ABSTRACT
Angiosarcomas are rare, clinically aggressive tumors with limited treatment options and a dismal prognosis. We analyzed angiosarcomas from 68 patients, integrating information from multiomic sequencing, NanoString immuno-oncology profiling, and multiplex immunohistochemistry and immunofluorescence for tumor-infiltrating immune cells. Through whole-genome sequencing (n = 18), 50% of the cutaneous head and neck angiosarcomas exhibited higher tumor mutation burden (TMB) and UV mutational signatures; others were mutationally quiet and non-UV driven. NanoString profiling revealed 3 distinct patient clusters represented by lack (clusters 1 and 2) or enrichment (cluster 3) of immune-related signaling and immune cells. Neutrophils (CD15+), macrophages (CD68+), cytotoxic T cells (CD8+), Tregs (FOXP3+), and PD-L1+ cells were enriched in cluster 3 relative to clusters 2 and 1. Likewise, tumor inflammation signature (TIS) scores were highest in cluster 3 (7.54 vs. 6.71 vs. 5.75, respectively; P < 0.0001). Head and neck angiosarcomas were predominant in clusters 1 and 3, providing the rationale for checkpoint immunotherapy, especially in the latter subgroup with both high TMB and TIS scores. Cluster 2 was enriched for secondary angiosarcomas and exhibited higher expression of DNMT1, BRD3/4, MYC, HRAS, and PDGFRB, in keeping with the upregulation of epigenetic and oncogenic signaling pathways amenable to targeted therapies. Molecular and immunological dissection of angiosarcomas may provide insights into opportunities for precision medicine.
Subject(s)
Hemangiosarcoma , Neoplasm Proteins , Cell Line, Tumor , Female , Hemangiosarcoma/classification , Hemangiosarcoma/genetics , Hemangiosarcoma/immunology , Humans , Inflammation/classification , Inflammation/genetics , Inflammation/immunology , Male , Neoplasm Proteins/genetics , Neoplasm Proteins/immunologyABSTRACT
PURPOSE: DNA methylation profiling has previously uncovered biologically and clinically meaningful subgroups within many tumor types, but was not yet performed in angiosarcoma. Angiosarcoma is a rare sarcoma with very heterogeneous clinical presentations, which may be based on differences in biological background. In this exploratory study, DNA methylation profiling of 36 primary angiosarcoma samples from visceral, deep soft tissue, radiation-induced, and UV-induced localizations was performed. EXPERIMENTAL DESIGN: Primary angiosarcoma formalin-fixed paraffin-embedded samples from visceral, soft tissue, radiation-induced, and UV-induced origin were collected from a nationwide search for angiosarcoma in the Netherlands. DNA was extracted for methylation profiling with the Illumina Infinium MethylationEPIC array. Quality control assessment and unsupervised hierarchical clustering were performed. Copy-number profiles were generated and analyzed for chromosomal stability. Clinical data were obtained from the Netherlands Cancer Registry. RESULTS: DNA methylation profiling by unsupervised hierarchical clustering of 36 angiosarcoma samples (6 visceral, 5 soft tissue, 14 radiation-induced, 11 UV-induced) revealed two main clusters (A and B), which were divided into four subclusters. The clusters largely corresponded with clinical subtypes, showing enrichment of UV-induced cases in cluster A1 and radiation-induced cases in cluster A2. Visceral and soft tissue cases almost exclusively fell into cluster B. Cluster A showed significantly increased chromosomal instability and better overall survival (22 vs. 6 months, P = 0.046) compared with cluster B. CONCLUSIONS: In this novel methylation profiling study, we demonstrated for the first time four different angiosarcoma clusters. These clusters correlated with clinical subtype, overall survival, and chromosomal stability.
Subject(s)
Biomarkers, Tumor/genetics , DNA Modification Methylases/genetics , DNA Repair Enzymes/genetics , Epigenome , Hemangiosarcoma/classification , Hemangiosarcoma/pathology , Molecular Typing/methods , Tumor Suppressor Proteins/genetics , Aged , Chromosomal Instability , Female , Hemangiosarcoma/genetics , Humans , Male , Neoplasm Grading , Neoplasm Staging , Prognosis , Promoter Regions, Genetic , Survival RateABSTRACT
Angiosarcoma is a rare malignant neoplasm of the liver. The various morphologic patterns seen with angiosarcomas of the liver have not been systematically studied and their recognition remains a major diagnostic challenge. In order to provide more comprehensive data on the morphologic patterns, angiosarcomas that had been diagnosed between 1996 and 2016 at a large medical referral center were reviewed. The major growth patterns were classified as sinusoidal (non-mass forming) versus mass forming. The mass-forming cases were further subdivided into epithelioid, spindled, or vasoformative. The study identified 21 patients with primary hepatic angiosarcoma: 13 men and 8 women. The ages ranged from 26 to 89 years. Seventeen angiosarcomas were mass-forming tumors, of which 9 showed predominantly vasoformative growth. Most of these vasoformative cases (6/9) were composed of small vessels, 2 cases had slit-like vascular spaces, and one case showed a mixture of small and large vessels. There were 7 mass-forming angiosarcomas without vasoformation: 3 had an epithelioid morphology and 4 were composed primarily of spindled cells. The final mass-forming tumor showed a mixture of vasoformative and nonvasoformative areas. Four of 21 cases were non-mass forming and showed either diffuse sinusoidal infiltration (N=2) or prominent peliotic changes (N=2). Finally, 3 uncommon patterns were identified. One case showed nodules of spindle cells arranged in prominent whorls in a background of loose connective tissue with abundant inflammation. A second case arose in the setting of the Blue Rubber Bleb Nevus Syndrome and showed numerous tumor nodules with an architectural pattern that resembled infantile hemangioma, some with areas of atypia consistent with malignant transformation to angiosarcoma. The third unusual pattern showed multiple nodules of thin walled large caliber vascular proliferations, some of which showed atypia that reached the level of angiosarcoma. The results from this study indicate that the majority of hepatic angiosarcomas are mass forming (two third of cases), a pattern that is recognizable on H&E when vasoformative, but can mimic carcinoma or undifferentatied sarcomas when nonvasoformative (one third of cases). The sinusoidal patterns are particularly challenging and are frequently missed on initial review. Finally, we describe several unsual patterns of angiosarcoma. Awareness of these classic and rare morphologic patterns can help make the diagnosis of angiosarcoma.
Subject(s)
Epithelioid Cells/pathology , Hemangiosarcoma/pathology , Liver Neoplasms/pathology , Adult , Aged , Aged, 80 and over , Biopsy , Cell Proliferation , Diagnosis, Differential , Female , Hemangiosarcoma/classification , Hemangiosarcoma/mortality , Hemangiosarcoma/therapy , Humans , Liver Neoplasms/classification , Liver Neoplasms/mortality , Liver Neoplasms/therapy , Male , Middle Aged , Neovascularization, Pathologic , Predictive Value of Tests , Prognosis , Tumor BurdenABSTRACT
O hemangiossarcoma é a neoplasia maligna originária do endotélio vascular. Os sítios primários mais comuns são baço, fígado, coração e pele, sendo considerado raro o acometimento da pálpebra e demais componentes oculares. Neste relato, descreve-se o caso de uma cadela da raça Boxer, de dez anos de idade, que apresentou aumento de volume, na borda livre da terceira pálpebra, de cor vermelho escuro. O tratamento de escolha foi a remoção cirúrgica e o diagnóstico de hemangiossarcoma foi confirmado ao exame histopatológico.(AU)
Hemangiosarcoma is malignant neoplasm originating from the vascular endothelium. The most common primary sites of this neoplasia are the spleen, liver, heart and skin. The involvement of the eyelid and other ocular components is unusual. In this report, we describe the case of a 10-year-old Boxer bitch who presented an increase in volume, at the free edge of the third eyelid, a deep red color. The mass was surgically removed and the diagnosis of hemangiossarcoma was confirmed by histopathological exam.(AU)
El hemangiosarcoma es una neoplasia maligna originada en el endotelio vascular, encontrado principalmente en el bazo, hígado, corazón y piel. Su presencia en párpados y otros componentes oculares es poco común. En este relato se describe el caso de una perra de la raza Boxer, de diez años, que presentó aumento de volumen, en el borde libre del tercer párpado, de color rojo oscuro. El tratamiento escogido fue la remoción quirúrgica y el diagnóstico de hemangiosarcoma fue confirmado por examen histopatológico.(AU)
Subject(s)
Animals , Female , Dogs , Hemangiosarcoma/surgery , Hemangiosarcoma/classification , Hemangiosarcoma/veterinary , Nictitating Membrane/abnormalitiesABSTRACT
The classification of vascular tumors of bone has been under debate over time. Vascular tumors in bone are rare, display highly overlapping morphology, and, therefore, are considered difficult by pathologists. Compared with their soft tissue counterparts, they are more often multifocal and sometimes behave more aggressively. Over the past decade, with the advent of next-generation sequencing, recurrent molecular alterations have been found in some of the entities. The integration of morphology and molecular changes has led to a better characterization of these separate entities.
Subject(s)
Bone Neoplasms/classification , Hemangioendothelioma, Epithelioid/classification , Hemangiosarcoma/classification , Vascular Neoplasms/classification , Bone Neoplasms/genetics , Bone Neoplasms/pathology , Diagnosis, Differential , Hemangioendothelioma, Epithelioid/genetics , Hemangioendothelioma, Epithelioid/pathology , Hemangiosarcoma/genetics , Hemangiosarcoma/pathology , High-Throughput Nucleotide Sequencing , Humans , Vascular Neoplasms/genetics , Vascular Neoplasms/pathologyABSTRACT
Lymphangiosarcomas are uncommon vascular neoplasms that arise from lymphatic endothelial cells (LECs). They efface and replace normal subcutaneous tissue and are characterised by arborising, vascular channels lined by a single layer of pleomorphic endothelial cells and a paucity of erythrocytes. Lymphangiosarcomas are architecturally similar to hemangiosarcomas, a common malignancy of vascular origin arising from blood vascular endothelial cells. Common immunohistochemical markers for vascular endothelium, such as Factor VIII-related antigen (F8RA) and CD31, have traditionally been used to confirm the diagnosis of tumours of vascular origin. However, these markers fail to differentiate between lymphangiosarcoma and hemangiosarcoma, which often show overlapping morphologic features, disparate clinical behaviour and require different treatment modalities. Here we describe the use of two novel LEC-specific markers, lymphatic vessel endothelial receptor-1 (LYVE-1) and prospero-related homeobox gene-1 (PROX-1), to further differentiate between vascular tumours of lymphatic (lymphangiosarcoma) and blood (hemangiosarcoma) endothelial cell origin in the dog.
Subject(s)
Dog Diseases/classification , Endothelial Cells/metabolism , Hemangiosarcoma/veterinary , Homeodomain Proteins/metabolism , Tumor Suppressor Proteins/metabolism , Vascular Neoplasms/veterinary , Vesicular Transport Proteins/metabolism , Animals , Antibodies , Biomarkers, Tumor , Dog Diseases/metabolism , Dogs , Gene Expression Regulation, Neoplastic/physiology , Hemangiosarcoma/classification , Homeodomain Proteins/genetics , Tumor Suppressor Proteins/genetics , Vascular Neoplasms/diagnosis , Vascular Neoplasms/metabolism , Vesicular Transport Proteins/geneticsABSTRACT
OBJECTIVES: Epithelioid hemangioendothelioma (EHE) and epithelioid angiosarcoma (EAS) are rare vascular neoplasms that share many morphological characteristics on histology but demonstrate different clinical behavior. Given the many reported clinical and morphological features shared between EAS and EHE, we examined all cases of EAS and EHE diagnosed primarily on fine needle aspiration (FNA) at our three institutions that were confirmed by a tissue diagnosis. STUDY DESIGN: A total of 29 cases from 25 patients were identified: 15 EHE from 11 patients and 14 EAS from 14 patients. RESULTS: Many cytomorphological features existed on a spectrum that overlapped considerably between EAS and EHE cases. Common features between the two entities include epithelioid morphology and eccentrically placed nucleus. Intracytoplasmic lumens (ICL), a morphological feature that may suggest vascular origin, can be found in both entities but are not always present. CONCLUSIONS: Given the general absence of vascular cytomorphological features, such as ICL, the proper classification of these tumors depends on the successful use of immunoperoxidase markers such as factor VIII-related antigen, ERG, or CD31 as well as a high index of suspicion. The distinction between EAS and EHE on FNA alone is treacherous at best.
Subject(s)
Epithelioid Cells/pathology , Hemangioendothelioma, Epithelioid/pathology , Hemangiosarcoma/pathology , Adolescent , Adult , Aged , Aged, 80 and over , Biopsy, Fine-Needle , Cell Lineage , Diagnosis, Differential , Epithelioid Cells/classification , Female , Hemangioendothelioma, Epithelioid/classification , Hemangiosarcoma/classification , Humans , Male , Middle Aged , Predictive Value of Tests , Prognosis , United States , Young AdultABSTRACT
The pseudoangiosarcomatous pattern has been described mostly in cutaneous and some visceral squamous cell carcinomas and is unique for its striking morphologic resemblance to angiosarcoma. Herein, we describe the clinicopathologic features of 7 pseudoangiosarcomatous urothelial carcinomas that occurred in the urinary bladder. The patients included 6 men and 1 woman ranging in age from 47 to 87 years (median 70 y). The pseudoangiosarcomatous morphology was observed in 7 urothelial carcinomas including 3 with squamous differentiation and comprised 35% to 85% of the invasive tumor. Histologically, the pseudoangiosarcomatous carcinomas were characterized by tumor cell discohesion and lysis that created pseudolumina formations surrounded by attached residual tumor cells. Detached degenerating tumor cells variably admixed with inflammatory cells were common in the false lumina. Partly intact urothelial carcinoma nests contained irregular or cleft-like spaces and disintegrating tumor cells with stretched intercellular bridges. The tumor was commonly associated with a dense collagenous matrix, often surrounding the lytic nests. Similar tumor cell discohesion and breakdown were observed in 3 tumors with foci of squamous cell differentiation, distinguished by the presence of dyskeratosis and keratin formation. All 7 tumors contained other nonpseudoangiosarcomatous carcinoma components such as conventional urothelial carcinoma (5), squamous differentiation (4), sarcomatoid spindle cell carcinoma (2), small cell carcinoma (1), micropapillary carcinoma (1), and glandular differentiation (1). The pseudoangiosarcomatous urothelial carcinomas were all (7/7) diffusely CK7 positive, most (6/7) were GATA3 positive, and none (0/7) expressed vascular-associated markers. There was no evidence to suggest that apoptosis (by TUNEL assay and cleaved caspase-3 immunostaining) or loss of the adhesion molecules CD138 and e-cadherin were possible causes for the tumor cell discohesion and breakdown. All 7 tumors were high stage at cystectomy and included 1 pT3a, 2 pT3b, and 4 pT4a tumors, and 3 had pelvic lymph node involvement. Follow-up data available in 6 cases revealed a poor outcome with an overall median survival of 8.5 months. In conclusion, we present an unusual morphology of bladder carcinoma that has a striking resemblance to a malignant vasoformative tumor. Our series showed that bladder pseudoangiosarcomatous carcinoma morphology is associated with a higher tumor stage at cystectomy, commonly admixed with other aggressive carcinoma variant morphologies, and portend a poorer outcome. Knowledge of this pattern is also important to avoid misdiagnosis, particularly in limited tissue samples.
Subject(s)
Carcinoma/pathology , Hemangiosarcoma/pathology , Urinary Bladder Neoplasms/pathology , Urothelium/pathology , Aged , Aged, 80 and over , Biomarkers, Tumor/analysis , Biopsy , Carcinoma/chemistry , Carcinoma/classification , Carcinoma/mortality , Cell Differentiation , Female , Hemangiosarcoma/chemistry , Hemangiosarcoma/classification , Hemangiosarcoma/mortality , Humans , Immunohistochemistry , Male , Middle Aged , Neoplasm Invasiveness , Neoplasm Staging , Predictive Value of Tests , Survival Analysis , Terminology as Topic , Time Factors , Urinary Bladder Neoplasms/chemistry , Urinary Bladder Neoplasms/classification , Urinary Bladder Neoplasms/mortality , Urothelium/chemistryABSTRACT
The haemangioma, the most common non-cystic hepatic lesion, most often discovered by chance, may in certain situations raise diagnostic problems in imaging. In this article, the authors first demonstrate that the radiological appearance of the hepatic haemangioma, in its typical form, is closely related to three known histological sub-types. They then show that certain atypical features should be known in order to establish a diagnosis. They also observe the potential interactions between the haemangioma, an active vascular lesion, and the adjacent hepatic parenchyma. Finally, they discuss the specific paediatric features of hepatic haemangiomas and illustrate the case of a hepatic angiosarcoma.
Subject(s)
Diagnostic Imaging/methods , Hemangioma/diagnosis , Liver Neoplasms/diagnosis , Adult , Child , Diagnosis, Differential , Diffusion Magnetic Resonance Imaging/methods , Hemangioma/classification , Hemangioma/pathology , Hemangiosarcoma/classification , Hemangiosarcoma/diagnosis , Hemangiosarcoma/pathology , Humans , Image Enhancement/methods , Incidental Findings , Infant , Liver/pathology , Liver Neoplasms/classification , Liver Neoplasms/pathology , Magnetic Resonance Imaging/methods , Prognosis , Rare Diseases , Tomography, X-Ray Computed/methods , Ultrasonography/methodsABSTRACT
PURPOSE: Non-epithelial breast neoplasms cover a large spectrum of histopathological entities. The demographics and clinical features are similar to epithelial breast lesions but the diagnosis, prognosis and management options are often very different. METHODS: During 2001-2010, 1362 patients were examined at the Pathology Department of the Aretaieion General Hospital for various breast lesions. All specimens were processed routinely and slides stained with hematoxylin-eosin were re-examined. The patient clinical records were examined for demographics, clinical presentation and therapeutic approach. RESULTS: In 23/1362 cases (1.68%) pathological examination showed non-epithelial lesions: in 12/1362 cases (0.8%) haemangiomas (11 women, one man), in 4 /1362 cases (0.3%) myofibroblastomas (MFB), in 2/1362 cases (0.1%) primary breast non-Hodgkin's lymphoma (NHL), in 3 /1362 cases (0.2%) granular cell tumor (GCT), and in 2/1362 cases (0.1%) angiosarcomas (one developed after radiotherapy for breast cancer). CONCLUSIONS: Non-epithelial primary breast tumors are rare (1.68%) and present significant difficulty in accurate preoperative diagnosis and in certain cases in pathological diagnosis as well, which is necessary for the selection of the appropriate treatment. Avoidance of inappropriate therapies requires a multidisciplinary management approach.
Subject(s)
Breast Neoplasms, Male , Breast Neoplasms , Hospitals, University , Adult , Aged , Biopsy , Breast Neoplasms/classification , Breast Neoplasms/pathology , Breast Neoplasms/surgery , Breast Neoplasms, Male/classification , Breast Neoplasms, Male/pathology , Breast Neoplasms, Male/surgery , Female , Granular Cell Tumor/classification , Granular Cell Tumor/pathology , Granular Cell Tumor/surgery , Greece , Hemangioma/classification , Hemangioma/pathology , Hemangioma/surgery , Hemangiosarcoma/classification , Hemangiosarcoma/pathology , Hemangiosarcoma/surgery , Humans , Immunohistochemistry , Lymphoma, Non-Hodgkin/classification , Lymphoma, Non-Hodgkin/pathology , Lymphoma, Non-Hodgkin/surgery , Male , Mastectomy/methods , Mastectomy, Modified Radical , Mastectomy, Segmental , Mastectomy, Simple , Middle Aged , Neoplasms, Muscle Tissue/classification , Neoplasms, Muscle Tissue/pathology , Neoplasms, Muscle Tissue/surgery , Treatment OutcomeSubject(s)
Eyelid Neoplasms/veterinary , Hemangiosarcoma/veterinary , Horse Diseases/pathology , Animals , Eyelid Neoplasms/diagnosis , Eyelid Neoplasms/pathology , Eyelid Neoplasms/surgery , Hemangiosarcoma/classification , Hemangiosarcoma/surgery , Horse Diseases/diagnosis , Horse Diseases/surgery , Horses , MaleSubject(s)
Neoplasms, Vascular Tissue/pathology , Vascular Malformations/pathology , Arteriovenous Malformations/classification , Arteriovenous Malformations/pathology , Hemangioendothelioma/classification , Hemangioendothelioma/pathology , Hemangioma/classification , Hemangioma/pathology , Hemangiosarcoma/classification , Hemangiosarcoma/pathology , Humans , Neoplasms, Vascular Tissue/classification , Terminology as Topic , Vascular Malformations/classificationABSTRACT
Vascular tumors of bone are a heterogeneous group. Numerous terms have been introduced as well as different classification systems. None of the classification schemes have been accepted due to lack of consistent terminology, accepted histologic criteria, and limited correlation with clinical outcome. It is acknowledged that vascular tumors of bone originate from endothelial cells, resulting in variable expression of endothelial markers. None of these markers are useful to discriminate between benign and malignant lesions. Although radiologic appearance is not specific, radiologic multifocality should trigger to include a vascular neoplasm in the differential diagnosis. This review gives an overview of current literature by describing all different histologic subtypes in correspondence with clinical, radiologic and genetic data. We propose the classification of vascular tumors of bone according to the three-tiered World Health Organization classification scheme for soft tissue tumors dividing entities into a benign, intermediate and malignant category. Hemangioma is the most often and commonly recognized benign lesion. Epithelioid hemangioma has been better defined over the past few years. Based on its locally aggressive behavior and occurrence of lymph node metastases, classification within the intermediate category could be considered. Angiosarcoma is the only accepted term for high-grade malignant vascular tumor of bone and so far, epithelioid hemangioendothelioma is the only accepted low-grade malignant vascular tumor of bone. It is still unclear whether other low-grade malignant vascular tumors of bone (e.g. hemangioendothelioma) truly exist. Unfortunately, molecular / genetic studies of vascular tumors of bone which might support the proposed classification are very sparse.
Subject(s)
Bone Neoplasms/diagnosis , Bone and Bones/blood supply , Hemangioendothelioma, Epithelioid/diagnosis , Hemangiosarcoma/diagnosis , Biomarkers, Tumor/metabolism , Bone Neoplasms/classification , Bone Neoplasms/metabolism , Female , Hemangioendothelioma, Epithelioid/classification , Hemangioendothelioma, Epithelioid/metabolism , Hemangiosarcoma/classification , Hemangiosarcoma/metabolism , Humans , MaleABSTRACT
AIMS: The term lymphangiosarcoma has largely been abandoned in the current classification of endothelial neoplasms. Recently, a number of lymphatic-associated antibodies have been developed for immunohistochemistry, which frequently stain angiosarcomas, implying lymphatic or mixed lymphatic and blood vascular differentiation is common. The aim was to investigate further lymphatic antigen expression, and to explore the relation of immunohistochemistry to morphological and clinical findings. METHODS AND RESULTS: Forty-nine angiosarcomas in tissue microarrays were analysed with D2-40 and antibodies to Prox-1 and vascular endothelial growth factor receptor (VEGFR)-3. D2-40 was positive in 53%, Prox-1 in 76%, and VEGFR-3 in 57%. Tumours with features attributable to lymphatic differentiation such as hobnail and kaposiform morphologies were more often positive with these markers, including a statistical association between D2-40 and hobnailing. Ten tumours had features suggestive of lymphatic differentiation, namely well-differentiated histology, interanastomosing channels devoid of red cells, prominent hobnailing, lymphoid aggregates, and multi-antigen expression of D2-40 (100%), Prox-1 (100%) and VEGFR-3 (60%), which might be deserving of the appellation lymphangiosarcoma. Nine were cutaneous scalp/facial tumours in elderly patients and one arose within chronic lymphoedema. CONCLUSIONS: Lymphatic differentiation is common in angiosarcoma, certain subsets show greater lymphatic differentiation than others, and lymphangiosarcoma may be defined pathologically, rather than clinically.
Subject(s)
Antibodies, Monoclonal , Endothelium, Lymphatic/pathology , Hemangiosarcoma/pathology , Lymphangiosarcoma/pathology , Aged , Aged, 80 and over , Antibodies, Monoclonal, Murine-Derived , Cell Differentiation , Endothelium, Lymphatic/metabolism , Female , Hemangiosarcoma/classification , Homeodomain Proteins/metabolism , Humans , Immunohistochemistry , Lymphangiosarcoma/classification , Male , Middle Aged , Receptors, Vascular Endothelial Growth Factor/metabolism , Tissue Array Analysis , Tumor Suppressor Proteins/metabolismABSTRACT
Epithelioid hemangiosarcoma is a specific variant of hemangiosarcoma that has recently been recognized in domestic animals. These malignant vascular neoplasms histologically resemble, and may be mistaken for, carcinomas. Four epithelioid hemangiosarcomas in the urinary bladders of 4 cows with severe enzootic hematuria are described in the current study. Grossly, the vesicular mucosa of the urinary bladder of each cow contained a single red elevated nodule. Histologically, each neoplasm was composed of short strands, cords, or nests of epithelioid, round, or slightly spindle-shaped endothelial cells that formed small vascular structures. Neoplastic cells were immunohistochemically positive for factor VIII-related antigen and vimentin, and were negative for cytokeratin and desmin. Ultrastructurally, the neoplastic cells often contained cytoplasmic intermediate filaments, a prominent granular endoplasmic reticulum, a Golgi complex, mitochondria, marked pinocytotic activity, and rare Weibel-Palade bodies. These neoplasms were diagnosed as epithelioid hemangiosarcomas based on their histologic, immunohistochemical, and ultrastructural features. The present report widens the spectrum of mesenchymal tumors of the bovine urinary bladder and aids in the characterization of these vascular neoplasms.
Subject(s)
Cattle Diseases/pathology , Hemangiosarcoma/veterinary , Immunohistochemistry/veterinary , Urinary Bladder Neoplasms/veterinary , Animals , Cattle , Female , Hemangiosarcoma/classification , Hemangiosarcoma/pathology , Urinary Bladder Neoplasms/pathologyABSTRACT
BACKGROUND: acantholytic squamous cell carcinomas (ASCC) and intraoral angiosarcoma share similar histopathological features. Aim of this study was to find marker for a clear distinction. METHODS: Four oral acantholytic squamous cell carcinomas and one intraoral angiosarcoma are used to compare the eruptive intraoral growth-pattern, age-peak, unfavourable prognosis and slit-like intratumorous spaces in common histological staining as identical clinical and histopathological features. Immunohistochemical staining for pancytokeratin, cytokeratin, collagen type IV, gamma2-chain of laminin-5, endothelial differentiation marker CD31 and CD34, F VIII-associated antigen, Ki 67-antigen, beta-catenin, E-cadherin, alpha-smooth-muscle-actin and Fli-1 were done. RESULTS: Cytokeratin-immunoreactive cells can be identified in both lesions. The large vascularization of ASCC complicates the interpretation of vascular differential markers being characteristic for angiosarcoma. Loss of cell-cell-adhesion, monitored by loss of E-cadherin and beta-catenin membrane-staining, are indetified as reasons for massive expression of invasion-factor ln-5 in ASCC and considered responsible for unfavourable prognosis of ASCC. Expression of Fli-1 in angiosarcoma and cellular immunoreaction for ln-5 in ASCC are worked out as distinguishing features of both entities. CONCLUSION: Fli-1 in angiosarcoma and ln-5 in ASCC are distinguishing features.
Subject(s)
Carcinoma, Squamous Cell/pathology , Hemangiosarcoma/pathology , Mouth Neoplasms/pathology , Mouth/pathology , Acantholysis , Aged , Biopsy, Needle , Carcinoma, Squamous Cell/classification , Diagnosis, Differential , Hemangiosarcoma/classification , Humans , Immunohistochemistry , Male , Middle Aged , Mouth Neoplasms/classificationABSTRACT
Cancer diagnosis and classification is extremely complicated and, for the most part, relies on subjective interpretation of biopsy material. Such methods are laborious and in some cases might result in different results depending on the histopathologist doing the examination. Automated, real-time diagnostic procedures would greatly facilitate cancer diagnosis and classification. Laser-induced breakdown spectroscopy (LIBS) is used for the first time to our knowledge to distinguish normal and malignant tumor cells from histological sections. We found that the concentration of trace elements in normal and tumor cells was significantly different. For comparison, the tissue samples were also analyzed by an inductively coupled plasma emission spectroscopy (ICPES) system. The results from the LIBS measurement and ICPES analysis were in good agreement.
Subject(s)
Hemangiosarcoma/classification , Hemangiosarcoma/diagnosis , Lasers , Liver Neoplasms/classification , Liver Neoplasms/diagnosis , Spectrum Analysis/methods , Feasibility Studies , Humans , Reproducibility of Results , Sensitivity and SpecificityABSTRACT
Cases filed as vascular tumor of bone other than ordinary hemangioma were reviewed. They were included in the study if there was adequate histologic material and clinical information, clear evidence of bone origin, and at least 5 years follow-up. The study group comprised 17 cases, of which 13 were categorized as hemangioendothelioma of bone, 1 as epithelioid hemangioendothelioma, and 3 as high-grade angiosarcoma. Hemangioendothelioma of bone had growth patterns varying from vasoformative to solid, but well-formed vessels were present in at least some area in all cases. The cells generally had a rounded, epithelioid character, regular nuclei, and relatively few mitotic figures; occasional features included spindle cells and scattered enlarged, hyperchromatic or pleomorphic nuclei. Lymphoplasmacytic and eosinophilic inflammatory infiltrate ranged from prominent to slight or absent, and myxoid or hyaline stroma was never more than focal. Epithelioid hemangioma could not be separated from hemangioendothelioma of bone. The single epithelioid hemangioendothelioma for the most part had cords of relatively uniform epithelioid cells in a prominent myxoid stroma but focally demonstrated an angiosarcoma-like appearance, with irregular vascular spaces and marked nuclear pleomorphism. The high-grade angiosarcomas exhibited predominantly irregular vasoformation combined with solid areas, diffuse nuclear hyperchromatism and pleomorphism, and, in 2 cases, numerous mitotic figures (the third case had only a small biopsy and a postradiation amputation specimen). Of the hemangioendotheliomas of bone, 7 were unicentric and 6 were regionally multicentric either concurrently or sequentially. Three patients had intraosseous local recurrence, 2 had discontinuous regional skin or soft tissue involvement (including the popliteal artery in 1), and 1 had a solitary lung metastasis, but none died of tumor. The patient with epithelioid hemangioendothelioma had multicentric tumors in widely separated bones and died with liver and lung metastases. Two of the high-grade angiosarcomas were unicentric, and the third was regionally multicentric, with a popliteal artery-soft tissue component as well. All 3 of these patients died with metastases in various sites.
Subject(s)
Bone Neoplasms/pathology , Hemangioendothelioma, Epithelioid/secondary , Hemangiosarcoma/secondary , Adolescent , Adult , Aged , Bone Neoplasms/classification , Bone Neoplasms/surgery , Female , Hemangioendothelioma, Epithelioid/classification , Hemangioendothelioma, Epithelioid/surgery , Hemangiosarcoma/classification , Hemangiosarcoma/surgery , Humans , Male , Middle Aged , Neoplasm Recurrence, Local , Radiotherapy, Adjuvant , Retrospective Studies , Treatment OutcomeABSTRACT
Vascular tumors and malformations can be challenging to diagnose. Although they can resemble one another, their classification into tumors, such as hemangiomas of infancy, and malformations, such as venous or arteriovenous malformations, is based not only on their divergent biological behavior, but also on their pathogenesis. This review examines the molecular pathobiology of the processes involved in the development of these vascular birthmarks as they are currently understood. The terms hemangioma, hemangiosarcoma, and vascular proliferation are often used interchangeably, even though these entities are clinically and biochemically distinct. A more precise classification is necessary to facilitate communication between basic scientists and clinicians. Vasculogenesis, the in situ differentiation of blood vessels, occurs very early in the developing embryo. In vivo and in vitro studies, as well as knockout models, seem to indicate that this mechanism is unlikely to be involved in the development of either vascular malformations or hemangiomas of infancy. Recent advances in embryonic angiogenesis, especially explorations of mechanisms of vascular remodeling, have brought new understanding of the pathogenesis of vascular malformations. Vascular remodeling, an integral part of angiogenesis that centers upon the interactions between pericytes and endothelial cells, has been shown to be defective in certain experimental models and in some familial cases of vascular malformation. The occurrences of arteriovenous malformations in territories susceptible to increased remodeling also point towards epigenetic events in the development of vascular malformations.