There is a need to improve the translation of gastric cancer molecular classification schemes, such as those proposed by the Cancer Genome Atlas (TCGA) and Tumour Microenvironment score (TME), to clinical specimens and three-dimensional organoid culture models. In this study, we validate a 107-gene Nanostring assay informed by previously established machine learning models using a prospective cohort of gastric adenocarcinoma tumours and tumour-organoid pairs. Thirty-eight gastric adenocarcinoma specimens and twelve parent tumour-tumour organoid pairs were assigned TCGA and TME subtypes using gene expression measured by our custom Nanostring gene set. Subtypes were validated using gold-standard tests for Epstein-Barr virus (EBV) and microsatellite instability (MSI). Molecular subtype scores were compared to known clinicopathologic characteristics. The correlation between dose-response and molecular subtypes using an organoid drug assay and the Cancer Cell Line Encyclopedia (CCLE) was investigated. TCGA and TME subtypes were successfully applied to all specimens. The relationship of molecular subtype scores in our population compared to public cohorts was statistically identical for Lauren Class and Signet Ring status. Our method achieved 100% accuracy in labeling EBV and MSI subtypes. We identified 81.8% and 63.6% concordance between parent tumour-tumour organoid pairs for TME and TCGA subtypes, respectively. No significant correlation was identified between dose response to chemotherapy and molecular subtype scores. Analysis of the CCLE identified promising personalized therapy candidates for each molecular subtype. Our 107-gene Nanostring test successfully assigns TCGA and TME molecular subtypes to clinical tumour and tumour organoid samples for use in future study.

Afatinib, an irreversible pan-ERBB family inhibitor, has demonstrated promising efficacy in non-small cell lung cancer (NSCLC) patients with uncommon EGFR activating mutations. However, besides the acquisition of the secondary T790M mutation, other resistance mechanisms to afatinib remain to be explored.

Ossifying fibromyxoid tumor (OFMT) is an extremely rare mesenchymal tumor of uncertain differentiation having a potential for local recurrences and metastasis. OFMT can be classified as typical, atypical, and malignant tumors based on nuclear grade, cellularity, and mitotic rate. However, predicting the biological behavior remains challenging. We report one of these challenging cases of OFMT with metastases after 19 years. The primary tumor did not show morphologic characteristics of malignancy. We performed targeted RNA sequencing, copy number variation (CNV) analysis on all lesions and additional DNA methylation profiling.

Many cutaneous adnexal tumors share molecular alterations with other homologous neoplasms occurring in salivary glands. Polymorphous adenocarcinoma (PAC) is a rare salivary gland tumor, usually associated with alterations in the PRKD gene family. In this report, we describe a primary cutaneous sweat gland adenocarcinoma of the scalp occurring in a 65-year-old female. Morphological features of the carcinoma were reminiscent of salivary gland PAC. Tumor cells were CK7+ S100+ SOX10+ p63 focally positive and p40-. Whole-transcriptome sequencing of the lesion showed the presence of an in-frame ATL2::PRKD3 fusion. PRKD1, 2 or 3 fusions are characteristic of the cribriform subtype of PAC (cribriform adenocarcinoma of salivary gland, CASG). No past history of salivary gland tumor nor existing salivary gland tumor was retrieved in the patient. After complete excision of the tumor, the patient has been in complete remission for 17 months. This case suggests that a subset of adnexal adenocarcinomas of not otherwise specified type (NOS) may carry PRKD alteration and may constitute the cutaneous counterpart of salivary gland PAC/CASG. This finding argues in favor of a more systematic molecular exploration of adnexal adenocarcinomas NOS for better classification and prognosis.

TRAF7 mutations have been reported in many tumor types, including subsets of meningiomas, mesothelioma, intraneural perineuriomas, and rare cases of aggressive fibromyxoid spindle cell tumors in adults. We expand the spectrum of TRAF7-mutated tumors by reporting a case of a TRAF7-mutated myxoid and spindle cell mesenchymal tumor in a 13-year-old female with a history of a heart and renal transplant. Histopathologic examination demonstrated hypocellular areas composed of bland spindle cells in a myxoid matrix and hypercellular areas with significant pleomorphism and up to 13 mitotic figures per 10 high-power fields. The spindle cells were positive for CD34 and negative for smooth muscle actin (SMA) and S100. Whole exome sequencing identified a TRAF7 p.S561R mutation. Methylation profiling illustrated that the tumor did not embed within a distinct tumor group. The tumor was resected, and the patient remains stable at 7 months follow-up. This report is the first known case of a TRAF7-mutated myxoid and spindle cell tumor in a pediatric patient.

Dermatofibroma/fibrous histiocytoma is a common tumor of the dermis, composed of myofibroblasts, dendrocytes, and macrophages with characteristic entrapment of dermal collagen fibers at the periphery of the tumor. Various subtypes of dermatofibroma, including cellular, aneurysmal, and atypical dermatofibroma, are associated with an increased risk of recurrence, especially with incomplete excision. Two cases of benign fibrous histiocytoma with recurrence and metastasis are described. Patient 1 had a cellular fibrous histiocytoma with KIRREL1::PRKCD fusion presenting as a superficial and deep soft tissue mass involving the scapula and lateral clavicle. Patient 1 subsequently developed metastasis to the chest wall and thigh. Patient 2 had a recurrent aneurysmal fibrous histiocytoma with LAMTOR1::PRKCD fusion presenting as a large shoulder mass with invasion of the clavicle and lymph node metastasis. Patient 2 developed rapid local recurrence and PET-avid pulmonary nodules, radiologically consistent with metastasis. Fibrous histiocytoma is typically a morphologically benign neoplasm that only rarely exhibits clinically aggressive behavior with multiple recurrences and metastases. Although uncommon, recognition of this entity is important so that pathologists and sarcoma oncologists can ensure accurate diagnosis, multidisciplinary management, and appropriate clinical surveillance. In addition, complex chromosomal abnormalities may serve as useful indicators of fibrous histiocytoma with the risk of aggressive clinical behavior.

We report a unique case of a 57-year-old man with a gastrointestinal stromal tumor (GIST) that developed a high-grade phenotype and additional genetic alterations in the subsequent recurrence. Histologically, the initial resected tumor showed a typical morphology with uniform spindle-shaped cells arranged in fascicular and whorling patterns. However, based on large tumor size and mitotic activity it was designated as high risk. Tumor cells were immunoreactive for CD117 and DOG1. Mutational analysis identified no KIT or PDGFRA hotspot mutations. Next-generation sequencing (NGS) further demonstrated an NF1 mutation (c.1466A>G) without KIT or PDGFRA mutations. In contrast, the recurrent tumor displayed a higher-grade morphology. Tumor cells were positive for MDM2, while showing decreased expression for CD117 and DOG1. NGS and molecular assays detected no KIT or PDGFRA mutations, but confirmed the NF1 mutation (c.1466A>G). In addition, NGS identified MDM2 and MYC amplification. This is the first report describing an NF1-mutant GIST harboring coamplification of MDM2 and MYC and associated with a higher-grade tumor progression.

Pediatric low-grade gliomas (pLGG) are the most common group of childhood brain tumors. Genetic alterations in the RAS-RAF-mitogen-activated protein kinase (MAPK) pathway are the molecular drivers in the vast majority of pLGG. A large proportion of pediatric pLGG are characterized by the presence of fusion genes. An institutional molecular analysis together with an RNA-NGS study was performed to reveal LGG-associated molecular alterations. In our cohort of pLGG patients, molecular alterations were identified in 318 out of 342 cases (92.9%) through a combination of RT-PCR, Sanger sequencing, and NGS methodologies. Fusion events were independently called using three fusion callers: Archer Analysis 6.0 and/or 7.0, Arriba version 2.4, and STAR-Fusion 24. Among these, STAR-Fusion had the lowest sensitivity, detecting rearrangements in only 67% of fusion-positive cases. In contrast, Arriba detected rearrangements in 97.77% of cases, while Archer detected rearrangements in 88.6% of cases. These findings highlight differences in detection efficiency among fusion callers, emphasizing the importance of tool selection in molecular diagnostics. The detection of fusion genes is very important for correct diagnosis, prognosis, and adequate targeted treatment.

EWSR1::CREM fusion positive intrabdominal sarcomas defines a rare emerging group of aggressive mesenchymal neoplasms with a predilection for the celomic cavity and often manifesting perplexing immunophenotypic profile. There is no specific standard of care therapeutic option though anecdotal reports response to pazopanib have been reported. We report herein a case of a 62-year-old lady who presented with lower abdominal mass and pain. Right hemicolectomy performed showed a malignant epithelioid neoplasm. By immunohistochemistry, the tumor cells were positive for CD117, keratins, and mutation analysis was positive for KIT p.V5301 mutation, initially prompting a diagnosis of epithelioid gastrointestinal stromal tumor. However, the patient developed omental relapses while on imatinib and progressive disease persisted despite change to sunitinib. A re-review of the histopathology of both the hemicolectomy and relapsed omental sites showed marked cellular atypia, increased cellularity and mitosis in metastatic omental sites. By immunohistochemistry, the tumors in addition to CD117 positivity were also immunoreactive to keratins, synaptophysin, chromogranin, CD56, and MUC4. Next generation sequencing performed on both the primary and relapsed sites were positive for EWSR1::CREM gene fusion in addition to the KIT. P.V5301 mutation. The tumor was then reclassified as EWSR1::CREM fusion positive intrabdominal unclassified epithelioid sarcoma with concomitant KIT mutation of unknown significance. The patient was treated with cytotoxic chemotherapy and radiation therapy with partial response, but treatment was stopped because of complications and lack of tolerance. Pazopanib as a single agent was then initiated, and patients have continued to respond for the past 7 months. We highlight the significant immunophenotypic heterogeneity in these tumors and perform an extensive review of the literature of this specific entity and broader group of EWSR1::CREM/FUS fusion positive tumors ranging from quasi-benign to malignant and finally we underscore the therapeutic utility of pazopanib as a single agent in this rare group of aggressive sarcomas.

Myxoid liposarcoma (MLS) accounts for 20%-30% of all liposarcomas, with most cases harboring the fusion gene FUS::DDIT3, while approximately 5% exhibit the EWSR1::DDIT3 fusion. We report the case of a 26-year-old male patient with a right upper arm mass. The tumor displayed the classic histological features of MLS, including small spindle/ovoid cells, variable univacuolated lipoblasts, and a prominent myxoid stroma with delicate arborizing vasculature. Despite these characteristic features, fluorescence in situ hybridization (FISH) revealed no apparent rearrangement of the DDIT3 locus. Next-generation sequencing (NGS) identified a novel fusion transcript in which SMARCA2 exon 4 was fused in-frame with DDIT3 exon 2. Chromosomal microarray analysis demonstrated the unbalanced nature of the rearrangement, with partial deletions of 0.243 and 0.176 Mb flanking the centromeric end of the DDIT3 locus on 12q13.3 (which also included GLI) and disrupting the SMARCA2 locus on 9p24, respectively. The resultant chimeric fusion protein is predicted to lack the SMARCA2 DNA-binding domains while retaining the DDIT3 leucine zipper dimerization domain. These findings indicate an unusual and complex rearrangement, leading to the recruitment of a novel DDIT3 partner gene. Moreover, they emphasize that the functional aspects of myxoid liposarcoma fusion genes depend on the retention of the key DDIT3 domain. Finally, this case illustrates how classic morphology can appropriately trigger reflex molecular analyses, which may, in turn, uncover novel fusion genes or other molecular alterations.

Conventional and dedifferentiated chondrosarcoma encompass a group of malignant neoplasms that produce cartilaginous matrix and arise within or on the surface of bone. Conventional chondrosarcomas are graded on a three-tiered scale, whereas dedifferentiated chondrosarcoma is typically not graded but is considered a high-grade sarcoma and represents the most aggressive subtype with a poor prognosis. IDH1 (isocitrate dehydrogenase-1) and IDH2 (isocitrate dehydrogenase-2) are the most commonly mutated genes in conventional and dedifferentiated chondrosarcoma, followed in frequency by COL2A1 and TP53. IDH1/2 driver mutations are also commonly found in enchondroma, considered a benign precursor lesion of chondrosarcoma, and other malignancies such as gliomas, cholangiocarcinoma, and acute myeloid leukemia. In acute myeloid leukemia, the presence of concurrent BCOR (BCL-6 corepressor) loss-of-function mutations has been linked to disease relapse and resistance to treatment with IDH inhibitors. After identifying an index case of conventional chondrosarcoma with unusually aggressive clinical evolution, we investigated the clinicopathological features of 12 cases of BCOR-mutated conventional and dedifferentiated chondrosarcomas against a control group of 15 BCOR-wildtype (WT) cases to determine whether BCOR-mutated tumors had patterns of biological progression different from tumors with intact BCOR. All identified BCOR alterations led to loss-of-function by either missense or nonsense mutations. The prevalence of BCOR mutations occurred in 5% of conventional and dedifferentiated chondrosarcoma, and these were associated with larger tumor size (p = 0.024), metastasis at the time of diagnosis (p ≤ 0.001) and higher T category (3-4 vs. 1-2) (p = 0.009). Although larger studies are necessary to clarify the full impact of BCOR mutations on patients with conventional and dedifferentiated chondrosarcoma, our data indicate that BCOR genetic aberrations are associated with adverse clinical features.

With the increasing use of next-generation sequencing, the classification of heretofore unclassified neoplasms is evolving rapidly. Specifically, gene fusions have emerged as context-specific defining genetic markers for an increasing number of entities, mostly of soft tissue, bone, and salivary gland origin. We describe four myoepithelial-like neoplasms of salivary (two) and pulmonary (two) origin, carrying recurrent NFATC2 fusions involving NUTM2B (three) and NUTM2A (one) as fusion partners. Patients were two females and two males aged 24-67 years (median, 33). The tumor size ranged from 1 to 4.5 cm. Treatment was surgery without (three) or with (one) adjuvant radiochemotherapy. No metastases or other primary tumors were found at the time of diagnosis. Three patients with follow-up (two with salivary, one with pulmonary tumor) were disease-free at 9, 11, and 31 months. Original diagnoses were "unclassified neoplasm" with consideration of adamantinoma-like Ewing sarcoma and myoepithelial neoplasm. Histology revealed infiltrating monotonous epithelioid to basaloid cells arranged into lobular aggregates, nests, and cords within variably sclerosed stroma containing extensive basement membrane-like hyaline material. Frankly malignant features (malignant cytology, high mitotic activity, necrosis, perineural or lymphovascular invasion) were absent. IHC showed coexpression of low and high molecular weight keratins (AE1/AE3 and CK5/6; 4/4), EMA (2/2), and CD99 (2/2). Negative markers included p63 (0/4), NUT (0/4), S100 (0/4), SOX10 (0/4), p40 (0/2), and SMA (0/2). This study introduces a novel salivary and lung tumor entity driven by NFATC2::NUTM2A/B fusions and displaying myoepithelial-like morphology but imperfect myoepithelial immunophenotype. Report of more cases should shed light on the biological properties and appropriate therapeutic strategies of this novel neoplasm.

The first induction therapy is critical in determining subsequent treatment strategies and patient outcomes in acute myeloid leukemia (AML). This study aimed to comprehensively analyze the genetic landscape of AML patients to construct risk prediction models for the first-treatment response.

B-cell precursor acute lymphoblastic leukemia (BCP-ALL) with the t(5;14)(q31;q32) chromosomal translocation resulting in an IGH::IL3 fusion is an exceptionally rare lymphoid malignancy presenting with hypereosinophilia. Germline PAX5 alterations, including sequence variants and deletions, are associated with a selective susceptibility to BCP-ALL and lymphomas, based on a limited number of affected families worldwide. Here, we report a 6-year-old male with BCP-ALL with the t(5;14)(q31;q32) translocation and harboring a novel constitutional PAX5 variant (NM_016734.3:c.[295dup];[=], p.[(Ile99Asnfs*3)];[(=)]). Despite the low representation of the leukemic clone in the bone marrow, the IGH::IL3 fusion was identified by both fluorescent in situ hybridization (FISH) and optical genome mapping (OGM). Although hypereosinophilia poses a risk of multiorgan damage, our patient exhibited only pneumonia and asymptomatic neuroimaging alterations in the central nervous system. The patient achieved remission by the end of induction and is currently continuing maintenance therapy. In line with existing literature, familial segregation of the PAX5 variant demonstrated high but incomplete penetrance, as two leukemia-free mutation carriers displayed only subclinical B lymphocyte maturation abnormalities without hypogammaglobulinemia. Our report underscores the diagnostic utility of OGM, which unequivocally demonstrated the characteristic translocation. Typically, BCP-ALL in affected family members exhibits secondary somatic aberrations involving the wild-type PAX5 allele, including structural variants or loss of heterozygosity (LOH) of chromosome 9p, as well as PAX5 somatic mutations. To our knowledge, this is the first human report aligning with animal models, which suggests that secondary alterations activating the JAK-STAT pathway may potentially contribute to leukemogenesis in a PAX5 mutation background.

KMT2A-rearranged sarcomas represent a heterogeneous group of tumors with clinical behaviors ranging from surgical cure to local recurrence and metastasis. Previously reported fusion partners include YAP1 and VIM: YAP1::KMT2A::YAP1 is associated with sclerosing epithelioid fibrosarcoma (SEF)-like histology, whereas VIM::KMT2A tumors exhibit a small round-to-spindle cell morphology. A third fusion, CBX6::KMT2A::PYGO1, was reported with a spindle-cell morphology somewhat different from the YAP1::KMT2A::YAP1 pattern. Here, we describe a novel LDB1::KMT2A fusion in a spindle-cell sarcoma. The case involves a 19-year-old male who presented with an 8 cm mass situated in the left erector spinae muscle. Histopathological examination revealed a biphasic pattern comprising hypercellular fascicular/matted regions and hypocellular fibroma-like areas. Immunohistochemistry revealed diffuse positivity for CD99, SATB2, cyclin D1, BCL2, TLE1, pan-TRK, and NKX2.2, with focal BCOR expression and a Ki-67 proliferation index of approximately 10%. The tumor was negative for MUC4, SS18-SSX, WT1, cytokeratin (CKpan), vimentin, CD34, S-100, SOX10, SMA, STAT6, desmin, and MyoD1. Comprehensive genomic profiling via next-generation sequencing (NGS) identified a novel LDB1::KMT2A fusion, involving exons 1-10 of LDB1 and exons 4-36 of KMT2A. The rearrangement was verified using fluorescence in situ hybridization (FISH) and reverse transcription PCR (RT-PCR) techniques. Additionally, a pathogenic BCOR frameshift mutation (c.3203dup, p.E1069Gfs*10) was identified. The patient underwent wide surgical excision and remains disease-free at a 5-month follow-up. This report presents the first known case of an LDB1::KMT2A fusion in a spindle-cell sarcoma, expanding the molecular spectrum of the emerging entity of KMT2A-rearranged sarcomas.

Mastermind-like transcriptional coactivator (MAML) gene fusions have been documented in Thymic Epithelial Tumors (TETs). Specifically, lysine methyltransferase 2A (KMT2A)::MAML2 gene fusions are associated with type B2 and B3 thymomas. Here, we report for the first time a young patient with invasive type B3 thymoma harboring a novel KMT2A::MAML3 gene fusion. MAML3 and MAML2 are paralogues. In addition to the classic type B3 thymoma histology, this article documents intratumor heterogeneity, characterized by a trabecular and fascicular pattern, as well as areas of clear cells. Immunohistochemistry showed keratin positivity in tumor cells, while neuroendocrine markers were negative in trabecular regions. DNA-based next-generation sequencing failed to identify pathogenic variants, but RNA sequencing detected the KMT2A::MAML3 gene fusion. We compared the gene fusion sites of MAML2 and MAML3, focusing on exon 2, and found that they share similar functional protein domains. Moreover, the same domain appeared downstream of the KMT2A::MAML2 fusion protein. Therefore, we hypothesize that MAML3 gene fusions, like MAML2, lead to abnormal Notch signaling pathways and increase the invasive potential of certain thymoma subtypes. Our findings expand the genetic landscape of aggressive thymomas and offer new insights for molecular studies in TETs.

We present a case of a 51-year-old male with a pseudoglandular cellular schwannoma arising from the brachial plexus, which contains the expected molecular aberrations for a schwannoma (chromosome 22q loss encompassing the NF2 and LZTR1 genes) as well as a FUS::KLF17 rearrangement. Pseudoglandular schwannomas are rare morphologic variants of schwannomas that contain gland-like spaces lined by S100-positive, cytokeratin-negative pseudocolumnar Schwann cells. Fusions involving FUS and EWSR are commonly found in myoepithelial tumors of bone and soft tissue. While the spectrum of tumors with fusions involving FUS and EWSR is relatively broad, no cases, to our knowledge, have been reported of schwannomas, let alone the morphologically distinct pseudoglandular schwannoma, containing a FUS rearrangement. This case thus expands the spectrum of FUS rearranged tumors, highlighting the need for documentation of similar cases to understand the clinical significance of this combination.

We report a uterine myxoid mesenchymal tumor with a novel SS18::VEZF1 gene fusion. The current lesion was identified in a 53-year-old woman who presented with symptomatic "fibroids" showing accelerated growth and heterogeneous morphology on radiologic assessment. Microscopic examination revealed a well-demarcated neoplasm, and the tumor exhibited alternating hypocellular/hyalinized and hypercellular areas, composed of a monomorphic proliferation of spindle, ovoid, and epithelioid cells arranged in sheets. These cells were embedded within either a hyalinized collagenous stroma or abundant myxoid stroma. Tumor cells were frequently located around blood vessels and exhibited amphophilic or eosinophilic cytoplasm and elongated or ovoid-shaped nuclei with coarsely clumped chromatin. No mitoses, pleomorphism, or necrosis was identified. Immunohistochemically, the tumor was positive for CD10, CD34, TLE1, estrogen, and progesterone receptors. It was negative for h-caldesmon, desmin, smooth muscle actin, smoothelin, myosin, cyclin D1, S100, ALK, EMA, panTRK, and SS18-SSX. Targeted RNA sequencing revealed an SS18::VEZF1 gene fusion (breakpoint: exon 9-exon 2), which was confirmed by FISH (SS18). In conclusion, RNA sequencing was useful in identifying the fusion event, thereby excluding potential mimics with uncommon morphology or ambiguous immunophenotype.

Molecular testing has significantly transformed the field of anatomic pathology over the past several decades. Despite these advances, acral mesenchymal neoplasms remain diagnostically challenging, requiring careful integration of clinical presentation, histologic features, and molecular findings for accurate classification. Herein, we present a case of an acral chondromyxoid mesenchymal neoplasm harboring a novel in-frame TCF4::ERG fusion involving the right index finger of a 26-year-old female. Morphologically, this tumor consisted of nests and sheets of monotonous small round-to-ovoid cells embedded in a background of chondromyxoid stroma and hyalinized collagen. The tumor cells were diffusely CD34, ERG, and focally p63 reactive, while S100 protein, cytokeratin AE1/AE3, Pan-TRK, ALK, smooth muscle actin, and desmin were negative. Albeit short follow-up (3 months), the patient continues to do well without evidence of metastasis or local recurrence.

Recurrent KMT2A and YAP1 related fusions have recently been reported in various mesenchymal neoplasms of different histogenesis. First, YAP1::KMT2A fusions have been described in a subset of MUC4-negative sclerosing epithelioid fibrosarcomas (SEF), while VIM::KMT2A fusions in a handful of cases associated with an undifferentiated spindle cell phenotype lacking stromal hyalinization. On the other hand, YAP1 gene rearrangements have been reported in a wide spectrum of sarcomas, including vascular neoplasms such as epithelioid hemangioendothelioma (EHE). Despite these molecular advances, occasional challenges in classification may occur even if the pathognomonic fusion is identified. In this study, we report such a case of a soft tissue sarcoma displaying an unusual morphology and immunoprofile, which remained unclassified even after a YAP1::KMT2A fusion was detected. The lesion occurred in the left leg of a 65-year-old female and microscopically closely resembled a SEF, with epithelioid morphology organized in cords, nests, and sheets in a heavy hyalinized background. Focally, the cells showed cytoplasmic vacuoles with eosinophilic material, reminiscent of the "blisters cells" seen in EHE. Moreover, by immunohistochemistry (IHC), the tumor showed diffuse reactivity for vascular markers, including ERG, CD31, CD34, and D2-40, as well as for TFE3, while being negative for MUC4, CAMTA1, smooth-muscle actin, desmin, S100 and keratins. Targeted RNA sequencing revealed a YAP1::KMT2A fusion. Based on this molecular result and the conflicting morphologic and IHC findings, a definitive distinction between a MUC4-negative SEF and an EHE could not been established. To further subclassify the lesion, subsequent clustering analysis using RNAseq signature was performed against a vast group of sarcoma types on the same array. Results showed that the tumor was in close proximity to the SEF group, admixed together with the other YAP1::KMT2A MUC4 negative SEF sarcomas. This case is highly instructive, as it shows another application of RNA sequencing in clinical practice when discordant or uncertain results between pathologic findings and fusion type may occur. Indeed, RNAseq signature could help, in this context, to better classify the tumor as a YAP1::KMT2A sarcoma instead of a vascular tumor. Larger series are needed to evaluate the pathogenesis of these tumors and the relevance of vascular markers expression.