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Results for “Soft-tissue sarcomas”

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At least 19 recordsLinked to original sources
PubMed1976

The management of soft-tissue sarcomas of the extremities.

Of fifty-four patients with a soft-tissue sarcoma of an extremity, having a projected five-year survival rate of 62 per cent, forty-six treated by an "adequate" surgical procedure (either radical local resection or ablation at an appropriate level, depending on defined circumstances) had a local recurrence rate of 2 per cent. In the other eight patients, whose surgical procedures were not adequate for one reason or another, the local recurrence rate was 100 per cent. The combined recurrence rate after both the adequate and the inadequate procedures was 16.7 per cent. The recurrences were noted prior to thirty months post-operatively and the metastases, prior to sixty months. Histogenesis of the sarcoma, one or more recurrences after previous operations, and treatment by an immediate definitive procedure at the time of biopsy and diagnosis by frozen section had no significant relationship to the rates of local recurrence or metastasis. Adequate radical local resection controlled these sarcomas as well as ablative surgery in terms of local recurrence and metastasis. The significant factors affecting local recurrence that were identified in this study were the location of the sarcoma and the adequacy of the surgical procedure.

Adolescent↗
PubMed2024

Oncogene-induced matrix reorganization controls CD8+ T cell function in the soft-tissue sarcoma microenvironment.

CD8+ T cell dysfunction impedes antitumor immunity in solid cancers, but the underlying mechanisms are diverse and poorly understood. Extracellular matrix (ECM) composition has been linked to impaired T cell migration and enhanced tumor progression; however, impacts of individual ECM molecules on T cell function in the tumor microenvironment (TME) are only beginning to be elucidated. Upstream regulators of aberrant ECM deposition and organization in solid tumors are equally ill-defined. Therefore, we investigated how ECM composition modulates CD8+ T cell function in undifferentiated pleomorphic sarcoma (UPS), an immunologically active desmoplastic tumor. Using an autochthonous murine model of UPS and data from multiple human patient cohorts, we discovered a multifaceted mechanism wherein the transcriptional coactivator YAP1 promotes collagen VI (COLVI) deposition in the UPS TME. In turn, COLVI induces CD8+ T cell dysfunction and immune evasion by remodeling fibrillar collagen and inhibiting T cell autophagic flux. Unexpectedly, collagen I (COLI) opposed COLVI in this setting, promoting CD8+ T cell function and acting as a tumor suppressor. Thus, CD8+ T cell responses in sarcoma depend on oncogene-mediated ECM composition and remodeling.

CD8-Positive T-Lymphocytes↗
PubMed1978

Early lymphatic spread of osteogenic and soft-tissue sarcomas.

Records of 374 patients referred to the National Cancer Institute with a diagnosis of sarcoma over a 24-year period were reviewed to study the incidence of lymph node involvement in this disease. One hundred and thirteen patients had operations involving the draining nodal area and evaluation of these nodes for tumor. Only three patients (2.6%) had evidence of sarcoma metastatic to draining lymph nodes. Prophylactic removal or radiotherapy of draining lymph node areas in most adults with sarcomas does not appear to be worthwhile. A comprehensive analysis of the literature is presented.

Adolescent↗
PubMed1978

Radiation-induced soft-tissue and bone sarcoma.

From the records of Memorial Hospital of the past 50 years, 47 cases with an established diagnosis of radiation-induced sarcoma were identified and divided into two groups: the first included 20 cases of soft-tissue sarcoma arising from irradiated tissues, and the second comprised 27 cases of bone sarcoma arising from normal bones in the irradiated field. Medians for the latent periods from irradiation to diagnosis of bone and soft-tissue sarcoma were 11 and 12, years, respectively. In bone sarcomas, the latent period was longer after larger radiation doses and children appeared to be more susceptible to cancer induction than adults. Criteria for establishing the diagnosis of radiation-induced sarcoma and the magnitude of the risk of bone sarcoma are discussed.

Adolescent↗
PubMed2025

The first case of GOLGA5-RET fusion-positive malignant spindle cell sarcoma of the head and neck responsive to selpercatinib.

Soft-tissue sarcoma (STS) is a rare malignancy that accounts for less than 1% of all cancers, and recent advances in molecular biology have led to its classification based on genomic information. Some RET-rearranged neoplasms have been reported to present pathological features similar to Neurotrophic Tyrosine Kinase Receptor-rearranged spindle cell neoplasms. Here, we report the first case of head and neck spindle cell sarcoma with a GOLGA5-RET fusion that demonstrated a sustained clinical response to selpercatinib, identified through targeted next-generation sequencing (NGS). The patient was a 43 year-old man with a tumor in the arytenoid region that was resected and diagnosed as a malignant spindle cell tumor. Despite initial treatment with surgical resection alone, local recurrence was confirmed, requiring salvage therapy with total laryngectomy and bilateral cervical dissection. Surgical specimen revealed a spindle tumor with a patternless pattern and collagenous stroma. Immunohistochemistry (IHC) with positivity for CD34, bcl-2 (focally), S100, and weak nuclear staining for STAT6, with absence of expression of CK AE1/3, desmin, c-kit, smooth muscle actin, myogenin, synaptophysin, and SOX10. Trk A/B/C were also negative on IHC. Following confirmation of multiple lung metastases, the patient was treated with doxorubicin monotherapy. Targeted NGS identified GOLGA5-RET rearrangement, FGF14 amplification (equivocal), CDKN2B loss, and CDKN2A loss. GOLGA5-RET rearrangements were validated through fluorescence in situ hybridization. The patient subsequently was enrolled in a phase 1/2 trial for the selective RET inhibitor selpercatinib, resulting in a sustained partial response over 5 years. Although solitary fibrous tumor (SFT) was initially considered as a differential diagnosis based on immunohistochemical findings, the lack of strong and diffuse STAT6 expression made this diagnosis unlikely. Subsequent next-generation sequencing (NGS) revealed a RET fusion, leading to the diagnosis of an RET-rearranged spindle cell neoplasm. This case highlights the importance of genomic testing for certain spindle cell sarcomas and the potential benefit of RET-specific inhibitors against RET-altered sarcomas.

Next-generation sequencing↗
PubMed1977

Thymus-dependent and nonthymus-dependent lymphocytes in patients with sarcomas.

Several measurements indicate that cellular and humoral immunity is depressed in patients with sarcoma; but whether such observations reflect diminished numbers of lymphocytes and their subpopulations is not known. We determined the numbers of peripheral leukocytes, lymphocytes, rosette-forming thymus-dependent cells (T cells), and nonthymus-dependent SmIg-bearing cells in 134 patients with various mesenchymal sarcoma and in 47 normal controls. In all of these determinations, patients and controls gave similar values. Furthermore, values for patients with or without tumor, with or without metastasis, and with bone or soft-tissue sarcomas were similar. All 134 patients were studied prospectively, and the 84 who remained free of disease after 6 months had virtually identical values to the 50 who showed disease progression.

B-Lymphocytes↗
PubMed1979

Genealogy of cancer in a family.

Three brothers had separate childhood cancers--osteogenic sarcoma, acute lymphoblastic leukemia, and bilateral malignant neurilemoma. Comprehensive family history showed a total of 16 cases of cancer among the descendants of the proband's great-great-great-grandmother, including a previously unsuspected cluster of similar neoplasms in an distant branch. The constellation of tumors in the family included bony and soft-tissue sarcomas, brain and neural tumors, leukemia, and breast carcinoma, occurring in a pattern suggesting the action of an incompletely penetrant autosomal dominant gene with pleiotropic effects. In some cases the genetic predisposition may have interacted with environmental determinants to produce particular tumors.

Adolescent↗
PubMed1979

Steroid receptors in sarcomatous lesions.

Clinical observations showed that the natural history of sarcomatous lesions may be different among males and females, and it may be influenced by hormonal factors. Estrogen receptors (ER) were measured on biopsy specimens of melanoma (two patients), soft-tissue sarcoma (four patients), cystosarcoma phylloides (five patients), benign breast tissues (27 patients), and breast carcinoma (109 patients). Thirty-four specimens also had progesterone receptors (PR) analyzed. One of the five cystosarcoma phylloides and five of the six nonmammary sarcoma tissues contained ER (mainly of the 4 Svedburg (S) variety) of more than 7 femtomoles (fmoles)/mg cytosol proteins (6/11 = 54%). For comparison three of the 14 fibroadenoma specimens and two of the 13 patients with other benign lesions had positive ERs (5/27 = 19%), whereas 56% of the breast carcinomas were ER positive. Since the amount of 8S ER found in sarcomatous tissues is relatively low, hormonal treatment would not be effective.

Adenocarcinoma↗
PubMed2026

Driver genomic lesions in MDM2, CDK4, and JUN co-opt targetable super-enhancer networks to impose liposarcomagenic core regulatory circuitry.

INTRODUCTION: Amplification of chromosome 12q13-15 spanning MDM2 and CDK4 genes serves as a molecular diagnostic hallmark of dedifferentiated liposarcoma (DDLPS), an aggressive soft-tissue sarcoma. Epigenetic activation of master transcription factors (RUNX proteins, FOSL2, and MYC) establishes a self-reinforcing oncogenic transcriptional circuitry in DDLPS. Nevertheless, the collaborative interplay between genomic alterations and epigenetic dysregulation in defining DDLPS cell identity remains elusive. OBJECTIVES: This work aimed to elucidate the primary genetic drivers and mechanistic basis of DDLPS-specific core transcriptional regulatory circuitry. METHODS: We performed integrative chromatin profiling analysis of DDLPS clinical specimens and cell lines to map cis-regulatory landscapes. Cistromes of MDM2, JUN, and E2F1 were delineated through chromatin immunoprecipitation sequencing in two DDLPS models. Essential driver functions and transcriptional regulatory effects of key regulators were assessed via various genetic manipulation approaches. Synergistic interactions between BET-targeting agents and MDM2/p53 or CDK4 inhibitors were quantified by cell viability assays. In vivo xenograft assays evaluated the oncogenic potential of key regulators and the therapeutic efficacy of novel strategies. RESULTS: Co-amplification of MDM2, CDK4, and JUN during sarcomagenesis converges with BET protein-dependent chromatin remodeling to fuel feed-forward transcriptional circuits among master transcription factors. Mechanistically, excessively expressed MDM2 stabilizes the core regulatory circuitry by forming chromatin-bound complexes with JUN/FOSL2 at cis-regulatory elements, especially super-enhancers across DDLPS genome. Concurrently, CDK4 maintains expression of E2F1 which further fosters transcriptional output of master transcription factors in DDLPS cells. Leveraging DDLPS-selective overexpression of MDM2 and its E3 ligase activity, targeted degradation of BET proteins by MDM2-recruiting proteolysis targeting chimera selectively disrupted the core regulatory circuitry, suppressing DDLPS growth and exhibiting strong synergy with CDK4 inhibitor. CONCLUSION: DDLPS-associated genomic lesions collaborate with BET-dependent chromatin regulation to establish disease-sustaining transcriptional circuitry. Our findings also provide a mechanistic rationale for harnessing MDM2's E3 ligase activity to therapeutically degrade oncoproteins in MDM2-amplified malignancies.

Core transcriptional regulatory circuitry↗
PubMed1979

Induction of new-bone formation in the host bed by human bone-tumor transplants in athymic nude mice.

UNLABELLED: Specimens of twelve osteosarcomas, five chondrosarcomas, one giant-cell tumor, and five extraskeletal soft-tissue sarcomas were transplanted into male athymic nude (nu/nu) mice. Survival of the transplant was determined by the volume-doubling time and the sex chromatin of the tumor cells obtained from two female patients. By these criteria and the similarity of the histological composition of the original tumor and the transplant, survival occurred in four of twelve osteosarcomas and four of five chondrosarcomas. Without any local infiltration of lymphocytes or plasma cells, or other evidence of cell-mediated immunity, the surviving tumors regressed by the fourth week after the operation. Transformed osteoblasts and osteoprogenitor cells were replaced by fibrous connective tissue or fibrogenic tumor-tissue cells. Osteocytes degenerated and disappeared from the lacunae. The one giant-cell tumor transplant survived, growing very slowly, but by the end of the first week after transplantation whorls of mononucleated cells appeared in sites previously occupied by multinucleated cells. Transplants of leiomyosarcoma, liposarcoma, and synovioma (one tumor of each) degenerated. One of two fibrosarcomas survived transplantation. The most striking reaction of the mouse host bed was to encompass six of twelve osteosarcomas and four of five chondrosarcomas in deposits of normal living cartilage, bone, and bone marrow. The incidence of new bone inducedy by living transplants was only slightly greater than by implants of freeze-dried killed osteosarcoma tissue. Not one of five extraskeletal sarcomas, living or dead, induced bone formation. These observations suggest that an osteoinductive agent is transmitted by some osteosarcomas and chondrosarcomas. This agent initiates differentiation of host mesenchymal cells into normal non-tumorous cartilage and bone, which later colonized by bone marrow. CLINICAL RELEVANCE: Our observations present experimental evidence of the origin of the envelope of normal non-tumorous bone that may surround tumorous bone. In 1926, Phemister recognized the clinical significane of this envelope as a pitfall in the differential diagnosis of malignant bone tumors, chondrosarcoma, myositis ossificans circumscripta, and other neoplasms. He emphasized the importance of examining the entire specimen for the distribution of deposits of tumorous and normal bone. The induction of normal bone formation in the host bed surrounding transplants of osteosarcomas and some chondrosarcomas (but not transplants of fibrosarcoma, liposarcoma, or leiomyosarcoma) is evidence of a specific tumor-cell characteristic. Thus, the bone inductive response is not an unspecific reaction to injury from expansion or of tumor growth but a biological response to tumor-cell products. Transplants of human malignant tumors growing in the thymus-deficient mouse can be treated by combinations of radiation, amputation, and new chemotherapeutic agents...

Adolescent↗
PubMed1978

Subsequent cancer in patients with chronic lymphocytic leukemia--a possible immunologic mechanism.

Among 4,869 patients with chronic lymphocytic leukemia (CLL) from the series of the End Results Program of the National Cancer Institute, Bethesda, Maryland, second primary cancers developed in 234 patients, compared to 204.9 expected. The risk was significantly elevated for malignant melanoma, soft-tissue sarcomas, and lung cancer. The frequency of rectal cancer was also elevated, but not significantly. The excess risk for these specific sites persisted throughout the period of follow-up, suggesting a susceptibility state that complicated the leukemic process rather than suggesting methodologic, diagnostic, or therapeutic effects. Immunologic defects to CLL may be involved in the etiology of excess risk for these sites, because a similar array of nonlymphoid tumors was seen following therapeutic immunosuppression among renal transplant recipients.

Colonic Neoplasms↗
PubMed1979

Quantitative scanning of osteogenic sarcoma with nitrogen-13-labeled L-glutamate.

N-13 L-glutamate was used to image an osteogenic sarcoma in a 9-year-old patient. Serial quantitative measurements of the amount of N-13 taken up by the primary tumor showed a decrease of 40% after 10 wk of chemotherapy. Blood-clearance data obtained from normal subjects indicate that more than 90% of the N-13 activity had left the blood before scanning of the tumor was begun. It appears that the N-13 label concentrated in the soft-tissue portion of this osteogenic sarcoma, whereas Tc-99m diphosphonate uptake was greatest in the regions where calcification was occurring.

Child↗
PubMed1977

Garré's osteomyelitis of the mandible. Report of a case.

A case of Garré's disease has been reported. This case is atypical in that the patient presented with only a periosteal bone mass and a negative history of toothache, abscess, or trauma to the area. Because of this, diagnosis was not possible without microscopic examination. Atypical cases of this nature cause diagnostic problems, and several disease states must be considered in a differential diagnosis. These include the following: 1. Ewing's sarcoma, which also occurs in this age group and may show cortical reduplication on radiographic examination. The prognosis in cases of Ewing's sarcoma is poor, and death may occur in a matter of weeks. 2. Infantile cortical hyperostosis (Caffey's disease), which is characterized by development of soft-tissue swelling and cortical thickening of the mandible. The disease runs a benign course and regresses without treatment. 3. Osteogenic sarcoma, which occurs in slightly older age groups but presents as a cortical expansion with facial deformity. The disease is highly malignant and carries a poor prognosis.

Child, Preschool↗