scholarly journals Mesenchymal/non-epithelial mimickers of neuroendocrine neoplasms with a focus on fusion gene-associated and SWI/SNF-deficient tumors

2021 ◽  
Author(s):  
Atsuko Kasajima ◽  
Björn Konukiewitz ◽  
Anna Melissa Schlitter ◽  
Wilko Weichert ◽  
Jan Hinrich Bräsen ◽  
...  
Keyword(s):  
Fusion Gene ◽  
Soft Part ◽  
Neuroendocrine Neoplasms ◽  
Malignant Neoplasms ◽  
Gene Fusions ◽  
Complex Deficiency ◽  
Genetic Abnormalities ◽  
Mesenchymal Neoplasm ◽  
Epithelial Neoplasms ◽  
Fibrous Tumor

AbstractMimickers of neuroendocrine neoplasms (NEN) include a number of important pitfall tumors. Here, we describe our experience with mesenchymal mimics of NENs to illustrate their spectrum and draw the attention particularly to a group of mesenchymal/non-epithelial neoplasms (MN) that combine epithelioid histology with neuroendocrine (NE-) features and peculiar genetic abnormalities. In a consultation series of 4498 cases collected between 2009 and 2021, 2099 neoplasms expressing synaptophysin and/or chromograninA were reviewed and analyzed. A total of 364 (18%) were diagnosed as non-NENs, while the remaining tumors were NEN. The group of mesenchymal/non-epithelial neoplasms with NE-features (MN-NE) included 31/364 (8%) cases. These mostly malignant neoplasms showed an epithelioid morphology. While all but one tumor expressed synaptophysin, mostly patchy, only 10/29 (34%) co-expressed chromograninA. A total of 13/31 (42%) of the MN-NE showed EWSR1-related gene fusions (6 Ewing sarcomas, 5 clear cell sarcomas, and 1 desmoplastic small round cell tumor, 1 neoplasm with FUS-CREM gene fusion) and 7 (23%) were SWI/SNF (SMARCB1 or SMARCA4)-deficient neoplasms. The remaining MN-NE included synovial sarcoma, sclerosing epithelioid mesenchymal neoplasm, melanoma, alveolar soft part sarcoma, solitary fibrous tumor, and chordoma. A total of 27/31 MN-NE were from the last 8 years, and 6 of them were located in the pancreas. Eleven MN-NE were initially diagnosed as neuroendocrine carcinomas (NECs). MN-NE with epithelioid features play an increasing role as mimickers of NECs. They mostly belong to tumors with gene fusions involving the EWSR1 gene, or with SWI/SNF complex deficiency. Synaptophysin expression is mostly patchy and chromograninA expression is infrequent in MN-NE of this series and data extracted from literature.

Identification Of Strn-Ntrk2 Rearrangement In A High Grade Sarcoma, With Good Clinical Response To Firstline Larotrectinib Therapy

2020 ◽  
Vol 154 (Supplement_1) ◽  
pp. S79-S79
Author(s):  
R Lin ◽  
Z Wang ◽  
W Jiang ◽  
A Basu-Mallick
Keyword(s):  
Clinical Response ◽  
Day Treatment ◽  
Symptomatic Relief ◽  
Gluteus Medius ◽  
Fusion Partner ◽  
Gene Fusions ◽  
Good Clinical Response ◽  
Mesenchymal Neoplasm ◽  
Fibrous Tumor ◽  
The Right

Abstract Casestudy Gene fusions involving tropomyosin receptor kinase genes, NTRK (NTRK1-3), are important in tumorigenesis. Larotrectinib, a selective NTRK inhibitor, is recently approved to treat NTRK fusion positive solid tumors. We herein report a case of soft tissue sarcoma harboring two STRN-NTRK2 gene fusions, with good clinical response to firstline larotrectinib treatment. Results A 35 year-old female presented with pain in the right gluteal region, and a large solid mass without overlying erythema, edema and induration was identified. Initial MRI study showed a heterogenous, vascular and partially necrotic mass (16.5 x 12.9 x 10.4 cm) centered in the right gluteus medius and maximus muscles. A core biopsy of the mass showed a cellular mesenchymal neoplasm with round/ovoid cells, high mitosis (21 per 10 HPFs) and focal staghorn type vessels, reminiscent of solitary fibrous tumor. However, STAT6 immunostaining was negative. Additional immunostains show no specific lineage. Our in-house NGS fusion panel showed two in-frame STRNNTRK2 fusions, containing the same 5’ partner sequence (exon 1-3) of STRN, with the 3’ fusion partner starting from either the exon 15 or the exon 16 of NTRK2. Due to the large size and location of the tumor, larotrectinib was initiated as firstline therapy. The patient noticed a quick amelioration of tumor related pain, and a significant shrinkage of the size of tumor following the initial 7-day treatment. On post-treatment day 52, MRI showed the tumor significantly decreased in size to 7.7 x 7.4 x 6.6 cm with satisfactory symptomatic relief. Conclusion NTRK2 fusions are relatively rare when compared with NTRK1 and NTRK3, especially in sarcoma. Of note, the only other report in the literature of NRTK2 fusion- positive sarcoma also showed SFT-like morphology, and the patient responded well to larotrectinib as second line therapy.

Identification Of Strn-Ntrk2 Rearrangement In A High Grade Sarcoma, With Good Clinical Response To Firstline Larotrectinib Therapy

2020 ◽  
Vol 154 (Supplement_1) ◽  
pp. S76-S77
Author(s):  
R Lin ◽  
Z Wang ◽  
W Jiang ◽  
A Basu-Mallick
Keyword(s):  
Clinical Response ◽  
Day Treatment ◽  
Symptomatic Relief ◽  
Gluteus Medius ◽  
Fusion Partner ◽  
Gene Fusions ◽  
Good Clinical Response ◽  
Mesenchymal Neoplasm ◽  
Fibrous Tumor ◽  
The Right

Abstract Casestudy Gene fusions involving tropomyosin receptor kinase genes, NTRK (NTRK1-3), are important in tumorigenesis. Larotrectinib, a selective NTRK inhibitor, is recently approved to treat NTRK fusion positive solid tumors. We herein report a case of soft tissue sarcoma harboring two STRN-NTRK2 gene fusions, with good clinical response to firstline larotrectinib treatment. Results A 35 year-old female presented with pain in the right gluteal region, and a large solid mass without overlying erythema, edema and induration was identified. Initial MRI study showed a heterogenous, vascular and partially necrotic mass (16.5 x 12.9 x 10.4 cm) centered in the right gluteus medius and maximus muscles. A core biopsy of the mass showed a cellular mesenchymal neoplasm with round/ovoid cells, high mitosis (21 per 10 HPFs) and focal staghorn type vessels, reminiscent of solitary fibrous tumor. However, STAT6 immunostaining was negative. Additional immunostains show no specific lineage. Our in-house NGS fusion panel showed two in-frame STRN- NTRK2 fusions, containing the same 5’ partner sequence (exon 1-3) of STRN, with the 3’ fusion partner starting from either the exon 15 or the exon 16 of NTRK2. Due to the large size and location of the tumor, larotrectinib was initiated as firstline therapy. The patient noticed a quick amelioration of tumor related pain, and a significant shrinkage of the size of tumor following the initial 7-day treatment. On post-treatment day 52, MRI showed the tumor significantly decreased in size to 7.7 x 7.4 x 6.6 cm with satisfactory symptomatic relief. Conclusion NTRK2 fusions are relatively rare when compared with NTRK1 and NTRK3, especially in sarcoma. Of note, the only other report in the literature of NRTK2 fusion- positive sarcoma also showed SFT-like morphology, and the patient responded well to larotrectinib as second line therapy.

scholarly journals A Giant Solitary Fibrous Tumor of the Liver with Metastasis and Local Recurrence

2020 ◽  
pp. 18-23
Author(s):  
Mostafa Hoseini ◽  
Hossein Fahimi ◽  
Mohammad Vaziri ◽  
Farnaz Vosough ◽  
Borna Farazmand ◽  
...  
Keyword(s):  
Local Recurrence ◽  
Solitary Fibrous Tumor ◽  
Left Lobe ◽  
Solitary Fibrous Tumour ◽  
Malignant Neoplasms ◽  
Rare Type ◽  
Mesenchymal Neoplasm ◽  
Magnetic Resonance Imaging Mri ◽  
Fibrous Tumor ◽  
Upper Abdominal

Solitary fibrous tumor (SFT) is a rare type of mesenchymal neoplasm. Although the majority of SFTs are benign, some cases have shown characteristics of malignant neoplasms. Weight loss, fatigue, and upper abdominal bloating are the main signs of these lesions. Clinical and radiographic features are not sufficient for the diagnosis of hepatic SFT and the definitive diagnosis depends on histopathological sampling and immunohistochemistry. One of the main issues in the diagnosis of this tumour is the ability of this tumour to grow to large sizes. A 69-year-old male presented to the clinic 2 years earlier with episodes of hypoglycemia and loss of consciousness. The symptoms improved after receiving glucose. The patient diagnosed as rare solitary fibrous tumour of the liver, a giant (10 × 10 cm in diameter) round and well-defined lesion in the left lobe of the liver which was obvious in magnetic resonance imaging (MRI). Surgery is the most common line of treatment for this disease and there is no evidence regarding the effectiveness of other approaches. According to the scarcity of hepatic SFT, long-term prognosis in these patients is highly challenging. Here, we present the case of a 69-year-old male patient with hepatic SFT with metastasis and local recurrence. In the very rare malignant form of liver solitary fibrous tumour which is surgically unresectable, liver transplantation is one of the potential options but maybe not amenable due to the malignant behaviour of the disease. Role of debulking surgery is also not clear in this situation.

scholarly journals Current recommendations for clinical surveillance and genetic testing in rhabdoid tumor predisposition: a report from the SIOPE Host Genome Working Group

2021 ◽  
Author(s):  
M. C. Frühwald ◽  
K. Nemes ◽  
H. Boztug ◽  
M. C. A. Cornips ◽  
D. G. Evans ◽  
...  
Keyword(s):  
Working Group ◽  
Soft Part ◽  
Genetic Disorders ◽  
Panel Discussion ◽  
Rhabdoid Tumor ◽  
Host Genome ◽  
Cancer Surveillance ◽  
Malignant Neoplasms ◽  
Pathogenic Variants ◽  
Increased Risk

AbstractThe rhabdoid tumor (RT) predisposition syndromes 1 and 2 (RTPS1 and 2) are rare genetic conditions rendering young children vulnerable to an increased risk of RT, malignant neoplasms affecting the kidney, miscellaneous soft-part tissues, the liver and the central nervous system (Atypical Teratoid Rhabdoid Tumors, ATRT). Both, RTPS1&2 are due to pathogenic variants (PV) in genes encoding constituents of the BAF chromatin remodeling complex, i.e. SMARCB1 (RTPS1) and SMARCA4 (RTPS2). In contrast to other genetic disorders related to PVs in SMARCB1 and SMARCA4 such as Coffin-Siris Syndrome, RTPS1&2 are characterized by a predominance of truncating PVs, terminating transcription thus explaining a specific cancer risk. The penetrance of RTPS1 early in life is high and associated with a poor survival. However, few unaffected carriers may be encountered. Beyond RT, the tumor spectrum may be larger than initially suspected, and cancer surveillance offered to unaffected carriers (siblings or parents) and long-term survivors of RT is still a matter of discussion. RTPS2 exposes female carriers to an ill-defined risk of small cell carcinoma of the ovaries, hypercalcemic type (SCCOHT), which may appear in prepubertal females. RT surveillance protocols for these rare families have not been established. To address unresolved issues in the care of individuals with RTPS and to propose appropriate surveillance guidelines in childhood, the SIOPe Host Genome working group invited pediatric oncologists and geneticists to contribute to an expert meeting. The current manuscript summarizes conclusions of the panel discussion, including consented statements as well as non-evidence-based proposals for validation in the future.

scholarly journals A Comprehensive Review on Solitary Fibrous Tumor: New Insights for New Horizons

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2913
Author(s):  
Javier Martin-Broto ◽  
Jose L. Mondaza-Hernandez ◽  
David S. Moura ◽  
Nadia Hindi
Keyword(s):  
Solitary Fibrous Tumor ◽  
Fusion Gene ◽  
Current Knowledge ◽  
Fusion Transcript ◽  
Chemotherapeutic Agents ◽  
Comprehensive Review ◽  
Molecular Events ◽  
In Series ◽  
Prospective Phase ◽  
Fibrous Tumor

Solitary fibrous tumor (SFT) is a rare mesenchymal, ubiquitous tumor, with an incidence of 1 new case/million people/year. In the 2020 WHO classification, risk stratification models were recommended as a better tool to determine prognosis in SFT, to the detriment of “typical” or “malignant” classic terms. The risk for metastasis is up to 35–45%, or even greater, in series with a longer follow-up. Over the last few decades, advances in immunohistochemistry and molecular diagnostics identified STAT6 nuclear protein expression and the NAB2–STAT6 fusion gene as more precise tools for SFT diagnosis. Recent evidence taken from retrospective series and from two prospective phase II clinical trials showed that antiangiogenics are active and their sequential use from first line should be considered, except for dedifferentiated SFT for which chemotherapy is the best option. Since the fusion transcript driver’s first description in 2013, new insights have been brought on key molecular events in SFT. This comprehensive review mainly focuses on the superior efficacy of antiangiogenics over chemotherapeutic agents in SFT, provides the current knowledge of key molecules that could co-drive the SFT behavior, and suggests new target candidates that deserve to be explored in preclinical and clinical research in SFT.

scholarly journals FOXO1 gene involvement in a non-rhabdomyosarcomatous neoplasm

2021 ◽  
Author(s):  
Simon Haefliger ◽  
Muriel Genevay ◽  
Michel Bihl ◽  
Romina Marone ◽  
Daniel Baumhoer ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Soft Tissue ◽  
Genetic Heterogeneity ◽  
Gene Fusion ◽  
Fusion Gene ◽  
Soft Tissue Tumors ◽  
Gene Fusions ◽  
Mesenchymal Tumors ◽  
Myoepithelial Differentiation ◽  
Foxo1 Gene

AbstractMyoepithelial neoplasms of soft tissue are rare tumors with clinical, morphological, immunohistochemical, and genetic heterogeneity. The morphological spectrum of these tumors is broad, and the diagnosis often requires immunostaining to confirm myoepithelial differentiation. Rarely, tumors show a morphology that is typical for myoepithelial neoplasms, while the immunophenotype fails to confirm myoepithelial differentiation. For such lesions, the term “myoepithelioma-like” tumor was introduced. Recently, two cases of myoepithelioma-like tumors of the hands and one case of the foot were described with previously never reported OGT-FOXO gene fusions. Here, we report a 50-year-old woman, with a myoepithelial-like tumor localized in the soft tissue of the forearm and carrying a OGT-FOXO1 fusion gene. Our findings extend the spectrum of mesenchymal tumors involving members of the FOXO family of transcription factors and point to the existence of a family of soft tissue tumors that carry the gene fusion of the OGT-FOXO family.

Solitary Fibrous Tumors Arising from Bilateral Ovaries: A Case Report and Review of the literature

2021 ◽  
Vol 17 ◽  
Author(s):  
Tongtong Tian ◽  
Jing Ye ◽  
Jun Sun
Keyword(s):  
Wide Spectrum ◽  
Surgical Excision ◽  
Integrated Approach ◽  
Late Relapse ◽  
Limited Information ◽  
Mesenchymal Neoplasm ◽  
Fibrous Tumor ◽  
Long Term Behavior

Background: A solitary fibrous tumor (SFT) is a distinct mesenchymal neoplasm. It was originally described as a tumor localized to the pleura but was later reported in several other anatomic sites and exhibited a wide spectrum of histological features. Owing to its rarity, the diagnosis of extrapleural SFT is challenging and requires an integrated approach comprising specific clinical, imaging, histological, and immunohistochemical findings. Case presentation: Herein, we report the imaging findings of a rare case of SFT arising from bilateral ovaries confirmed by surgical excision and histological examination. No adjuvant radiotherapy or chemotherapy was given to the patient, and she was disease-free with no evidence of recurrence or metastasis at the 96-month postoperative follow-up. Although it mostly follows a favorable course, SFT is notoriously difficult for prognostication because of its propensity for late relapse or even metastases in 10–39% of cases. Conclusion: Close follow-up is recommended because of the limited information on its long-term behavior.

SOLITARY FIBROUS TUMOR OF PROSTATE – A CASE REPORT

2021 ◽  
pp. 17-18
Author(s):  
Shaila Shaila ◽  
Aparna. C ◽  
Sowmiya. J ◽  
Geetha Sree. A
Keyword(s):  
Case Report ◽  
Benign Prostatic Hyperplasia ◽  
Solitary Fibrous Tumor ◽  
Prostatic Hyperplasia ◽  
Mesenchymal Neoplasm ◽  
Fibrous Tumor ◽  
Cut Surface ◽  
Made In

Solitary Fibrous Tumor (SFT) of prostate is an unusual mesenchymal neoplasm. We report SFT in a 62 year-old man which was clinically misdiagnosed as benign prostatic hyperplasia (BPH). The specimen of surgically resected two prostate mass, we received were solid grey-white nodular on cut surface. Based on histopathological ndings and IHC assessment, a diagnosis of SFT was made. In addition, we review the literature and discuss the challenging issues of misdiagnosis. The case is presented in view of its rarity.

Intraarticular Nodular Fasciitis of the Knee With MHY9-USP6 Fusion: A Case Report

2020 ◽  
Vol 28 (6) ◽  
pp. 672-677 ◽  
Author(s):  
Jasminka Igrec ◽  
Iva Brčić ◽  
Renato Igrec ◽  
Marko Bergovec ◽  
Karl Kashofer ◽  
...  
Keyword(s):  
Giant Cell Tumor ◽  
Giant Cell ◽  
Smooth Muscle Actin ◽  
Malignant Lesion ◽  
Cell Tumor ◽  
Malignant Neoplasms ◽  
Low Grade ◽  
Nodular Fasciitis ◽  
Tenosynovial Giant Cell Tumor ◽  
Mesenchymal Neoplasm

Background. Nodular fasciitis (NF) is a self-limiting, benign mesenchymal neoplasm of fibroblastic/myofibroblastic origin. Due to the fast growth, cellularity, and frequently observed high mitotic count, it is commonly misdiagnosed as a sarcoma, often resulting in overtreatment. Intraarticular examples of NF are extremely rare. Radiologically, NF can mimic fibroma of the tendon sheath, tenosynovial giant cell tumor, and synovial chondromatosis. Histology can vary from hypercellular, mitotically active lesions to fibrotic, less cellular ones, and can, therefore, mimic other benign and low-grade malignant neoplasms. Recently, the MYH9-USP6 fusion has been found in up to 92% of NF. Case Presentation. In this article, we report a case of a 38-year-old patient with an intraarticular lesion, radiologically suspicious of tenosynovial giant cell tumor. Histology demonstrated a spindle cell lesion composed of fibroblasts/myofibroblasts embedded in a highly collagenous/hyalinized stroma, partly arranged in short fascicles. Extravasated erythrocytes and rare mitotic figures were present. Immunohistochemically, tumor cells expressed smooth muscle actin and were negative for desmin, β-catenin, CD34, and SOX10. These findings rendered the diagnosis of NF. Molecular analysis using next-generation sequencing (Archer FusionPlex Sarcoma Panel) revealed gene rearrangement involving USP6 and MYH9 supporting the diagnosis of NF in the knee joint. Conclusions. Radiological and histological features of NF can overlap with other benign and low-grade malignant lesion. Identification of the USP6 gene rearrangements or finding of the MYH9-USP6 fusion, especially in core needle biopsies and in the lesions occurring at unusual sites, can result in adequate therapeutic approach avoiding overtreatment.

Common and variant gene fusions predict distinct clinical phenotypes in rhabdomyosarcoma.

1997 ◽  
Vol 15 (5) ◽  
pp. 1831-1836 ◽  
Author(s):  
K M Kelly ◽  
R B Womer ◽  
P H Sorensen ◽  
Q B Xiong ◽  
F G Barr
Keyword(s):  
Metastatic Disease ◽  
Fusion Gene ◽  
Gene Fusions ◽  
Event Free Survival ◽  
Free Survival ◽  
Clinical Phenotypes ◽  
Significant Difference ◽  
The Common ◽  
Polymerase Chain ◽  
Gene Status

PURPOSE We evaluated the clinical features of the common PAX3-FKHR and variant PAX7-FKHR gene fusions observed in rhabdomyosarcoma. PATIENTS AND METHODS Reverse-transcriptase polymerase chain reaction (RT-PCR) assays were used to detect the gene fusions in 34 cases of rhabdomyosarcoma. Clinical data were obtained retrospectively and compared with the molecular results. RESULTS The PAX3-FKHR and PAX7-FKHR gene fusions were present in tumors from 18 and 16 patients, respectively. The group with a PAX7-FKHR fusion was younger (P = .01) and presented more often with an extremity lesion (82% v 22%; P = .001). PAX7-FKHR tumors were more often localized than PAX3-FKHR tumors (P = .03). In patients with metastatic disease at diagnosis, the patterns were different: PAX7-FKHR patients had metastatic disease that involved only bone (n = 2) and distant nodes (n = 2), while the PAX3-FKHR group had multiple sites involved, including bone (n = 7), marrow (n = 7), lungs (n = 3), distant nodes (n = 2), skin (n = 1), and brain (n = 1). No significant difference in relapse rate was observed. A trend toward improved overall survival in the PAX7-FKHR group was noted (P = .09). Event-free survival for this PAX7-FKHR group was significantly longer (P = .04). CONCLUSION Our results suggest that the common PAX3-FKHR and the variant PAX7-FKHR fusions are associated with distinct clinical phenotypes. Identification of fusion gene status may be a useful diagnostic tool in rhabdomyosarcoma.

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