Soft Tissue Fibrosarcoma Research Articles

Comparison of clinical features between patients with bone and soft tissue fibrosarcomas.

Fibrosarcomas predominantly arise in soft tissues, but can also develop in bone. Because of their rarity, whether bone development has an impact on clinical features has not been addressed. We included fibrosarcoma patients diagnosed between 1983 and 2016 in the Surveillance, Epidemiology, and End Results database. Differences in clinical features between fibrosarcoma of bone (FS-B) and fibrosarcoma of soft tissue (FS-ST) were investigated. After excluding patients without information regarding cause of death, site of origin, distant tumor or survival, 1443 patients were included. Of those, 98 patients had FS-B. Patients with FS-B were younger, more frequently male, with fibrosarcomas that more often developed in an extremity and were histologically high-grade. In contrast, no difference in potential to metastasize was observed. Survival was almost equal between FS-B and FS-ST (FS-B/FS-ST: cancer-specific survival, hazard ratio [HR]: 1.2, 95% confidence interval [CI]: 0.8-1.7; overall survival, HR: 1.3, 95% CI: 0.9-1.7). Our results clearly indicated that patient backgrounds differed, such as younger age and greater tendencies to affect males, develop in an extremity and show high-grade tumor in patients with FS-B. In contrast, no differences were observed in distant metastatic potential or survival.

Expanding the Molecular Genetic Spectrum of Bone and Soft Tissue Fibrosarcomas: An Institutional Experience.

Introduction. Fibrosarcomas, once comprising the majority of unclassifiable spindle-cell sarcomas, are now regarded as a diagnosis of exclusion. Objectives. Prompted by an index report of neurotrophic receptor tyrosine kinase (NTRK)3 fusion in fibrosarcomas by Yamazaki et al bone/soft tissue tumors diagnosed as fibrosarcoma at our institution were evaluated in an attempt to expand the genetic spectrum of fibrosarcomas and identify therapeutically targetable cases. Methods. Institutional archives were searched for cases diagnosed as "fibrosarcoma" involving bone/soft tissue from 2000 to present. Twenty-one cases meeting inclusion criteria were identified, 10 of which had formalin-fixed paraffin-embedded tissue available for molecular testing. One case, at the submitting clinician's request, underwent outside deoxyribonucleic acid/ribonucleic acid (DNA/RNA) sequencing while the 9 remaining cases underwent in-house next-generation sequencing RNA fusion analysis. Results. At the time of diagnosis the mean age was 54.5 (range 14-88) with a male to female ratio of 1.5:1. Locations included soft tissue of the lower extremity (3), trunk (2), pelvis (2), head (1), upper extremity (1), and bone (1). Of the 10 cases, 1 demonstrated an FNDC3B-PIK3CA gene fusion and 1 demonstrated a BRAF (p.G469A) mutation and CDKN2A/B loss. Conclusion. In conclusion, our study demonstrated gene fusions in 1 (10%) of 10 fibrosarcomas diagnosed at our institution in the past 20 years, including FNDC3B-PIK3CA gene fusion. Additionally, 1 case harbored BRAF (p.G469A) mutation and CDKN2A/B loss with no evidence of gene fusion. NTRK rearrangements were not detected. The significance of these molecular aberrations is presently unclear and future studies are needed to establish whether these findings carry any clinicopathologic significance.

Radiogenic Vaginal Angiosarcoma: a Clinical Case

Background. Vaginal sarcomas are rare malignant mesenchymal neoplasms. Incidence rate of vulvar and vaginal sarcomas ranges from 1 to 3%. Vaginal sarcomas are usually represented by leiomyosarcomas in reproductive-age women. More seldom are soft tissue fibrosarcomas, angiosarcomas, malignant fi brous histiocytomas and alveolar soft tissue sarcomas. Tumours induced by prior radiation therapy deserve special concern. In oncogynaecology, radiation therapy is commonly applied in cervical and endometrial cancer therapy. According to some evidence, average development time of a secondary tumour after completion of radiation therapy is 10.8 years. The relative risk of vaginal cancer increases by a factor of 300 after radiation therapy.Materials and methods. The reported clinical case represents a rare vaginal tumour, angiosarcoma, developed 26 years after radiation therapy for gynaecological cancer.Results and discussion. A 78 years-old patient underwent combined tumourectomy of the posterior vaginal wall with resection of the anterior rectal wall and application of preventive transversostoma. No postoperative complications were observed.Conclusion. Surgical treatment is a method of choice with patients of such kind and allows local containment of the disease.

Head and neck soft tissue fibrosarcoma in nine year old child: A case report

Head and neck soft tissue fibrosarcoma in nine year old child: A case report - JOOO- Print ISSN No: - 2395-6186 Online ISSN No:- 2395-6194 Article DOI No:- 10.18231/j.jooo.2020.024, Journal of Oral Medicine, Oral Surgery, Oral Pathology and Oral Radiology-J Oral Med Oral Surg Oral Pathol Oral Radiol

Descending thoracic aortic aneurysm revealing metastasis of a soft tissue fibrosarcoma: a case report and review of the literature

BackgroundReview of the first documented case of aortic wall metastasis from a limb sarcoma.Case presentationIn a 56-year-old woman with a diagnosis of a high-grade limb fibrosarcoma, an aortic metastasis was revealed by a fast growing aneurysm of the descending thoracic aorta. This was managed with an endoprosthesis.ConclusionThe presence of an aneurysm in a patient with a sarcoma with a high potential for metastasis and poor cardiovascular risk factors should alert physicians.

Abstract B33: Assessing macrophage polarization in sarcomas with PD-L1 correlates

Abstract The role of innate and adaptive immunity in a wide range of human tumors has shown critical roles, though sometimes competing, in numerous immune components in both the tumor and the tumor microenvironment (TME). The PD-1/PD-L1 interaction in both tumor and the TME has become high priority in correlative biomarkers of human disease with increasing number of targeted agents showing high levels of durable response. The in situ analysis of viral defense pathway, interferon response, and PD-L1 status has provided strong preliminary data of correlative staining by immunohistochemistry in colon and lung carcinomas. Generally, such human tumors arise in organs with frequent and high exposure to external/foreign antigens. Here we expand our IHC staining to include human tumors arising from sites with varied immune activity to include uterine wall (leiomyosarcoma), subcutaneous connective tissue to include dermatofibrosarcoma protuberans (DFSP), soft tissue sarcoma, fibrosarcoma, and osteosarcoma. IHC panel includes immune markers of CD4, CD8, CD68 (M1 macrophages), CD163 (M2 macrophages); dsRNA antibodies (J2 and K1); MDA 5, RIG 1, STAT 1, and pSTAT1; PD-L1 and PD-1; and interferon response markers IRF 3, IRF 7, and IFIT 1. Immunostaining is ongoing and supports preliminary sarcoma phenotype of quite varied PD-L1 immunoreactivity with lower prevalence than lung and colon carcinomas. Immune markers of T-cell subset and macrophage M1 and M2 are significantly lower in sarcoma samples and detailed analysis of M1 and M2 macrophages in DFSP, STS, fibrosarcomas, and osteosarcoma. Each tumor type is represented on single TMA with 8-12 samples each from the Van Andel Institute Biorepository Core. In our experience, tissue site density and macrophage subtypes and difference in polarized macrophages (M2) in relation to CD4 and CD8 markers were significant in relation to PD-L1 and require further exploration. Improved characterization of PD-L1 pathway and potential surrogate markers to compile immune competency profiles will include early results from our IHC staining for dsRNA fragments to lend support to endogenous retroviral activation in a wide range of both carcinomas and sarcomas. Citation Format: Galen Hostetter, Lorenzo Sempere, Scott Jewell, Steve Baylin. Assessing macrophage polarization in sarcomas with PD-L1 correlates [abstract]. In: Proceedings of the AACR Conference on Advances in Sarcomas: From Basic Science to Clinical Translation; May 16-19, 2017; Philadelphia, PA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(2_Suppl):Abstract nr B33.

Cardiac herniation following right lower lobectomy—a rare clinical entity

Cardiac herniation and torsion may rarely occur following lobectomy with partial pericardectomy. High index of suspicion is required to diagnose this near fatal event. We report an unusual case of acute right sided cardiac dextroversion with torsion in a 58-year-old female following a right lower lobectomy, pericardectomy, and excision of infiltrated part of right hemi diaphragm for recurrent soft tissue fibrosarcoma.

A Giant Soft Tissue Fibrosarcoma of Posterior Head and Neck: A Case Report

Sarcomas are malignant neoplasms originating from mesodermal tissues that constitute connective tissues of the body. This seven years old girl was born after an uncomplicated full term pregnancy. Her physical status at birth was unremarkable. Her younger sister is healthy. At age of one and a half year she developed swelling over posterior head and neck region that was gradually increasing. The rate of growth was more rapid from October 2014. She was admitted in National Institute of Neurosciences & Hospital (NINS). Local examination showed a giant swelling 22X17X21 cm in size over posterior head and neck region, fixed to the sub-occipital bone, firm in consistency. Her general and neurological examination revealed no abnormalities.The authors present a case of a giant soft tissue fibrosarcoma of posterior head and neck of a seven years old girl. The case has been discussed.Journal of National Institute of Neurosciences Bangladesh 2015;1(2): 65-68

A novel rat fibrosarcoma cell line from transformed bone marrow-derived mesenchymal stem cells with maintained in vitro and in vivo stemness properties

Increasing evidence suggests a possible relationship between mesenchymal stem cells (MSCs) and sarcoma. MSCs are hypothesized to be the cells initiating sarcomagenesis, and cancer stem cells (CSCs) sharing features of MSCs have been identified in sarcomas. Here, we report on the characteristics of a bone marrow-derived rat mesenchymal stem cell line that spontaneously transformed in long-term culture. The rat transformed mesenchymal stem cells (rTMSCs) produced soft-tissue fibrosarcomas in immunocompromised mice and immunocompetent rats. In vitro, the rTMSCs displayed increased proliferation capacity compared to the untransformed cell line. The transformed MSCs maintained the mesenchymal phenotype by expression of the stem cell marker CD 90 and the lack of hematopoietic and endothelial markers. Cytogenetic analysis detected trisomy 6 in the rTMSCs. Side population (SP) isolation and tumorsphere cultivation of the transformed cells confirmed the presence of CSCs among the rTMSCs. Importantly, the rTMSCs retained their differentiation capacity towards osteogenic and adipogenic lineages. This transformed MSC-based cell line may be valuable in examining the balance in a mixed cell population between cancer stem cell properties and the ability to differentiate to specific non-transformed cell populations. Moreover, it may also be a useful tool to evaluate the efficacy of novel targeted immunotherapies in vivo.

Abstract A46: Identification of NTRK fusions in pediatric tumors via comprehensive genomic profiling

Abstract Purpose: NTRK1-3 fusions are oncogenic drivers in lung and other carcinomas in adults, suggest benefit from targeted therapy. We examined a large series of pediatric/adolescent advanced cancer cases to identify those with NTRK fusions. Background: The NTRK, neurotrophic tyrosine kinase receptor, genes encode proteins essential for normal neuronal growth and development. Fusions of NTRK family members have recently been linked to oncogenesis as well as identified as potential targets of therapy. In this study, a hybrid capture based comprehensive genomic profiling (CGP) assay was used to study a large series of pediatric solid tumors to search for NTRK gene fusions. Methods: CGP using hybridization capture of at least 3,320 exons from 182 cancer-related genes and 37 introns of 14 genes commonly rearranged in cancer (previous version of the test) was applied to ≥ 50ng of DNA extracted from 1351 pediatric/adolescent/young adult tumors (<22). Results:, From 1351 pediatric/adolescent young adult advanced cancer patients, 7 (0.52%) harbored NTRK family member fusions. Of these, 5 were pediatric (<18 years) (0.51% from 986 total cases). Ages of the patients ranged from <1 to 22 years, with 4 cases being <5 years and included 5 males and 2 females. Histologic diagnoses of these neoplasms were 2 soft tissue fibrosarcomas, soft tissue sarcoma NOS, soft tissue solitary fibrous tumor, soft tissue hemangioma, soft tissue schwanoma and a soft tissue dendritic cell neoplasm. The fusions identified were LMNA-NTRK1 (twice) and SQSTM1-NTRK1, TPM3-NTRK1, TPR-NTRK1, TFG-NTRK3, and ETV6-NTRK3. Four (57%) of 7 of these patients also harbored a CDKN2A/B homozygous deletion. Other genomic alterations in these cases included in one case each: PTRPO R231H, EP300 E628fs*7, MAP3K14 R218fs*731 and KDM4C amplification. One case was that of a 1.5 year old boy initially diagnosed with infantile fibrosarcoma (IFS) on a morphologic basis. CGP demonstrated his tumor harbored LMNA-NTRK1 and CDNK2A/B loss, and the patient then received crizotinib for pulmonary and skeletal metastases. He achieved an ongoing complete response exceeding 8 months. Conclusions: 0.5% pediatric/adolescent/young advanced cancers harbor NTRK1 and NTRK3 fusions, and all such tumors are mesenchymal in origin. Of these, an index case benefitted from crizotinib treatment, suggesting pathways to clinical benefit for such cases. Citation Format: Dean Pavlick, Siraj Mahamed Ali, Julia A. Elvin, Phil J. Stephens, Vincent A. Miller, Jeffrey S. Ross, James H. Suh, Jo-Anne Vergilio, Juliann Chmielecki, Tim Brennan, John R. Crawford, Denise M. Malicki, Hyunah Ahn, Victor N. Wong. Identification of NTRK fusions in pediatric tumors via comprehensive genomic profiling. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Pediatric Cancer Research: From Mechanisms and Models to Treatment and Survivorship; 2015 Nov 9-12; Fort Lauderdale, FL. Philadelphia (PA): AACR; Cancer Res 2016;76(5 Suppl):Abstract nr A46.

Soft Tissue Fibrosarcoma Neck Mimicking as Thyroid Swelling

ABSTRACTFibrosarcomas are relatively uncommon tumors, commonly arise in the extremities; approximately 10% occur in the head and neck region, most commonly in the sinonasal tract and neck. We hereby report a case of fibrosarcoma in neck clinically mimicking as a thyroid swelling in a 14 years old boy. The patient reported with difficulty in breathing along with stridor at the time of presentation so endotracheal intubation was done to secure the airway. Subsequent ultrasonography guided fine needle aspiration cytology (FNAC) showed atypical cells suggestive of mesenchymal origin. Contrast-enhanced computed tomography scan showed a large heterogeneously enhancing mass lesion in right side of neck with retrosternal extension, while the right lobe of thyroid was displaced superiorly and left lobe was normal. We performed a complete surgical excision of the tumor and histopathological examination showed intermediate to high grade spindle cell sarcoma, favoring fibrosarcoma. Postoperative period was uneventful and the patient was referred to oncology unit for radiotherapy and chemotherapy, but the patient succumbed to the disease 5 weeks after surgery.How to cite this articleBist SS, Mishra S, Varshney S, Agrawal V, Harsh M. Soft Tissue Fibrosarcoma Neck Mimicking as Thyroid Swelling. Int J Otorhinolaryngol Clin 2014; 6(1):50-52.

Intraoral Soft Tissue Fibrosarcoma: A Case Report and Review

ABSTRACTAdult fibrosarcoma (FS), defined by the World Health Organization as ‘malignant neoplasm composed of fibroblasts with variable collagen production and, in classical cases, a ‘herringbone’ architecture’, is a very rare soft tissue sarcoma. The earlier literature revealed that the adult fibrosarcoma was the most commonly occurring lesion, however the incidence of which has declined dramatically over the past several decades. This is due to evolution in the classification of soft tissue tumors, recognition of its subtypes and increased understanding of the many other mesenchymal and nonmesenchymal tumors.Sarcomas are the rare group of malignancies which accounts for less than 1% of all the body sarcomas of which 5 to 15% occurs in head and neck region. It involves deep soft tissues of extremities, trunk, head and neck. Among the head and neck region, intraoral adult fibrosarcomas are very rare without any sex predilection. A case of primary soft tissue FS in posterior mandible of an 13-year-old female patient is documented here, which will be an addition to the cases reported earlier in the literatures.How to cite this articleTupkari JV, Chettiakandy TJ, Padawe D, kumar k, Sardar M, Gupta N. Intraoral Soft Tissue Fibrosarcoma: A Case Report and Review. J Contemp Dent 2014;4(2):118-123.

The Contribution of Electron Microscopy to the Characterization of Soft Tissue Fibrosarcomas

In recent years, with the application of immunohistochemical and cytogenetic methods, numerous lesions formerly diagnosed as fibrosarcoma were reclassified as other malignant soft tissue tumors, and therefore conventional fibrosarcoma has largely become a diagnosis of exclusion. On the other hand, several new entities belonging to the group of fibrosarcomas have been characterized, including low-grade fibromyxoid sarcoma / hyalinizing spindle cell tumor with giant rosettes, sclerosing epithelioid fibrosarcoma, acral myxoinflammatory fibroblastic sarcoma, and the epithelioid variant of myxofibrosarcoma. Electron microscopy has contributed to the identification of the fibroblastic phenotype in these fibrosarcoma variants and still retains a central role in the differential diagnosis of these soft tissue sarcomas, thus helping to render specific diagnoses and to broaden the spectrum of fibrosarcoma variants.

Interplay between steroid receptors and neoplastic progression in sarcoma tumors

Steroid hormones are expressed at low levels in mesenchymal cells and are highly expressed in soft tissue sarcoma. In human soft tissue fibrosarcoma cell line (HT-1080), the epidermal growth factor (EGF) stimulates the express of matrix metal (MMPs) expression through a Src-dependent mechanism. In human fibrosarcomas, increased expression of MMPs correlates with the metastatic progression. Our recent data in human breast cancer cell line MCF-7, demonstrates that EGF stimulates estradiol receptor (ER) phosphorylation on tyrosine at position 537 thereby promoting the association of a complex among EGF receptor (EGFR), androgen receptor (AR), ER, and Src that activates EGF-dependent signaling pathway. In the present study, we demonstrate that, in HT-1080 cells, the Src kinase activity is involved in EGFR phosphorylation and this activity is regulated by an interplay between Src, steroid receptors, and EGFR. In these cells, estradiol (E(2) )/ER and synthetic androgen (R1881)/AR trans-activate EGFR leading to the downstream signaling and to ERK activation. Indeed, the association between ER/AR and EGFR enhances metastatic progression of fibrosarcoma tumors. A population pilot study performed on 16 patients with soft tissue neoplasias highlights that MMPs expression correlates with progression of anaplastic sarcoma as well as overexpression of EGFR. These findings suggest that there is a crosstalk among AR, ER, and EGFR that lead to src activation also in fibrosarcoma cells.

Immunohistochemical Expression of c-KIT Protein in Feline Soft Tissue Fibrosarcomas

C-KIT is the cellular homolog of the feline sarcoma viral oncogene v-KIT, which encodes the tyrosine kinase receptor protein KIT. Mutations and varied expression of this gene have been demonstrated within multiple neoplasms in people and domestic animals. The purpose of this study was to determine if KIT protein is expressed in feline soft tissue fibrosarcomas (ST FSA) using immunohistochemistry (IHC). The computer database at the Oklahoma Animal Disease Diagnostic Laboratory was searched from January 1, 2006, to December 31, 2007, for any domestic cat with an ST FSA. Routinely stained slides from 46 feline ST FSAs were reviewed and graded based on the scale outlined by Kuntz et al. Immunohistochemistry for KIT protein was performed on one representative section from each cat. There were a total of 12/46 (26%) cats that were immunoreactive for KIT. Immunoreactivity was detected in greater than 80% of the neoplastic cells in 4/46 (9%) cats. Immunoreactivity was detected in less than 10% of the neoplastic cells in 8/46 (17%) cats. Immunoreactivity was characterized by evenly distributed cytoplasmic stippling within the neoplastic spindle-shaped cells and/or multinucleated giant cells. Based on these results, KIT immunoreactivity can be detected within feline ST FSAs using IHC. The results of this study also indicate that KIT immunoreactivity in feline ST FSA does not correlate with the histologic grade (P = .141, X(2) = 2.166), survivability (P = .241, X(2) = 1.373), or whether the neoplasm was a spontaneous or an injection site FSA (P = .074, X(2) = 3.184).

Large left ventricular metastasis causing left ventricular outflow tract obstruction and haemolysis

Although post-mortem studies would suggest that cardiac metastases occur frequently, many of these metastases remain clinically silent. However, symptomatic lesions may also remain unrecognized due to overshadowing by other symptoms of the primary malignancy. Patients undergoing treatment for cancer are not routinely screened using echocardiography, unless their chemotherapeutic regimen includes cardiotoxic agents. The current era of research and development of targeted biological agents (such as trastuzumab and epidermal growth factor receptor inhibitors) for cancer may lead to prolonged survival of oncology patients. In future, metastases that were once rare may become increasingly recognized as these new treatments augment the natural history of the disease. There have been several case reports of small, asymptomatic left ventricular metastases, but clinically significant ventricular metastases are very rare. There are no reports in the current literature of a symptomatic ventricular metastasis, occurring in the absence of other metastatic disease. We report an unusual case of a large solitary ventricular metastasis, leading to left ventricular outflow tract obstruction and haemodynamic compromise. Echocardiographic imaging led to the diagnosis of a recurrence of soft-tissue fibrosarcoma 9 years after original resection.

Contrast-enhanced right atrial mass: tumour or thrombus?

We present a case of a 61-year-old female diagnosed with soft-tissue fibrosarcoma of the shoulder with a right atrial mass on transthoracic echocardiogram. To further assess the mass, contrast transoesophageal echo was performed. The mass was highly considered to be a thrombus due to the presence of multiple risk factors: atrial fibrillation, catheter use, and pulmonary embolism. However, a metastatic fibrosarcoma could not be excluded, given its enhancement with echo contrast. Finally, it was proved to be a thrombus with its rapid resolution while on anticoagulation. Therefore, it should be noted that in rare circumstances, thrombus may show enhancement with echo contrast and one needs to integrate all of the patient information to arrive at the correct diagnosis.

Sclerosing Epithelioid Fibrosarcoma of the Pituitary

Primary pituitary sarcoma in the absence of previous radiation therapy is very rare, only eight cases having been reported. We present the first reported case of sclerosing epithelioid fibrosarcoma of the pituitary, a 56-year-old woman presenting with diplopia and panhypopituitarism. Magnetic resonance imaging showed a 1.2 x 0.4 x 0.5-cm sellar mass invading the right cavernous sinus. Despite surgery and radiation therapy, our patient developed intracranial metastases and died 2 years after the initial diagnosis. Sclerosing epithelioid fibrosarcoma is an infrequently occurring, distinct variant of soft tissue fibrosarcoma. Its immunophenotype includes vimentin and occasionally CD-34, B cell lymphoma-2, S-100 protein, or keratin expression. Although initially thought to be a low-grade lesion, sclerosing epithelioid fibrosarcomas may also behave in a high-grade manner.

Inhibition of Chemical Carcinogenesis in Mice by Ixora Coccinea Flowers

Topical application of 100 mg/kg body weight of the active fraction of Ixora coccinea flower inhibited the growth and delayed the onset of papilloma formation in mice, initiated and promoted with 7,12–dimethylbenz(a)anthracene (DMBA) and croton oil, respectively. The active fraction at the same dose, when administered orally, inhibited the growth of subcutaneously injected 3–methylcholanthrene – induced soft tissue fibrosarcomas.

Inhibition of chemical carcinogenesis by Psoralea corylifolia seeds

Psoralea corylifolia L. (Fabaceae) seeds are extensively used in Ayurvedic medicine. Topical application of 100 mg/kg body weight of the active fraction (AF) of P. corylifolia seeds inhibited the growth and delayed the onset of papilloma formation in mice, initiated with 7,12-dimethyl benz(a) anthracene and promoted using croton oil. The AF at the same dose, when administered orally, inhibited the growth of subcutaneously injected 20-methylcholanthrene (MCA) — induced soft tissue fibrosarcomas significantly. The AF has been shown by gas chromatography analysis to be composed of a mixture of glycerides of fatty acids.