TEST:

Archer® FusionPlex® Sarcoma kit

When myositis ossificans presents with typical clinical history and a clear zonal pattern on imaging, diagnosis is relatively straightforward. However, in early lesions without typical clinical features the diagnosis may be more challenging and sometimes requires a biopsy. Our case shows that FNAB with supported by immunocytochemistry and RNA genotyping proving COL1A1::USP6 fusion allows accurate diagnosis in less than 6 days and implicates the potential use of molecular methods on FNAB samples of soft tissue lesions.

After unsuccessful chemotherapy, Alectinib (ALK inhibitor) combined with radiotherapy was initiated... Intraosseous spindle cell rhabdomyosarcoma (RMS) with TFCP2 rearrangement is a highly aggressive tumour with an early onset, fast progression and poor response to standard therapies. Our case, one of the few cases described with two gene fusions, contributes to understanding its molecular profile. Further clinical studies are required to explore the efficacy of targeted therapy for ALK and for the development of new effective treatment approaches.

Atypical SS18-break apart FISH pattern with loss of green signal should be interpreted as a peculiar unbalanced rearrangement of the SS18 gene and subsequent SS18-SSX fusion (IHC or/and NGS) test should be recommended in such cases. Reseach are partially supported by grant of the The National Centre for Research and Development no. GOSPOSTRATEG-VI/0016/2021.

Identifying patients with NTRK gene fusions is crucial, as they could benefit from targeted therapy using TRK inhibitors. This requires a detailed description of emerging entities like NTRK-RSCNs because testing for NTRK rearrangement is not routinely performed. In two cases, we report a spectrum of histological grades, including a high-grade phenotype.

Rhabdomyosarcomas are a heterogenous group of malignant neoplasms rarely occurring in adults. Immunohistochemical ALK-positivity has been described in RMS, however underlying ALK rearrangements are rare events. This is the first case harboring THBS1::ALK fusion, which was previously described in inflammatory myofibroblastic tumours.

Our cases on atypical presentations of SS shows unusual morphological, immunophenotype, and molecular features. We consider it relevant to include SS as a differential diagnosis when faced with pseudo-vascular/alveolar patterns. Even in cases with more typical morphology of SS, there is a possibility of finding negative results in either IHC or FISH techniques due to cryptic or complex rearrangement.

Fibroblastic reticular cell tumour (FRCT) is a rare tumour with 21 cases reported in the literature. FRCTs are characterized by cells arranged in a whorls, fascicles or sheets accompanied by lymphoplasmacytic infiltrate. FRCT shows overlapping morphological features with follicular dendritic cell sarcoma (FDCS) and interdigitating dendritic cell sarcoma (IDCS).

In this particular case, the immunohistochemical and molecular results support a diagnosis of a fibroblastic/myofibroblastic tumour of uncertain behaviour. Notably, there have been no reported cases in the literature of a soft tissue tumour harboring FGFR1::TACC1 fusion as a primary occurrence in this anatomical location. The patient remains in good health without any evidence of disease recurrence at the 5-month follow-up post-surgical intervention.

Our findings support the notion that among soft-tissue neoplasms with fibroblastic/myofibroblastic phenotype, USP6 rearrangement is not limited to benign tumours, and warrants further investigation of genetic changes in myofibroblastic sarcomas.

"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%)."

Various NGS technologies and platforms are increasingly used in oncology centers, primarily for therapeutic indications. Unlike most cancer types, the indication of NGS to provide some aid in diagnosis is paradigmatic in the case of sarcomas, given the pleiad and complexity of the histotypes of sarcomas. On the other hand, the therapeutic options for patients with sarcoma are limited, and NGS testing offers the promise of finding targetable alterations.

Our study revealed 6 new cases of quadruple wild-type GIST or GIST-like tumors with possible oncogenic driver alterations (2.4 % of all our archival cases of GIST). While the case with BCOR-CCNB3 fusion rather represents a CD117-positive GIST-like BCOR -rearranged sarcoma, the remaining 5 cases probably belong to the category of true quadruple wild-type GIST. Whereas mutations in MAX and TP53 were already described previously, we are not aware of any study reporting on mutations of ATM , GNAQ and NUP93 in GIST.

"Integrated DNA Technologies, Inc....announced it closed on the purchase of Next Generation Sequencing (NGS) research assays from Invitae Corporation (NYSE: NVTA) under the trademarked name Archer. The integration of IDT’s portfolio with the acquired NGS research assays—which have been foundational in researching novel cancer fusions—will empower labs with an all-in-one solution to uncover biomarkers and advance cancer discoveries. The transaction enables IDT to expand its existing operations, build upon the legacy Archer portfolio, and welcome more than 100 new associates globally....Transaction Details-IDT purchased Archer NGS research assays—which reported high double-digit growth since 2019—from Invitae for cash consideration of approximately $48 million, subject to certain adjustments. The transaction is structured as an asset deal and includes a license to intellectual property related to the AMP technology."

Altogether, this is a rare and diagnostically challenging case of a uterine sarcoma harbouring a novel GLI1 fusion. Emerging GLI/Hedgehog inhibitors provide clinical relevance to recognising these tumours in modern pathology.

However, in 18 cases, fragmentation was strong, and high-quality libraries could not be obtained. Nevertheless, comprehensive analysis of fusion genes with high sequence specificity by NGS can be a powerful alternative to reverse transcription-polymerase chain reaction and fluorescence in situ hybridization methods.

There is a wide variety of uterine mesenchymal tumours whose understanding improved thanks to recent advances in molecular biology, that allowed to define a new group of uter-ine fibrosarcoma like neoplasms. It includes a new entity with COL1A1- PDGFB fusion, with only 4 cases reported in the lit-erature and not yet described in the WHO classification of female genital tumours. At the time of this work, our patient is doing well, waiting for a radiological examination and neovaginal dehiscence surgery.

Frozen section evaluation of chondroid lipomas present diagnostic challenges. Detection of MKL2 gene fusion is helpful in distinguishing this rare pseudosarcomatous entity from its morphologic differentials and in guiding appropriate patient management.

Infantile fibrosarcoma is a tumour classically known to be characterized by ETV6-NTRK3 gene fusion, may have other genetic mutations including EGFR gene rearrangement. Prognostic significance of this new mutation is yet unknown.

Along with the previously reported frequent EWSR1 and other rare fusion partners, PRRC1 can also be a fusion partner of NR4A3 in extraskeletal myxoid chondrosarcoma.

To the best of our knowledge, this forms the third report of GLI1-rearranged uterine sarcoma. Previous reports showed low-grade epithelioid morphology and harboured canonical fusions (ACTB-GLI1, PTCH1-GLI1). In contrast, this case shows high grade, predominantly spindled morphology and harbours a novel fusion, PAMR1-GLI1.

Chemotherapy was administrated to 36/41 patients (Ewing sarcoma drugs in 16/22 CIC-DUX-4 and 8/11 BCOR-CCNB3; osteosarcoma drugs in 2/11 BCOR-CCNB3, and doxorubicin/ifosfamide in 2/22 CIC-DUX4 and 2/5 URCS; not specified in 6 cases). Prevalence of URCS characterized by a combination of morphologic observation ad molecular techniques is provided. The majority of the cases underwent surgery or surgery combined with radiotherapy, and Ewing-like chemotherapy. The survival difference among different entities underscores the need of accurate subclassification of round cell sarcomas.

"While the MYH9 gene was the most common partner for USP6 in this study, the MYH9-USP6 transcript was present in less than half of this limited cohort. To our knowledge, the HDLBP-USP6 fusion identified represents a yet undescribed fusion in NF. Furthermore, while a SPARC-USP6 fusion transcript has been previously identified in a conventional FTS, we report a SPARC-USP6 fusion in a cellular FTS, illustrating the morphologic and molecular diversity of these lesions."

In this study, we identified a novel GLI1 fusion in a low-grade ESS that metastasized. ACTB:GLI1 and PTCH1:GLI1 fusions were previously described in a series of ESS (Brahmi et al., Cancers 2020), but authors related them to other soft tissue tumors. Further studies will determine if GLI1 fusions represent a prognostic biomarker and potential target in low-grade ESS.

Undifferentiated round cell sarcoma can be further characterized by a combination of morphologic observation ad molecular techniques, which is also helpful in differentiating them from Ewing sarcoma. The survival difference among different entities underscores the need of their accurate subclassification.

Our IHC and molecular results support the hypothesis that the studied cases are indeed related to C-MIFS. Recognizing HG variant of MIFS may prevent undercalling cases with HG areas but predominantly C-MIFS morphology as low-grade sarcomas. Moreover, it seems that BRAF rearrangements are significantly more common in tumors with HG MIFS morphology than in myxofibrosarcomas.

Intracranial mesenchymal tumors which harbor a FET-CREB fusion have shown a wide range of morphologic features. Here, we present four cases with variable appearances and morphologic findings mimicking other neoplastic and non-neoplastic processes.

We demonstrated the continuing utility of RT-PCR/qRT-PCR, FISH and NGS for tumor diagnosis, and that each has advantages in specific contexts. These ancillary molecular tests are important tools in both defining and excluding diagnoses of tumors. Despite the fact that false-negative results due to poor quality samples can be encountered, these methods demonstrated excellent diagnostic utility for translocation detection in bone and soft tissue tumors.

"An ALK-CARS fusion was found, supporting the diagnosis of IMT. This report emphasizes the added value of broad molecular analysis in cases with unusual clinical presentation, equivocal immunohistochemistry, and a wide differential diagnosis."