A Rare Case of Pulmonary Artery Sarcoma.

Pulmonary artery sarcoma (PAS) is a rare and aggressive mesenchymal tumor with an overall poor prognosis1-5. Due to similar clinical and radiologic findings, PAS is often misdiagnosed as a pulmonary embolism (PE) frequently leading to prolonged anticoagulation therapy, which delays the correct diagnosis 1-3. By presenting this clinical case our objective is to emphasize characteristic CT findings that favour a neoplastic origin of a pulmonary intravascular filling defect. PET-CT and MRI have also an important potential role in its diagnosis and therapeutical management.

Rapidly Progressive and Debilitating Epithelioid Hemangioendothelioma: An Atypical Presentation of a Rare Malignant Cutaneous Vascular Neoplasm.

ABSTRACT: Epithelioid hemangioendothelioma (EHE) is a rare vascular malignant tumor that comprises less than 1% of all vascular tumors. Cutaneous involvement in EHE can occur either by spreading from underlying bone or rarely could be limited to the skin and mostly presents as solitary well-circumscribed mass to an ill-defined infiltrative lesion. We present a case of rapidly progressive and debilitating EHE presenting multiple vascular papules and nodules. Histopathology showed an ill-circumscribed nodular proliferation of epithelioid and spindled cells in the dermis that extended into the subcutaneous tissue. The tumor cells had moderate eosinophilic cytoplasm, vesicular chromatin, and prominent nucleoli. In addition, they showed evidence of lumen formation and intracytoplasmic vacuoles. Brisk mitosis was noted. On immunohistochemistry, the cells were strongly positive for CD31, CD34, and ERG (ETS [erythroblast transformation-specific]-related gene). MIB-1 labeling index was more than 75% in the highest proliferating areas. A high degree of clinical suspicion and immunopathological examination is recommended for early diagnosis of this rare condition before it becomes function or life-threatening.

Engineering tumoral vascular leakiness with gold nanoparticles.

Delivering cancer therapeutics to tumors necessitates their escape from the surrounding blood vessels. Tumor vasculatures are not always sufficiently leaky. Herein, we engineer therapeutically competent leakage of therapeutics from tumor vasculature with gold nanoparticles capable of inducing endothelial leakiness (NanoEL). These NanoEL gold nanoparticles activated the loss of endothelial adherens junctions without any perceivable toxicity to the endothelial cells. Microscopically, through real time live animal intravital imaging, we show that NanoEL particles induced leakiness in the tumor vessels walls and improved infiltration into the interstitial space within the tumor. In both primary tumor and secondary micrometastases animal models, we show that pretreatment of tumor vasculature with NanoEL particles before therapeutics administration could completely regress the cancer. Engineering tumoral vasculature leakiness represents a new paradigm in our approach towards increasing tumoral accessibility of anti-cancer therapeutics instead of further increasing their anti-cancer lethality.

Inhibiting redox-mediated endothelial migration by gadofullerenes for inducing tumor vascular normalization and improving chemotherapy.

Tumor vascular normalization (TVN) reverses abnormal tumor vasculatures, which could boost anti-cancer efficiency and especially increase drug intratumoral delivery. Endothelial cells play a vital role in angiogenesis, yet continuous modulating endothelial cell migration to improve TVN is ingenious but challenging. Here we propose a potential strategy for TVN based on inhibiting endothelial migration using antioxidative fullerene nanoparticles (FNPs). We demonstrate that FNPs inhibit cell migration upon their anti-oxidation effects in vitro. The optimized alanine-modified gadofullerene (GFA) exhibits superior TVN ability and inhibits tumor growth in vivo. Mechanically, facilitated with the protein microarray, we confirm that GFA could suppress the focal adhesion pathway to restrain endothelial migration. Subsequently, remarkable anti-tumor efficacy of chemotherapy synergy was obtained, which benefited from a more normalized vascular network by GFA. Together, our study introduces the potential of FNPs as promising TVN boosters to consider in cancer nanomedicine design.

Pediatric hepatic vascular tumors: clinicopathologic characteristics of 33 cases and proposed updates to current classification schemes.

Pediatric hepatic vascular tumors (HVTs) are rare neoplasms with features distinct from their cutaneous counterparts. Their behavior ranges from benign to malignant, with each subtype having therapeutic differences. Histopathologic descriptions of large cohorts are scarce in the literature. Thirty-three putative HVTs diagnosed from 1970 to 2021 were retrieved. All available clinical and pathologic materials were reviewed. Lesions were reclassified according to the World Health Organization (WHO) classification of pediatric tumors [1] as hepatic congenital hemangioma (HCH; n = 13), hepatic infantile hemangioma (HIH; n = 10), hepatic angiosarcoma (HA; n = 3), and hepatic epithelioid hemangioendothelioma (HEH; n = 1). Vascular malformations (n = 5) or vascular-dominant mesenchymal hamartoma (n = 1) were excluded. HCH frequently showed involutional changes, whereas HIH often had anastomosing channels and pseudopapillae formation. HA had solid areas with epithelioid and/or spindled endothelial morphology, significant atypia, increased mitoses, high proliferation index, and occasionally necrosis. On morphology analysis, a subset of HIH showed features worrisome for progression to HA including solid glomeruloid proliferation, increased mitoses, and epithelioid morphology. The widely metastatic and fatal HEH was observed in a 5-year-old male with multiple liver lesions. Immunohistochemically, HIHs and HA were Glucose transporter isoform 1 (GLUT-1) positive. One HIH patient died from postoperative complications, whereas 3 are alive without disease. Five HCH patients are alive and well. Two of three HA patients died of disease, and 1 is alive without recurrence. To our knowledge, this is the largest series of pediatric HVTs reviewing clinicopathologic features based on current Pediatric WHO nomenclature [1]. We highlight diagnostic challenges and propose inclusion of an intermediate category between HIH and HA which warrants closer follow-up.

[Infantile hemangioma : Clinical manifestation, treatment, and differential diagnoses]. / Infantile Hämangiome : Manifestationsformen, Therapie, Differenzialdiagnosen.

With an incidence of approximately 4% infantile hemangiomas are the most common vascular tumors in children and show characteristic growth dynamics. In order to avoid erroneous treatment, they need to be differentiated from other vascular tumors (granuloma pyogenicum and kaposiform hemangioendothelioma) and vascular malformations. Of all infantile hemangiomas 85% are uncomplicated and undergo spontaneous resolution starting towards the end of the first year of life. First-line treatment for complicated infantile hemangiomas (15%), i.e. those with imminent obstruction (eyes and nose), ulceration or permanent disfigurement, is oral propranolol (2 mg/kg BW and day for at least 6 months).

Angiosarcoma gastrointestinal multifocal, con compromiso extenso de estómago, intestino delgado y colon. Reporte de un caso / Multifocal gastrointestinal angiosarcoma, with extensive gastric, small intestine and colon involvement. A case report

Introducción. El angiosarcoma es una neoplasia vascular originada a nivel del endotelio, de baja frecuencia, conocido por su agresividad y crecimiento acelerado. Alcanza solo el 1 al 2 % del total de los sarcomas. La presentación gastrointestinal es infrecuente y su incidencia es poco conocida debido al escaso reporte de casos en la literatura. Suele identificarse en etapas avanzadas debido a la dificultad del diagnóstico histopatológico por sus características morfológicas, siendo necesario aplicar tinciones especiales o estudio inmunohistoquímico. Caso clínico. Por su interés y singularidad, presentamos el caso de un paciente masculino de 54 años, quien consultó con hemorragia digestiva profusa, anemización y requerimiento de terapia transfusional. Resultados. Durante el proceso diagnóstico, en la endoscopia encontraron diversas lesiones multifocales que se extendían por gran parte del tracto gastrointestinal. El estudio histopatológico mostró angiosarcoma gastrointestinal. Discusión. El angiosarcoma del tracto gastrointestinal es extremadamente infrecuente, de difícil diagnóstico y bajas posibilidades de manejo curativo, con opciones terapéuticas limitadas, lo que configura un mal pronóstico a corto plazo

Introduction. Angiosarcoma is a vascular neoplasm originating from endothelial cells, known for its aggressiveness, accelerated growth and reduced frequency. Reach only 1 to 2% of total sarcomas. Gastrointestinal presentation is extremely rare, the true incidence is poorly known, due to the limited reports of this entity in the literature. It is usually identified in advanced stages in view of the difficulty of the histopathological diagnosis, attributable to its morphological characteristics, being necessary to apply special stains or immunohistochemical study. Case report. Due to their interest and uniqueness, we present the case of a 54-year-old male patient, who presented with a profuse gastrointestinal bleeding, anemia, and requirement for transfusion therapy. Results. The endoscopy detected several multifocal lesions that extended most of the gastrointestinal tract. The histopathological study showed gastrointestinal angiosarcoma. Discussion. Angiosarcoma of the gastrointestinal tract is extremely uncommon, difficult to diagnose and has low possibilities of curative management, with limited therapeutic options, which configures a poor prognosis in the short term

How we approach genetics in the diagnosis and management of vascular anomalies.

Vascular anomalies are a heterogeneous group of disorders that are currently classified based on their clinical and histological characteristics. Over the past decade, there have been significant advances in molecular genetics that have led to identification of genetic alterations associated with vascular tumors, vascular malformations, and syndromes. Here, we describe known genetic alterations in vascular anomalies, discuss when and how to test, and examine how identification of causative genetic mutations provides for better management of these disorders through improved understanding of their pathogenesis and increasing use of targeted therapeutic agents in order to achieve better outcomes for our patients.

Epithelioid Vascular Lesions: The Differential Diagnosis and Approach in Cytology and Small Biopsies.

Vascular neoplasms are rare tumors with a multitude of clinical presentations and behavior, which make accurate identification and subclassification challenging on limited small biopsies. Within the spectrum of these lesions, the ones with epithelioid morphology, such as epithelioid hemangioendothelioma and epithelioid angiosarcoma, are particularly challenging given the morphologic overlap with nonvascular lesions and the limited cells due to hemodilution on sampling. Herein, we review the differential diagnosis of epithelioid vascular neoplasms, with a focus on the cytomorphology, differential diagnoses, and ancillary studies that pathologists should be aware of when evaluating small biopsies and aspirates, including novel translocations, and associated monoclonal immunohistochemistry antibodies, that can help in the diagnosis of some of these tumors. Awareness of these morphologic and ancillary study findings in these rare tumors will hopefully allow pathologists to recognize and render-specific diagnoses on limited samples of these challenging lesions.

Acceptor engineering for NIR-II dyes with high photochemical and biomedical performance.

It is highly important and challenging to develop donor-acceptor-donor structured small-molecule second near-infrared window (NIR-II) dyes with excellent properties such as water-solubility and chem/photostability. Here, we discovery an electron acceptor, 6,7-di(thiophen-2-yl)-[1,2,5]thiadiazolo[3,4-g]quinoxaline (TQT) with highest stability in alkaline conditions, compared with conventional NIR-II building block benzobisthiadiazole (BBT) and 6,7-diphenyl-[1,2,5] thiadiazolo[3,4-g]quinoxaline (PTQ). The sulfonated hydrophilic dye, FT-TQT, is further synthesized with 2.13-fold increased quantum yield than its counterpart FT-BBT with BBT as acceptor. FT-TQT complexed with FBS is also prepared and displays a 16-fold increase in fluorescence intensity compared to FT-TQT alone. It demonstrates real-time cerebral and tumor vessel imaging capability with µm-scale resolution. Dynamic monitoring of tumor vascular disruption after drug treatment is achieved by NIR-II fluorescent imaging. Overall, TQT is an efficient electron acceptor for designing innovative NIR-II dyes. The acceptor engineering strategy provides a promising approach to design next generation of NIR-II fluorophores which open new biomedical applications.

Rare case of spindle cell haemangioma of oral cavity.

Spindle cell haemangioma (SCH) is a slow growing, benign vascular lesion with a preference for the distal extremities. Its occurrence in the oral cavity is rare. Clinically, it presents as solitary or multiple subcutaneous nodules, therefore, it could be considered in the differential diagnosis of benign soft tissue tumours. Microscopically it mimics some malignant vascular tumours and it is necessary to differentiate it from other malignant vascular lesions. We report a case of SCH in anterior mandibular region of a young male in his 20s. Although it is a benign lesion, the reported case displayed extensive areas of muscle infiltration and necrosis. After studying the radiographic findings and considering the absence of cellular atypia, a final diagnosis of SCH was made. Literature survey suggests that this is the eleventh case of SCH reported in oral cavity.

Management of Pulmonary Artery Synovial Sarcoma: The 3-Step Surgical Approach.

Primary pulmonary artery sarcoma is an uncommon neoplasm. Given its clinical and radiographic resemblance to pulmonary embolism, initial diagnostic steps may be complicated, leading to delay in diagnosis. This report presents the case of a 52-year-old-woman who was admitted with pulmonary embolism. She underwent pulmonary embolectomy, and histopathologic examination revealed synovial sarcoma.

Multifocal hepatic small vessel neoplasm with spleen dissemination.

Among liver vascular tumours, hepatic small vessel neoplasm (HSVN) has been recently identified as a rare infiltrative vascular neoplasm whose malignant potential is yet to be fully ascertained. About 30 cases of HSVN have been described so far. The most common clinical presentation is an asymptomatic solitary liver lesion. Multifocal disease has been described in literature; however, to date, there are no reports of disease dissemination to other organs. Here we report a case of multifocal HSVN with synchronous spleen secondary lesions.

Rapidly involuting congenital haemangioma: diagnostic and therapeutic approach regarding two case reports.

Two unrelated neonates were born with a large purplish congenital mass of the thigh and forearm. Both showed signs of heart dysfunction, and one of them had anaemia and thrombocytopenia. The imaging assessment of the lesions showed well-defined subcutaneous solid masses with an exuberant vascular component. Both were kept under surveillance and maintenance therapy. A progressive dimensional reduction of the lesions supported the diagnosis of rapidly involuting congenital haemangioma (RICH). RICH is a rare vascular tumour that presents as a congenital purplish bulky mass. The diagnosis depends on the clinical evaluation of the lesion and the imaging characterisation of its solid components and vascular network. RICH may be complicated by high-output heart failure, anaemia and thrombocytopenia. Despite its exuberant presentation, it undergoes involution in the first year of life; therefore, early invasive therapies should be avoided. It is essential to detect any dimensional increase, suggesting more aggressive diagnoses, such as kaposiform haemangioendothelioma.

Pulmonary Artery Sarcoma Complete Resection Facilitated by 3-Dimensional Printed Model.

Primary pulmonary artery sarcomas are rare tumors and are commonly misdiagnosed as pulmonary embolism. Primary pulmonary sarcomas demonstrate intraluminal growth into the vessel, rather than through the wall; require complete resection to enhance survival; and require complex surgical planning. The purpose of this case report is to describe an optimal team approach with multidisciplinary planning facilitated by a customized 3-dimensional model to guide intervention and enhance communication.

Liver mesenchymal neoplasms: something old, something new.

Histological examination of liver biopsies and resection specimens remains the gold standard to establish a definitive diagnosis of liver lesions. While hepatocellular carcinoma remains the most commonly encountered liver lesion on mass-directed biopsies, surgical pathologists must be aware of other entities that may pose diagnostic challenges, as an accurate diagnosis is key for patient management. Mesenchymal tumours of the liver are relatively uncommon, therefore many pathologists are unfamiliar with these tumours. While the clinical presentation and radiological features of these lesions often overlap, careful attention to histological clues can assist in weeding out various congeners to arrive at the most accurate diagnosis. An additional challenge when diagnosing mesenchymal tumours is the specimen type, as mass-directed core biopsies are limited and have become standard clinical practice. Besides careful attention to histological features, radiological findings and clinical history, immunohistochemical analysis and molecular studies have become of immense diagnostic value. In this review, we discuss several common and rare mesenchymal hepatic lesions as defined in the current World Health Organization (WHO) classification and most up-to-date literature. We also discuss immunohistochemistry panels and relevant molecular findings that may assist in rendering an accurate diagnosis when encountering these lesions in daily practice.