Undifferentiated High-grade Pleomorphic Sarcoma Research Articles

Undifferentiated High-Grade Pleomorphic Bone Sarcoma: A Case Report

Undifferentiated High-Grade Pleomorphic Bone Sarcoma: A Case Report

Undifferentiated pleomorphic sarcoma in a white-eared opossum (Didelphisalbiventris)

We report a case of high-grade undifferentiated pleomorphic sarcoma in a free-living white-eared opossum (Didelphis albiventris) in Central Brazil. Grossly, it appeared as a soft yellow mass, approximately 8 cm in diameter, with an irregular, adherent and ulcerated surface, which extended from the proximal epiphysis of the femur to the proximal third of the tibia and fibula. The mass invaded the medullary cavity and had a necrotic centre. Multiple nodular metastases (0.5–1.5 cm) were present in the liver, lungs and spleen. Histologically, the neoplasm was characterized by pleomorphic cells with indistinct boundaries, many multinucleated cells, necrosis and tissue invasion. There was intense cytoplasmic immunolabelling of neoplastic cells for vimentin and moderate cytoplasmic and nuclear labelling for human muscle actin, human smooth muscle actin and lysozyme. Immunolabelling for Iba1, CD18, CD1A, cytokeratin AE1/AE3, glial fibrillary acidic protein and desmin was negative. To our knowledge, this is the first report of an undifferentiated pleomorphic sarcoma in this species.

High-grade Undifferentiated Pleomorphic Sarcoma Presenting as Acquired Lymphangioma Circumscriptum

A previously healthy woman in her 40s presented to the dermatology clinic with a 1-year history of a tender, draining, enlarging mass on the left buttock. Physical examination revealed an extensively indurated hyperpigmented nodule with numerous overlying clustered exophytic verrucous papules on the L medial buttock (see figure 1). Initial skin biopsy of verrucous lesions was notable for lymphangioma with overlying condyloma, D2-40 positive. MRI abdomen and pelvis with contrast demonstrated a left gluteal enhancing subcutaneous soft tissue mass, 10.3 x 8.2 x 8.8 cm in size, overlying and involving the left gluteus maximus, along with satellite nodules present in the medial gluteus maximus and paraspinal muscles, with bilateral pelvic and inguinal adenopathy. Excisional deep tissue biopsy revealed a diagnosis of a high-grade, multifocal spindle and undifferentiated pleomorphic sarcoma. The patient subsequently underwent 4 cycles of neoadjuvant chemotherapy AIM (doxorubicin, iphosphamide, MESNA), followed by radical resection of the left gluteal region, with positive margins, followed by repeat surgical resection and reconstruction with left-sided latissimus dorsi myocutaneous free flap. The patient has now completed radiation therapy.
 Soft tissue sarcoma is a heterogeneous group of rare malignancies of mesenchymal origin, that represents 0.8% of all adult cancers. Prognostic factors associated with poor outcome include high histologic grade, large tumor size, presence of metastases, and unresectability1. Herein, we report a novel case of high-grade soft-tissue undifferentiated pleomorphic sarcoma, masquerading as acquired lymphangioma circumscriptum (ALC), as noted on initial skin biopsy of grouped flesh-colored verrucous papules overlying an indurated tender mass. ALC is a lymphatic malformation occurring as sequela to any process which interrupts previously normal lymphatic drainage. As such, subcutaneous lymphatic cisterns are unable to drain completely into the general lymphatic system, resulting in lymphatic dilation and subsequent development of vesicular and papular lesions on the trunk, extremities, and anogenital areas.2 ALC can mimic common infectious growths including molluscum contagiosum and condyloma accuminata, and accordingly be mismanaged. Etiologic causes of ALC including malignancy, and has previously been reported in the setting of cervical carcinoma, vulvar carcinoma, endometrial carcinoma, Hodgkin lymphoma, rhabdomyosarcoma, rectal carcinoma, melanoma, and high-grade penile dysplasia2,3,4. Other etiologic causes can include surgery, trauma, radiation therapy, chronic inflammatory conditions including hidradenitis suppurativa, and inflammatory bowel disease.
 To date, acquired lymphangioma circumscriptum has not been reported in the setting of underlying high-grade pleomorphic soft tissue sarcoma. As such, clinical presence of grouped frogspawn-like or verrucous papules, in an area of tender induration or lymphedema, should prompt a work-up to exclude an underlying malignant etiology as new onset ALC may be masquerading an underlying malignancy.

A case of undifferentiated high-grade pleomorphic sarcoma of bone in the mandible

A case of undifferentiated high-grade pleomorphic sarcoma of bone in the mandible

Neoadjuvant radiation influences the pseudocapsule in soft tissue sarcoma: A histopathologic and radiographic evaluation

Background and objectivesA pseudocapsule surrounds soft tissue sarcoma (STS). Its composition, response to neoadjuvant radiation, and clinical significance are poorly understood. MethodsSeventeen cases of high-grade undifferentiated pleomorphic sarcoma (UPS) were reviewed, ten of which were treated with neoadjuvant radiation. Magnetic resonance imaging (MRI) studies, pathology slides, and patient records were reviewed. ResultsIrradiated pseudocapsules were well-demarcated with fewer viable tumor cells and were thicker on both pathology and MRI measurements when compared to non-irradiated pseudocapsules (p < 0.001, p = 0.04, respectively). Pseudocapsule mean pathology width (MPW) was positively correlated with tumor necrosis percentage (p = 0.044), and negatively correlated with mitotic rate (p = 0.043), though pseudocapsule width measured on MRI did not correlate with these prognostic factors. Despite an evident treatment response to neoadjuvant radiation, viable tumor cells were present within the pseudocapsule and the surrounding healthy tissue. ConclusionsThe pseudocapsule in STS responds to radiation and there appears to be a correlation between pseudocapsule width and tumor necrosis and mitotic activity. As viable tumor cells are present beyond the pseudocapsule, surgeons should remain cautious in determining margins of resection in STS when using the pseudocapsule as a palpable landmark. This novel study is the most detailed to date to describe the histopathologic and radiographic characteristics of the STS pseudocapsule. Further studies are needed to determine the clinical significance of the pseudocapsule.

Undifferentiated high-grade pleomorphic sarcoma of the colon: a rare case report and literature review

BackgroundUndifferentiated pleomorphic sarcoma (UPS), also known as malignant fibrous histiocytoma (MFH), hardly originates from the colorectum.Case presentationWe reported a 65-year-old female presented with UPS in the descending colon. Computed tomography (CT) revealed an irregularly thickened descending colon. On colonoscopy examination, an ulcerative tumour was identified. The patient received radical resection of the left colon and partial enterectomy. The resected tumor was ulcerative, 10 cm × 8 cm × 5 cm in size, and infiltrated the serosa layer. Postsurgical pathology showed that the tumor was high-graded UPS in the colon with large amounts of necrotic tissues.ConclusionsUPS in the large intestine is a rare malignant tumor with a poor prognosis and unknown pathogenesis. The main treatment for UPS is early complete resection. Postsurgery adjuvant radiotherapy or chemotherapy can be attempted.

High-grade undifferentiated pleomorphic sarcoma in the gluteus with a v-y flap: a case report

High-grade undifferentiated pleomorphic sarcoma in the gluteus with a v-y flap: a case report

A case of undifferentiated pleomorphic sarcoma of a retro-gastric origin, case report and review of literature.

Introduction and importanceUndifferentiated pleomorphic sarcoma (UPS) is one of the most common sarcomas affecting elderly patients, majority of UPS usually in the extremities, trunk, and retroperitoneum. However, its rarely observed in the digestive system. There are minimal data published regarding this topic.Case presentationHere we present a 58 years old female patient with a rare case of the pleomorphic sarcoma of retro-gastric mass measures about (24.7 × 23.5 × 17.4 cm) who underwent exploration laparotomy founded a freely and mobile retro-gastric mass measuring 30 × 20 cm with a cystic and solid component. The mass was freely and mobile located with no true gastric relation is the first one to be reported.Clinical discussionThe undifferentiated pleomorphic sarcomas or MFH has been regarded as the most common soft tissue sarcoma for many years (Kabashima et al., 2017). The incidence increases with age, with an inclusive incidence of about 1–2 cases per 100,000 patients per year, predominately 1.2:1 for males. Undifferentiated pleomorphic sarcoma of the stomach is rare and counted to have a worse prognosis when compared to the other types of pleomorphic malignant fibrous histiocytoma.ConclusionWe present a rare case of high-grade undifferentiated pleomorphic sarcoma of the retro-gastric mass with no invasion to the surrounding structures, managed with surgical resection of the tumor.

High-grade undifferentiated pleomorphic cardiac sarcoma: A rare malignant primary cardiac tumor mimicking double mitral lesion

High-grade undifferentiated pleomorphic cardiac sarcoma: A rare malignant primary cardiac tumor mimicking double mitral lesion

High-grade Pleomorphic Sarcoma Associated with Metallosis in a Patient with Total Hip Arthroplasty.

Although the relationship between hip arthroplasty and the development of sarcoma was first described in the literature about forty years ago, this association is extremely rare. In the present case report, we describe the association between orthopedic implants and soft tissue sarcoma in a 79-year-old man who underwent primary total hip arthroplasty (THA) for coxarthrosis 24 years ago. In the present case report, we describe the clinical evolution and the radiographic and histopathological findings of the lesion. In the intraoperative period of the second revision surgery, loosening of the acetabular and femoral components in association with extensive areas of necrosis and metallosis was evidenced. We performed debridement of the hip and right thigh region and removed the implants. Due to the extent of the lesion and to necrosis, it was not possible to perform a new joint reconstruction. The histopathological diagnosis of high-grade undifferentiated pleomorphic sarcoma associated with extensive areas of metallosis was confirmed in tissue adjacent to the implant. The patient developed pulmonary metastases and died 6 months after the diagnosis. Despite the rarity of this association, sarcomas should be considered in the differential diagnosis of aseptic loosening, especially in the presence of metallosis in the peri-implant tissue. To our knowledge, the 24-year latency period between primary THA and the establishment of a sarcoma diagnosis is one of the longest reported to date.

S1721 A Rare Finding in the Colon: Undifferentiated Pleomorphic Sarcoma

Introduction: Undifferentiated pleomorphic sarcoma (UPS) is a rare and incompletely understood condition that commonly appears in the extremities and retroperitoneum. Involvement of the bone and digestive organs is rare. We describe the case of a 78-year-old man who was incidentally diagnosed with UPS of the colon after workup of uncontrolled lower back pain. Case Description/Methods: A 78-year-old man with extensive tobacco use initially presented to his primary care provider with intractable back pain and a 10lb weight loss. His exam was notable for paraspinal muscle tenderness, but otherwise unremarkable. A subsequent computed tomography (CT) abdomen and pelvis was negative. Given these findings and a suspicion for a musculoskeletal diagnosis, he was treated conservatively. Despite initial therapies, he experienced no clinical improvement. Further imaging with magnetic resonance imaging (MRI) of the spine showed a pathologic fracture of T12 and metastatic vertebral disease causing spinal cord compression. A follow up CT showed pulmonary nodules at the lung bases also concerning for metastatic disease. A set of follow up labs showed an elevated carcinoembryonic antigen (CEA) level of 7.4 ng/mL. He was referred to gastroenterology for expedited colonoscopy and malignancy workup in the setting of an elevated CEA. Colonoscopy revealed one 5-9 mm sessile cecal polyp. Cold snare removal of the polyp was unsuccessful because of resistance and the firmness of the lesion. A biopsy was obtained instead. While awaiting pathology, he underwent decompressive laminectomy and spinal stabilization with tumor biopsy of T12 for further neoplastic workup. Pathology of both the cecal polyp and the T12 intervertebral disc revealed high-grade UPS. Given the extent of disease, palliative radiation and chemotherapy were offered however the patient passed away shortly thereafter. Discussion: UPS is a rare and aggressive neoplasm; diagnosis is challenging because patients are often asymptomatic unless there is nerve involvement and because of its rapid development. Our patient presented with back pain which was attributed to a musculoskeletal ailment. Upon further investigation with a colonoscopy and biopsy, UPS was discovered. Although gastrointestinal metastasis is rare, it is important to consider a broad differential when a benign appearing polyp cannot be excised in a standard fashion.

Update and interpretation of 2021 National Comprehensive Cancer Network (NCCN) "Clinical Practice Guidelines for Bone Tumors"

The incidence of primary malignant bone tumors is low, and clinical cognition is insufficient. The establishment of diagnostic criteria is of great significance for prognosis of tumors. National Comprehensive Cancer Network (NCCN) regularly publishes "Clinical Practice Guidelines for Bone Tumors" to summarize the latest treatment progress of bone tumors. In the latest version of the guidelines released in November 2020, surgery is the main treatment for chondrosarcoma, chordoma, and giant cell tumor of bone, which can be combined with radiotherapy or targeted therapy. Ewing's sarcoma and osteosarcoma are treated by surgery combined with chemotherapy. Immunotherapy can be used to treat high-grade undifferentiated pleomorphic sarcoma. For recurrent tumors, surgery combined with radiotherapy, chemotherapy, and/or targeted therapy can be used for control. The guidelines provide a reference for the standard treatment of bone tumors.

An Undifferentiated High-Grade Pleomorphic Sarcoma of Spleen Presenting as a Splenic Abscess

An Undifferentiated High-Grade Pleomorphic Sarcoma of Spleen Presenting as a Splenic Abscess

The 'other' bone sarcomas in Japan: a retrospective study of primary bone sarcomas other than osteosarcoma, Ewing sarcoma and chondrosarcoma, using data from the Bone Tumuor Registry in Japan.

To date, no standard treatments for primary bone sarcomas other than those for osteosarcoma, Ewing sarcoma and chondrosarcoma have been developed. The clinical characteristics and prognostic factors of 330 patients with primary bone sarcomas other than osteosarcoma, Ewing sarcoma and chondrosarcoma, listed in a nationwide tumour registry (Bone and Soft Tissue Tumor Registry in Japan) were investigated. The effects of adjuvant chemotherapy were determined by comparing the outcomes of patients with non-metastatic bone tumours who received surgery plus chemotherapy with those of patients who underwent surgery alone. The most common diagnosis was undifferentiated high-grade pleomorphic sarcoma. Axial site tumours (47.8%) and distant metastases at presentation (24.5%) were frequent. The 5-year overall and progression-free survival rates were 44.9 and 39.9%, respectively. Prognostic factor analysis identified surgery as an independent predictor of overall survival, and distant metastases at presentation was significant and independent predictor of both overall and progression-free survival. No significant difference in outcome was observed between patients treated with surgery alone and those treated with surgery plus chemotherapy (P=0.71). Patients with bone sarcomas other than osteosarcoma, Ewing sarcoma and chondrosarcoma without metastasis at presentation have a relatively good prognosis with definitive surgery; however, the benefit of adjuvant chemotherapy is unclear.

High-grade Undifferentiated Pleomorphic Sarcoma

High-grade Undifferentiated Pleomorphic Sarcoma

Highly Cancellous Titanium Alloy (TiAl6V4) Surfaces on Three-Dimensionally Printed, Custom-Made Intercalary Tibia Prostheses: Promising Short- to Intermediate-Term Results.

Custom-made, three-dimensionally-printed (3D) bone prostheses gain increasing importance in the reconstruction of bone defects after musculoskeletal tumor resections. They may allow preservation of little remaining bone stock and ensure joint or limb salvage. However, we believe that by constructing anatomy-imitating implants with highly cancellous titanium alloy (TiAl6V4) surfaces using 3D printing technology, further benefits such as functional enhancement and reduction of complications may be achieved. We present a case series of four patients reconstructed using custom-made, 3D-printed intercalary monobloc tibia prostheses treated between 2016 and 2020. The mean patient age at operation was 30 years. Tumor resections were performed for Ewing sarcoma (n = 2), high-grade undifferentiated pleomorphic bone sarcoma (n = 1) and adamantinoma (n = 1). Mean resection length was 17.5 cm and mean operation time 147 min. All patients achieved full weight-bearing and limb salvage at a mean follow-up of 21.25 months. One patient developed a non-union at the proximal bone-implant interface. Alteration of implant design prevented non-union in later patients. Mean MSTS and TESS scores were 23.5 and 88. 3D-printed, custom-made intercalary tibia prostheses achieved joint and limb salvage in this case series despite high, published complication rates for biological and endoprosthetic reconstructions of the diaphyseal and distal tibia. Ingrowth of soft tissues into the highly cancellous implant surface structure reduces dead space, enhances function, and appears promising in reducing complication rates.

Sarcoma pleomorfico indiferenciado de alto grado de auricula izquierda una entidad infrecuente: reporte de un caso

Introducción: La prevalencia de tumores cardíacos primarios en la autopsia varía de 0.001% a 0.3%. Las neoplasias primarias benignas son más comunes que las masas malignas. Los tumores cardíacos malignos primarios son predominantemente de naturaleza sarcomas, pueden presentarse con una variedad de síntomas. La presentación clínica depende principalmente del tamaño del tumor.&#x0D; Objetivo: Describir un caso clínico de sarcoma pleomórfico indiferenciado de alto grado de aurícula izquierda una entidad infrecuente.&#x0D; Material y métodos: Estudio descriptivo retrospectivo, presentación de caso clínico sarcoma pleomórfico indiferenciado de alto grado de aurícula izquierda una entidad infrecuente.&#x0D; Resultados: Se presenta el caso de una paciente de 66 años de edad que ingresa por presentar cuadro compatible con neumonía atípica, tratándose como tal, al no evidenciarse mejoría se solicitaron complementarios concluyéndose sarcoma pleomórfico indiferenciado de alto grado, se realiza exceresis de masa, sin embargo paciente fallece aproximadamente a los 3 meses por complicaciones cardiopulmonares.&#x0D; Conclusiones: La escasa frecuencia de presentación de sarcomas primarios de corazón, así como el reto diagnóstico que implican hace que sea importante conocer su situación actual y manejo y cobra vital importancia el diagnostico precoz para un adecuado abordaje, siendo herramientas diagnosticas con especial valor la ecocardiografía transesofágica principalmente al realizar un diagnóstico diferencial y la resonancia magnética que demuestra con gran precisión la masa tumoral y la extensión a pericardio o vasos de gran calibre.

Abstract 1117: XenoSarc: Patient-derived xenograft (PDX) models of soft tissue sarcoma (STS) and their histopathological and molecular characterization

Abstract Background: STS constitutes a rare family of mesenchymal tumors with more than 70 subtypes classified by WHO (2013). The limited treatment options available for advanced STS underline the need for reliable preclinical models, especially from ultra-rare subtypes, to test novel therapeutic strategies. Methods: A panel of PDX models was established by subcutaneous implantation of fresh tumor specimens in immunodeficient, athymic nude NMRI mice. Once tumor growth was observed, pieces of tumor were re-transplanted to next generations of mice. At each passage tumor fragments were collected for histopathological and molecular characterization. A model was considered “established” after observing stable histological and molecular features for at least two passages. Furthermore, ex-mouse tumor tissue samples were stored, further characterized by immunocytology and flow cytometry and cultured to be used for in vitro drug testing. Results: Between September 2011 and November 2019, 375 STS samples from 325 consenting patients treated at the University Hospitals, Leuven, Belgium have been transplanted. A total of 56 PDX models were established, maintaining the histopathological and molecular features of the original tumor. Detailed clinical information about the donor patient and tumor characteristics (including sensitivity to standard and experimental agents), is known for every model. At present the XenoSarc platform includes ready to use models of dedifferentiated liposarcoma (11 models), gastrointestinal stromal tumor (8), myxofibrosarcoma (8), leiomyosarcoma (7), malignant peripheral nerve sheath tumor (3), synovial sarcoma (2), pulmonary artery intimal sarcoma (2), epithelioid hemangioendothelioma (1), mesenchymal chondrosarcoma (1), pleomorphic rhabdomyosarcoma (1), CIC-rearranged round cell sarcoma (1), myxoinflammatory fibroblastic sarcoma (1), rhabdomyosarcoma not otherwise specified (NOS) (1), telangiectatic extraskeletal osteosarcoma (1), extraskeletal osteosarcoma (1) and high-grade undifferentiated pleomorphic sarcoma (7). These models are well-characterized, including molecular information on copy number changes (by low-coverage whole genome sequencing), gene expression profile (by RNA-Seq) and targeted sequencing to detect mutations in genes involved in tumorigenesis. In addition, we have constructed tissue microarrays (TMA) from the xenografts which are used for target identification and model selection for preclinical studies. We are using the xenografts for in vivo testing of novel agents, including targeted and cytotoxic (pro-)drugs, and results already served as rationale for a number of prospective clinical trials. A total of 27 other xenografts are still in early stages of engraftment, not yet fulfilling our criteria of an “established” model. Conclusion: The XenoSarc platform offers a lot of opportunities for studying the biology of a variety of important sarcoma subtypes including ultra-rare entities, and has proven efficiency for early drug screening in STS in preparation of clinical testing of novel compounds. The platform is well maintained and continuously expanded, and available to collaborators from academia and industry. Citation Format: Agnieszka Wozniak, Britt Van Renterghem, Jasmien Cornillie, Yannick Wang, Che-Jui Lee, Jasmien Wellens, Ulla Vanleeuw, Madita Nysen, Daphne Hompes, Friedl Sinnaeve, Hazem Wafa, Baki Topal, Tom Verbelen, Maria Debiec-Rychter, Raf Sciot, Patrick Schöffski. XenoSarc: Patient-derived xenograft (PDX) models of soft tissue sarcoma (STS) and their histopathological and molecular characterization [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1117.

Vertical restrictive strabismus associated with proptosis: Similar clinical signs, different etiopathogenetic causes. A report of three patients.

To report the different uncommon pathogenesis of three cases of severe vertical restrictive strabismus associated with progressive unilateral proptosis with similar clinical features. Case series of three patients who presented to the Orbit Outpatient Service of Policlinico Gemelli with a history of left progressive unilateral proptosis, slowly worsening vertical strabismus and the left eye fixed in downward position. A thorough hematologic work up was performed. All patients underwent complete abdomen ultrasonography, orbital contrast enhanced magnetic resonance imaging, forced duction test under general anesthesia, and orbital biopsy. Patients were 30, 60, and 46 years old respectively. MRI showed left inferior rectus enlargement in two cases and superior rectus enlargement in one case, with contrast enhanced combined muscle belly and tendon enlargement in all cases. Patients underwent forced duction test, muscle weakening (in two cases), and muscle biopsy with histopathologic examination. The superior rectus appeared infiltrated by an undifferentiated high-grade pleomorphic sarcoma, whereas the two inferior recti were positive for idiopathic orbital inflammatory disease with fibrosis areas and neuromuscular choristoma, respectively. Although proptosis and acquired vertical restrictive strabismus are most commonly associated with thyroid associated orbitopathy (TAO), they can also be a manifestation of many other conditions and the differential diagnosis can be particularly challenging. The three reported cases presented indeed with similar clinical features but had three distinct underlying orbital etiologies, two of which were extremely uncommon.

Antiproliferative effect of bupivacaine on patient-derived sarcoma cells.

Sarcomas are rare tumors with limited treatment options. Although chemotherapy is standard for certain subtypes, overall survival has not improved in several decades. Bupivacaine has been shown to induce apoptosis and prevent cell growth in multiple different types of malignancies but has not been studied in sarcoma. The current study evaluated the effects of bupivacaine on multiple patient-derived sarcoma cells and a commercial sarcoma cell line. Multiple patient-derived sarcoma cell subtypes and a commercial synovial cell sarcoma cell line were exposed to bupivacaine for different durations and at different concentrations. The patient-derived cells included a high-grade conventional osteosarcoma, a high-grade undifferentiated pleomorphic sarcoma of bone, and a high-grade synovial sarcoma. Flow cytometry and an MTT assay were used to evaluate whether a treatment effect was observed. Treatment of all the subtypes of sarcomas in this study with bupivacaine demonstrated a time- and dose-dependent increase in apoptosis and decrease in cell viability. A cell viability assay demonstrated that the IC50 was between 0.04 and 0.05% and that the treatment effect occurred at clinically relevant doses in vitro. Bupivacaine was toxic to both the patient-derived cells and the commercial cell line at doses commonly used in the clinical setting. These findings provide a foundation for further in vivo studies to evaluate whether these effects will translate to the clinical setting. Although further research is necessary, bupivacaine shows promise as not only an adjunct for pain management but as a treatment modality for sarcoma.