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
TFE3 rearrangements characterize histogenetically, topographically, and biologically diverse neoplasms. Besides being a universal defining feature in alveolar soft part sarcoma (ASPS) and clear cell stromal tumor of the lung, TFE3 fusions have been reported in subsets of renal cell carcinoma, perivascular epithelioid cell tumor (PEComa), epithelioid hemangioendothelioma and ossifying fibromyxoid tumors. TFE3 -related neoplasms are rare in the head and neck and may pose diagnostic challenges. We herein describe 22 TFE3 fusion neoplasms affecting 11 males and 11 females aged 4 to 79 years (median, 25) and involving different head and neck sites: sinonasal cavities (n = 8), tongue (n = 4), oral cavity/oropharynx (n = 3), salivary glands (n = 2), orbit (n = 2), and soft tissue or unspecified sites (n = 3). Based on morphology and myomelanocytic immunophenotype, 10 tumors qualified as ASPS, 7 as PEComas (3 melanotic; all sinonasal), and 5 showed intermediate (indeterminate) histology overlapping with ASPS and PEComa. Immunohistochemistry for TFE3 was homogeneously strongly positive in all cases. Targeted RNA sequencing/FISH testing confirmed TFE3 fusions in 14 of 16 successfully tested cases (88%). ASPSCR1 was the most frequent fusion partner in ASPS (4 of 5 cases); one ASPS had a rare VCP::TFE3 fusion. The 6 successfully tested PEComas had known fusion partners as reported in renal cell carcinoma and PEComas ( NONO, PRCC, SFPQ , and PSPC1 ). The indeterminate tumors harbored ASPSCR1::TFE3 (n = 2) and U2AF2::TFE3 (n = 1) fusions, respectively. This large series devoted to TFE3-positive head and neck tumors illustrates the recently proposed morphologic overlap in the spectrum of TFE3 -associated mesenchymal neoplasms. While all PEComas were sinonasal, ASPS was never sinonasal and occurred in diverse head and neck sites with a predilection for the tongue. The indeterminate (PEComa-like) category is molecularly more akin to ASPS but shows different age, sex, and anatomic distribution compared with classic ASPS. We report VCP as a novel fusion partner in ASPS and PSPC1 as a novel TFE3 fusion partner in PEComa (detected in one PEComa). Future studies should shed light on the most appropriate terminological subtyping of these highly overlapping tumors.
- MeSH
- alveolární sarkom měkkých tkání * genetika patologie MeSH
- dítě MeSH
- dospělí MeSH
- fenotyp MeSH
- genetická predispozice k nemoci MeSH
- genová přestavba * MeSH
- hybridizace in situ fluorescenční MeSH
- imunohistochemie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- nádorové biomarkery * genetika analýza MeSH
- nádory hlavy a krku * genetika patologie chemie MeSH
- nádory z perivaskulárních epiteloidních buněk * genetika patologie chemie MeSH
- předškolní dítě MeSH
- senioři MeSH
- transkripční faktory BHLH-Zip * genetika MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
AIMS: CIC-rearranged sarcomas (CRS) are clinically aggressive undifferentiated round cell sarcomas (URCS), commonly driven by CIC::DUX4. Due to the repetitive nature of DUX4 and the variability of the fusion breakpoints, CIC::DUX4 fusion may be missed by molecular testing. Immunohistochemical (IHC) stains have been studied as surrogates for the CIC::DUX4 fusion. We aim to assess the performance of DUX4 IHC in the work-up of CRS and its expression in non-CRS round cell or epithelioid neoplasms. METHODS AND RESULTS: Cases of molecularly confirmed CRS (n = 48) and non-CRS (n = 105) were included. CRS cases consisted of 35 females and 13 males, with ages ranging from less than 1 year to 67 years (median = 41 years). Among the molecularly confirmed non-CRS cases, C-terminal DUX4 expression was investigated in Ewing sarcomas (38 cases), alveolar rhabdomyosarcomas (18 cases), desmoplastic small round cell tumours (12 cases) and synovial sarcomas (n = five), as well as in non-mesenchymal neoplasms such as SMARCA4/SMARCB1-deficient tumours (n = five), carcinomas of unknown primary (n = three) and haematolymphoid neoplasms (four cases). DUX4 IHC was considered positive when strong nuclear expression was detected in more than 50% of neoplastic cells. When used as a surrogate for the diagnosis of CRS, the sensitivity and specificity of DUX4 IHC was 98 and 100%, respectively. Only one CRS case was negative for DUX4 IHC and harboured a CIC::FOXO4 fusion. CONCLUSIONS: DUX4 IHC is a highly sensitive and specific surrogate marker for the presence of CIC::DUX4 fusion, demonstrating its utility in establishing a diagnosis of CRS.
- MeSH
- dítě MeSH
- dospělí MeSH
- fúzní onkogenní proteiny * genetika MeSH
- genová přestavba MeSH
- homeodoménové proteiny * metabolismus genetika MeSH
- imunohistochemie * MeSH
- kojenec MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- nádorové biomarkery * metabolismus analýza genetika MeSH
- nádory měkkých tkání diagnóza patologie genetika metabolismus MeSH
- předškolní dítě MeSH
- sarkom * diagnóza patologie genetika metabolismus MeSH
- senioři MeSH
- senzitivita a specificita MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- kojenec MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články 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: Dermatofibrosarcoma protuberans (DFSP) is a cutaneous sarcoma with an infiltrative growth pattern that makes it challenging to clear margins. High quality data regarding DFSP natural history, management, and outcomes are limited. METHODS: Data were retrospectively collected for adult DFSP patients who underwent resection at 10 institutions in eight countries. Demographics, tumor characteristics, treatment strategies, and outcomes were analyzed. RESULTS: Analysis included 347 patients consisting of young (median, 42 years), White (76.2%), males (54.2%) with truncal lesions (57.3%). The majority (76.8%) were symptomatic at presentation. Preoperative imaging was used in 55.9% of cases. Diagnosis was established with excisional biopsy in 50.9% versus incisional biopsy in 25.0% of cases. Despite planned margins of >1.0 cm in 67.4% of cases, only 69.0% of patients achieved R0 resection. Twenty-two percent of patients underwent at least one re-excision. R0 resection was achieved at a second procedure in 80.2% and a third procedure in 86.2%. Ultimately, R0 resection was feasible in 89.5% of all patients. Fibrosarcomatous transformation (FST) was observed in 12.6%. In total, 6.6% (N = 23) recurred (17 local, six distant). Of the six distant recurrences, 50.0% had FST. With a median follow-up of 47.0 months, disease-specific survival rate was 98.8%. In multivariable analysis, R0 margins at index resection were associated with wider circumferential margins and non-FST histology. CONCLUSIONS: In this international, multicenter collaborative, DFSP practice patterns were heterogeneous but achieved favorable recurrence rates and survival. Multiple excisions to clear margins remain commonplace and can inform future efforts to optimize margin selection.
- MeSH
- dermatofibrosarkom * patologie chirurgie terapie mortalita MeSH
- dospělí MeSH
- internacionalita * MeSH
- lidé středního věku MeSH
- lidé MeSH
- lokální recidiva nádoru patologie MeSH
- mladiství MeSH
- mladý dospělý MeSH
- nádory kůže * patologie chirurgie mortalita terapie MeSH
- resekční okraje MeSH
- retrospektivní studie MeSH
- senioři MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
Laryngeálny chondrosarkóm (LC) je raritné ochorenie, zodpovedajúce za 0,2 % všetkých laryngeálnych malignít a zhruba 3 % všetkých chondrosarkómov. Histologická diagnostika je kľúčová, kedže väčšina laryngeálnych chondrosarkómov je nízkeho stupňa (low-grade) a ich diferenciácia od benígneho chondrómu je náročná. Rast LC je pomalý s neskorým nástupom príznakov. Jedná sa o rádio-rezistentný typ nádoru, vzhľadom k čomu je liečbou prvej voľby chirurgická resekcia. Rozsah resekcie sa odvíja od histopatologického stupňa, miery rastu a rekurencie, so zohľadnením ďalšej kvality života. Prognóza pri nízko diferencovanom LC je dobrá s veľmi nízkym rizikom vzdialených metastáz. Prezentujeme prípady 62a 68-ročných pacientov s chondrosarkómom prstienkovej chrupky nízkeho stupňa s dvomi rozličnými spôsobmi rastu, ktorí podstúpili debulkizáciu (kazuistika 1) a totálnu laryngektómiu (kazuistika 2).
Laryngeal chondrosarcoma (LC) is a rare disease, accounting for 0.2% of all laryngeal malignancies and approximately 3% of all chondrosarcomas. Histological diagnosis is crucial as most laryngeal chondrosarcomas are low-grade and differentiation from benign chondroma is difficult. The growth of LC is slow with a late onset of symptoms. It is a radio-resistant type of tumor, hence why surgical resection is the first choice of treatment. The extent of resection depends on the histopathological grade, growth rate, and recurrence with consideration of future quality of life. The prognosis for low-differentiated LC is good with a very low risk of distant metastasis. We present the cases of 62and 68-year-old patients with low-grade chondrosarcoma of the annular cartilage with two different growth patterns who underwent debulking (case report 1) and total laryngectomy (case report 2).
- MeSH
- chondrosarkom * chirurgie diagnóza radioterapie MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory hrtanu * chirurgie diagnóza radioterapie MeSH
- senioři MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- Publikační typ
- kazuistiky MeSH
Úvod: Pleomorfný dermálny sarkóm (PDS) je zriedkavý malígny mezenchýmový nádor kože. Klinicky aj histogeneticky zdieľa podobné črty s atypickým fibroxantómom (AFX) a predpokladá sa, že tieto dva nádory predstavujú morfologické spektrum jednej neoplázie. Kazuistika: 60-ročný muž s anamnézou karcinómu hlasivky pozoroval niekoľko mesiacov rast ulcerovaného tumoru na koži kapilícia. Odstránený bol chirurgickou excíziou. Histologicky išlo o solídne rastúci mezenchýmový nádor pozostávajúci z atypických buniek epiteloidného a histiocytoidného vzhľadu. Na spodine infiltroval podkožný tuk a zasahoval až po hlbokú fasciu. Prítomná bola krvná cieva vyplnená nádorovým trombom. Imunohistochemicky exprimoval CD68, CD10, CD163, CD99 a sčasti aj αSMA a CD31. Nález zodpovedal PDS. Pacient absolvoval PET/CT vyšetrenie s negatívnym výsledkom. Krčné lymfatické uzliny neboli zväčšené. Vykonaná bola široká reexcízia miesta jazvy bez nádorových reziduí. Pacient je ďalej sledovaný, aktuálne bez známok recidívy. Záver: PDS predstavuje pre patológov diagnostickú výzvu. Najčastejšie vzniká u starých mužov na vlasatej časti hlavy a v tejto lokalite, typickej pre nemelanómovú rakovinu kože, predstavuje významnú diferenciálnu diagnózu. Jeho odlíšenie od histogeneticky a štrukturálne príbuzného, ale klinicky omnoho priaznivejšieho AFX môže byť veľmi obtiažne, ale z hľadiska ďalšej prognózy a klinického manažmentu pacienta zásadné.
Introduction: Pleomorphic dermal sarcoma (PDS) is a rare malignant mesenchymal tumor of the skin. It clinically and histogenetically shares similar features with atypical fibroxanthoma (AFX) and they are thought to represent the morphologic spectrum of one neoplasia. Case report: A 60-year-old man with a history of vocal cord carcinoma had observed an ulcerated skin tumor in the scalp growing for several months. It was removed by surgical excision. Histology revealed a solid mesenchymal tumor consisting of atypical cells population of epithelioid and histiocytoid appearance. At the base, it infiltrated the subcutaneous fat and extended into the deep fascia. A blood vessel filled with a tumor thrombus was found. The tumor was positive for CD68, CD10, CD163, CD99 and partly reactive for αSMA and CD31. The diagnosis of PDS was established. The patient underwent PET/CT examination with a negative result. The cervical lymph nodes were not enlarged. A wide re-excision of the scar region was performed without evidence of residual tumor. The patient continues to be monitored, currently without signs of recurrence. Conclusion: PDS represents a diagnostic challenge for pathologists. It mostly occurs in old men in the capillitium and in this location, which is typical for non-melanoma skin cancer, represents an important differential diagnosis. Its differentiation from the histogenetically and structurally related but clinically much more favorable AFX can be very difficult, but essential in terms of further prognosis and clinical management of the patient.
- MeSH
- histologické techniky MeSH
- imunohistochemie MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory kůže diagnóza patologie terapie MeSH
- sarkom * diagnóza patologie terapie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
PURPOSE: Necrosis quantification in the neoadjuvant setting using pathology slide review is the most important validated prognostic marker in conventional osteosarcoma. Herein, we explored three deep-learning strategies on histology samples to predict outcome for osteosarcoma in the neoadjuvant setting. EXPERIMENTAL DESIGN: Our study relies on a training cohort from New York University (NYU; New York, NY) and an external cohort from Charles University (Prague, Czechia). We trained and validated the performance of a supervised approach that integrates neural network predictions of necrosis/tumor content and compared predicted overall survival (OS) using Kaplan-Meier curves. Furthermore, we explored morphology-based supervised and self-supervised approaches to determine whether intrinsic histomorphologic features could serve as a potential marker for OS in the neoadjuvant setting. RESULTS: Excellent correlation between the trained network and pathologists was obtained for the quantification of necrosis content (R2 = 0.899; r = 0.949; P < 0.0001). OS prediction cutoffs were consistent between pathologists and the neural network (22% and 30% of necrosis, respectively). The morphology-based supervised approach predicted OS; P = 0.0028, HR = 2.43 (1.10-5.38). The self-supervised approach corroborated the findings with clusters enriched in necrosis, fibroblastic stroma, and osteoblastic morphology associating with better OS [log-2 hazard ratio (lg2 HR); -2.366; -1.164; -1.175; 95% confidence interval, (-2.996 to -0.514)]. Viable/partially viable tumor and fat necrosis were associated with worse OS [lg2 HR; 1.287; 0.822; 0.828; 95% confidence interval, (0.38-1.974)]. CONCLUSIONS: Neural networks can be used to automatically estimate the necrosis to tumor ratio, a quantitative metric predictive of survival. Furthermore, we identified alternate histomorphologic biomarkers specific to the necrotic and tumor regions, which could serve as predictors.
- MeSH
- deep learning MeSH
- dítě MeSH
- dospělí MeSH
- Kaplanův-Meierův odhad MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- nádory kostí * mortalita patologie MeSH
- nekróza * MeSH
- neoadjuvantní terapie * metody MeSH
- neuronové sítě * MeSH
- osteosarkom * mortalita patologie terapie MeSH
- prognóza MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví 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
AIMS: Spindle-cell/sclerosing rhabdomyosarcomas (SS-RMS) are clinically and genetically heterogeneous. They include three well-defined molecular subtypes, of which those with EWSR1/FUS::TFCP2 rearrangements were described only recently. This study aimed to evaluate five new cases of SS-RMS and to perform a clinicopathological and statistical analysis of all TFCP2-rearranged SS-RMS described in the English literature to more comprehensively characterize this rare tumour type. METHODS AND RESULTS: Cases were retrospectively selected and studied by immunohistochemistry, fluorescence in situ hybridization with EWSR1/FUS and TFCP2 break-apart probes, next-generation sequencing (Archer FusionPlex Sarcoma kit and TruSight RNA Pan-Cancer Panel). The PubMed database was searched for relevant peer-reviewed English reports. Five cases of SS-RMS were found. Three cases were TFCP2 rearranged SS-RMS, having FUSex6::TFCP2ex2 gene fusion in two cases and triple gene fusion EWSR1ex5::TFCP2ex2, VAX2ex2::ALKex2 and VAX2intron2::ALKex2 in one case. Two cases showed rhabdomyoblastic differentiation and spindle-round cell/sclerosing morphology, but were characterized by novel genetic fusions including EWSR1ex8::ZBTB41ex7 and PLOD2ex8::RBM6ex7, respectively. In the statistical analysis of all published cases, CDKN2A or ALK alterations, the use of standard chemotherapy and age at presentation in the range of 18-24 years were negatively correlated to overall survival. CONCLUSION: EWSR1/FUS::TFCP2-rearranged SS-RMS is a rare rhabdomyosarcoma subtype, affecting predominantly young adults with average age at presentation 34 years (median 29.5 years; age range 7-86 years), with a predilection for craniofacial bones, rapid clinical course with frequent bone and lung metastases, and poor prognosis (3-year overall survival rate 28%).
- MeSH
- dítě MeSH
- DNA vazebné proteiny genetika MeSH
- dospělí MeSH
- fúze genů MeSH
- hybridizace in situ fluorescenční MeSH
- lidé středního věku MeSH
- lidé MeSH
- lysinhydroxylasa genetika MeSH
- mladiství MeSH
- mladý dospělý MeSH
- nádorové biomarkery genetika MeSH
- protein EWS vázající RNA genetika MeSH
- proteiny vázající RNA genetika MeSH
- retrospektivní studie MeSH
- rhabdomyosarkom * genetika patologie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- transkripční faktory * genetika MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH