With the first series of PRRX1-rearranged tumors published in 2019, the spectrum of these so-called fibroblastic tumors has been expanded. Since then, several smaller case series have been published; however, our understanding of them continues to be quite limited given their rarity. We herein studied 18 additional cases, the largest series to date. Eighteen tumors present in 9 male, 8 female, and 1 nonbinary patient with a median age of 35 years (range: 11 to 70 y) and involved the neck (5), the chest region (4), thigh (3), back (1), shoulder (1), forehead (1), lower leg (1), axilla (1), and the parapharyngeal region (1). Clinical follow-up (9/18 tumors; 50%; median: 10 mo; range: 4 to 40 mo) showed consistent indolent behavior without local recurrences or distant metastases. On morphology, these tumors were characterized by well-circumscription and distinctive peripheral crescent-shaped vessels. They were composed of uniform spindle and round cells growing in short fascicles within often densely hyalinized collagen lacking significant mitotic activity, necrosis, or cytologic atypia. Immunohistochemically, about half of the tested tumors expressed focal to rarely diffuse S100 with occasional co-expression of SOX10. Interestingly, almost half of the tested cases also showed complete loss of RB expression. All but 1 tumor harbored a PRRX1::NCOA1 fusion, while 1 case harbored a novel PRRX1::EP300 fusion. We herein provide additional data on these exceptionally uncommon tumors, expand their molecular spectrum, and compare them to their close morphologic mimics to aid in accurate diagnosis and avoid confusion with potentially more aggressive neoplasms.

• Klíčová slova
• fibroblastic tumor,
• Publikační typ
• časopisecké články MeSH

Solitary fibrous tumor (SFT) is a fibroblastic neoplasm characterized by prominent, staghorn, or delicate "hemangiopericytoma (HPC)-like vasculature", NAB2::STAT6 gene fusion, and its surrogate STAT6 expression. SFT may exhibit an unpredictable clinical course, necessitating risk assessment based on tumor characteristics. Renal SFTs are rare and have not been well characterized. Forty-three primary kidney SFT cases are reviewed for clinical, morphological, and immunohistochemical (STAT6, BCL2, CD34, and PAX8) features. A four-variable risk stratification by Demicco was applied based on patient age, tumor size, mitotic activity, and tumor necrosis. The mean age was 49 years (range 11-83 years) with a slight female predominance (male:female = 20:23). The mean tumor size was 7.8 cm (1.6-32 cm). Tumors were mainly located at the hilus (22/32, 68%) and had well-demarcated borders (31/42, 74%). Morphologically, tumors were categorized as 1) Fibrous ("SFT-like", 19/43, 44%), characterized by hypocellularity and prominent fine-reticular or keloidal collagen; 2) Cellular ("HPC-like", 8/43, 19%), with hypercellularity, short spindle to small cell-like proliferation, and lacking a collagenous background; 3) mixed fibrous/cellular (16/43, 37%) displaying both components. Four cases featured a lipomatous component. BCL2 was positive in all tested cases (28/28), CD34 in all but 3 cases (93%), and STAT6 in all but one case (39/40, 97.5%). PAX8 was positive in 6/34 (18%) cases. Most cases (29/43, 68%) were classified as low-risk, followed by intermediate (12/43, 27%) and high-risk (2/43, 5%) groups. Five of 29 (18%) patients had metastatic disease, and two patients with high-risk and one with intermediate-risk tumors died from the disease, while 25 patients with low- or intermediate-risk tumors were alive for an average of about 36 months. We emphasize the usefulness of the risk stratification system in predicting prognosis. PAX8 expression in a subset of renal SFT represents a potential diagnostic pitfall.

• Klíčová slova
• Hemangiopericytoma, Kidney, PAX8, Prognosis, Renal, STAT6, Solitary fibrous tumor, Stratification,
• Publikační typ
• časopisecké články MeSH

Angiomatoid fibrous histiocytoma (AFH) is a rare mesenchymal neoplasm of borderline malignancy (locally recurring, rarely metastasizing), most often involving the limbs, trunk, and head/neck. Rarely, AFH may involve unusual locations. Herein, we characterize the clinicopathologic features of 26 AFH of the distal extremities, including acral sites. The tumors occurred in 19 females and 7 males ranging in age from 12 to 76 years (median, 23 years). Tumors involved the upper (n = 19) and lower (n = 6) distal extremity; one affected an unspecified digital site. Twenty-two cases occurred in acral locations (hands and feet). Subsets of cases showed the following morphologic features: multinodular architecture (26/26), lymphoid cuffs (23/26), prominent stromal myxoid change (11/25), angiomatoid features (9/26), and cytologic pleomorphism (8/26). The average mitotic count was 1/10 HPF; 3 cases showed brisk mitotic activity (> 10 mitoses/10 HPF). Immunohistochemistry revealed variable expression of desmin (16/25), EMA (14/21) and ALK (5/8). Molecular testing revealed EWSR1 rearrangements in 17/18 cases (94%). Among 12 tumors with known fusion partners, the fusions partner was CREB1 in 6 cases (50%), CREM in 4 tumors (33%), ATF1 in one tumor (8%) and PBX3 (8%) in another tumor. Prominent myxoid features were noted in 75% CREM versus 33% of CREB1 versus 0% of ATF1-fused tumors. AFH occurring in distal extremity/acral locations have a predilection for females, upper extremity locations, frequent unusual (solid, non-angiomatoid and myxoid) morphology and higher frequency of CREM over ATF1 fusions. Awareness of the morphologic spectrum of these rare neoplasms is essential for correct classification.

• Klíčová slova
• Clear cell sarcoma, Genetic landscape, Mimics, Precision medicine, Profiling, Targeted next generation sequencing,
• MeSH
• dítě MeSH
• dospělí MeSH
• fúzní onkogenní proteiny genetika   MeSH
• genotyp MeSH
• hybridizace in situ fluorescenční MeSH
• končetiny patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• maligní fibrózní histiocytom * genetika   patologie   MeSH
• mladiství MeSH
• mladý dospělý MeSH
• nádorové biomarkery genetika   analýza   MeSH
• nádory měkkých tkání * patologie   genetika   MeSH
• protein EWS vázající RNA genetika   MeSH
• senioři MeSH
• Check Tag
• dítě MeSH
• 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
• Názvy látek
• EWSR1 protein, human MeSH Prohlížeč
• fúzní onkogenní proteiny MeSH
• nádorové biomarkery MeSH
• protein EWS vázající RNA MeSH

• Publikační typ
• tisková chyba MeSH

Malignant chondroblastoma is a recently described variant of chondroblastoma showing a distinct age/site distribution and morphology along with the typical H3-3B p.K36M mutation. We sought to further compare conventional and malignant chondroblastoma. Malignant chondroblastomas were collected. H3-3 K36M immunohistochemistry, as well as DNA methylation and copy number profiling, were performed and compared with conventional chondroblastoma. Forty-one samples from 26 patients were identified (20 males, 6 females; age: 19-62 years; median: 39 years). Anatomical sites included rib (7), pelvis (4), acromion (4), scapula (4), spine (2), long bone (3), calcaneus (1), and talus (1). Imaging showed an expansile mass with variable cortical erosion and/or breakthrough. Most patients (n = 17) showed sheets of atypical ovoid cells deposited in a myxoid stroma. Osteoclast-like giant cells/matrix formation was scarce. Six patients had tumors with features of conventional chondroblastoma but significant cytologic atypia. Three tumors demonstrated a morphology indistinguishable from conventional chondroblastoma except for extensive permeation, and one of these cases showed a transition to high-grade sarcoma. The final case was composed only of high-grade pleomorphic sarcoma that harbored an H3F3A p.K36M mutation. When an adjacent host bone was present, permeative growth through the cortex and native trabeculae was noted. All samples tested positive for the H3-3 K36M-specific antibody (26 of 26). Methylome profiling of 28 specimens from 24 patients revealed that 26 of these specimens formed a distinct cluster on a uniform manifold approximation and projection dimension reduction plot separate from conventional chondroblastoma and high-grade osteosarcoma. Of 26 methylomes from which interpretable copy number profiles can be derived, 12 had no variations, whereas 14 had copy number changes. Of 22 patients, 11 experienced local recurrence, 8 patients developed metastasis, and 3 patients died of disease. Malignant chondroblastoma is a rare, clinically and epigentically distinct variant of chondroblastoma with a predilection for the flat bones of skeletally mature individuals and high rates of local recurrence and distant metastases. A subset transforms into high-grade pleomorphic sarcoma, either de novo or in subsequent recurrences. Malignant chondroblastoma with high-grade features and/or copy number variations appears to have a higher propensity for adverse events, including death from disease.

• Klíčová slova
• bone, chondroblastoma, malignant chondroblastoma, methylation, orthopedic,
• MeSH
• chondroblastom * genetika   patologie   MeSH
• dospělí MeSH
• epigeneze genetická * MeSH
• histony genetika   MeSH
• imunohistochemie MeSH
• lidé středního věku MeSH
• lidé MeSH
• metylace DNA MeSH
• mladý dospělý MeSH
• mutace MeSH
• nádorové biomarkery genetika   analýza   MeSH
• nádory kostí * genetika   patologie   MeSH
• variabilita počtu kopií segmentů DNA MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• histony MeSH
• nádorové biomarkery MeSH

Lipoblastoma is a benign adipocytic lesion with embryonal fat cell differentiation. The tumors most commonly occur in children, however, rare cases have been reported to occur in adults and are generally considered to represent "maturing" or long-standing lipoblastomas. Approximately 60%-80% of these tumors harbor a gene fusion involving the PLAG1 gene, which is known to rearrange with numerous unique fusion partners. Herein, we present two additional cases of so-called maturing lipoblastoma with a review of the literature. Both tumors occurred in adult females and both harbored a yet-unreported DLEU2::PLAG1 fusion transcript. Clinically, both tumors behaved in a benign fashion. The histology was characterized by a prominence of fibroblastic growth with only partial or minimal lipomatous components. This report serves to provide additional characterization of the clinical, histologic, and molecular features of this rare tumor type.

• Klíčová slova
• DLEU2, PLAG1, adult lipoblastoma, lipoblastoma, mature lipoblastoma,
• MeSH
• DNA vazebné proteiny * genetika   MeSH
• dospělí MeSH
• fibroblasty patologie   MeSH
• fúzní onkogenní proteiny genetika   MeSH
• genová přestavba * MeSH
• lidé středního věku MeSH
• lidé MeSH
• lipoblastom * genetika   patologie   MeSH
• nádorové supresorové proteiny * genetika   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• Názvy látek
• DNA vazebné proteiny * MeSH
• fúzní onkogenní proteiny MeSH
• nádorové supresorové proteiny * MeSH
• PLAG1 protein, human MeSH Prohlížeč

BACKGROUND: Perivascular epithelioid cell tumours (PEComas) constitute a unique group of neoplasms with a distinctive myomelanocytic immunohistochemical phenotype and uncommonly occur in the head and neck region. We herein report the clinicopathologic features of a case of a sinonasal PEComa occurring in an 18-year-old male with a novel TRAF3::TFE3 fusion. CASE PRESENTATION: The patient presented with an infiltrative nasal cavity tumour. Histologic examination showed a tumour composed of sheets and nests of epithelioid cells with clear to eosinophilic granular cytoplasm, round to oval nuclei, inconspicuous nucleoli and no mitotic activity. The tumour cells featured strong diffuse expression of smooth muscle actin and nuclear TFE3, with patchy expression of HMB45. Neoplastic cells showed no immune-reactivity for Melan A. Molecular genetic analysis revealed a novel TRAF3(ex8)::TFE3(ex6) fusion. CONCLUSIONS: This report contributes to the expanding molecular spectrum of TFE3-altered PEComas of the head and neck region and discusses the differential diagnoses of these tumours. We further describe the evolving understanding of TFE3-altered PEComas.

• MeSH
• faktor 3 asociovaný s receptory TNF * genetika   MeSH
• fúzní onkogenní proteiny * genetika   MeSH
• lidé MeSH
• mladiství MeSH
• nádory nosu * genetika   patologie   MeSH
• nádory z perivaskulárních epiteloidních buněk * genetika   patologie   MeSH
• nosní dutina patologie   MeSH
• transkripční faktory BHLH-Zip * genetika   metabolismus   MeSH
• Check Tag
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• přehledy MeSH
• Názvy látek
• faktor 3 asociovaný s receptory TNF * MeSH
• fúzní onkogenní proteiny * MeSH
• TFE3 protein, human MeSH Prohlížeč
• TRAF3 protein, human MeSH Prohlížeč
• transkripční faktory BHLH-Zip * MeSH

Dermatofibrosarcoma protuberans (DFSP) is a locally infiltrative mesenchymal neoplasm usually characterized by a COL1A1::PDGFB fusion. A minority of DFSPs have recently been shown to harbor alternative fusions, involving the PDGFD gene. The aim of this case series and literature review is to highlight the clinicopathologic and molecular features of PDGFD-rearranged DFSPs. Eighteen patients (twelve females and six males) with PDGFD-rearranged DFSPs were collected from the authors' institutional archives. Eight (44%) cases harbored a COL6A3::PDGFD fusion, five (28%) an EMILIN2::PDGFD fusion, and two (11%) an EMILIN1::PDGFD fusion. In three (17%) cases, the fusion partner was unknown. A literature review revealed 29 additional cases. Cumulatively, four alternative fusion genes have been detected: COL6A3::PDGFD (24/47, 51%), EMILIN2::PDGFD (12/47, 26%), EMILIN1::PDGFD (2/47, 4%), and TNC::PDGFD (1/47, 2%). In eight (17%) cases, the fusion partner was unknown. Most (20/24, 83%) COL6A3::PDGFD-fused DFSPs occurred in females with only four (17%) cases described in males. Additionally, half of them (12/24, 50%) developed in the breast/chest wall. EMILIN2::PDGFD-fused DFSPs often occurred in males, were located in the extremities (9/12, 75%), exhibited fibrosarcomatous transformation (9/12, 75%), were confined exclusively or primarily to the subcutis (10/12, 83%), and had a well-circumscribed contour (10/12, 83%). Specific molecular alterations in DFSPs correlate with certain clinicopathologic features. Notably, EMILIN2::PDGFD-fused DFSPs have a slight predilection for males, develop almost exclusively in the subcutis, tend to be well-circumscribed, and often exhibit fibrosarcomatous transformation, while COL6A3::PDGFD-fused DFSPs might have a predilection for the breast/chest wall of female patients. To the best of our knowledge, this is the first report of EMILIN1::PDGFD-fused DFSP.

• Klíčová slova
• EMILIN1, PDGFD, DFSP, Dermatofibrosarcoma protuberans,
• MeSH
• dermatofibrosarkom * genetika   patologie   MeSH
• destičkový růstový faktor MeSH
• dítě MeSH
• dospělí MeSH
• fúzní onkogenní proteiny * genetika   MeSH
• genová přestavba * MeSH
• lidé středního věku MeSH
• lidé MeSH
• lymfokiny * genetika   MeSH
• membránové glykoproteiny * genetika   MeSH
• mladiství MeSH
• mladý dospělý MeSH
• nádorové biomarkery * genetika   MeSH
• nádory kůže * genetika   patologie   MeSH
• senioři MeSH
• Check Tag
• dítě MeSH
• 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
• přehledy MeSH
• Názvy látek
• destičkový růstový faktor MeSH
• elastin microfibril interface located protein MeSH Prohlížeč
• fúzní onkogenní proteiny * MeSH
• lymfokiny * MeSH
• membránové glykoproteiny * MeSH
• nádorové biomarkery * MeSH
• PDGFD protein, human MeSH Prohlížeč

This investigation describes the clinicoradiologic, pathologic, and molecular features of a unique soft tissue tumor characterized by a peripheral shell of bone and composed of bland myoid spindle and epithelioid cells that are keratin-positive. Our study cohort consists of 6 men and 6 women, with a mean age of 32 years. The tumors arose in the extremities (n = 9) and proximal limb girdle (n = 3) and were equally distributed between deep and superficial soft tissues. Patients reported dull painless masses of several months to >10 years duration (mean: 2.9 years). Imaging demonstrated a complete or partial peripheral shell of bone that could extend centrally, and the tumor's mean size was 5.7 cm. Histologically, the tumors were composed of uniform, eosinophilic myoid spindled cells growing in sheets and intersecting fascicles, surrounded by mature lamellar and/or woven bone. Also present was an admixed component of intermediate-sized epithelioid cells with eosinophilic cytoplasm. Mitotic activity was consistently low. Immunohistochemistry showed strong multifocal staining for keratins, and 50% (5/10) showed focal staining for S100; however, all were negative for SMA, desmin, SOX10, ERG, and CD34. Genetic analysis by multiple targeted RNA sequencing panels was negative (n = 10); however, whole transcriptome sequencing (n = 8) revealed a recurrent and novel in-frame SRSF7::NFATC3 fusion in 4 tumors. Dual fluorescence in situ hybridization probes for SRSF7::NFATC3 successfully confirmed this fusion and identified a fifth case, which had not undergone whole transcriptome sequencing but was negative by a targeted RNA fusion panel. Methylation profiling (n = 8) demonstrated a shared epigenetic profile distinct from other entities. Clinical follow-up (n = 11) showed no evidence of recurrence after primary excision with a mean of 41.6 months. In summary, we describe a novel soft tissue tumor designated "ossifying spindled and epithelioid tumor" as a descriptive histologic term that also emphasizes its close radiologic mimic, ossifying fibromyxoid tumor. All cases have behaved in a benign fashion without recurrence following simple excision. Awareness of this entity is important, so that it can be distinguished from other neoplasms that have more aggressive biological potential.

• Klíčová slova
• SRSF7::NFATC3, myositis ossificans, ossifying fibromyxoid tumor, ossifying spindled and epithelioid tumor, radiology, soft tissue tumor,
• Publikační typ
• časopisecké články MeSH

Molecular classification of endometrial carcinomas (EC) divides these neoplasms into four distinct subgroups based on their molecular background. Given its clinical significance, genetic examination is becoming integral to the diagnostic process. This study aims to share our experience with the molecular classification of EC using immunohistochemistry (IHC) and next-generation sequencing (NGS). We included all ECs diagnosed at two institutions from 2020 to the present. All cases were prospectively examined by IHC for MMR proteins and p53, followed by NGS using a customized panel covering 18 genes, based on which ECs were classified into four molecular subgroups: POLE mutated, hypermutated (MMR deficient), no specific molecular profile (NSMP), and TP53 mutated. The cohort comprised 270 molecularly classified ECs: 18 (6.6%) POLE mutated, 85 (31.5%) hypermutated, 137 (50.7%) NSMP, and 30 (11.1%) TP53 mutated. Twelve cases (4.4%) were classified as 'multiple classifier' EC. Notably, most of these cases with available follow-up (6/9) behaved aggressively. Within the POLEmut EC group, 3/4 cases had advanced tumors, including one patient who died of the disease. Similarly, in the MMRd/TP53mut group, 3/5 patients with available follow-up had metastatic disease, leading to death of the patient in 1 case. ECs of NSMP showed multiple genetic alterations, with the most common mutations being PTEN (44% within the group of NSMP), followed by PIK3CA (30%), ARID1A (21%), and KRAS (9%). Our findings suggest that combining immunohistochemistry with NGS offers a more reliable classification of ECs, including 'multiple classifier' cases, which, based on our observations, tend to exhibit aggressive behavior. Additionally, our data highlight the complex genetic background of NSMP ECs, which can facilitate further stratification of tumors within this group and potentially help select patients for dedicated clinical trials.

• Klíčová slova
• Endometrial carcinoma, Molecular classification, Multiple classifier, Next-generation sequencing,
• MeSH
• dospělí MeSH
• imunohistochemie MeSH
• lidé středního věku MeSH
• lidé MeSH
• mutace MeSH
• mutační analýza DNA MeSH
• nádorové biomarkery * genetika   analýza   MeSH
• nádorový supresorový protein p53 genetika   MeSH
• nádory endometria * genetika   patologie   klasifikace   MeSH
• prospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• vysoce účinné nukleotidové sekvenování * 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
• Názvy látek
• nádorové biomarkery * MeSH
• nádorový supresorový protein p53 MeSH
• TP53 protein, human MeSH Prohlížeč