Uterine Sarcomas with Recurrent KDM2B Gene Fusions: Three Cases of a Possible Novel Subtype of High-Grade Endometrial Stromal Sarcoma.

The advent of widespread genomic testing of uterine mesenchymal tumors has led to novel insights into the biology of these diverse tumors, and many genomically-defined entities have been described in recent years. During a larger study of endometrial stromal sarcomas and unclassified uterine sarcomas, we identified three tumors harboring KDM2B gene fusions. Patients were 32, 61, and 67 years old and all initially underwent incomplete sampling via laparoscopic myomectomy (n=1), laparoscopic biopsy (n=1), or hysteroscopic myomectomy (n=1).

Endometrial carcinoma and immune escape: prognostic relevance of HLA class I loss in NSMP subtype.

Aims: This study aims to define and characterize human leukocyte antigen class I (HLA-I) expression in a consecutive series of molecularly classified endometrial carcinomas (ECs), and to evaluate its association with clinicopathologic features, spatial cancer-immune phenotypes and patient prognosis, with a focus on the NSMP (no specific molecular profile) subtype.

Methods And Results: HLA-I expression was assessed by immunohistochemistry on whole tissue sections from 208 ECs, classified into POLE-mutated, MMR-deficient (MMRd), p53-abnormal (p53abn) and NSMP subtypes. Loss of HLA-I was identified in 31% of cases and was associated with adverse features including high-grade, aggressive histotypes, deep myometrial invasion, substantial lymphovascular space invasion (LVSI), extensive tumour necrosis and an 'excluded' immune phenotype.

Deep Learning Can Accurately Predict the Prognosis of Gynecologic Smooth Muscle Tumors of Uncertain Malignant Potential: A Multicenter Pilot Study.

Smooth muscle tumors of uncertain malignant potential (STUMP) of the gynecologic tract are a heterogeneous group of tumors, with ambiguous or worrisome features, whose biological behavior is difficult to predict. Several ancillary techniques have been used to try to predict their prognosis, with limited success. This study aimed to explore whether deep learning (DL)-based features can be used to predict progression-free survival (PFS) in STUMP and identify high-risk patients, directly from histological slides.

Low-Grade Endometrial Stromal Sarcoma: Clinicopathologic and Prognostic Features in a Cohort of 102 Tumors.

Low-grade endometrial stromal sarcomas (LG-ESS) are the second most common malignant uterine mesenchymal tumors, but in contrast to the more common leiomyosarcomas, they are often characterized by a prolonged and relatively indolent course. However, a subset of patients experience significant morbidity or die of disease, and it is difficult to predict which tumors will behave aggressively, with most published studies limited in either the number of tumors or the depth of pathologic parameters evaluated. Thus, we studied the clinicopathologic features of LG-ESS in 102 patients ranging from 21 to 74 (median: 47) years.

The new 2023 endometrial cancer FIGO staging system: balancing innovation with complexity.

In August 2023, the International Federation of Gynecology and Obstetrics introduced an updated staging system for endometrial cancer that integrates histopathologic and molecular characteristics (optional) of the tumor alongside with anatomic extent of the disease. This innovative approach aims to improve the prognostication of the system and the identification of treatment-relevant patient populations by more accurately stratifying patients based on tumor biology, representing a significant advancement toward personalized medicine. However, its implementation poses challenges, including the heterogeneous availability of molecular testing worldwide, and the need for further standardization and prospective validation of some of the newly introduced histopathological parameters.

Fertility-sparing approach for uterine smooth muscle tumors of uncertain malignant potential.

Objective: Uterine smooth muscle tumors of uncertain malignant potential (STUMP) are a category of tumors that present diagnostic/therapeutic challenges since they cannot be assigned to either a benign or a malignant entity. Hysterectomy is the mainstay of treatment of STUMP. However, in most cases, STUMPs represent an incidental diagnosis following myomectomy.

The MEF2D::NCOA2 Fusion Defines a Distinct Emerging Vulvovaginal Myxoid Epithelioid Tumor With Smooth Muscle Differentiation.

Myocyte-specific enhancer factor 2D gene and nuclear receptor coactivator 2 gene fusion (MEF2D::NCOA2) was recently reported in 2 vulvovaginal myxoid epithelioid smooth muscle tumors. We aimed to perform an integrated approach combining clinical, morphologic, immunohistochemical, and molecular profiling analyses, including targeted RNA sequencing, targeted gene expression analysis profiling with clustering, DNA mutational analysis, and array comparative genomic hybridization in a series of 3 MEF2D::NCOA2 fusion-associated vulvovaginal tumors, to better describe this entity. The median age at diagnosis was 45 years.

Challenges of a tailored immunohistochemistry algorithm for uterine leiomyosarcoma: an integrated analysis of leiomyomas with bizarre nuclei and fumarate hydratase (FH) deficiency.

Aims: Leiomyomas (LM) are the most common uterine mesenchymal neoplasms and encompass a variety of histological subtypes. Bizarre nuclei are described in both leiomyomas with bizarre nuclei (LM-BN) and fumarate hydratase-deficient leiomyomas (FH-LM), which raise diagnostic concerns regarding leiomyosarcoma (LMS). Recently, an immunohistochemical algorithm to support the diagnosis of LMS based on the genomic landscape of these neoplasms was proposed.

[Translocation-associated uterine mesenchymal tumors: The new without forgetting the old. An integrated diagnostic approach].

This review focuses on uterine mesenchymal tumors that are defined on a molecular level by a single and unique genetic alteration, that is somehow necessary and sufficient to allow tumor growth and progression. Although diverse from a clinical, morphological and immunohistochemical point of view, the different entities we are going to talk about share both a simple genomic profile with a low number of chromosomal alterations observed by CGH Array (few deletions, gains or amplifications..

Uterine Inflammatory Myofibroblastic Tumors: p16 as a Surrogate for CDKN2A Deletion and Predictor of Aggressive Behavior.

Uterine inflammatory myofibroblastic tumors (IMTs) are rare mesenchymal neoplasms of uncertain malignant potential. Aside from the recently described risk stratification score, which has not been validated by other studies, and rare reports of aberrant p16 expression in malignant tumors, there are no criteria to reliably predict behavior. Herein, we evaluated the clinicopathologic features and p16 expression patterns in 30 IMTs, with genomic profiling performed in a subset (13 malignant, 3 benign).

SMARCB1 (INI1) Deficient Tumours of the Uterine Cervix: Report of Two Cases, Including One Associated With an NTRK Fusion.

Pathogenic variants (mutations) and other molecular events involving subunits of the SWItch/Sucrose Non-Fermentable chromatin remodelling complex are common in a wide variety of malignancies. Many of these neoplasms are characterized by undifferentiated morphology. They arise at a variety of sites in the female genital tract but have rarely been reported in the uterine cervix.

Pan-TRK immunohistochemistry in gynaecological mesenchymal tumours: diagnostic implications and pitfalls.

Aims: NTRK-rearranged sarcomas of the female genital tract mainly occur in the uterus (more commonly cervix than corpus) and are characterized by a "fibrosarcoma-like" morphology and NTRK gene rearrangements. These neoplasms may exhibit histological overlap with other entities and can present diagnostic difficulties without molecular confirmation. Pan-TRK immunohistochemistry was developed to identify tumours harbouring NTRK rearrangements.

DICER1-mutated rhabdomyosarcoma of the ovary with teratoid features.

DICER1-mutated rhabdomyosarcoma is a rare, emerging entity with a predilection for the gynecologic and genitourinary tracts. We report here a case of DICER1-mutated rhabdomyosarcoma of the ovary in a 14 years old girl which displayed interspersed mature teratoid glands, neuroectodermal rosettes and immature blastematous-like tubes. Morphologically the sarcomatous component predominated, corresponding to a high grade spindle cell rhabdomyosarcoma with botryoid features.

Low-Grade Uterine Leiomyosarcoma Is Highly Sensitive to Hormonal Treatment.

Purpose: According to the World Health Organization classification system, uterine leiomyosarcomas (ULMS) are high-grade. A diagnosis of smooth-muscle tumors of uncertain malignant potential (STUMP) is made when Stanford Criteria for ULMS are not met. When a STUMP recurs, the tumor is diagnosed as ULMS and medical treatment is the same as for ULMS.

Dissecting the Origin of Heterogeneity in Uterine and Ovarian Carcinosarcomas.

Unlabelled: Gynecologic carcinosarcomas (CS) are biphasic neoplasms composed of carcinomatous (C) and sarcomatous (S) malignant components. Because of their rarity and histologic complexity, genetic and functional studies on CS are scarce and the mechanisms of initiation and development remain largely unknown. Whole-genome analysis of the C and S components reveals shared genomic alterations, thus emphasizing the clonal evolution of CS.

Unusual Aspects of Small Cell Carcinoma of the Ovary of Hypercalcaemic Type: Retained SMARCA4 Immunohistochemical Staining and Positive Staining With TLE1.

Small cell carcinoma of the ovary of hypercalcaemic type (SCCOHT) is a rare and aggressive ovarian neoplasm that is most common in the second and third decades. Molecular studies have established inactivating SMARCA4 alterations as the driver of SCCOHT, these being present in over 95% of these neoplasms. SMARCA4 alterations almost always result in loss of immunoreactivity with SMARCA4 (BRG1) antibody, and this is an extremely useful adjunct in the diagnosis of SCCOHT.

[Uterin sarcoma, high-grade stroma, indifferenciated, referential].

High-grade endometrial stromal sarcoma (HGESS) and uterine undifferentiated sarcoma (UUS) are rare uterine malignancies arising from mesenchymal endometrial cells. They are characterized by aggressive behavior and poor prognosis. Median age of diagnostic is 55years.