new therapeutic targets.
Assuntos
Neoplasias do Endométrio , Sarcoma do Estroma Endometrial , Feminino , Humanos , Sarcoma do Estroma Endometrial/diagnóstico , Sarcoma do Estroma Endometrial/genética , Biomarcadores Tumorais/metabolismo , Perfilação da Expressão Gênica , Neoplasias do Endométrio/diagnóstico , Neoplasias do Endométrio/genética , Biologia ComputacionalRESUMO
The landscape of uterine sarcomas is becoming more complex with the description of new entities associated with recurrent driver molecular alterations. Uterine sarcomas, in analogy with soft tissue sarcomas, are distinguished into complex genomic and simple genomic sarcomas. Leiomyosarcomas and undifferentiated uterine sarcomas belong to complex genomic sarcomas group. Low-grade and high-grade endometrial stromal sarcomas, other rare tumors associated with fusion transcripts (such as NTRK, PDGFB, ALK, RET ROS1) and SMARCA4-deficient uterine sarcoma are considered simple genomic sarcomas. The most common uterine sarcoma are first leiomyosarcoma and secondly endometrial stromal sarcomas. Three different histological subtypes of leiomyosarcoma (fusiform, myxoid, epithelioid) are identified, myxoid and epithelioid leiomyosarcoma being more aggressive than fusiform leiomyosarcoma. The distinction between low-grade and high-grade endometrial stromal sarcoma is primarily morphological and immunohistochemical and the detection of fusion transcripts can help the diagnosis. Uterine PEComa is a rare tumor, which is distinguished into borderline and malignant, according to a risk assessment algorithm. Embryonal rhabdomyosarcoma of the uterine cervix is more common in children but can also occur in adult women. Embryonal rhabdomyosarcoma of the uterine cervix is almost always DICER1 mutated, unlike that of the vagina which is wild-type DICER1, and adenosarcoma which can be DICER1 mutated but with less frequency. Among the emerging entities, sarcomas associated with fusion transcripts involving the NTRK, ALK, PDGFB genes benefit from targeted therapy. The integration of molecular data with histology and clinical data allows better identification of uterine sarcomas in order to better treat them.
Assuntos
RNA Helicases DEAD-box , Neoplasias do Endométrio , Neoplasias dos Genitais Femininos , Leiomiossarcoma , Rabdomiossarcoma Embrionário , Ribonuclease III , Sarcoma do Estroma Endometrial , Neoplasias de Tecidos Moles , Neoplasias do Colo do Útero , Neoplasias Uterinas , Adulto , Criança , Feminino , Humanos , Leiomiossarcoma/diagnóstico , Leiomiossarcoma/genética , Leiomiossarcoma/terapia , Rabdomiossarcoma Embrionário/diagnóstico , Rabdomiossarcoma Embrionário/genética , Rabdomiossarcoma Embrionário/terapia , Sarcoma do Estroma Endometrial/diagnóstico , Sarcoma do Estroma Endometrial/genética , Sarcoma do Estroma Endometrial/terapia , Proteínas Tirosina Quinases , Proteínas Proto-Oncogênicas , Neoplasias Uterinas/diagnóstico , Neoplasias Uterinas/genética , Neoplasias Uterinas/terapia , Receptores Proteína Tirosina Quinases , DNA Helicases , Proteínas Nucleares , Fatores de TranscriçãoRESUMO
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.
Assuntos
Doenças do Gato , Neoplasias do Endométrio , Sarcoma do Estroma Endometrial , Neoplasias Uterinas , Humanos , Feminino , Gatos , Animais , Sarcoma do Estroma Endometrial/veterinária , Sarcoma do Estroma Endometrial/diagnóstico , Sarcoma do Estroma Endometrial/patologia , Neoplasias do Endométrio/veterinária , Neoplasias do Endométrio/diagnóstico , Neoplasias do Endométrio/patologia , Neoplasias Uterinas/veterinária , Neoplasias Uterinas/patologia , Receptores de ProgesteronaRESUMO
Endometrial stromal tumors represent the second most common category of uterine mesenchymal tumors. Several different histologic variants and underlying genetic alterations have been recognized, one such being a group associated with BCORL1 rearrangements. They are usually high-grade endometrial stromal sarcomas, often associated with prominent myxoid background and aggressive behavior. Here, we report an unusual endometrial stromal neoplasm with JAZF1-BCORL1 rearrangement and briefly review the literature. The neoplasm formed a well-circumscribed uterine mass in a 50-yr-old woman and had an unusual morphologic appearance that did not warrant a high-grade categorization. It was characterized by a predominant population of epithelioid cells with clear to focally eosinophilic cytoplasm growing in interanastomosing cords and trabeculae set in a hyalinized stroma as well as nested and fascicular growths imparting focal resemblance to a uterine tumor resembling ovarian sex-cord tumor, PEComa, and a smooth muscle neoplasm. A minor storiform growth of spindle cells reminiscent of the fibroblastic variant of low-grade endometrial stromal sarcoma was also noted but conventional areas of low-grade endometrial stromal neoplasm were not identified. This case expands the spectrum of morphologic features seen in endometrial stromal tumors, especially when associated with a BCORL1 fusion and highlights the utility of immunohistochemical and molecular techniques in the diagnosis of these tumors, not all of which are high grade.
Assuntos
Neoplasias do Endométrio , Tumores do Estroma Endometrial , Sarcoma do Estroma Endometrial , Neoplasias Uterinas , Feminino , Humanos , Tumores do Estroma Endometrial/diagnóstico , Tumores do Estroma Endometrial/genética , Neoplasias do Endométrio/diagnóstico , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/química , Sarcoma do Estroma Endometrial/diagnóstico , Sarcoma do Estroma Endometrial/genética , Neoplasias Uterinas/patologia , Útero/patologia , Proteínas de Ligação a DNA/genética , Proteínas Correpressoras/genética , Proteínas Repressoras/genéticaRESUMO
Several defining molecular alterations have recently been identified underlying high-grade endometrial stromal sarcomas, such as YWHAE: NUTM2A/B fusions, ZC3H7B: BCOR fusions, and BCOR internal tandem duplication (ITD). BCOR is a useful immunohistochemical marker for identifying these tumors. A 37-year-old lady was presented with a 10-cm-sized tumor in the pouch of Douglas, involving the vaginal vault, bilateral adnexa, and peritoneum. A 53-year-old lady with a prior hysterectomy was presented with a 12-cm-sized tumor in the vault with abdominal deposits. Histopathological examination of both tumors revealed atypical cells comprising oval to spindle-shaped nuclei, a variable amount of myxoid stroma, and mitotic figures exceeding 10/10 high power fields. Immunohistochemically, the former tumor was diffusely positive for CD10, and the second tumor displayed patchy staining. Both tumors were positive for BCOR. Estrogen receptor (ER) showed variable staining in both tumors. By fluorescence in-situ hybridization (FISH), both tumors lacked YWHAE gene rearrangement. Both tumors had an aggressive clinical course, including extensive involvement This constitutes the first report of BCOR-positive high-grade sarcomas involving the female genital tract from our subcontinent. BCOR is a useful immunostain for identifying these relatively aggressive tumors. The differential diagnoses and the prognosis of these ultra-rare tumors are discussed herewith.
Assuntos
Neoplasias do Endométrio , Sarcoma do Estroma Endometrial , Sarcoma , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Sarcoma do Estroma Endometrial/diagnóstico , Sarcoma do Estroma Endometrial/genética , Proteínas Repressoras/genética , Proteínas Proto-Oncogênicas/genética , Sarcoma/patologia , Biomarcadores Tumorais/genética , Neoplasias do Endométrio/diagnóstico , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/químicaRESUMO
High-grade endometrial stromal sarcomas with ZC3H7B-BCOR fusion are rare. They are predominantly located in the endomyometrium, with morphologic features characterized as haphazardly arranged fascicles of spindle cells with mild to moderate atypia, abundant myxoid matrix, high mitotic index, and tongue-like/pushing patterns of myometrial invasion. Furthermore, conventional or variant low-grade endometrial stromal sarcomas are often not present. Clinically, they present at a higher stage and are associated with worse prognosis compared with low-grade endometrial stromal sarcoma. Given the limited number of reported cases, we describe the case of a ZC3H7B-BCOR fusion high-grade endometrial stromal sarcoma initially diagnosed on the hysterectomy specimen as low-grade endometrial stromal sarcoma based on an endometrial stromal tumor showing tongue-like myometrial and lymphovascular invasion, minimal cytologic atypia, low-mitotic activity (0-1/10 high-power field), round/spindle cell component and immunohistochemical stain results (positive for CD10, estrogen receptor, progesterone receptor, and focally positive for cyclin D1). At the time of pathologic diagnosis, she was Stage Ia and managed conservatively. Subsequent molecular analysis revealed a ZC3H7B (exon 10)- BCOR (BCL-6 corepressor) (exon 7) gene fusion. On follow-up, she showed no evidence of disease at 37 months from the time of diagnosis. This case report expands the morphologic spectrum of ZC3H7B-BCOR fusion high-grade ESS, which includes an intramural location, morphologic and immunophenotypic features similar to LG-ESS, as well as the presence of round and spindle cell components. This case also underscores the value of molecular analysis in the proper classification of ESS.
Assuntos
Neoplasias do Endométrio , Tumores do Estroma Endometrial , Sarcoma do Estroma Endometrial , Feminino , Humanos , Sarcoma do Estroma Endometrial/diagnóstico , Sarcoma do Estroma Endometrial/genética , Sarcoma do Estroma Endometrial/cirurgia , Tumores do Estroma Endometrial/diagnóstico , Proteínas Repressoras/metabolismo , Neoplasias do Endométrio/genética , Proteínas Proto-Oncogênicas/genética , Fatores de Transcrição , Proteínas de Ligação a RNARESUMO
BACKGROUND: Uterine sarcomas are uncommon mesenchymal tumors of the uterus. The clinical problem is that the features of uterine sarcomas can sometimes mimic uterine fibroids. This study aims to investigate the clinical characteristics of patients with uterine sarcomas who were preoperative presenting mainly with uterine masses. METHODS: A retrospective analysis of patients who underwent gynecological surgery for uterine sarcomas at the Obstetrics & Gynecology Hospital of Fudan University, between January 2016 and December 2021. RESULTS: Over the 5-year period, 277 patients were final diagnosed of uterine sarcomas. A total of 162 patients were preoperatively diagnosed as uterine fibroids for surgical treatment, the majority of whom were diagnosed of uterine leiomyosarcoma (uLMS) (49/162) and low-grade endometrial stromal sarcoma (LG-ESS) (100/162). Ninety people underwent total hysterectomy and bilateral salpingo-oophorectomy (TH + BSO), while 72 underwent myomectomy followed by supplemental TH + BSO. The group with direct hysterectomy had a higher average age than the group with prior myomectomy (47.20 ± 8.94 vs. 40.86 ± 5.88, p < 0.001). Among patients preoperatively diagnosed as uterine fibroids, patients with uLMS had a higher proportion of previous myomectomy (26.53% vs. 5.00%, p < 0.001), a larger uterine mass diameter on ultrasound (8.38 ± 3.39 cm vs. 6.41 ± 1.92 cm, p < 0.001), and richer hypervascularity (34.69% vs. 18%, p = 0.024) compared with LG-ESS. CONCLUSIONS: Analysis of our data showed that a large proportion of uterine sarcomas, especially uLMS and LG-ESS, present mainly with uterine masses. Ultrasound features including a large uterine mass diameter and rich hypervascularity, and with a history of myomectomy may alert clinicians in suspicion of uLMS when compared with LG-ESS.
Assuntos
Neoplasias do Endométrio , Leiomioma , Leiomiossarcoma , Neoplasias Pélvicas , Sarcoma do Estroma Endometrial , Sarcoma , Neoplasias Uterinas , Feminino , Humanos , Estudos Retrospectivos , Sarcoma do Estroma Endometrial/diagnóstico , Sarcoma do Estroma Endometrial/cirurgia , Sarcoma do Estroma Endometrial/patologia , Neoplasias Uterinas/diagnóstico por imagem , Neoplasias Uterinas/cirurgia , Sarcoma/diagnóstico por imagem , Sarcoma/cirurgia , Leiomiossarcoma/diagnóstico por imagem , Leiomiossarcoma/cirurgia , Leiomioma/cirurgia , Histerectomia , Neoplasias do Endométrio/patologiaRESUMO
Endometrial stromal sarcomas (ESSs) are a rare form of uterine malignancy representing <10% of all uterine sarcomas and <1% of all primary malignant tumours of the uterus. Invasion of the vascular system by low-grade ESS has been reported in the literature. Here we report the first case of a high-grade ESS invading the pelvic and gonadal vein and extending through the inferior vena cava to the right atrium, the diagnostic challenges and multidisciplinary management of the case.
Assuntos
Neoplasias do Endométrio , Sarcoma do Estroma Endometrial , Neoplasias Uterinas , Feminino , Humanos , Veia Cava Inferior/diagnóstico por imagem , Veia Cava Inferior/patologia , Sarcoma do Estroma Endometrial/cirurgia , Sarcoma do Estroma Endometrial/diagnóstico , Neoplasias Uterinas/patologia , Átrios do Coração/diagnóstico por imagem , Átrios do Coração/patologia , Neoplasias do Endométrio/patologiaRESUMO
PURPOSE: The unique chromosomal rearrangements of endometrial stromal sarcoma (ESS) make it possible to distinguish high-grade ESS (HGESS) and low-grade ESS (LGESS) from the molecular perspective. Analysis of ESS at the genomic and transcriptomic levels can help us achieve accurate diagnosis of ESS and provide potential therapy options for ESS patients. Materials and Methods: A total of 36 ESS patients who conducted DNA- and/or RNA-based next-generation sequencing were retrospectively enrolled in this study. The molecular characteristics of ESS at genomic and transcriptomic levels, including mutational spectrum, fusion profiles, gene expression and pathway enrichment analysis and features about immune microenvironment were comprehensively explored. RESULTS: TP53 and DNMT3A mutations were the most frequent mutations. The classical fusions frequently found in HGESS (ZC3H7B-BCOR and NUTM2B-YWHAE) and LGESS (JAZF1-SUZ12) were detected in our cohort. CCND1 was significantly up-regulated in HGESS, while the expression of GPER1 and PGR encoding estrogen receptor (ER) and progesterone receptor (PR) did not differ significantly between HGESS and LGESS. Actionable mutations enriched in homologous recombination repair, cell cycle, and phosphoinositide 3-kinase/AKT/mammalian target of rapamycin pathways were detected in 60% of HGESS patients. Genes with up-regulated expression in HGESS were significantly enriched in five immune-related pathways. Most HGESS patients (85.7%) had positive predictors of immunotherapy efficacy. Moreover, immune microenvironment analysis showed that HGESS had relatively high immune infiltration. The degree of immune infiltration in HGESS patients with ZC3H7B-BCOR fusion was relatively higher than that of those with NUTM2B-YWHAE fusion. CONCLUSION: This study investigated the molecular characteristics of ESS patients at the genomic and transcriptomic levels and revealed the potentially high sensitivity of targeted therapy and immunotherapy in a subset of HGESS with specific molecular features, providing a basis for guiding decision-making of treatment and the design of future clinical trials on precision therapy.
Assuntos
Neoplasias do Endométrio , Sarcoma do Estroma Endometrial , Feminino , Humanos , Sarcoma do Estroma Endometrial/genética , Sarcoma do Estroma Endometrial/terapia , Sarcoma do Estroma Endometrial/diagnóstico , Neoplasias do Endométrio/tratamento farmacológico , Neoplasias do Endométrio/genética , Transcriptoma , Estudos Retrospectivos , Fosfatidilinositol 3-Quinases/metabolismo , Fatores de Transcrição/genética , Genômica , Imunoterapia , Microambiente Tumoral/genéticaRESUMO
MEIS1::NCOA1/2 sarcomas are a newly recognized group of exceedingly rare low-grade spindle cell sarcomas that often involve the genitourinary and gynecologic tracts. Due to its deceptively low-grade morphology and the non-specific immunoprofile, these neoplasms may pose a diagnostic challenge by histologically mimicking other entities such as endometrial stromal sarcoma, smooth muscle tumor, or uterine perivascular epithelioid cell tumor (PEComa). Histologically, MEIS1::NCOA1/2 sarcomas typically show spindle cell proliferation with hyperchromatic nuclei and a generalized cytologic uniformity, arranged in short fascicles and exhibiting alternating zones of hypo- and hypercellularity. Among the previously reported cases, molecular analysis revealed the MEIS1::NCOA2 fusion as the most commonly detected fusion gene, whereas the MEIS1::NCOA1 fusion gene has been reported in only a single case that involved kidney. Herein we report the first case of uterine sarcoma harboring the MEIS1::NCOA1 fusion gene that was initially misclassified as low-grade endometrial stromal sarcoma, demonstrating its clinicopathologic features, and highlighting the essential role of molecular pathology to arrive at the accurate diagnosis that may alter disease classification and inform therapy.
Assuntos
Neoplasias do Endométrio , Sarcoma do Estroma Endometrial , Neoplasias Uterinas , Humanos , Feminino , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/análise , Neoplasias do Endométrio/diagnóstico , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/patologia , Sarcoma do Estroma Endometrial/diagnóstico , Sarcoma do Estroma Endometrial/genética , Sarcoma do Estroma Endometrial/patologia , Neoplasias Uterinas/diagnóstico , Neoplasias Uterinas/genética , Útero/patologia , Coativador 1 de Receptor Nuclear/genéticaRESUMO
Introduction. High-grade endometrial stromal sarcomas (HGESS) are rare malignant mesenchymal tumors of the uterus with aggressive poor clinical outcome, which frequently exhibit YWHAE::NUTM2 and ZC3H7B::BCOR fusions. In this study, we aimed to investigate HGESSs with YWHAE and BCOR translocations through our archive materials, and to identify morphological, immunohistochemical and molecular features of these tumors. We also assessed the diagnostic value of BCOR immunohistochemistry (IHC) in HGESSs, low-grade endometrial stromal sarcomas (LGESS) and uterine leiomyosarcomas. Methods. One hundred fifty-one uterine sarcomas diagnosed between 2000-2019 were reevaluated, and tumors of 39 patients with specific features were included in the study. Fluorescence in situ hybridization (FISH) studies using YWHAE and BCOR break-apart probes and BCOR IHC were performed. BCOR IHC was also performed in 20 leiomyosarcomas and 19 LGESSs. Results. In six HGESSs, translocations involving YWHAE or BCOR were detected. Five tumors showed high-grade morphology and revealed YWHAE translocation. One HGESS with myxoid morphology revealed BCOR translocation. In immunohistochemistry, three (3/4) YWHAE translocated HGESSs showed BCOR expression. However, the BCOR translocated HGESS was BCOR negative. The study showed that all LGESSs were immunohistochemically negative with BCOR. Although 15% (3/20) leiomyosarcomas reveal focal weak-moderate BCOR expression. Conclusion. BCOR IHC is a useful marker to distinguish LGESS from HGESS. A small percentage of uterine leiomyosarcomas reveal BCOR expression; however, it is not as diffuse and strong as in HGESSs. Strong and diffuse BCOR IHC expression is highly suggestive for HGESS. The diagnosis of HGESS should be supported by molecular studies such as FISH.
Assuntos
Neoplasias do Endométrio , Leiomiossarcoma , Sarcoma do Estroma Endometrial , Sarcoma , Neoplasias Uterinas , Feminino , Humanos , Neoplasias do Endométrio/diagnóstico , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/metabolismo , Sarcoma do Estroma Endometrial/diagnóstico , Sarcoma do Estroma Endometrial/genética , Hibridização in Situ Fluorescente , Imuno-Histoquímica , Neoplasias Uterinas/diagnóstico , Neoplasias Uterinas/genética , Translocação GenéticaAssuntos
Neoplasias da Mama , Neoplasias do Endométrio , Sarcoma do Estroma Endometrial , Feminino , Humanos , Sarcoma do Estroma Endometrial/diagnóstico , Sarcoma do Estroma Endometrial/patologia , Neoplasias do Endométrio/diagnóstico , Neoplasias do Endométrio/patologia , Biomarcadores Tumorais , Neoplasias da Mama/diagnósticoRESUMO
ABSTRACT: Leiomyoma is the most common benign uterine tumor, whereas endometrial stromal tumors are rare uterine tumors with limited clinical experience. The distinction between highly cellular leiomyoma and endometrial stromal sarcoma can pose a diagnostic challenge to the pathologists as both these tumors have considerable overlapping features on histology.