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 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.

scholarly journals A Case of Glomangiopericytoma at the Nasal Septum

2017 ◽  
Vol 12 (4) ◽  
pp. 572-575 ◽  
Author(s):  
Takashi Anzai ◽  
Tsuyoshi Saito ◽  
Sho Tsuyama ◽  
Miri Toh ◽  
Katsuhisa Ikeda ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Nasal Septum ◽  
Low Grade ◽  
Beta Catenin ◽  
Mesenchymal Neoplasm ◽  
Resected Tumor ◽  
Vascular Structures ◽  
Borderline Malignancy ◽  
Fibrous Tumor ◽  
The Right

Abstract Glomangiopericytoma (GPC) is a rare sinonasal perivascular tumor that accounts for < 0.5–1% of all sinonasal tumors. GPC is categorized as a low-grade neoplasm with borderline malignancy and a tendency of local recurrence. GPC is a rare mesenchymal neoplasm characterized by the perivascular proliferation of tumor cells, and it requires being distinguished from solitary fibrous tumors. Here, we report a case of GPC in a 68-year-old male patient who presented at the emergency room of our hospital with a complaint of sudden epistaxis. A small, reddish, protruding tumor was observed on the right nasal septum. A biopsy revealed a possible perivascular tumor such as a GPC or solitary fibrous tumor. Thus, we performed complete resection with endoscopic surgery. The size of the resected tumor was 12 × 5 mm, and it showed a uniform proliferation of oval-to-short spindle-shaped cells with slightly branching vascular structures. The tumor cells showed minimal cytologic atypia and there were an average of 3 mitoses in 10 high power fields. Necrosis was not observed. The tumor cells showed strong and diffuse nuclear immunostaining with beta catenin and were negative with STAT6, CD34 and bcl-2. The MIB-1 labeling index was approximately 5%. Genetic testing revealed CTNNB1 mutation (p.S33C). Thus, a diagnosis of low grade GPC was made on the biopsy and the patient could be successfully treated with endoscopic resection.

scholarly journals SUN-129 Hipoinsulinemic Hipoglycemia Caused by Solitary Fibrous Tumor IGF-2 Producer: Case Report

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Flavia Tedesco Motta ◽  
Thamiris Freitas Maia ◽  
Paulo Enrique Peinado Noriega ◽  
Hially Ribeiro Cabral ◽  
Juliana Farhat ◽  
...  
Keyword(s):  
Solitary Fibrous Tumor ◽  
Oral Prednisone ◽  
Tumor Resection ◽  
Lower Lobe ◽  
Oral Glucose ◽  
Intravenous Glucose ◽  
Breath Sounds ◽  
Mesenchymal Neoplasm ◽  
Fibrous Tumor ◽  
The Right

Abstract BACKGROUND: Solitary Fibrous Tumor is a mesenchymal neoplasm composed of CD34+ fibroblastic cells that can produce spontaneous hypoglycemia by the overproduction of IGF-2. It closely resembles the hypoglycemia characteristic of functioning islet cell tumors. CLINICAL CASE A 77-year-old male was found unconscious and taken to an emergency department with evidence of hypoglycemia and clinical improvement following intravenous glucose administration. He did not have a history of diabetes mellitus and was not taking any glucose lowering medications. He was discharged with nutritional orientation and for control of capillary glycaemia to prevent hypoglycemia. He had 3 episodes of capillary hypoglycemia (50, 45 and 38) at home, that was predominant in the fasting morning and during its occurrence he presented mild sweating, speech difficulty, staring and diplopia, with complete improvement of symptoms after oral glucose replacement. Months earlier, he sought an otolaryngologist for intermittent mild dyspnea; denied cough, hemoptysis, chest pain and unintentional weight loss. He performed chest X-ray with evidence of large right hemithorax mass. Physical examination revealed diminished breath sounds in the right middle and lower lung fields and dullness to percussion. Despite marked hypoglycemia (31 mg/dl), the serum insulin level was less than 0.6  μIU/mL (less than 3 μIU/mL), the C-peptide level was 0.24 nmol/L (less than 0,6 nmol/L), had negative ketonemia and a positive response after glucagon administration (glycaemia increased in 50 mg/dl). Anti-insulin antibodies were negative. Serum cortisol secretion and adrenocorticotropic hormone were normal. The serum level of growth hormone (GH) was 0,03 (less than 0,97ng/ml). The serum IGF-2 level was 227 ng/ml  (267 - 616 ng/ml), the IGF-I level was 72 ng/ml (37,1 - 172 ng/ml) and the IGF2/ IGF1 was 3,15 (equal or greater than 3). Computed tomographic (CT) scan revealed a large heterogeneous mass with dimensions of 17,4 × 15× 12.2 cm. It determines almost total atelectasis of the lower lobe on this side and maintains broad medial contact with the mediastinum, compressing the right atrium and the inferior pulmonary vein on this side. Preoperatively, was administered 40 mg oral prednisone with capillary glucose normalization. The tumor was completely resected and was a grayish-white solid, with dimensions of 17 x 16 x 12 cm. Immunohistochemical stains demonstrated positivity for CD34 and IGF2 expression. Postoperatively, serum glucose and insulin levels returned to normal, and episodes of hypoglycemia are resolved. CONCLUSION This case reinforce the importance of investigate IGF-2 tumor production as a cause of hypoinsulinemic hypoglycemia and reports the complete resolution of hypoglycemia after corticoid administration and/or tumor resection.

CLINICAL CASE OF A MALIGNANT PECOMA OF THE LUNG

2019 ◽  
Vol 65 (5) ◽  
pp. 756-759
Author(s):  
Mikhail Postolov ◽  
Nadezhda Kovalenko ◽  
K. Babina ◽  
Stanislav Panin ◽  
Yelena Levchenko ◽  
...  
Keyword(s):  
Good Condition ◽  
Lung Neoplasm ◽  
Rare Condition ◽  
Epithelioid Cell ◽  
X Ray ◽  
Perivascular Epithelioid Cell ◽  
Mesenchymal Neoplasm ◽  
Preoperative Ct ◽  
Lymph Duct ◽  
The Right

Perivascular epithelioid cell tumor (PEComa) is a rare mesenchymal neoplasm characterized by expression of both mela-nocytic and smooth muscle markers. Only 10 primary malignant lung PEComas have been reported up to date. We report a 59-year-old male who presented with a lung neoplasm, found during the routine X-ray examination. Preoperative CT-scan revealed the 3,5-cm-sized mass, located at the border of the upper, middle and lower lobes of the right lung. Patient underwent a thoracotomy, resection of the upper, middle and lower lobes of the right lung accompanied with mediastinal lymphadenectomy. After surgery, chylothorax was revealed. Conservative treatment was unsuccessful, so we performed laparoscopic clipping of the thoracic lymph duct. Patient was dismissed from hospital on the 10-th day after the second operation in good condition. In this report, we intend to increase the limited knowledge relating to natural history and optimal treatment of such a rare condition as a primary malignant lung PEComa.

IL‐1 receptor antagonist defect (DIRA) in a pediatric patient, receiving adalimumab with good clinical response

2021 ◽  
Author(s):  
Juan Carlos Bustamante‐Ogando ◽  
Selma Scheffler‐Mendoza ◽  
Marco Antonio Yamazaki‐Nakashimada ◽  
Marimar Saez‐de‐Ocariz
Keyword(s):  
Receptor Antagonist ◽  
Clinical Response ◽  
Pediatric Patient ◽  
Good Clinical Response

scholarly journals A Novel NFIX-STAT6 Gene Fusion in Solitary Fibrous Tumor: A Case Report

2021 ◽  
Vol 22 (14) ◽  
pp. 7514
Author(s):  
David S. Moura ◽  
Juan Díaz-Martín ◽  
Silvia Bagué ◽  
Ruth Orellana-Fernandez ◽  
Ana Sebio ◽  
...  
Keyword(s):  
Solitary Fibrous Tumor ◽  
Gene Fusion ◽  
Wide Spectrum ◽  
Bioinformatic Analysis ◽  
Fusion Partner ◽  
Rna Seq ◽  
Genomic Location ◽  
Nuclear Factor I ◽  
New Gene ◽  
Fibrous Tumor

Solitary fibrous tumor is a rare subtype of soft-tissue sarcoma with a wide spectrum of histopathological features and clinical behaviors, ranging from mildly to highly aggressive tumors. The defining genetic driver alteration is the gene fusion NAB2–STAT6, resulting from a paracentric inversion within chromosome 12q, and involving several different exons in each gene. STAT6 (signal transducer and activator of transcription 6) nuclear immunostaining and/or the identification of NAB2–STAT6 gene fusion is required for the diagnostic confirmation of solitary fibrous tumor. In the present study, a new gene fusion consisting of Nuclear Factor I X (NFIX), mapping to 19p13.2 and STAT6, mapping to 12q13.3 was identified by targeted RNA-Seq in a 74-year-old female patient diagnosed with a deep-seated solitary fibrous tumor in the pelvis. Histopathologically, the neoplasm did not display nuclear pleomorphism or tumor necrosis and had a low proliferative index. A total of 378 unique reads spanning the NFIXexon8–STAT6exon2 breakpoint with 55 different start sites were detected in the bioinformatic analysis, which represented 59.5% of the reads intersecting the genomic location on either side of the breakpoint. Targeted RNA-Seq results were validated by RT-PCR/ Sanger sequencing. The identification of a new gene fusion partner for STAT6 in solitary fibrous tumor opens intriguing new hypotheses to refine the role of STAT6 in the sarcomatogenesis of this entity.

scholarly journals A case report of unilateral conductive hearing loss as a consequence of malignant sinonasal melanoma: the importance of completing a full clinical history and examination

2020 ◽  
Vol 36 (1) ◽  
Author(s):  
Victoria Blackabey ◽  
Olivia Kenyon ◽  
Rishi Talwar
Keyword(s):  
Hearing Loss ◽  
Case Report ◽  
Clinical Symptoms ◽  
Symptomatic Relief ◽  
Clinical History ◽  
Histological Diagnosis ◽  
Unusual Presentation ◽  
Sinus Surgery ◽  
Cancer Management ◽  
The Right

Abstract Background Sinonasal melanoma is a rare head and neck tumour. It is associated with a poor prognosis, high rates of loco-regional recurrence and distant metastasis. Treatment of the disease is therefore complicated, and because of limited data regarding the cancer, management is frequently tailored to the individual patient. We describe an unusual presentation of sinonasal melanoma with relevant histology, radiology and clinical photography. Case presentation The case report describes the presentation of a 64-year-old man to the Ear, Nose and Throat department with progressive right-sided hearing loss. A thorough history highlighted other clinical symptoms including unilateral nasal obstruction and epistaxis. Clinical examination showed a right middle ear effusion with a polypoidal lesion in the right nasal cavity. Relevant imaging demonstrated a destructive process that required further assessment. An endoscopic sinus procedure was performed to obtain histological diagnosis as well as providing symptomatic relief. Histology confirmed malignant mucosal melanoma. The patient underwent maxillectomy and orbital exenteration (due to further progression of disease) at a tertiary centre with a plan for subsequent immunotherapy. This however has been delayed due to further surgery to excise a metastatic lesion to the right femur. Conclusions This case report highlights the importance of a thorough clinical history and examination. An unusual presentation of a sinonasal tumour can easily be missed leading to a significant delay in treatment. The case report also describes the use of functional endoscopic sinus surgery in order to obtain histological diagnosis and to debulk the tumour, providing symptomatic relief. The current literature regarding management will be discussed as well as current developments guiding future treatment.

scholarly journals Treatment for Severe Coronavirus Disease 2019 with a biomimetic sorbent hemoperfusion device in patients on hemodialysis

2021 ◽  
Author(s):  
Diego A Sandoval ◽  
Inés Rama ◽  
María Quero ◽  
Miguel Hueso ◽  
Francisco Gómez ◽  
...  
Keyword(s):  
Clinical Response ◽  
Mortality Risk ◽  
Hemodialysis Patients ◽  
Morbidity And Mortality ◽  
Good Clinical Response ◽  
Simultaneous Treatment ◽  
Excellent Tool

Abstract Hemodialysis patients present more morbidity and mortality risk in coronavirus disease 2019. In patients who may develop severe symptoms the process called “viral sepsis” seems to be a crucial mechanism. In those cases, the hemodialysis procedure provides an excellent tool to explore the benefit of some extracorporeal therapies. We reported the outcome of 4 hemodialysis patients with severe COVID-19 treated with Seraph®100 hemoperfusion device. Three of four cases presented a good clinical response after hemoperfusion. In conclusion, the treatment with Seraph®100 device may be a simultaneous treatment to improve the hemodialysis patients with severe SARS-CoV-2.

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