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Ecancermedicalscience 2023Soft tissue sarcomas make up 7%-15% of childhood solid tumours. The aetiology of this disease is unknown. It is a fast-growing, painless tumour; histologically similar...
INTRODUCTION
Soft tissue sarcomas make up 7%-15% of childhood solid tumours. The aetiology of this disease is unknown. It is a fast-growing, painless tumour; histologically similar to adult fibrosarcoma, but having a lesser risk of metastasis and a better prognosis. The treatment is aimed towards localised intervention; complete surgical resection is the appropriate treatment as long as it can be performed.
CASE REPORT
An 11 years old female was referred for resection of a soft tissue tumour on the right elbow with significant peripheral vascularisation. Tumour resection was scheduled, with the placement of a partial thickness skin graft, and a piece was sent to pathology; a histological type consistent with paediatric fibrosarcoma was obtained with margins less than 1 mm from the lesion. Therefore, the patient was referred to the paediatric oncology unit. Further studies with positron emission tomography were requested, in which no evidence of macroscopic anatomy-metabolic tumour activity was found. Subsequently, treatment was started by paediatric oncology with 2 sessions of chemotherapy and 20 sessions of radiotherapy with sufficient progress; finally, assessment by plastic and reconstructive surgery was performed and an adequate quality of graft was observed, without the need for any other intervention by their service.
CONCLUSION
The involvement of the vascular surgeon in performing the tumour resection permitted the preservation of the best circulation to the extremity, thereby, avoiding amputation. The difficult decision made by the reconstructive surgeon to place a partial thickness graft over the surgical site, and to start radiotherapy/chemotherapy by paediatric oncology, were key to the success in achieving the patient's satisfactory progress.
PubMed: 38414962
DOI: 10.3332/ecancer.2023.1608 -
Cytokine & Growth Factor Reviews Dec 2022Neurotrophic Tyrosine Receptor Kinase (NTRK) genes undergo chromosomal translocations to create novel open reading frames coding for oncogenic fusion proteins; the... (Review)
Review
Neurotrophic Tyrosine Receptor Kinase (NTRK) genes undergo chromosomal translocations to create novel open reading frames coding for oncogenic fusion proteins; the N-terminal portion, donated by various partner genes, becomes fused to the tyrosine kinase domain of either NTRK1, NTRK2, or NTRK3. NTRK fusion proteins have been identified as driver oncogenes in a wide variety of tumors over the past three decades, including Pediatric Gliomas, Papillary Thyroid Carcinoma, Spitzoid Neoplasms, Glioblastoma, and additional tumors. Importantly, NTRK fusions function as drivers of pediatric sarcomas, accounting for approximately 15% of childhood cancers including Infantile Fibrosarcoma (IFS), a subset of pediatric soft tissue sarcoma (STS). While tyrosine kinase inhibitors (TKIs), such as larotrectinib and entrectinib, have demonstrated profound results against NTRK fusion-positive cancers, acquired resistance to these TKIs has resulted in the formation of gatekeeper, solvent-front, and compound mutations. We present a comprehensive compilation of oncogenic fusions involving NTRKs focusing specifically on pediatric STS, examining their biological signaling pathways and mechanisms of activation. The importance of an obligatory dimerization or multimerization domain, invariably donated by the N-terminal fusion partner, is discussed using characteristic fusions that occur in pediatric sarcomas. In addition, examples are presented of oncogenic fusion proteins in which the N-terminal partners may contribute additional biological activities beyond an oligomerization domain. Lastly, therapeutic approaches to the treatment of pediatric sarcoma will be presented, using first generation and second-generation agents such as selitrectinib and repotrectinib.
Topics: Humans; Child; Receptor, trkA; Biomarkers, Tumor; Gene Fusion; Sarcoma; Neoplasms; Oncogene Proteins, Fusion; Protein Kinase Inhibitors
PubMed: 36153202
DOI: 10.1016/j.cytogfr.2022.08.003 -
Cancer Genetics Apr 2022NTRK fusions are rare oncogenic drivers that occur across a range of pediatric cancers. These include infantile fibrosarcoma and secretory breast cancer in which such... (Review)
Review
NTRK fusions are rare oncogenic drivers that occur across a range of pediatric cancers. These include infantile fibrosarcoma and secretory breast cancer in which such fusions are nearly pathognomonic, and a spectrum of more common pediatric cancers in which NTRK fusions occur at a lower frequency. Within the last 5 years, two TRK inhibitors, larotrectinib and entrectinib, have demonstrated histology-agnostic activity against NTRK fusion driven cancers and achieved FDA approval. Here the data supporting the use of these TRK inhibitors for the treatment of cancers harboring NTRK fusions is reviewed, with a particular focus on the pediatric experience. Mechanisms of acquired resistance to these first generation TRK inhibitors are discussed and investigational second generation TRK inhibitors that may overcome some of these mechanisms of resistance are highlighted.
Topics: Child; Humans; Neoplasms; Oncogene Proteins, Fusion; Protein Kinase Inhibitors; Receptor, trkA
PubMed: 35108663
DOI: 10.1016/j.cancergen.2022.01.004 -
Cureus Jan 2021The soft tissues are comprised of various structures and supportive tissues in the body, including muscle, connective tissues, endothelium, synovium, fat, lymphatics,...
The soft tissues are comprised of various structures and supportive tissues in the body, including muscle, connective tissues, endothelium, synovium, fat, lymphatics, and fascia. Soft tissue sarcomas may arise in any part of the body. The most common sites are the trunk and the extremities. Fibrosarcoma is the most common non-rhabdomyosarcoma soft tissue sarcoma (NRSTS) in children, in whom two peaks in incidence are observed. The first is in children younger than five years, and the second is in children and adolescents aged 10-15 years. Infantile fibrosarcoma (IFS) is almost exclusively observed in children younger than two years. Many of these sarcomas are congenital. This tumor is locally aggressive, but rarely metastatic, and occurs in the extremity in 70% of patients. A 29-year-old lady presented to the Oncology unit with the fifth recurrence of fibrosarcoma which was transformed into very vascular and high-grade leiomyosarcoma from the fourth recurrence onwards. Initially, it was diagnosed when she was two days old and radiologically diagnosed as lymphangioma. It was documented as a large lump at the right lumbar region with uniform echogenicity and was excised and the postoperative period was uneventful. At the age of 12 years, she presented with a large mass at the right lumbar region over the surgical scar and complete excision done with R0 resection. Histology revealed well-differentiated fibrosarcoma with varying sizes of fibroblasts and no alignment features. The third relapse was at the age of 27. Complete excision was done and histology reported as spinel cell tumor with the possibility of fibrosarcoma or leiomyosarcoma. It was R0 resection and adjuvant treatment was not offered. Tumour recurred over the same scar within a year. Since the tumor is very big with 10 cm craniocaudal and 9 cm wide neoadjuvant chemotherapy is given: IV doxorubicin and IV cisplatin. Surgery was performed after four cycles and found necrotic tissue only. There were no tumor tissues or any form of spindle cells. Due to the aggressive nature, there was no exact solid tumor to assess margins for recommended adjuvant radiotherapy; IMRT. Due to the delay in finding a spacer to keep the bowel away from the radiotherapy field, radiotherapy was delayed and the tumor recurred within six months. It was a radiologically very vascular tumor and she had severe neuropathy and autotoxicity and could not offer any more chemotherapy. The tumor was rapidly growing and was bigger than the last time. Tumor growth was controlled with antiangiogenesis inhibitor; IV bevacizumab and high dose steroids and opioids for pain. After four months, we could not continue bevacizumab due to very high blood pressure and the patient died while waiting for palliative surgery. Childhood fibrosarcoma, including IFS, has classically been treated with surgery alone or with neoadjuvant chemotherapy and surgery. In cases that are not amenable, surgical resection is done upfront. Patients with IFS have an excellent prognosis, with survival rates of more than 90% in some series. A multidisciplinary approach is essential in managing infantile fibrosarcoma as it has a high potency of recurrence during teenage or later in life with malignant transformation. This could have been prevented when the clinicians are well aware of this risk of recurrence and primary surgery has to be planned very carefully with multidisciplinary involvement.
PubMed: 33604210
DOI: 10.7759/cureus.12672 -
Turk Patoloji Dergisi 2012In this study, we aimed to give a documentation of 37 cases of childhood fibroblastic/myofibroblastic tumors retrieved from the archives of 6 reference centers in Ankara... (Review)
Review
OBJECTIVE
In this study, we aimed to give a documentation of 37 cases of childhood fibroblastic/myofibroblastic tumors retrieved from the archives of 6 reference centers in Ankara along with a comprehensive review on the subject.
MATERIAL AND METHOD
A retrospective archive search was carried out for the period between 2006-2010 in 6 reference centers in Ankara covering patients with ages ranging between 0-18 years. All the tumors categorized under fibroblastic and myofibroblastic group according to World Health Organization criteria were collected.
RESULTS
The study comprised 407 soft tissue tumors in total. Fibroblastic/myofibroblastic tumors constituted 9,1 % (37 cases) of these tumors. According to histopathology; 16 cases were categorized as fibromatosis, 8 cases as inflammatory myofibroblastic tumor, 6 cases as infantile fibrous hamartoma, 3 cases as nodular fasciitis and 2 cases as infantile myofibroblastic tumor/myofibromatosis and 1 case as cranial fasciitis. The only malignant case was an infantile fibrosarcoma.
CONCLUSION
Infantile fibrosarcoma was lower than reported series and a male predominance was noted. The low incidence of newly described entities as well suggests that these tumors may have been unrecognized.
Topics: Adolescent; Child; Child, Preschool; Female; Fibroma; Humans; Infant; Infant, Newborn; Male; Myofibroma; Retrospective Studies; Soft Tissue Neoplasms
PubMed: 22207428
DOI: 10.5146/tjpath.2012.01093 -
Scientific Reports Nov 2022Infantile fibrosarcoma is a rare childhood tumour that originates in the fibrous connective tissue of the long bones for which there is an urgent need to identify novel...
Infantile fibrosarcoma is a rare childhood tumour that originates in the fibrous connective tissue of the long bones for which there is an urgent need to identify novel therapeutic targets. This study aims to clarify the role of the extracellular matrix component hyaluronan in the invasion of child fibroblasts and Infantile fibrosarcoma into the surrounding environment. Using nanoscale super-resolution STED (Stimulated emission depletion) microscopy followed by computational image analysis, we observed, for the first time, that invasive child fibroblasts showed increased nanoscale clustering of hyaluronan at the cell periphery, as compared to control cells. Hyaluronan was not observed within focal adhesions. Bioinformatic analyses further revealed that the increased nanoscale hyaluronan clustering was accompanied by increased gene expression of Hyaluronan synthase 2, reduced expression of Hyaluronidase 2 and CD44, and no change of Hyaluronan synthase 1 and Hyaluronidases 1, 3, 4 or 5. We further observed that the expression of the Hyaluronan synthase 1, 2 and 3, and the Hyaluronidase 3 and 5 genes was linked to reduced life expectancy of fibrosarcoma patients. The invasive front of infantile fibrosarcoma tumours further showed increased levels of hyaluronan, as compared to the tumour centre. Taken together, our findings are consistent with the possibility that while Hyaluronan synthase 2 increases the levels, the Hyaluronidases 3 and 5 reduce the weight of hyaluronan, resulting in the nanoscale clustering of hyaluronan at the leading edge of cells, cell invasion and the spread of Infantile fibrosarcoma.
Topics: Humans; Child; Hyaluronan Synthases; Hyaluronic Acid; Hyaluronoglucosaminidase; Fibrosarcoma; Fibroblasts; Cluster Analysis
PubMed: 36400790
DOI: 10.1038/s41598-022-21952-4 -
Magyar Onkologia Mar 2014Soft tissue sarcomas comprise around 1% of all malignant tumors, but they are relatively more frequent in childhood and adolescence. This latter fact emphasizes the need... (Review)
Review
Soft tissue sarcomas comprise around 1% of all malignant tumors, but they are relatively more frequent in childhood and adolescence. This latter fact emphasizes the need that timely diagnosis should be established for optimal treatment. The very recent WHO classification (2013) lays down the following main categories: adipocyte tumors, fibroblast/myofibroblast tumors, so-called fibrohistiocyte tumors, smooth-muscle tumors, pericyte tumors, skeletal-muscle tumors, vascular tumors, chondro-osseous tumors, gastrointestinal stromal tumors, nerve sheath tumors, tumors of uncertain differentiation and undifferentiated/unclassified sarcomas (including the former malignant fibrous histiocytoma). Beside the proper diagnosis it is also important to give the grade which basically determines the therapy. We use the French Federation of Cancer Centers Sarcoma Group (FNCLCC) grading system. The choice of preoperative diagnosis can be both fine needle and core biopsy and together with radiological image analysis they define the type of surgical intervention. The modern pathological diagnosis of soft tissue sarcomas is still based on the examination of H&E slides but it is also necessary to have a wide immunohistochemical panel and to use molecular methods for the sake of precise diagnosis and the broadening possibilities of targeted therapy.
Topics: Diagnosis, Differential; Female; Fibrosarcoma; Gastrointestinal Stromal Tumors; Gene Deletion; Histiocytoma, Malignant Fibrous; Humans; Leiomyoma; Mutation; Myosarcoma; Neoplasm Grading; Proto-Oncogene Proteins c-kit; Receptor, Platelet-Derived Growth Factor alpha; Sarcoma; Uterine Neoplasms
PubMed: 24712002
DOI: No ID Found -
Actas Dermo-sifiliograficas Dec 2012Dermatofibrosarcoma protuberans (DFSP) is a fibrohistiocytic tumor of intermediate malignancy that is very rare in childhood. Only 6% of these tumors present in... (Review)
Review
Dermatofibrosarcoma protuberans (DFSP) is a fibrohistiocytic tumor of intermediate malignancy that is very rare in childhood. Only 6% of these tumors present in children. Clinical diagnosis is very difficult in the early stages of disease, but to ensure appropriate treatment it is important to identify DFSP as early as possible and rule out benign conditions that are more common at this age. The clinical presentation and histopathologic and molecular characteristics of DFSP are similar in children and adults. Clinical diagnosis is, however, more difficult in children and requires a high degree of suspicion. The absence of characteristic features and the rarity of this tumor explain why diagnosis is often delayed. Complete surgical excision of the tumor is very important to reduce the risk of recurrence. This article presents a review of current knowledge about the management of DFSP in children and examines the latest treatment options.
Topics: Child; Decision Trees; Dermatofibrosarcoma; Humans
PubMed: 23154247
DOI: 10.1016/j.adengl.2011.12.002