The challenge of running trials in advanced angiosarcoma: A systematic review of the literature from EORTC/STBSG to guide the development of angiosarcoma-specific trials.

INTRODUCTION: While available systemic treatments have modest long term efficacy in advanced angiosarcoma, immunotherapy represents an interesting new therapeutic opportunity. To establish its benefit, it is required to conduct a clinical trial assessing its efficacy and toxicity compared to standard treatments. MATERIAL AND METHODS: This is a literature review from PubMed search. RESULTS: Several systemic treatments (chemotherapy and TKI) are currently used in advanced angiosarcoma with ORR ranging from 12.5 to 68 % and PFS from 2 to 7 months. However, few randomized trials, mainly phase II, has been conducted to compare these treatments. While most centers propose doxorubicin containing regimens or paclitaxel in 1st or 2nd line, a high heterogeneity of regimens administered in this setting is observed even across sarcoma specialized centers with no consensual standard treatment. Encouraging signals of immunotherapy activity have been reported in angiosarcoma from several retrospective and phase II studies assessing anti-PD1 either alone or in combination with anti CTLA4 or TKI. Although cutaneous and head and neck location seems to benefit more from immunotherapy, response may be observed in any angiosarcoma subtype. In sarcoma in general and AS in particular, no biomarker has been clearly established to predict the efficacy of immunotherapy: high tumor mutational burden and presence of tertiary lymphoid structures are under assessment. DISCUSSION: Even essential, developing a randomized clinical trial in AS struggles with the heterogeneity of the disease, the lack of consensual standard regimen, the uncertainty on optimal immunotherapy administration and the absence of established predictive biomarkers. CONCLUSION: International collaboration is essential to run randomized trial in advanced AS and asses the efficacy of immune therapy in this rare and heterogeneous disease.

Angiosarcoma: clinical outcomes and prognostic factors, a single-center analysis.

PURPOSE: This study sought to investigate oncological outcomes and prognostic factors for patients with angiosarcomas (AS). METHODS: This single-center, retrospective cohort study, analyzed histopathologically confirmed AS cases. Primarily diagnosed, locally recurrent and metastatic AS were included. Overall survival (OS), local control (LC) and local progression-free survival (LPFS) were assessed by Kaplan-Meier estimator. Multivariable Cox regression analysis was performed to detect factors associated with OS and LPFS. RESULTS: In total, 118 patients with a median follow-up of 6.6 months were included. The majority presented with localized disease (62.7%), followed by metastatic (31.4%) and locally recurrent (5.9%) disease. Seventy-four patients (62.7%) received surgery, of which 29 (39.2%) were treated with surgery only, 38 (51.4%) with surgery and perioperative radiotherapy or chemotherapy, and 7 (9.4%) with surgery, perioperative radiotherapy and chemotherapy. Multivariable Cox regression of OS showed a significant association with age per year (hazard ratio (HR): 1.03, p = 0.044) and metastatic disease at presentation (hazard ratio: 3.24, p = 0.015). For LPFS, age per year (HR: 1.04, p = 0.008), locally recurrent disease at presentation (HR: 5.32, p = 0.013), and metastatic disease at presentation (HR: 4.06, p = 0.009) had significant associations. Tumor size, epithelioid components, margin status, and perioperative RT and/or CTX were not significantly associated with OS or LPFS. CONCLUSION: Older age and metastatic disease at initial presentation status were negatively associated with OS and LPFS. Innovative and collaborative effort is warranted to overcome the epidemiologic challenges of AS by collecting multi-institutional datasets, characterizing AS molecularly and identifying new perioperative therapies to improve patient outcomes.

Exosome Therapy for a Nonhealing Scalp Wound Following Chemoradiation and Surgical Therapy.

This case report describes the safety and utility of a noninvasive therapy, Purified Exosome Product (PEP), for poorly healing scalp wounds in the setting of prior chemoradiation and surgery. A man in his 60s with a history of high-grade angiosarcoma of the right temporoparietal scalp reconstruction had a 1-year history of 2 nonhealing scalp wounds after neoadjuvant chemotherapy followed by concurrent chemoradiation therapy, wide local excision, and latissimus dorsi free flap and split-thickness skin graft. The patient underwent débridement followed by 4 collagen (Bellafill)-PEP and 4 fibrin (Tisseel)-PEP applications during 7 months in 2022. Photographs of the area of exposed bone of the temporoparietal wound were measured and standardized by ImageJ open-source software. The frontal wound was not routinely measured and therefore was qualitatively assessed by reviewing photographs over time. The frontal wound completely healed, and the temporoparietal wound showed a 96% decrease in overall size. The patient had no adverse effects of treatment and continues to demonstrate ongoing healing. This case exhibits the safety and utility of topical PEP therapy for noninvasive treatment of poorly healing scalp wounds and offers the potential for an alternative treatment of patients who are poor candidates for additional surgical intervention.

Outcome improvement with chemotherapy and radiotherapy in primary, localized, radiation-associated angiosarcoma of the breast region: a retrospective case series analysis.

BACKGROUND: We report on a series of consecutive patients with localized radiation-associated angiosarcoma (RAAS) of the breast region (BR) treated at two Italian sarcoma reference centers. MATERIALS AND METHODS: We retrospectively reviewed all cases of primary, localized, resectable RAAS of the BR, treated at one of the two participating institutions from 2000 to 2019. Relapse-free survival (RFS) and overall survival (OS) were calculated. The prognostic role of several variables was investigated. A propensity score matched (PSM) analysis was carried out. RESULTS: Eighty-four patients were retrospectively identified. Nineteen out of 84 patients (22.6%) were pretreated with an anthracycline-based regimen for previous cancer. All patients but one underwent surgery, with 37/84 (44.1%) receiving surgery alone and 46/84 (54.8%) a multimodal approach: 18/84 (21.4%) received radiation therapy (RT) and 46/84 (54.9%) received chemotherapy. An anthracycline-based regimen was used in 10/84 patients (11.9%), while a gemcitabine-based regimen was used in 33/84 (39.3%). With a median follow-up of 51 months (interquartile range: 30-126 months), 36/84 patients (42.9%) relapsed and 35/84 patients (41.7%) died (8/84, 9.5% in the lack of metastatic disease). Five-year OS and 5-year RFS were 57% [95% confidence interval (CI) 43% to 68%] and 52% (95% CI 39% to 63%), respectively. Both (neo)adjuvant RT and chemotherapy were associated with better RFS [hazard ratio (HR) 0.25, 95% CI 0.08-0.83; HR 0.45, 95% CI 0.23-0.89] with a trend towards a better OS (HR 0.51, 95% CI 0.18-1.46; HR 0.60, 95% CI 0.29-1.24). Gemcitabine-based regimens seemed to perform better (HR 4.28, 95% CI 1.29-14.14). PSM analysis retained the above results. CONCLUSIONS: This retrospective study supports the use of (neo)adjuvant RT and chemotherapy, in primary, localized resectable RAAS of the BR. An effort to prospectively validate the role of (neo)adjuvant RT and chemotherapy is warranted.

Etiology, pathogenesis, and management of angiosarcoma associated with implants and foreign body: Clinical cases and research updates.

Angiosarcomas are rare and highly malignant soft tissue sarcomas originating from endothelial cells lining the lymphatic or vascular system. While they predominantly emerge from (sub)cutaneous regions, occurrences have been reported throughout the body. The etiology of angiosarcoma remains elusive in most clinical cases. Nevertheless, several prognosis risk factors play a pivotal role, including chronic lymphedema, therapeutic irradiation, environmental carcinogens, familial syndromes, and the presence of foreign materials like metallic objects and biomedical implants. Despite evidence implicating retained foreign material in angiosarcoma development, understanding its prognosis and pathogenesis remains limited. The pathogenesis of angiosarcoma appears to involve a complex interplay of chronic inflammation, tissue remodeling, and genetic factors that create a conducive microenvironment for malignant transformation. Management of these sarcomas remains challenging due to their infiltrative nature owing to the high chance of metastasis and local recurrence. The primary treatment modalities currently include surgery, radiotherapy, and chemotherapy, but recent advances in targeted immunotherapy and gene therapy hold promise for more effective approaches. This comprehensive review delves into the potential etiological and pathogenic roles of foreign materials, such as metallic objects, biomedical implants, and biomaterials, in the development of angiosarcoma. Further research into the underlying molecular mechanisms could provide valuable insights for tailored management and developing novel targeted therapeutic strategies.

Generation of sarconoids from angiosarcoma patients as a systematic-based rational approach to treatment.

Angiosarcoma is a rare subtype of malignant neoplasm originating from vascular or lymphatic endothelial cells; its low incidence has posed significant challenges for comprehensive investigations into its pathogenic mechanisms and the development of innovative treatment modalities through in vitro and in vivo models. Recent endeavors spearheaded by patient-partnered research initiatives have aimed to elucidate the intricacies of angiosarcomas by leveraging biological omics approaches, with the overarching objective of enhancing prognostic indicators and therapeutic options for this uncommon pathology. To bridge the gap between preclinical research and translational applications, we engineered angiosarcoma-derived organoids from surgically resected primary tumors, hereafter referred to as "sarconoids," as a proof-of-concept model. A novel protocol for the establishment of these sarconoids has been developed and validated. To ensure that the sarconoids faithfully recapitulate the heterogeneity and complexities of the patients' original tumors, including transcriptomic signatures, cell-type specificity, and morphological traits, exhaustive histological and transcriptomic analyses were conducted. Subsequently, we expanded the scope of our study to include an evaluation of a sarconoid-based drug screening platform; for this purpose, a drug library (AOD IX), supplied by the National Cancer Institute's Developmental Therapeutics Program, was screened using 96-well plates. Our findings suggest that sarconoids can be reliably generated from angiosarcoma patient-derived tissues and can serve as accurate models for evaluating therapeutic responses, thereby holding far-reaching implications for translational research and clinical applications aimed at advancing our understanding and treatment of angiosarcoma.

Case report: Fatal overwhelming post-splenectomy infection in a patient with metastatic angiosarcoma treated with immunotherapy.

A patient in his 40s with splenic angiosarcoma metastatic to the liver underwent splenectomy, chemotherapy, and partial hepatectomy before being treated on a clinical trial with CTLA4 and PD1 inhibitors. He had received pneumococcal and meningococcal vaccines post-splenectomy. On week 10, he developed grade 3 immune-related colitis, successfully treated with the anti-tumor necrosis factor-alpha inhibitor infliximab and steroids. After 4 cycles of treatment, scans showed partial response. He resumed anti-PD1 therapy, and 6 hours after the second dose of anti-PD1 he presented to the emergency room with hematemesis, hematochezia, hypotension, fever, and oxygen desaturation. Laboratory tests demonstrated acute renal failure and septicemia (Streptococcus pneumoniae). He died 12 hours after the anti-PD1 infusion from overwhelming post-splenectomy infection (OPSI). Autopsy demonstrated non-viable liver tumors among other findings. In conclusion, patients undergoing immunotherapy and with prior history of asplenia should be monitored closely for OPSI as they may be at increased risk.

Lower Extremity Angiosarcoma: A Life-Threatening Complication of Lymphedema.

ABSTRACT: When angiosarcoma, a rare and aggressive tumor of the soft tissue, develops in the setting of chronic lymphedema, it is referred to as Stewart-Treves syndrome. It is usually seen in chronic lymphedema of the upper limbs postmastectomy. Angiosarcoma developing in the lower limb in the setting of chronic lymphedema is rare and has a poor outcome. The presentation of angiosarcoma can vary, ranging from a bleeding papule to a plaque or a subcutaneous mass, which can later progress to ulceration or necrosis. Treatment for Stewart-Treves syndrome is aggressive because of its poor prognosis and usually requires a multidisciplinary approach of surgery, radiation, and chemotherapy. Several theories have been put forth to explain the mechanism of Stewart-Treves syndrome, but it remains ambiguous. The current literature regarding angiosarcoma developing in the setting of chronic lymphedema in the lower limb is limited to single case reports. Herein, the authors report a series of six cases of biopsy-proven angiosarcoma in the setting of lower extremity lymphedema. Providers should include angiosarcoma in the differential diagnosis of ulcerative or vascular tumors arising in the context of lower extremity lymphedema.

Radiotherapy combined with anti-PD-1 and TKI for primary cardiac angiosarcoma considering the joint assessment of TLSs and PD-L1: a case report.

BACKGROUND: Primary cardiac angiosarcoma(PCA) has a low incidence rate and poor prognosis. Currently, no unified clinical treatment standards are available. CASE PRESENTATION: We report the case of a 48-year-old man presenting chest tightness, breathlessness, and dyspnea. Imaging and postoperative histopathologic studies confirmed PCA and that the tumor had invaded the entire right atrium. The patient developed progressive disease (PD) during postoperative radiotherapy. We used immunotherapy combined with targeted therapy based on the results of molecular profile and evaluation of tertiary lymphoid structures (TLSs) and programmed cell death-ligand 1 (PD-L1). After treatment, the metastatic lymph nodes of the patient were reduced to a certain extent, indicating that combination therapy was effective. CONCLUSION: To the best of our knowledge, this is the first report of radiotherapy combined with anti-PD-1 and tyrosine kinase inhibitors(TKI) for PCA. In addition, this is the first report on immunotherapy for PCA based on new evaluation methods, including TLSs, PD-L1, and genomic profile.

Primary splenic angiosarcoma: a case series of a rare oncological entity and diagnostic challenge.

BACKGROUND AND PURPOSE: Primary angiosarcoma of the spleen (PAS), an exceptionally rare and aggressive neoplasm with high metastatic risk (70%-85%), is frequently diagnosed in an advanced or metastatic stage. It presents diagnostic challenges due to its nonspecific symptomatology and resemblance to benign vascular lesions in various imaging modalities. PATIENTS AND METHODS: This case series aims to clarify the diagnostic difficulties by comparing imaging characteristics (CT-scan, MRI, and [18F]FDG-PET/CT) as well as pathological findings of three PAS cases diagnosed in different stages of the diseases (localized, metastatic, and metastatic with organ failure). Furthermore, a brief review on diagnostic and therapeutic features is included. RESULTS AND INTERPRETATION: We suggest [18F]FDG-PET/CT as a differentiating tool between benign and malignant splenic lesions and propose a flowchart of a diagnostic algorithm for PAS. For treatment, we advocate for early splenectomy and when systemic therapy is warranted, paclitaxel emerges as a viable first-line option. While it is crucial to acknowledge that further trial data is required to evaluate the efficacy of emerging treatment regimens, designing and conducting trials for PAS is challenging given its scarcity and aggressive behavior. Therefore case reporting remains important.

Treatment Monitoring of a Patient with Synchronous Metastatic Angiosarcoma and Breast Cancer Using ctDNA.

Angiosarcoma is a rare and aggressive type of soft-tissue sarcoma with high propensity to metastasize. For patients with metastatic angiosarcoma, prognosis is dismal and treatment options are limited. To improve the outcomes, identifying patients with poor treatment response at an earlier stage is imperative, enabling alternative therapy. Consequently, there is a need for improved methods and biomarkers for treatment monitoring. Quantification of circulating tumor-DNA (ctDNA) is a promising approach for patient-specific monitoring of treatment response. In this case report, we demonstrate that quantification of ctDNA using SiMSen-Seq was successfully utilized to monitor a patient with metastatic angiosarcoma. By quantifying ctDNA levels using 25 patient-specific mutations in blood plasma throughout surgery and palliative chemotherapy, we predicted the outcome and monitored the clinical response to treatment. This was accomplished despite the additional complexity of the patient having a synchronous breast cancer. The levels of ctDNA showed a superior correlation to the clinical outcome compared with the radiological evaluations. Our data propose a promising approach for personalized biomarker analysis to monitor treatment in angiosarcomas, with potential applicability to other cancers and for patients with synchronous malignancies.

Clinical recommendations for treatment of localized angiosarcoma: A consensus paper by the Italian Sarcoma Group.

Angiosarcoma (AS) represents a rare and aggressive vascular sarcoma, posing distinct challenges in clinical management compared to other sarcomas. While the current European Society of Medical Oncology (ESMO) clinical practice guidelines for sarcoma treatment are applicable to AS, its unique aggressiveness and diverse tumor presentations necessitate dedicated and detailed clinical recommendations, which are currently lacking. Notably, considerations regarding surgical extent, radiation therapy (RT), and neoadjuvant/adjuvant chemotherapy vary significantly in localized disease, depending on each different site of onset. Indeed, AS are one of the sarcoma types most sensitive to cytotoxic chemotherapy. Despite this, uncertainties persist regarding optimal management across different clinical presentations, highlighting the need for further investigation through clinical trials. The Italian Sarcoma Group (ISG) organized a consensus meeting on April 1st, 2023, in Castel San Pietro, Italy, bringing together Italian sarcoma experts from several disciplines and patient representatives from "Sofia nel Cuore Onlus" and the ISG patient advocacy working group. The objective was to develop specific clinical recommendations for managing localized AS within the existing framework of sarcoma clinical practice guidelines, accounting for potential practice variations among ISG institutions. The aim was to try to standardize and harmonize clinical practices, or at least highlight the open questions in the local management of the disease, to define the best evidence-based practice for the optimal approach of localized AS and generate the recommendations presented herein.

Brain radiotherapy and anlotinib control primary cardiac angiosarcoma with metastases: A case report.

RATIONALE: Primary cardiac angiosarcoma (PCA) is a rare and fatal disease with a poor prognosis. Whether the survival of PCA patients can be prolonged with additional treatment following complete surgical excision is controversial. PATIENT CONCERNS: In this case study, a 52-year-old male complained of chest tightness and pain for 7 days before admission into the hospital. Subsequently, he revisited the hospital because of dizziness and headache. DIAGNOSES: Initially, the patient was diagnosed with PCA in the right atrium by thoracic computed tomography (CT). Palliative resection identified brain, lung, and liver metastases. INTERVENTION: The patient accepted multimodal combination therapy, including first-line chemotherapy and then second-line anlotinib concurrent with brain radiotherapy and immunotherapy. OUTCOME: Although anlotinib combined with brain radiotherapy controlled the growth of intracranial lesions, progression-free survival (PFS) was only 5 months, and the overall survival (OS) was only 12 months. LESSON: The treatment for metastatic PCA needs an in-depth exploration.

Cutaneous Angiosarcoma Subtypes: A Quantitative Systematic Review of Demographics, Treatments, and Outcomes Within Published Patient-Level Cases.

BACKGROUND: Cutaneous angiosarcoma (cAS) is a highly aggressive malignancy arising from the vascular endothelium. Given its rarity, there is insufficient data detailing patient demographics, management, and survival outcomes. OBJECTIVE: To systematically compile published patient-level cases of cAS and to quantify and analyze data on demographics, management, and outcomes while determining prognostic indicators. MATERIALS AND METHODS: Searches of EBSCOhost, MEDLINE, EMBASE, and the Cochrane Library generated 1,500 cases of cAS with individual level data available. PRISMA guidelines were followed. RESULTS: Cutaneous angiosarcoma presented most often on the scalp of elderly men. Metastasis occurred in 36.3% of cases. Aggregate 5-year survival was 31.6% with the median survival of 25 months. The best 5-year survival was in the radiation-associated subtype (48.8%), whereas the worst was in the Stewart-Treves subtype (21.6%). Using multivariate analysis, gender, age group, disease subtype, treatment modality, and metastasis at presentation had significant effects on survival outcomes ( p < .05). CONCLUSION: The breadth of information obtained enables this study to serve as a resource that clinicians may reference when they encounter cAS.

Metastatic Maxillary Gingival Angiosarcoma with Aggressive Growth: A Case Report.

Angiosarcoma is a rare malignant tumor of endothelial origin. It is an aggressive neoplasm with early metastasis and poor prognosis and accounts for approximately 2% of all soft tissue sarcomas. Primary tumors arising in the oral cavity account for only 1% of all angiosarcomas. Here, we report a rare case of metastatic angiosarcoma of the gingiva originating from a primary mediastinal lesion. The patient was an 83-year-old man who presented with a maxillary interincisor tumor; it was a painless mass with rounded superficial necrosis measuring 23 mm× 17 mm on the labial side and 20 mm× 17 mm on the palatal side. The histopathological diagnosis was of an epithelioid angiosarcoma. Imaging revealed lesions in the mediastinum, lungs, liver, and skin. The primary lesion was considered a mediastinal lesion. As the tumor had spread throughout the body, palliative therapy was administered. However, the patient's general condition deteriorated rapidly, and he died 3 weeks after the first visit. Identifying oral metastatic malignancies may result in detection of malignant tumors at other sites; thus, oral and maxillofacial surgeons must maintain a heightened awareness of angiosarcoma.

Treatment of retroperitoneal sarcoma results in improved outcomes.

OBJECTIVE: To report the clinical characteristics, treatments, and outcomes in a cohort of dogs with histologically confirmed retroperitoneal sarcoma (RPS) and to identify potential variables of prognostic significance. ANIMALS: 46 client-owned dogs from 10 clinics with histopathologic diagnosis of a sarcoma originating from the retroperitoneal space. METHODS: Medical records were retrospectively reviewed to obtain information regarding clinical characteristics, treatments, and outcomes. Recorded variables were analyzed to report descriptive data for all cases and overall survival time. Multivariate analysis was utilized to evaluate prognostic factors for overall survival. RESULTS: Hemangiosarcoma was the most common histologic subtype diagnosed (76.1%). Cytoreductive and curative intent surgical excision of the RPS was attempted in 12 and 22 dogs, respectively; 12 dogs underwent no surgery or had an exploratory laparotomy with incisional biopsy only. Nineteen dogs received adjuvant chemotherapy, either injectable or metronomic, and 1 dog received adjuvant radiation therapy. Fourteen of the 34 (41.2%) surgically treated dogs developed evidence of local recurrence, but there was no difference in local recurrence when comparing dogs categorized as curative intent versus cytoreductive surgery. The median overall survival time was 238 days. On multivariable analysis, treatment approach was associated with survival with surgical excision (vs palliative treatment) and adjuvant chemotherapy following surgery being protective against death. A diagnosis of hemangiosarcoma was associated with a greater hazard of death. CLINICAL RELEVANCE: This study demonstrates a substantially greater survival time than previously published and suggests a survival benefit from surgical excision and adjuvant chemotherapy.

Isolated primary cardiac angiosarcoma.

Cardiac angiosarcoma (CAS) is the most prevalent malignant primary cardiac tumor in adults, often affecting young males. We present a case of this rare entity in a young female, highlighting the multidisciplinary team's role and multimodality imaging in the diagnosis and management.

Feline ventral abdominal wall angiosarcoma: haemangiosarcoma or lymphangiosarcoma? Clinical and pathological characteristics in nine cases.

OBJECTIVES: Angiosarcomas are rare malignant mesenchymal neoplasms of endothelial cell origin with a predilection to the ventral abdominal wall in cats. Larger case series describing this entity are lacking. METHODS: Two referral centre laboratory databases were searched for angiosarcoma of the ventral abdominal wall. Nine cases with a histological diagnosis were included. Immunohistochemistry (factor VIII and PROX-1 antibodies) was used to phenotype them as haemangiosarcoma or lymphangiosarcoma. RESULTS: All cats presented with a ventral abdominal mass, five of which were producing a serosanguinous discharge. Eight underwent tumour staging and pulmonary metastases were suspected in one cat (but not histologically confirmed). With histopathology alone, a diagnosis of angiosarcoma and lymphangiosarcoma was made in four and five cases, respectively. After immunohistochemistry, five cases had a haemangiosarcoma phenotype and four had a lymphangiosarcoma phenotype, including two cases of lymphangiosarcoma that were reclassified as hemangiosarcoma. Eight cats received treatment (either surgery with or without adjuvant therapies or medical management alone). Six cats were euthanased due to local disease progression. The median survival time for haemangiosarcoma was 166 days (range 137-381), and for lymphangiosarcoma it was 197 days (range 67-208). Two cats with haemangiosarcoma remained alive for a follow-up period of 329 and 580 days, respectively. CONCLUSIONS AND RELEVANCE: Feline ventral abdominal angiosarcomas are rare locally aggressive neoplasms. While histology often provides a diagnosis of angiosarcoma, immunohistochemistry is ultimately required to differentiate between haemangiosarcoma and lymphangiosarcoma phenotypes. Further studies are required to evaluate whether the different phenotypes have an impact on treatment response and outcome.

Tumor-Infiltrating Mast Cells in Angiosarcoma Correlate With Immuno-Oncology Pathways and Adverse Clinical Outcomes.

Recent studies have described several molecular subtypes and deregulation of immuno-oncologic signaling pathways in angiosarcoma. Interestingly, mast cells were enriched in subsets of angiosarcoma, although their significance remains unknown. In this study, we aim to verify this observation using immunohistochemistry (H scores) and NanoString transcriptomic profiling and explore the association between mast cells with clinical and biological features. In the study cohort (N = 60), H scores showed a significant moderate correlation with NanoString mast cell scores (r = 0.525; P < .001). Both H score and NanoString mast cell scores showed a significant positive correlation (P < .05) with head and neck location, nonepithelioid morphology, and lower tumor grade. Mast cell enrichment significantly correlated with higher NanoString regulatory T-cell scores (H score, r = 0.32; P = .01; NanoString mast cell score, r = 0.27; P = .04). NanoString mast cell scores positively correlated with signaling pathways relating to antigen presentation (r = 0.264; P = .0414) and negatively correlated with apoptosis (r = -0.366; P = .0040), DNA damage repair (r = -0.348; P = .0064), and cell proliferation (r = -0.542; P < .001). Interestingly, in the metastatic setting, patients with mast cell-enriched angiosarcoma showed poorer progression-free survival (median, 0.2 vs 0.4 years; hazard ratio = 3.05; P = .0489) along with a trend toward worse overall survival (median, 0.2 vs 0.6 years; hazard ratio, 2.86; P = .0574) compared with patients with mast cell-poor angiosarcoma. In conclusion, we demonstrated the presence of mast cells in human angiosarcoma and provided initial evidence of their potential clinical and biological significance. Future research will be required to elucidate their specific roles and mechanisms, which may uncover novel avenues for therapeutic intervention.

Gingival metastasis of angiosarcoma of the breast as a first manifestation of spreading disease: Case report and review of the literature.

BACKGROUND: Angiosarcoma is an aggressive malignant neoplasm of vascular origin. Oral metastases of angiosarcoma are rare and have a non-specific clinical presentation, thus the diagnosis may be challenging. CASE REPORT: Herein we report a case of a 34-year-old female patient after treatment of a high-grade angiosarcoma of the breast, who presented an asymptomatic bleeding purplish nodule in the maxillary interdental papilla between the first and second premolar. A biopsy was performed, and the histological examination revealed infiltration by malignant neoplasm of epithelioid and fusocellular pattern. Immunohistochemical analysis demonstrated that neoplastic cells were positive for ERG and CD31, and negative for cytokeratins AE1/AE3, confirming the diagnosis of metastatic angiosarcoma. After investigation, multiple metastases were discovered. The patient is under management with chemotherapy and palliative radiotherapy for the bone lesions. CONCLUSION: Metastases should be considered in the differential diagnosis of oral lesions in patients with a previous history of cancer. Due to the morphology of angiosarcomas, the metastatic lesions may resemble benign vascular lesions, therefore, biopsy is mandatory to exclude malignancy.