Primary breast angiosarcoma: A case report.

RATIONALE: Primary breast angiosarcoma is a rare tumor, accounting for only 0.05% of all malignant breast tumors. The primary breast angiosarcoma typically presents with nonspecific clinical manifestations, which can easily lead to misdiagnosis. Potential factors contributing to misdiagnosis include skin changes that may be erroneously attributed to breast trauma-induced bruising and breast swelling that may be mistaken for inflammatory diseases or other benign tumors. PATIENT CONCERNS: A 19-year-old female was admitted to the hospital due to repeated lump formation in the left breast for 9 months after left breast trauma. DIAGNOSES: The diagnosis of primary breast angiosarcoma was confirmed on hematoma biopsy. INTERVENTIONS: Due to the patient's condition, no special treatment was given postoperatively. After then, there was a recurrence in the chest wall, and the patient received 2 cycles of chemotherapy, resulting in a reduction in the size and lightening of the recurrent chest wall mass. When chemotherapy intolerance happened, the patient chose to discontinue treatment. OUTCOMES: After an 18-month follow-up, the recurrent chest wall mass increased and the patient died from bleeding. LESSONS: Primary breast angiosarcoma has a low incidence but high malignancy, with a high recurrence and metastasis rate, leading to a poor prognosis. The adjuvant chemotherapy, radiotherapy, targeted therapy, and other treatments should be considered to reduce the local recurrence rate and prolong patient survival.

Primary Pulmonary Angiosarcoma Found Incidentally in a Complicated Patient: A Rare Case Report.

INTRODUCTION: Primary pulmonary angiosarcoma (PPA) is a highly aggressive and rare malignancy originating from the endothelial cells of blood vessels in the lungs. PPA is an extremely rare subtype, with less than 30 cases reported to date. PPA is not only challenging to diagnose but also has a poor prognosis, often resulting in a high mortality rate within a year of diagnosis, regardless of the treatment approach. METHOD: We present the case of a 33-year-old woman with no significant past medical history who presented with abdominal pain and was incidentally found to have a right hilar mass with pleural effusion and empyema. After undergoing surgery for a perforated gastric ulcer, her pulmonary lesions were further worked up. Despite an extensive diagnostic evaluation, including imaging, bronchoscopy, and thoracotomy, establishing a diagnosis was challenging. Ultimately, PPA was diagnosed on surgical lung biopsy, and the patient was started on pazopanib and paclitaxel chemotherapy but expired after 1 month due to multiple complications. CONCLUSION: This case highlights the difficulty in diagnosing this rare tumor and its poor prognosis regardless of therapy. Greater awareness of PPA and more research are needed to improve early detection and treatment options for this deadly disease.

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.

Cutaneous Angiosarcoma.

This case report describes a 42-year-old woman with cutaneous angiosarcoma and venous malformation of the nasal tip.

An Update on Cutaneous Angiosarcoma Diagnosis and Treatment.

Cutaneous angiosarcoma (CAS) is a rare aggressive malignancy that most commonly manifests in White men older than 60 years and often appears as an enlarging ecchymosis on the head, neck, or scalp. Surgery with negative margins is the first-line treatment. The role of Mohs micrographic surgery (MMS) is uncertain but can be used in smaller, well-circumscribed lesions on the head and neck. The greatest impact that dermatologists can have in the management of CAS is through a thorough total-body skin examination and heightened awareness resulting in a shortened time to diagnosis. Until quality evidence allows for the creation of consensus guidelines, multidisciplinary care at a cancer center that specializes in rare difficult-to-treat tumors is essential in optimizing patient outcomes.

Angiosarcoma: hiding in plain sight.

Angiosarcoma is a rare, aggressive soft-tissue sarcoma of endothelial origin that necessitates early recognition, diagnosis, and treatment. The most commonly reported presentation consists of violaceous patches and plaques on the head and neck of elderly white men, with fewer reports affecting patients with Skin of Color. Most cases of angiosarcoma are idiopathic and tend to recur locally with early metastasis, conferring a poor prognosis. We report a case of an 83-year-old Fitzpatrick skin type IV man who presented with a large violaceous-to-black mamillated plaque on the frontotemporal scalp that was clinically highly suggestive of cutaneous angiosarcoma. However, unrevealing histopathology complicated our diagnostic process and delayed management. Immunohistochemistry was invaluable in determining the diagnosis of angiosarcoma. Our case highlights the aggressive nature of cutaneous angiosarcoma, necessitating close clinicopathologic correlation to confirm the diagnosis and initiate treatment.

Imaging primary cardiac angiosarcoma: case-based illustrations with multimodality imaging and emphasis on the role of positron emission tomography-CT.

Primary cardiac angiosarcomas are extremely rare, highly aggressive tumours with rapid progression and high metastatic capability. More than 60% of tumours are detected after the onset of a metastatic disease. In the two cases presented, we demonstrate the role of muti-modality imaging in the diagnosis of the lesion and provide valuable input in prognosticating the disease burden. In both cases, the diagnosis was suspected initially by imaging, based on radiological observations, before the final histopathology confirmation was made. Positron emission tomography- (PET-CT) was a critical component of the diagnostic workup for the detection of disease extent and volume of total disease burden. Hence, PET-CT imaging should be performed in all aggressive appearing cardiac tumours. In view of misleading clinical presentation, we suggest that aggressive workup to be performed in suspected patients. Young patients presenting with vague symptoms and those with recurrent, unresolving, unexplained pericardial effusion deserves special consideration.

Porcine-derived Acellular Dermal Matrix for Temporary Soft Tissue Coverage in Locally Advanced Angiosarcoma of the Face - A Soft Tissue Odyssey?

BACKGROUND/AIM: Angiosarcomas of the face are rare but present significant treatment challenges due to their origin in the supportive tissues of blood or lymphatic vessels. Achieving optimal balance between oncological efficacy and aesthetic outcomes requires a multidisciplinary approach, particularly in cases where radical R0 resection is necessary. Delays often occur, especially during histopathological examinations, which can complicate primary plastic reconstruction before definitive pathological findings. CASE REPORT: To address this issue, we present a case with the use of porcine-derived acellular dermal matrix for temporary soft tissue coverage as a viable option in a case of angiosarcoma of the face. This is particularly useful in situations where frozen sections risk the loss of critical anatomical structures and intraoperative diagnosis is not feasible. This approach allowed for satisfactory wound coverage and granulation during diagnostic phases, paving the way for oncologically manageable situations and functional rehabilitation. CONCLUSION: Temporary soft tissue coverage with porcine-derived acellular dermal matrix is a valuable option in tumor surgery of rare and complex situations.

Primary Epithelioid Angiosarcoma of the Submandibular Gland-A Case Report with Histology-Cytology Correlation and Comprehensive Molecular Analysis.

BACKGROUND: Angiosarcoma is a sarcoma that occurs in a range of tissue types, and only rarely in the salivary glands, showing a predilection for the parotid glands of older patients. Preoperative diagnosis may be challenging, especially on cytology, with significant morphological overlap with high-grade primary salivary gland carcinomas. The molecular alterations of this rare salivary gland neoplasm are also not well-characterized. METHODS AND RESULTS: We present a case of right submandibular gland swelling in a 73-year-old male. On fine needle aspiration, including immunohistochemical stains on cell block, the tumor was initially diagnosed as poorly differentiated carcinoma. Resection of the submandibular gland revealed epithelioid angiosarcoma. We performed molecular work-up of the tumor, utilizing targeted next-generation sequencing, DNA methylation profiling and fluorescence in-situ hybridization. Histopathologic assessment revealed an infiltrative tumor comprising solid sheets of epithelioid cells. The tumor cells formed haphazardly anastomosing vascular channels with intracytoplasmic lumina containing red blood cells. On immunohistochemistry, the tumor cells were positive for CD31, CD34 and ERG. Approximately 40% of the tumor cells showed nuclear expression of GATA3. A pathogenic TP53 R267W mutation was detected on next-generation sequencing. DNA methylation analysis did not cluster the tumor with any known sarcoma type. Copy number analysis showed possible MYC amplification and CDKN2A losses, although only the latter was confirmed on fluorescence in-situ hybridization. CONCLUSION: Epithelioid angiosarcoma is an important differential diagnosis to high-grade salivary gland carcinoma. In particular, GATA3 expression may be encountered in both angiosarcoma and high-grade salivary gland carcinomas and cause diagnostic confusion. Identification of TP53 mutations and CDKN2A losses suggest shared oncogenic pathways with soft tissue angiosarcomas, and should be further investigated.

Prognostic value of tumour-related factors associated with canine retroperitoneal hemangiosarcoma in comparison with other anatomic presentations: A retrospective observational study.

BACKGROUND: Dogs with retroperitoneal hemangiosarcoma (HSA) exhibit variable postoperative median survival times (MST). OBJECTIVE: To retrospectively evaluate the prognostic value of selected tumour-related factors, such as tumour size, rupture, invasion into adjacent tissue, involvement of lymph node and distant metastasis, they were analysed in dogs with retroperitoneal HSA. METHODS: Ten dogs with retroperitoneal HSA managed solely with surgical excision were reviewed and compared with spleen (71) and liver (9) HSA. The Kaplan-Meier method and log-rank analysis were used compare MSTs between factors. Multivariable Cox proportional-hazard analysis was used to compare differences between arising sites. RESULTS: Retroperitoneal HSA showed comparatively longer postoperative MST compared with that of spleen and liver HSA and demonstrated significantly longer MST (p = 0.003) for tumours ≥5 cm (195 days) than <5 cm (70 days). Spleen HSA revealed significantly shorter MSTs in involvement of distant lymph nodes (23 days) and distant metastasis (39 days) than those in negative (83 days, p = 0.002 and 110 days, p < 0.001, respectively). Liver HSA also revealed significantly shorter MST (16.5 days compared with 98 days, p = 0.003) for distant metastasis. Additionally, hazard ratios (HRs) and their forest plot for overall HSA revealed as poor prognostic factors, arising sites (spleen; HR 2.78, p = 0.016 and liver; HR 3.62, p = 0.019), involvement of distant lymph nodes (HR 2.43, p = 0.014), and distant metastasis (HR 2.86, p < 0.001), and as better prognostic factor of tumour size ≥5 cm (HR 0.53, p = 0.037). CONCLUSION: In combination with overall HSA, retroperitoneal HSA shows comparatively longer postoperative MST compared to spleen and liver HSA, associated with tumour size ≥5 cm suggesting better prognostic factor.

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.

Pseudolymphomatous Cutaneous Angiosarcoma Presenting With Persistent Firm Facial Edema in a Patient With Systemic Sclerosis.

ABSTRACT: Pseudolymphomatous cutaneous angiosarcoma (cAS) is a rare subtype characterized by a prominent lymphocytic infiltrate, posing diagnostic challenges due to its resemblance to lymphoid neoplastic processes. We present a novel case highlighting the clinical and histopathological features, notably its association with persistent firm facial edema in a patient with systemic sclerosis (SSc). A 47-year-old woman with a 21-year history of SSc presented with firm palpebral edema evolving to involve the entire face and cervical region over six months. Diagnostic imaging revealed inflammatory changes in orbital regions, supradiaphragmatic lymphadenopathies, and lytic lesions. Skin biopsy demonstrated a diffuse neoplasm with vascular channels and solid areas, accompanied by dense lymphocytic proliferation. Pseudolymphomatous cutaneous angiosarcoma, a rare malignant neoplasm, exhibits variable clinical presentations and rapid progression. Histologically, it manifests as irregularly shaped vascular channels lined by prominent endothelial cells. Immunohistochemistry, particularly markers such as v-ets erythroblastosis virus E26 oncogene homolog (avian) (ERG), aids in diagnosis. Notably, this case marks the first presentation of cAS with persistent facial edema in SSc, highlighting the association between SSc and cancer risk. This case underscores the diagnostic challenges posed by cAS and emphasizes the importance of early detection for optimal patient outcomes. Further understanding of its association with autoimmune disorders such as SSc is crucial for comprehensive management strategies.

Clinicopathologic and molecular correlates to neoadjuvant chemotherapy-induced pathologic response in breast angiosarcoma.

Both primary and secondary breast angiosarcoma (AS) are characterized by multifocal presentation and aggressive behavior. Despite multimodality therapy, local and distant relapse rates remain high. Therefore, neoadjuvant chemotherapy (NACT) is employed to improve the R0 resection rates and survival, but its benefits remain controversial. Herein, we investigate pathologic and molecular correlates to NACT-induced histologic response in a group of 29 breast AS, 4 primary and 25 radiation-associated (RA). The two NACT regimens applied were anthracycline- and non-anthracycline-based. The pathologic response grade was defined as: I: ≤ 50%, II: 51%-90%, III: 91%-99%, and IV: 100%. An additional 45 primary AS and 102 RA-AS treated by surgery alone were included for survival comparison. The genomic landscape was analyzed in a subset of cases and compared to a cohort of AS without NACT on a paired tumor-normal targeted DNA NGS platform. All patients were females, with a median age of 31 years in primary AS and 68 years in RA-AS. All surgical margins were negative in NACT group. The NACT response was evenly divided between poor (Grades I-II; n = 15) and good responders (Grades III-IV; n = 14). Mitotic count >10/mm2 was the only factor inversely associated with pathologic response. By targeted NGS, all 10 post-NACT RA-AS demonstrated MYC amplification, while both primary AS harbored KDR mutations. TMB or other genomic alterations did not correlate with pathologic response. All four patients with Grade IV response remained free of disease. The good responders had a significantly better disease-specific survival (p = 0.04). There was no survival difference with NACT status or the NACT regimens applied. However, NACT patients with MYC-amplified tumors showed better disease-free survival (p = 0.04) compared to MYC-amplified patients without NACT. The overall survival of NACT group correlated with size >10 cm (p = 0.02), pathologic response (p = 0.04), and multifocality (p = 0.01) by univariate, while only size >10 cm (p = 0.03) remained significant by multivariate analysis.

Metastasizing aneurysmal dermatofibroma initially diagnosed as angiosarcoma confirmed by CD63::PRKCD fusion gene detection with nanopore sequencing.

Dermatofibroma (DF) is a benign tumor that forms pedunculated lesions ranging in size from a few millimeters to 2 cm, usually affecting the extremities and trunks of young adults. Histopathologically, DF is characterized by the storiform proliferation of monomorphic fibroblast-like spindle cells. In addition to neoplastic cells, secondary elements such as foamy histiocytes, Touton-type giant cells, lymphoplasmacytes, and epidermal hyperplasia are characteristic histological features. Several histological variants, including atypical, cellular, aneurysmal, and lipidized variants, have been reported; cases with variant histologies are sometimes misdiagnosed as sarcomas. We present a case of metastasizing aneurysmal DF that was initially diagnosed as an angiosarcoma on biopsy. A 26-year-old woman was referred to our hospital with a gradually enlarging subcutaneous mass in her lower left leg. Positron emission tomography-computed tomography revealed high fluorodeoxyglucose uptake not only in the tumor but also in the left inguinal region. On biopsy, ERG and CD31-positive atypical spindle cells proliferated in slit-like spaces with extravasation, leading to the diagnosis of angiosarcoma. Histology of the wide-resection specimen was consistent with DF, and lymph node metastasis was also observed. Nanopore DNA sequencing detected CD63::PRKCD fusion and copy number gain, although CD63 was not included in the target region of adaptive sampling. This report highlights the importance of recognizing the unusual clinical, radiological, and pathological features of DF to avoid misdiagnosis, and the potential diagnostic utility of nanopore sequencer.

Recurrent fever leading to the diagnosis of an angiosarcoma of the adrenal gland: a case report.

BACKGROUND: Angiosarcoma of the adrenal gland is a very rare malignant vascular neoplasm. The clinical symptoms are atypical or completely absent. Angiosarcomas of the adrenal gland are therefore often discovered incidentally, and the diagnosis is made histologically after resection. CASE PRESENTATION: A 46-year-old white Spanish male who was a previous smoker and nondrinker and was slightly overweight (92 kg, 176 cm, body mass index 29.7 kg/m2) with no relevant medical history presented to the internal medicine emergency department of our hospital with an unclear 12 cm tumor of the right adrenal gland. Prior to the computed tomography scan, he had had persistent evening fevers for 4 months and unintentional weight loss of 5 kg. The laboratory results showed anemia and an elevated C-reactive protein, but no hormone production. We performed an open adrenalectomy of the right adrenal gland. Finally, the histologic findings revealed an angiosarcoma of the adrenal gland. CONCLUSION: Even though angiosarcomas of the adrenal gland are rare, the differential diagnosis of an angiosarcoma should be considered if a malignant tumor of the adrenal gland is suspected. Treatment decisions should be made on an interdisciplinary basis and preferably in a specialized center. Owing to the rarity of angiosarcomas of the adrenal gland, it is necessary to continue to share clinical experience to gain a better understanding of this particular tumor entity.

Hemangiosarcoma Cells Promote Conserved Host-derived Hematopoietic Expansion.

Hemangiosarcoma and angiosarcoma are soft-tissue sarcomas of blood vessel-forming cells in dogs and humans, respectively. These vasoformative sarcomas are aggressive and highly metastatic, with disorganized, irregular blood-filled vascular spaces. Our objective was to define molecular programs which support the niche that enables progression of canine hemangiosarcoma and human angiosarcoma. Dog-in-mouse hemangiosarcoma xenografts recapitulated the vasoformative and highly angiogenic morphology and molecular characteristics of primary tumors. Blood vessels in the tumors were complex and disorganized, and they were lined by both donor and host cells. In a series of xenografts, we observed that the transplanted hemangiosarcoma cells created exuberant myeloid hyperplasia and gave rise to lymphoproliferative tumors of mouse origin. Our functional analyses indicate that hemangiosarcoma cells generate a microenvironment that supports expansion and differentiation of hematopoietic progenitor populations. Furthermore, gene expression profiling data revealed hemangiosarcoma cells expressed a repertoire of hematopoietic cytokines capable of regulating the surrounding stromal cells. We conclude that canine hemangiosarcomas, and possibly human angiosarcomas, maintain molecular properties that provide hematopoietic support and facilitate stromal reactions, suggesting their potential involvement in promoting the growth of hematopoietic tumors. SIGNIFICANCE: We demonstrate that hemangiosarcomas regulate molecular programs supporting hematopoietic expansion and differentiation, providing insights into their potential roles in creating a permissive stromal-immune environment for tumor progression.

Proposed diagnostic and prognostic markers of primary malignant hepatic vascular neoplasms.

INTRODUCTION: Primary malignant hepatic vascular tumors with various malignant potentials include epithelioid hemangioendothelioma (EHE) and angiosarcoma (AS), which may overlap pathologically. This study aimed to compare the pathological findings of hepatic EHE with those of AS, in association with patient outcomes. METHODS: Fifty-nine histologically confirmed patients with 34 EHE and 25 AS were admitted to a tertiary hospital from 2003 to 2020. Their EHE and AS pathological features were compared. Immunohistochemistry for CD31, ERG, CAMTA-1, TFE3, P53, and Ki-67 labeling was performed on paraffin-embedded blocks. Markers, along with histological findings, were analyzed for the purposes of diagnostic and prognostic significance by multivariate analysis. RESULTS: CAMTA-1 was 91.2% positive in EHE, but negative in AS (p = < 0.001). AS was significantly correlated to an aberrant p53 expression, high Ki-67 labeling, and high mitotic activity, compared to EHE (all, p = < 0.001). EHE can be classified as low grade (LG) and high grade (HG) using the prognostic values of mitotic activity and ki-67 labeling (sensitivity = 1, specificity = 1). Low grade-EHE showed significantly better overall survival than high grade-EHE (p = 0.020). CONCLUSIONS: Immunohistochemistry for CAMTA-1, P53, and Ki-67 labeling may help distinguish EHE and AS in histologically ambiguous cases, especially small biopsied tissue. Moreover, the combination of mitotic activity and Ki-67 labeling can be a prognostic factor for EHE with various clinical features.