Malignant transformation of an intraparenchymal hemangioma in the cervical spinal cord of a German shepherd dog.

An 8-year-old female spayed German shepherd dog was presented for evaluation of a 1-week history of right thoracic limb monoparesis. Magnetic resonance imaging (MRI) identified an intraparenchymal, T2 hypointense and T1 isointense, strongly heterogeneously contrast-enhancing mass with moderate internal susceptibility artifact on T2* images at the level of the cranial extent of the C5 vertebral body. Euthanasia was elected after a rapid neurologic decline in the 24 hours after MRI. Necropsy and histopathology identified an intraparenchymal hemangiosarcoma arising from a hemangioma in the cervical spinal cord, with no evidence of neoplastic disease in any other examined organs. The spectrum of vasoproliferative disorders in the central nervous system in veterinary species has been codified recently, but hemangiosarcoma is considered metastatic to the central nervous system. Herein we describe the clinical, imaging, and histologic findings in a dog with a novel primary location of hemangiosarcoma in the cervical spinal cord.

Molecular Analysis of Renal/Adrenal Angiosarcomas Reveals High Frequency of Recurrent Genetic Alterations.

Angiosarcomas of the kidney and adrenal gland are rare, highly aggressive vascular neoplasms. Their genomic profile has not been systematically studied to date. We report the clinicopathologic and molecular features of six angiosarcomas centered in the kidney/adrenal gland. All patients were male adults, ranging from 58 to 77 years of age. Tumor sizes ranged from 2.5 to 22.5 cm. Half of the cases demonstrated hot spot mutations in the KDR gene, while one-third demonstrated mutations in the PIK3CA gene; both of these gene alterations being previously described, preferentially in breast angiosarcomas. In addition, two cases each demonstrated BRIP1 gene amplification, CTNNB1 and ETV6 mutations, which have not been previously reported in angiosarcoma. Notably, molecular studies were critical in establishing the correct diagnoses in three cases: one was an epithelioid angiosarcoma originally misdiagnosed as metastatic adenocarcinoma to the adrenal gland, the second was a vasoformative angiosarcoma that mimicked hemangioma, and the third was a collision tumor between a high-grade angiosarcoma and a chromophobe renal cell carcinoma which was originally diagnosed as a sarcomatoid renal cell carcinoma. In summary, angiosarcomas of the kidney and adrenal gland have a high frequency of recurrent genetic alterations, some of them being shared with other angiosarcoma subtypes, while other appear to be novel. In particular, activating hot spot KDR and PIK3CA mutations represent potential therapeutic targets for these highly aggressive cancers.

HEMANGIOSARCOMA IN RED WOLVES (CANIS RUFUS) AND GRAY WOLVES (CANIS LUPUS) IN HUMAN CARE: SIX CASES.

Wolves are commonly housed in zoological institutions and captive breeding facilities that are essential for maintaining genetic diversity and for the recovery of declining populations. Neoplasia is a common cause of mortality in wolves, but hemangiosarcoma has not previously been described. This condition was diagnosed in four red wolves (Canis rufus) and two gray wolves (Canis lupus) housed at five different institutions between 2008 and 2018. Animals were 11-16 yr of age at the time of presentation. Clinical signs included loss of body condition, abdominal distension, lethargy, weakness, ataxia, and hyporexia. Three animals were mildly anemic. All animals were humanely euthanized within an average of 3 d from onset of clinical signs. Two animals had primary splenic tumors, two had pelvic tumors with one originating from the aorta, and one had a cranial mediastinal mass. Diagnosis was made on postmortem histologic examination in all cases. Four wolves had evidence of metastases with foci in the lungs, lymph nodes, mesentery, liver, subcutis/skeletal muscle, kidney, adrenal, and thyroid gland. Hemangiosarcoma should be considered in geriatric wolves presenting with nonspecific signs, particularly if abdominal distension, free peritoneal fluid, or anemia is present.

Circulating nucleosomes as a potential cancer biomarker in dogs with splenic nodular lesions.

Splenic nodular lesions in dogs can be either benign or malignant. They might be discovered incidentally or, in case of rupture, they may lead to hemoabdomen. Nevertheless, splenectomy followed by histopathology is essential for diagnosis and to prevent rupture. Yet, this invasive procedure might be postponed for dogs with benign splenic nodular lesions. Conversely, owners may opt for euthanasia over surgery for malignancies with poor prognosis like hemangiosarcoma. Thus, anticipating diagnosis with non-invasive biomarkers is crucial for proper patient management. In this prospective study, plasma samples were collected from 66 dogs with histologically confirmed splenic nodular lesions. A canine-specific ELISA kit was applied to assess nucleosome concentration, with histopathology of the spleen serving as the gold standard. Nucleosome concentration was found to be significantly higher in dogs with malignant splenic nodular lesions, particularly in those with hemangiosarcoma and other malignancies. The presence of hemoabdomen, more prevalent in dogs with splenic malignancy, also resulted in increased plasmatic nucleosome concentrations. Plasma nucleosomes could serve as a biomarker for detecting malignant splenic nodular lesions in dogs. More research is needed to understand how nucleosome concentration relate to disease stage and prognosis in dogs with hemangiosarcoma.

Recognising angiosarcoma presenting as an enlarging ecchymotic plaque.

Cutaneous angiosarcoma (cAS) is a rare malignant neoplasm of vascular endothelial origin with an unfavourable prognosis. Its diagnosis often faces delays due to its manifestation as an inconspicuous 'bruise-like' lesion in an otherwise asymptomatic individual, leading to a generally low index of suspicion for angiosarcoma. Here, we present a case of a man who presented to his general practitioner with an ecchymotic plaque on his forehead, initially thought to be benign. Over the subsequent 6 weeks, the lesion progressively enlarged and became ulcerated, prompting the patient to represent to his general practitioner. He was urgently referred to a dermatologist and a subsequent biopsy confirmed the diagnosis of cAS. Our presentation of this case serves as a reminder for physicians to maintain a high index of suspicion and low threshold for biopsy for patients with atraumatic ecchymotic lesions.

Synchronous primary breast angiosarcoma with invasive ductal carcinoma.

Primary angiosarcoma (PAS) of the breast is an extremely uncommon variant of breast malignancies. Highly aggressiveness and dismal prognosis characterize this endothelial neoplasm. We report here an unusual case of PAS of the breast occurring in a 46-year-old woman associated with concurrent bilateral invasive ductal carcinoma and ovarian metastases.

Imaging features of hepatic angiosarcoma: retrospective analysis of two centers.

PURPOSE: Identifying primary hepatic angiosarcoma (PHA) preoperatively is challenging, often relying on postoperative pathology. Invasive biopsy increases bleeding risk, emphasizing the importance of early PHA diagnosis through imaging. However, comprehensive summaries of ultrasound, abdominal computed tomography (CT), magnetic resonance imaging (MRI), and whole- body positron emission tomography-CT (PET-CT) in this context are lacking. This study aimed to investigate the comprehensive imaging characteristics of PHA. PATIENTS AND METHODS: Imaging data were collected from 7 patients diagnosed with PHA via pathology between January 2000 and December 2019 in two provincial grade III hospitals. All patients underwent routine color ultrasound examinations before surgery, with 3 patients receiving contrast-enhanced ultrasound (CEUS).CT scans, both plain and enhanced, were performed on 5 patients, and whole-body PET-CT examinations were conducted on 2 patients. RESULTS: Among the 7 patients with PHA, 4 presented with a single solid intrahepatic mass (2 of which were large), 1 with a single exophytic macroblock type, 1 with a mixed type featuring multiple masses and nodules, and 1 with a multiple nodule type. Conventional ultrasound of PHA showed uneven echoes within the tumor, potentially accompanied by septal zone echoes, and a blood flow grade of 0-I. CEUS displayed early-stage circular high enhancement, a central non-enhancement area, and a "vascular sign" around the tumor. CT scans revealed low-density shadows in the plain scan stage, high peripheral ring enhancement, and punctate nodular enhancement in the arterial phase, with varying intensities and the presence of a "vascular sign." During the portal vein stage, the interior of the tumor was consistently unfilled and exhibited structural disorder. PET-CT showed low-density lesions in the liver and low fluorodeoxyglucose metabolism. CONCLUSIONS: Imaging diagnosis plays a crucial role in PHA diagnosis. When liver tumor imaging matches the above characteristics, consider PHA.

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.

Clinical course and vascular endothelial growth factor signaling system expression in maxillary angiosarcoma: A case report.

Maxillary angiosarcoma, an aggressive tumor derived from vascular endothelial cells, is very rare. Recently, antivascular endothelial growth factor (VEGF) therapies have attracted considerable attention. We describe the clinical course of a patient with maxillary angiosarcoma and discuss the expression of VEGF signaling molecules assessed via immunohistological analysis. An 81-year-old man presented with an aggressive tumor in the left maxillary sinus. Biopsy revealed atypical nuclear cell proliferation, and the tumor was suspected to be a sarcoma. The maxillary malignancy was treated using a multidisciplinary approach with a combination of surgery, radiotherapy, and regional chemotherapy. Examination of the specimen obtained in the first surgery revealed maxillary angiosarcoma, found to be positive for CD31, while negative for CD34, D2-40, and factor Ⅷ. Although no pathological residual tumor was observed after the planned wide surgery, cervical lymph node and distant metastases occurred. The patient died 24 months after the first surgery. Staining revealed VEGF receptor (VEGFR) 1, VEGFR2, phosphorylated Ak strain transforming, mitogen-activated protein kinase, and signal transducer and activator of transcription 3 positivity. Although our findings do not indicate that anti-VEGF therapy is beneficial for treating maxillary angiosarcomas, we found that VEGFR signaling pathways were activated in maxillary angiosarcomas similar to angiosarcomas originating at other sites. Herein, we report a case of maxillary angiosarcoma, focused on VEGFR and signaling pathway activation. To our knowledge, this is the first report to describe VEGFR system immunostaining findings in maxillary angiosarcoma.

Rapidly progressive cystic lung disease in a patient with a scalp lesion.

We describe an elderly patient presenting with pneumothorax, cystic lung disease and a scalp lesion. The pneumothorax resolved after placing a chest tube and suction but recurred within a week. Progression of cystic features was also seen, and biopsies of the lung and scalp lesions were performed. Immunohistochemistry was positive for markers of endothelial cells (CD31 and ERG) and negative for markers expected to be positive in alveolar cells (keratin AE1/AE3 and TTF-1), supporting the diagnosis of metastatic angiosarcoma. Palliative chemotherapy did not prevent progression and the patient expired soon after. In describing the clinico-radiological correlation of metastatic angiosarcoma, we also briefly describe the approach to cystic lung disease. Understanding the pathophysiology of cyst formation in metastatic angiosarcoma may help clinicians to better appreciate and manage the full spectrum of cystic lung disease, especially with atypical features.

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.

Molecular and immune pathobiology of human angiosarcoma.

Angiosarcoma is a rare endothelial-derived malignancy that is extremely diverse in anatomy, aetiology, molecular and immune characteristics. While novel therapeutic approaches incorporating targeted agents and immunotherapy have yielded significant improvements in patient outcomes across several cancers, their impact on angiosarcoma remains modest. Contributed by its heterogeneous nature, there is currently a lack of novel drug targets in this disease entity and no reliable biomarkers that predict response to conventional treatment. This review aims to examine the molecular and immune landscape of angiosarcoma in association with its aetiology, anatomical sites, prognosis and therapeutic options. We summarise current efforts to characterise angiosarcoma subtypes based on molecular and immune profiling. Finally, we highlight promising technologies such as single-cell spatial "omics" that may further our understanding of angiosarcoma and propose strategies that can be similarly applied for the study of other rare cancers.

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.

Cutaneous Angiosarcoma.

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

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.

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.