Targeted RNA expression profiling identifies high-grade endometrial stromal sarcoma as a clinically relevant molecular subtype of uterine sarcoma

Boroujeni, Amir Momeni; Mohammad, Nissreen; Wolber, Robert; Yip, Stephen; Köbel, Martin; Dickson, Brendan C.; Hensley, Martee L.; Leitao, Mario M.; Antonescu, Cristina R.; Benayed, Ryma; Ladanyi, Marc; Lee, Cheng‐Han; Chiang, Sarah

doi:10.1038/s41379-020-00705-6

Cited by 30 publications

(31 citation statements)

References 46 publications

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“…SMA and caldesmon seem to be negative [ 77 , 93 , 108 ]. There is strong and diffuse cytoplasmic expression of pan-Trk [ 109 ].…”

Section: High-grade Endometrial Stromal Sarcoma (Hg-ess)mentioning

confidence: 99%

“…Mutations in STAG2, PASK, SMARCB1, ATRX, CTNNB1 and ARID1A were also seen in the minority of the tested BCOR-ITDs cases [ 105 ]. Upregulation of the expression of NTRK3, FGFR3, RET, BCOR , GLI1 and PTCH1 genes has also been reported [ 109 ].…”

Section: High-grade Endometrial Stromal Sarcoma (Hg-ess)mentioning

confidence: 99%

“…A single case (1/23) harbouring HMGA2-RAD51B fusion has been described, which also demonstrated high expression of NTRK3, FGFR3, RET, BCOR, GLI1 and PTCH1, and low expression of ESR1 . [ 109 ]. Other cases have demonstrated low expression of these genes along with low ESR1 (17/23) expression; however, no fusions have been observed [ 109 ].…”

Section: Undifferentiated Uterine Sarcomas (Uus)mentioning

confidence: 99%

“…[ 109 ]. Other cases have demonstrated low expression of these genes along with low ESR1 (17/23) expression; however, no fusions have been observed [ 109 ].…”

Section: Undifferentiated Uterine Sarcomas (Uus)mentioning

confidence: 99%

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Update on Endometrial Stromal Tumours of the Uterus

2021

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Endometrial stromal tumours (ESTs) are rare, intriguing uterine mesenchymal neoplasms with variegated histopathological, immunohistochemical and molecular characteristics. Morphologically, ESTs resemble endometrial stromal cells in the proliferative phase of the menstrual cycle. In 1966 Norris and Taylor classified ESTs into benign and malignant categories according to the mitotic count. In the most recent classification by the WHO (2020), ESTs have been divided into four categories: Endometrial Stromal Nodules (ESNs), Low-Grade Endometrial Stromal Sarcomas (LG-ESSs), High-Grade Endometrial Stromal Sarcomas (HG-ESSs) and Undifferentiated Uterine Sarcomas (UUSs). ESNs are clinically benign. LG-ESSs are tumours of low malignant potential, often with indolent clinical behaviour, with some cases presented with a late recurrence after hysterectomy. HG-ESSs are tumours of high malignant potential with more aggressive clinical outcome. UUSs show high-grade morphological features with very aggressive clinical behavior. With the advent of molecular techniques, the morphological classification of ESTs can be integrated with molecular findings in enhanced classification of these tumours. In the future, the morphological and immunohistochemical features correlated with molecular categorisation of ESTs, will become a robust means to plan therapeutic decisions, especially in recurrences and metastatic disease. In this review, we summarise the morphological, immunohistochemical and molecular features of ESTs with particular reference to the most recent molecular findings.

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“…SMA and caldesmon seem to be negative [ 77 , 93 , 108 ]. There is strong and diffuse cytoplasmic expression of pan-Trk [ 109 ].…”

Section: High-grade Endometrial Stromal Sarcoma (Hg-ess)mentioning

confidence: 99%

Section: High-grade Endometrial Stromal Sarcoma (Hg-ess)mentioning

confidence: 99%

Section: Undifferentiated Uterine Sarcomas (Uus)mentioning

confidence: 99%

“…[ 109 ]. Other cases have demonstrated low expression of these genes along with low ESR1 (17/23) expression; however, no fusions have been observed [ 109 ].…”

Section: Undifferentiated Uterine Sarcomas (Uus)mentioning

confidence: 99%

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Update on Endometrial Stromal Tumours of the Uterus

2021

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“…ESS, including high‐grade tumors, also lack the inflammatory component that is characteristic of IMT. By immunohistochemistry, ALK positivity, either negative or focal BCOR expression in <50% tumor cells, and absence of pan‐Trk expression distinguish IMT from high‐grade ESS, including tumors harboring ZC3H7B‐BCOR fusion 92,93,112 …”

Section: Inflammatory Myofibroblastic Tumormentioning

confidence: 99%

Recent advances in smooth muscle tumors with PGR and PLAG1 gene fusions and myofibroblastic uterine neoplasms

Chiang

2020

Genes Chromosomes & Cancer

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Uterine epithelioid and myxoid leiomyosarcomas and inflammatory myofibroblastic tumors are rare mesenchymal neoplasms. Next‐generation sequencing recently detected novel PGR fusions in uterine epithelioid leiomyosarcomas that demonstrate characteristic rhabdoid and spindled morphology. PLAG1 gene fusions have also been identified in a subset of myxoid leiomyosarcomas and are associated with PLAG1 overexpression. ALK rearrangements underpin the vast majority of uterine inflammatory myofibroblastic tumors, which demonstrate morphologic, and immunohistochemical features similar to those of inflammatory myofibroblastic tumors elsewhere. This review summarizes the morphologic, immunophenotypic, and molecular genetic features of PGR fusion‐positive epithelioid leiomyosarcoma, PLAG1 fusion‐positive myxoid leiomyosarcoma, and inflammatory myofibroblastic tumors of the uterus.

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Expanding the spectrum of GLI1‐altered mesenchymal tumors—A high‐grade uterine sarcoma harboring a novel PAMR1::GLI1 fusion and literature review of GLI1‐altered mesenchymal neoplasms of the gynecologic tract

Punjabi

Hong

Sittampalam

2022

Genes Chromosomes & Cancer

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GLI1‐altered mesenchymal tumors comprise a group of seemingly unrelated entities, including pericytoma with t(7;12) translocation, plexiform fibromyxoma, gastroblastoma, malignant epithelioid neoplasm with GLI1 rearrangements, and GLI1‐amplified mesenchymal neoplasms. Herein, we report a high‐grade uterine sarcoma harboring a novel PAMR1::GLI1 fusion and present a literature review of GLI1‐altered mesenchymal neoplasms of the gynecologic tract. A 57‐year‐old female presented with an abdomino‐pelvic mass, felt since a decade prior. Magnetic resonance imaging showed a heterogenous myometrial mass extending beyond the serosa. The patient underwent oncologic surgical resection. Gross examination revealed a perforated multi‐nodular uterine tumor (21 cm) with a firm white and soft fleshy cut surface, featuring hemorrhage and necrosis. The tumor was morphologically heterogenous, disclosing frankly sarcomatous areas composed of pleomorphic spindle and focally epithelioid cells, intermingled with a component of low‐grade spindle cells arranged in fascicles. There was a rich vascular network and zones of necrosis with peripheral amianthoid‐like collagen plaques. Lymphovascular invasion and metastasis to lymph nodes and omentum were present. The tumor was immunopositive for CD10 and cyclinD1, and negative for cytokeratins, myogenic, melanotic, and hormonal markers. ArcherTM Fusion Sarcoma Assay detected PAMR1(exon1)::GLI1(exon4) fusion, confirmed on RT‐PCR and Sanger sequencing. The patient received chemo‐radiotherapy, however, developed metastatic recurrence and demised 18 months post‐surgery. Altogether, this is a rare and diagnostically challenging case of a uterine sarcoma harboring a novel GLI1 fusion. Emerging GLI/Hedgehog inhibitors provide clinical relevance to recognizing these tumors in modern pathology.

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Targeted RNA expression profiling identifies high-grade endometrial stromal sarcoma as a clinically relevant molecular subtype of uterine sarcoma

Cited by 30 publications

References 46 publications

Update on Endometrial Stromal Tumours of the Uterus

Update on Endometrial Stromal Tumours of the Uterus

Recent advances in smooth muscle tumors with PGR and PLAG1 gene fusions and myofibroblastic uterine neoplasms

Expanding the spectrum of GLI1‐altered mesenchymal tumors—A high‐grade uterine sarcoma harboring a novel PAMR1::GLI1 fusion and literature review of GLI1‐altered mesenchymal neoplasms of the gynecologic tract

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