Uterine sarcomas with KAT6B/A::KANSL1 fusion represent a new entity characterized by bland morphology, commonly with hybrid features of low-grade endometrial stromal sarcoma (LG-ESS) and tumors with smooth muscle differentiation. In our study, we performed a detailed morphological, immunohistochemical, and molecular analysis of 9 cases of these tumors. Six of those had been originally diagnosed as LG-ESS, one as leiomyoma, one as leiomyosarcoma, and the remaining case as sarcoma with the KAT6B/A::KANSL1 fusion. Seven cases showed overlapping features between endometrial stromal and smooth muscle tumors, one case resembled cellular leiomyoma, and one case resembled high-grade endometrial stromal sarcoma. Immunohistochemically, the tumors showed a common expression of smooth muscle markers and endometrial stromal markers. Molecular findings showed the KAT6B/A::KANSL1 fusion in all cases (by NGS and FISH). In addition, mutations affecting genes such as TP53, PDGFRB, NF1, RB1, PTEN, ATM, RB1, FANCD2, and TSC1 were present in all 5 cases with aggressive behavior. One patient with no evidence of disease showed no additional mutations, while another harbored a mutation of a single gene (ERCC3). Of the 8 patients with available follow-up, two died of disease, 3 are currently alive with disease, and 3 have no evidence of disease. The correct recognition of tumors with the KAT6B/A::KANSL1 fusion is essential because despite the bland morphological features of most cases, these tumors have a propensity for aggressive behavior.

• MeSH
• dospělí MeSH
• endometriální stromální sarkom genetika   patologie   MeSH
• fúzní onkogenní proteiny genetika   MeSH
• histonacetyltransferasy genetika   MeSH
• imunohistochemie MeSH
• lidé středního věku MeSH
• lidé MeSH
• mutace MeSH
• nádorové biomarkery * genetika   analýza   MeSH
• nádory dělohy * patologie   genetika   MeSH
• sarkom genetika   patologie   MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Adult granulosa cell tumors (AGCTs) of the ovary are characterized by their propensity for late recurrences and are primarily managed surgically due to the limited efficacy of systemic treatment. The FOXL2 p.C134W somatic mutation has been identified in ∼95% of AGCT cases, and TERT promoter alterations have been linked to worse overall survival. This study highlights the potential prognostic significance of FOXO1 mutations, suggesting that they may be associated with poorer overall survival and shorter time to recurrence. A total of 183 primary AGCTs and 44 recurrences without corresponding primary tumors were analyzed. The primary AGCTs were categorized into 3 groups: 77 nonrecurrent tumors, 18 tumors that later recurred (including 9 cases with matched primary-recurrence pairs), and 88 tumors with unknown recurrence status. Targeted next-generation sequencing was conducted on 786 cancer-related genes to investigate their genetic profile. The study aimed to identify the molecular alterations associated with AGCT pathogenesis and recurrence rate, comparing primary versus recurrent tumors, and primary recurrent versus primary nonrecurrent cases. Our findings confirmed the high prevalence (99%) of the FOXL2 p.C134W mutation in AGCTs. Secondary truncating FOXL2 mutations were observed in 5% of cases. Two cases with typical AGCT morphology were FOXL2 wild-type, harboring mutations in KRAS or KMT2D instead, suggesting alternative genetic pathways. TERT promoter mutations were found in 43% of cases, more frequently in recurrences. Other recurrent mutations detected in the cohort included KMT2D (10%), FOXO1 (7%), CHEK2 (5%), TP53 (3.5%), PIK3CA (3.5%), and AKT1 (3%). Two recurrent, FOXL2-mutated cases also carried DICER1 mutations. One tumor exhibited MSI-high status and a tumor mutation burden of 19 mut/Mb.Our results indicate the need for further investigation into the role of FOXO1 as a potential prognostic marker in AGCTs.

• MeSH
• dospělí MeSH
• forkhead box protein O1 * genetika   metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lokální recidiva nádoru * genetika   MeSH
• mutace * MeSH
• nádor z folikulárních buněk * genetika   patologie   MeSH
• nádory vaječníků * genetika   patologie   MeSH
• prognóza MeSH
• progrese nemoci MeSH
• protein FOXL2 genetika   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• telomerasa genetika   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Endometrial stromal tumors are rare lesions with a diverse morphology, which may make achieving the correct diagnosis challenging in some cases. We report a case of a uterine mesenchymal tumor diagnosed as endometrial stromal nodule with a peculiar whorled morphology and GREB1::CTNNB1 fusion confirmed by transcriptome RNA sequencing. The tumor was sharply demarcated, lacked invasive growth, and had benign behavior, as the patient remained without disease recurrence 15 years later. Immunohistochemically, the tumor cells showed diffuse nuclear expression of beta-catenin, confirming the activation of the beta-catenin pathway. Our case represents only the 4th reported case of CTNNB1-rearranged endometrial stromal tumor with extensive whorling. The biological nature of uterine tumors characterized by whorled morphology and rearrangement of CTNNB1 is not yet clear, which underscores the importance of genetic profiling for accurate diagnosis and potential targeted therapies in malignant cases.

• MeSH
• beta-katenin * genetika   MeSH
• endometriální stromální nádory * patologie   genetika   diagnóza   MeSH
• fúzní onkogenní proteiny genetika   MeSH
• genová přestavba MeSH
• imunohistochemie MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádorové biomarkery genetika   analýza   MeSH
• nádorové proteiny MeSH
• nádory endometria * genetika   patologie   diagnóza   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH

BACKGROUND: Juvenile granulosa cell tumor (JGCT) of the ovary is a rare tumor with distinct clinicopathological and hormonal features primarily affecting young women and children. We conducted a complex clinicopathological, immunohistochemical, and molecular analysis of five cases of JGCT. METHODS: The immunohistochemical examination was performed with 32 markers, including markers that have not been previously investigated. Moreover, DNA next-generation sequencing (NGS) and PTEN methylation analysis was performed. RESULT: We found the expression of calretinin, inhibin A, SF1, FOXL2, CD99, CKAE1/3, ER, PR, AR in all cases. WT1 was expressed in one case. Conversely, the expression of p16, OCT3/4, SALL4, GATA3, Napsin A, SATB2, MUC4, TTF1, and CAIX was completely negative. All tumors showed the wild-type pattern of p53 expression. Regarding predictive markers, all tumors were HER2 negative and did not express PD-L1. Mismatch repair proteins (MMR) showed no loss or restriction of expression, similarly to ARID1A, DPC4, BRG1, and INI1. The molecular analysis revealed AKT1 internal tandem duplication in two tumors. Two other cases exhibited mutations in TERT and EP400 and both developed recurrence. All AKT1-wild type tumors exhibited immunohistochemical loss of PTEN expression. However, no mutations, deletions (as assessed by CNV analysis), or promoter hypermethylation in the PTEN gene were detected. CONCLUSION: The results of our study further support the hypothesis that the pathogenesis of JGCT may be driven by activation of the PIK3/AKT/mTOR pathway. These findings could potentially have future therapeutic implications, as treatment strategies targeting the PTEN/mTOR pathways are currently under investigation.

• MeSH
• dítě MeSH
• fosfatidylinositol-3-kinasy genetika   metabolismus   MeSH
• fosfohydroláza PTEN genetika   metabolismus   MeSH
• imunohistochemie * MeSH
• lidé MeSH
• metylace DNA MeSH
• mladiství MeSH
• nádor z folikulárních buněk * patologie   genetika   metabolismus   MeSH
• nádorové biomarkery * genetika   analýza   metabolismus   MeSH
• nádory vaječníků * patologie   genetika   metabolismus   MeSH
• protoonkogenní proteiny c-akt * metabolismus   genetika   MeSH
• signální transdukce * MeSH
• TOR serin-threoninkinasy * metabolismus   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

CONTEXT.—: Non-smooth muscle uterine sarcomas are mostly represented by low-grade endometrial stromal sarcoma. However, several other rare, distinct types of uterine sarcoma are recognized, including high-grade endometrial stromal sarcoma, tumors with kinase fusions, uterine tumors resembling ovarian sex cord tumors, soft tissue-type sarcoma, and emerging entities such as KAT6A/B-rearranged tumors. The landscape of uterine sarcomas has changed, mostly because of the increasing knowledge concerning their molecular aberrations. OBJECTIVE.—: To offer a comprehensive review of the literature focusing on fusions occurring in tumors other than smooth muscle mesenchymal uterine tumors with respect to their type, frequency, and overlap between diagnostic categories and entities. DATA SOURCES.—: The data were mined from the PubMed/MEDLINE database covering the time period from January 1988 to June 2023. In total, 156 studies focusing on the problematics of fusions occurring in non-smooth muscle mesenchymal uterine tumors were selected, and thus became the basis for this review. CONCLUSIONS.—: One hundred ten fusions were identified in 703 tumors. The diagnostic significance of the molecular aberrations occurring in these tumors can be unclear in some cases. This can be related to the rare aberrations with a limited number of reported cases. Additionally, even well-known aberrations considered as specific for a certain distinct entity can occur in other lesions, the biological behavior and clinical significance of which can differ substantially.

• MeSH
• endometriální stromální nádory genetika   patologie   diagnóza   MeSH
• endometriální stromální sarkom genetika   patologie   MeSH
• fúze genů MeSH
• lidé MeSH
• nádory dělohy * genetika   patologie   diagnóza   MeSH
• sarkom genetika   patologie   diagnóza   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

• Publikační typ
• úvodníky MeSH

Dedifferentiated and undifferentiated ovarian carcinomas (DDOC/UDOC) are rare neoplasms defined by the presence of an undifferentiated carcinoma. In this study, we detailed the clinical, pathological, immunohistochemical, and molecular features of a series of DDOC/UDOC. We collected a multi-institutional cohort of 23 DDOC/UDOC and performed immunohistochemistry for core switch/sucrose nonfermentable (SWI/SNF) complex proteins (ARID1A, ARID1B, SMARCA4, and SMARCB1), mismatch repair (MMR) proteins, and p53. Array-based genome-wide DNA methylation and copy number variation analyses were performed on a subset of cases with comparison made to a previously reported cohort of undifferentiated endometrial carcinoma (UDEC), small cell carcinoma of the ovary, hypercalcemic type (SCCOHT), and tubo-ovarian high-grade serous carcinoma (HGSC). The age of all 23 patients with DDOC/UDOC ranged between 22 and 71 years (with an average age of 50 years), and a majority of them presented with extraovarian disease (16/23). Clinical follow-up was available for 19 patients. Except for 2 patients, the remaining 17 patients died from disease, with rapid disease progression resulting in mortality within a year in stage II-IV settings (median disease-specific survival of 3 months). Eighteen of 22 cases with interpretable immunohistochemistry results showed loss of expression of core SWI/SNF protein(s) that are expected to result in SWI/SNF complex inactivation as 10 exhibited coloss of ARID1A and ARID1B, 7 loss of SMARCA4, and 1 loss of SMARCB1. Six of 23 cases were MMR-deficient. Two of 20 cases exhibited mutation-type p53 immunoreactivity. Methylation profiles showed coclustering of DDOC/UDOC with UDEC, which collectively were distinct from SCCOHT and HGSC. However, DDOC/UDOC showed an intermediate degree of copy number variation, which was slightly greater, compared with SCCOHT but much less compared with HGSC. Overall, DDOC/UDOC, like its endometrial counterpart, is highly aggressive and is characterized by frequent inactivation of core SWI/SNF complex proteins and MMR deficiency. Its molecular profile overlaps with UDEC while being distinct from SCCOHT and HGSC.

• MeSH
• dědičné nádorové syndromy * MeSH
• DNA-helikasy genetika   metabolismus   MeSH
• dospělí MeSH
• epiteliální ovariální karcinom MeSH
• jaderné proteiny genetika   MeSH
• karcinom * patologie   MeSH
• kolorektální nádory * MeSH
• lidé středního věku MeSH
• lidé MeSH
• malobuněčný karcinom * MeSH
• mladý dospělý MeSH
• nádorové biomarkery genetika   metabolismus   MeSH
• nádorový supresorový protein p53 genetika   MeSH
• nádory endometria * patologie   MeSH
• nádory mozku * MeSH
• nádory vaječníků * genetika   patologie   MeSH
• senioři MeSH
• transkripční faktory genetika   metabolismus   MeSH
• variabilita počtu kopií segmentů DNA MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

OBJECTIVE: Patients with TNM T1a cervical cancer have excellent prognosis; however, the risk for recurrence remains an issue of concern and management guidelines are based on limited data. Here we performed subgroup analysis of the Surveillance in Cervical Cancer (SCCAN) consortium with the objective of defining the prognosis of T1a cervical cancer patients. METHODS: SCCAN was an international, multicentric, retrospective cohort study of patients with cervical cancer undergoing surgical treatment in tertiary centers. Inclusion criteria included: histologically confirmed cervical cancer treated between 2007 and 2016; TNM T1a; primary surgical management; and at least 1-year of follow-up data availability. Exclusion criteria included treatment with primary chemo-radiation, and missing treatment-related or clinical data. RESULTS: Out of 975 patients included, 554 (57 %) were T1a1 and 421 (43 %) T1a2. The majority had squamous-cell carcinoma (78 %). 79 patients (8.1 %) had lymphovascular space invasion (LVSI). 455 patients (47 %) underwent radical hysterectomy/ parametrectomy. Laparoscopic and open surgery was performed in 401 (41 %) and in 361 (37 %) patients, respectively. Adjuvant treatment was administered to 56 patients (5.7 %). Assessment of lymph nodes (LN) was performed in 524 patients (54 %), with LN involvement found in 15 (2.9 %). There were 40 (4.1 %) recurrences, occurring at a median of 26 months (4-106), out of which 33 (82.5 %) occurred in pelvis. Among T1a1 cases, there were 10 recurrences (2.0 %) if LVSI was negative, and 3 recurrences (6.7 %) if LVSI was positive. Among T1a2 cases, there were 23 recurrences (6.7 %) if LVSI was negative, and 4 recurrences (5.1 %) if LVSI was positive. There were 3 recurrences in the LN+ group (recurrence rate 20 %). CONCLUSIONS: The risk of recurrence in T1a cervical cancer was 4.1 % corresponding to the rates seen in patients with FIGO 1B cancer in recently published prospective trials. LN involvement represents a risk factor for disease recurrence. Our results indicate that stage T1a cervical cancer, apart from T1a1 LVSI negative disease, should follow the same principles in the management as that of FIGO stage 1B cancer.

• MeSH
• dospělí MeSH
• hysterektomie MeSH
• kohortové studie MeSH
• lidé středního věku MeSH
• lidé MeSH
• lokální recidiva nádoru patologie   MeSH
• nádory děložního čípku * patologie   terapie   chirurgie   MeSH
• prognóza MeSH
• retrospektivní studie MeSH
• senioři MeSH
• spinocelulární karcinom patologie   terapie   chirurgie   MeSH
• staging nádorů * MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH

Uterine tumor resembling ovarian sex cord tumor (UTROSCT) is a rare tumor of uncertain lineage and low malignant potential. Most tumors behave in a benign manner, but a subset of UTROSCT exhibit an aggressive clinical course with recurrences and metastases. The recurrent molecular alterations in UTROSCT mostly represent gene fusions involving NCOA1-3. We performed a comprehensive clinicopathological, morphologic, immunohistochemical, and molecular analysis on a cohort of 35 UTROSCT. The tumors exhibited various architectural patterns (diffuse, corded/trabecular, tubular, sertoliform, fascicular, whorled, nested, microfollicular, and pseudoglandular), often in combination. The immunohistochemical analysis confirmed the polyphenotypic immunoprofile, often with coexpression of sex cord-stromal, smooth muscle, and epithelial markers, as well as hormone receptors. Next-generation sequencing RNA analysis revealed recurrent NCOA1-3 gene fusions in 22/32 analyzed cases (69%), including ESR1::NCOA3 (11/22), GREB1::NCOA2 (7/22), ESR1::NCOA2 (3/22), and GREB1::NCOA1 (1/22). Tumor mutation burden was low in all cases. The fusion-positive cases exhibited statistically significant association with whorled architecture, conversely necrosis was associated with fusion-negative status. We did not find a significant relationship between any architectural pattern and GREB1 alterations, but the NCOA2-altered tumors were associated with pseudoglandular architecture. The GREB1-altered cases occurred in older patients and tended to be more often intramural masses compared with ESR1-altered cases. On the contrary, the ESR1-altered cases presented more often like submucosal or polypoid tumors. Two tumors exhibited aggressive behavior with recurrent disease. Both of these cases harbored a GREB1::NCOA2 fusion. Unsupervised hierarchical cluster analysis of our cohort revealed 2 main clusters. The tumors with GREB1 or NCOA2 fusion cluster together, suggesting that there are underlying molecular differences between these cases and cases with ESR1::NCOA3 fusion or without fusion. Our findings contribute to the growing knowledge about a rare neoplasm with currently uncertain biological behavior.

• MeSH
• dospělí MeSH
• gonadální stromální nádory * genetika   patologie   MeSH
• imunohistochemie * MeSH
• koaktivátor 2 jaderných receptorů genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• nádorové biomarkery * genetika   analýza   MeSH
• nádory dělohy * genetika   patologie   MeSH
• nádory vaječníků genetika   patologie   MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Přehledový článek se věnuje především možnostem a limitacím moderních zobrazovacích metod v předoperační diferenciální diagnostice mezenchymových nádorů dělohy. Při plánování vhodného chirurgického výkonu se řídíme nejen klinickými symptomy, věkem a reprodukčními plány, ale i zobrazovacími metodami, zejména ultrazvukovým vyšetřením a magnetickou rezonancí (MR). U těchto dvou zobrazení lze na základě recentních studií definovat znaky, které svědčí pro přítomnost malignity. V případě ultrazvukového vyšetření se jedná o obraz objemného, většinou solitárního nádoru nehomogenní struktury s cystami nepravidelného tvaru, s porušeným zevním pouzdrem, absencí kalcifikací a akustických stínů a střední nebo vysokou vaskularizací intraparenchymatózně. Maligním znakem je rovněž rychlý růst nádoru v průběhu sledování, zvláště peri- a postmenopauzálně. Při zobrazení MR mají děložní sarkomy nepravidelné ohraničení, jsou patrné hyperintenzní oblasti na T1 i T2 vážených sekvencích a centrální nekrotická oblast bez sycení kontrastní látkou. Při difuzně váženém zobrazení (DWI/MR) je patrná výrazná restrikce, ale tento znak se může objevovat i u některých variant myomů. Při suspektních nálezech v rámci předoperačního zobrazení ultrazvukem či MR lze využít biopsii silnou jehlou či hysteroskopicky, a to zejména při plánování fertilitu zachovávajících výkonů, nebo zvažujeme-li konzervativní management u asymptomatických pacientek. Co se týče dalších zobrazovacích metod, přínos výpočetní tomografie (CT) nebo pozitronové emisní tomografie v kombinaci s CT (PET/CT) je v rámci diferenciální diagnostiky značně omezený. Obě metody slouží pouze pro stanovení rozsahu onemocnění. Význam laboratorních markerů, především laktátdehydrogenázy, v diferenciální diagnostice nebyl dosud prokázán. Závěr: Ultrazvukové vyšetření anebo magnetická rezonance mohou přispět k předoperačnímu rozlišení děložních sarkomů od mnohem častějších myomů na základě přítomnosti kombinace maligních znaků. V této skupině žen se suspektními nálezy je potřeba zvolit adekvátní typ a rozsah chirurgického výkonu, především je nutné vyvarovat se intraperitoneální morcelace, která by mohla vést k iatrogenní diseminaci a zhoršení prognózy.

The narrative review article is focused on the strengths and limitations of modern imaging methods in the preoperative differential diagnosis of uterine mesenchymal tumours. In order to tailor the surgical procedures, imaging methods, namely ultrasound and magnetic resonance imaging (MRI), should be taken into account as well as clinical symptoms, age, and fertility plans. On ultrasound scans, uterine sarcomas have the appearance of large, usually solitary tumours of non-homogenous structure with irregular cysts, ill-defined outline borders (interrupted capsule), absence of calcifications with acoustic shadowing, and moderate to rich internal vascularisation. Rapid growth between follow-ups or atypical growth in peri- or post-menopause is also a sign of malignancy. On MRI, uterine sarcomas are characterized by irregular borders, hyperintense areas on T1-weighted and T2- weighted images, and central non-enhancing necrotic areas. On diffusion-weighted imaging (DWI/MRI), sarcomas exhibit markedly restricted diffusion but there is a significant overlap with some variants of fibroids. Core-needle or hysteroscopic biopsy can be used preoperatively if suspicious features are detected on ultrasound or MRI scans, particularly before myomectomy if fertility preservation is required or when conservative management is considered in asymptomatic women. Other imaging methods, such as positron emission tomography fused with CT (PET-CT) or computed tomography (CT) have limited role to distinguish uterine sarcomas from myomas and are suitable only for staging purposes. The importance of tumour markers including lactate dehydrogenase in preoperative work-up have not been verified yet. Conclusion: Uterine sarcomas can be distinguished from much more common myomas based on a combination of malignant features on ultrasound or MR imaging. In these suspicious cases the type and extent of surgery should be adjusted, avoiding intraperitoneal morcellation, which could lead to iatrogenic tumour spread and worsening of the patient’s prognosis.

• MeSH
• biologické markery MeSH
• biopsie metody   MeSH
• diferenciální diagnóza MeSH
• leiomyom chirurgie   diagnóza   MeSH
• lidé MeSH
• magnetická rezonanční tomografie metody   MeSH
• nádory dělohy * chirurgie   diagnostické zobrazování   diagnóza   MeSH
• předoperační vyšetření MeSH
• sarkom chirurgie   diagnóza   MeSH
• ultrasonografie metody   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH