VASOPROLIFERATIVE TUMORS IN INTERMEDIATE UVEITIS.

PURPOSE: To describe patients with intermediate uveitis complicated by vasoproliferative tumors (VPTs). METHODS: Data were collected at seven Uveitis/Ocular Oncology centers on demographic, ophthalmic findings at baseline and at follow-up, and on imaging. The therapeutic intervention, final visual acuity, and duration of follow-up were recorded. RESULTS: A total of 36 eyes from 34 patients (12 men, 22 women; mean age 35.3 ± 14.2 years) were included in this study. Visual acuity at presentation ranged from 20/40 to counting fingers. At the time of VPT diagnosis, intermediate uveitis was active in all eyes. The mean VPT thickness was 3.06 ± 0.86 mm. Local treatment to the VPT was provide in 22 eyes (61.1%) and no local treatment to the VPT in 14 eyes (38.9%). After the VPT was detected, systemic or local treatment for the inflammation was initiated and on follow-up FAs 94.4% of the eyes showed resolution of the vascular leakage. During follow-up of 35.8 months, the 22 VPTs treated locally had a reduction in the tumor thickness to 1.25 mm, whereas the 14 VPTs untreated remained stable (final mean tumor thickness 2.65 mm). CONCLUSION: The presence of active intermediate uveitis accompanied by VPTs suggests the need for an aggressive uveitis treatment.

Multifocal vascular lesions.

Multifocal vascular lesions are important to recognize and appropriately diagnose. Generally first noticed on the skin, multifocal vascular lesions may have systemic involvement. Distinguishing among the different types of multifocal vascular lesions is often based on clinical features; however, radiological imaging and/or biopsy are frequently needed to identify distinct features and guide treatment. Knowledge of the systemic associations that can occur with different vascular anomalies may reduce life-threatening complications, such as coagulopathy, bleeding, cardiac compromise, and neurologic sequelae. This review provides a synopsis of the epidemiology, pathogenesis, presentation, workup, and treatment of several well-recognized multifocal vascular tumors and malformations.

Post-radiation atypical vascular proliferation on the head of a young woman: a diagnostic challenge.

With improved outcomes associated with radiotherapy (RT), post-irradiation tumors are increasingly seen in long-term cancer survivors. We report a case of a young woman who presented with a three-year history of a vascular lesion on the temple, previously irradiated for a childhood brain tumor. The history of radiation, the clinical appearance, and the biopsy findings of an atypical vascular proliferation in the dermis, were worrisome for a malignant vascular neoplasm and prompted surgical excision. However, further tissue analysis of the excised specimen confirmed a benign atypical vascular lesion (AVL) overlying a banal pilar cyst. Distinguishing post-radiation benign from malignant vascular lesions can be difficult because they share overlapping clinical and histopathologic features. Thus, any vascular lesion that occurs in a previously irradiated field should be excised completely with tumor-free margins and examined histologically.

Notch signaling in vascular development and physiology.

Notch signaling is an ancient intercellular signaling mechanism that plays myriad roles during vascular development and physiology in vertebrates. These roles include regulation of artery/vein differentiation in endothelial and vascular smooth muscle cells, regulation of blood vessel sprouting and branching during both normal development and tumor angiogenesis, and the differentiation and physiological responses of vascular smooth muscle cells. Defects in Notch signaling also cause inherited vascular and cardiovascular diseases. In this review, I summarize recent findings and discuss the growing relevance of Notch pathway modulation for therapeutic applications in disease.

Localized reactive angioendotheliomatosis.

We present a unique case of a woman with multiple painful dermal lesions localized to the left upper quadrant of the body. Histological investigation revealed microvascular thrombosis with capillary-wall proliferation. Further investigation revealed a very high anticardiolipin IgG titre and a left subclavian stenosis, presumably providing the reduced blood flow and relative hypoxia to allow microthromboses to occur in the presence of a thrombophilic tendency. Similar clinical and histological features have been reported in patients with the antiphospholipid syndrome and cases of reactive angioendotheliomatosis (RAE). This case represents a unique variant of RAE.

[Pathogenesis and genetics of vascular anomalies]. / Pathogénie et génétique des anomalies vasculaires.

Vascular anomalies, divided into vascular tumors and vascular malformations, are localized defects of angiogenesis. Hemangiomas appear soon after birth, grow quickly, and then spontaneously, but slowly, disappear. In contrast, vascular malformations are congenital defects of vascular development that grow proportionately with the child. Most vascular anomalies are considered non-hereditary. However, due to detailed analysis inherited forms have been observed, which has led to identify mutations in three genes causing familial vascular malformations: in the angiopoietin receptor TIE2 in mucocutaneous venous malformations (VMCM), in glomulin in glomuvenous malformations (GVM) and in RASA1 in the newly recognized phenotype capillary malformation-arteriovenous malformation (CM-AVM). Identification of the causative genes has permitted more precise diagnosis and differential diagnosis, evaluation of phenotypic variability among patients with a proven mutation, study of used treatments in more homogeneous patient groups, and elucidation of the etiopathogenic mechanisms behind vascular malformations. Further studies are needed to unravel the role of genetic variations in the various vascular malformations and to unravel the precise molecular mechanisms that lead to development of these vascular lesions. This should provide development of new-targeted therapies.

Vascular update: morphogenesis, tumors, malformations, and molecular dimensions.

This vascular review is organized under the following headings: vasculogenesis and angiogenesis; vascular endothelial growth factors, their receptors, TIE receptors, and angiopoietins; other factors in blood vessel formation; parallel patterning in blood vessels and nerves; physiological and pathological neovascularization; the role of VEGF receptors in metastasis; anti-angiogenic therapy for tumors; association of blood vessels with fat; vascular malformations and vascular tumors; infantile hemangiomas; congenital hemangiomas; lymphatic malformations; molecular characteristics of some disorders with vascular malformations; Kasabach-Merritt phenomenon; Sturge-Weber syndrome, Klippel-Trenaunay syndrome, and Parkes Weber syndrome; diagnostic and laboratory studies; and future perspectives.

Perivascular myoma of myopericytoma and myofibromatosis-type arising in a chronic scar.

We describe a case of a cutaneous perivascular myoma with features overlapping between the myofibromatosis and the myopericytoma type. The patient is a 58-year-old woman with a painless plaque-like and multinodular lesion in the pretibial dermis and subcutaneous tissue. She had repeated trauma to this site, first in her early youth that left an area of hyperpigmentation, and then again at age 40. The biopsy showed a biphasic pattern with a myofibromatosis-type component composed of spindle cell myoid nodules and more cellular round cell areas. The myopericytoma-like areas appeared to be infiltrating along vessels. These areas contained aggregates of immature-appearing cells arranged concentrically around vascular lumina in a manner reminiscent of pericytes. Immunohistochemical stains showed focal positivity for smooth muscle actin. Immunohistochemical and ultrastructural studies have showed these pericyte-like cells to be of a myoid origin. The reason for the neoplastic proliferation of perivascular myoid cells is presently unknown. The association of trauma and neoplastic transformation of the skin is rare. We report the first case of a cutaneous perivascular myoma arising in a chronic scar.

Spindle cell angiosarcoma following irradiation therapy for cervical carcinoma.

BACKGROUND: Angiosarcomas arise in the scalp and face in the elderly, in association with chronic lymphedema (Stewart-Treves syndrome), and in irradiated areas. Rarely in these settings, angiosarcomas exhibit pure spindle cell phenotype. METHODS: Herein, the clinicopathologic features of a 72-year-old-woman with spindle cell angiosarcoma are described. RESULTS: A 72-year-old woman presented with numerous nodules and diffuse induration from the lower abdomen to the right buttock, corresponding to the area exposed to 60Co-irradiation during treatment for cervical carcinoma 10 years earlier. Histopathological examination revealed inflitrative, atypical, spindle cells that labeled with antibodies to CD31, CD34, and factor VIII-related antigen. Ultrastructurally, these malignant spindle cells contained Weibel-Palade bodies. No features suggesting radiation dermatitis (sclerosis or bizarre, large fibroblasts) were identified, but lymphangiectases and widely spaced collagen bundles(lymphedema) were prominent in the skin surrounding the angiosarcoma. Computed tomographic scan of the abdomen highlighted this histologic finding by demonstrating tumor masses limited to areas of lymphedema. Treatment with intravenous and local injections of recombinant interleukin 2 (rIL 2) followed by electron beam irradiation were initially effective with tumor remission for 2 months. However, the recurrent tumor did not respond to a second course of one-shot injection of rIL 2 through the abdominal aorta and the patient succumbed to her angiosarcoma 19 months after diagnosis. CONCLUSIONS: Radiation-induced lymphedema may be a factor in angiosarcoma associated with radiotherapy.

Mucocutaneous neoplasms in patients with human immunodeficiency virus infection.

Neoplastic disorders of the skin are commonly encountered in patients with human immunodeficiency virus infection. As patients survive longer, they are at ever increased risk to acquire one of a number of different malignant neoplasms of the skin. These may be of many different types including epithelial, lymphoreticular, vascular, smooth muscle, and melanocytic. Because of the immunocompromised status of these patients, many of these disorders behave in more aggressive fashions and require more aggressive treatment.

Tumores vasculares del globo ocular y sus anexos. III. Hemangiomas / Vascular tumors in the ocular globe and annexs. III. Hemangiomas

Los hemangiomas se clasifican según su variedad histológica en capilares, cavernosos, esclerosantes, venosos (racemosos) para las variedades benignas y dentro de éstas existen otras subvariedades que dependen de la respuesta de los tejidos vecinos, como el angioqueratoma, etc. La forma maligna es el angiosarcoma. El hemangioendotelioma y hemangiopericitoma son entidades específicas que constituyen cuadros bien definidos con patrón histológico diferente y comportamiento biológico específico. Cada una de esta entidades tiene un tratamiento específico y el diagnóstico de certeza es histopatológico.

Tumores vasculares del globo ocular y sus anexos. II. Pseudotumores vasculares / Vascular tumors in ocular globe and annexs. II. Pseudotuors are

Los tumores vasculares deben diferenciarse con lesiones pseudotumorales o psudoneoplásicas en la práctica de la oftalmología y patología. El reconocimiento de los pseudotumores tiene importancia en el tratamiento y el pronóstico. Las entidades más importantes que engloban los pseudotumores son el Granuloma piógeno, el hemangioendotelioma vegetante intravascular y las malformaciones vasculares. Desde punto de vista histopatológico son muchas entidades que poseen componente vascular prominente y con las que puedieran confundirse pero que representan entidades bien definidas y de fácil diagnóstico con experiencia y tomando en cuenta todos los marcadores tisulares.

Tumores vasculares del globo ocular y sus anexos. I. Conceptos generales / The vascular tumors in the ocular globe and annexs

Los tumores vasculares representan un espectro amplio que incluye hamartomas y neoplasias benignas y malignas. Las lesiones proliferativas reactivas y las malformaciones arteriovenosas deben ser excluidas. Los tumores vasculares pueden originarse en vasos sanguíneos, linfáticos o en cualquiera de sus componentes estructurales. Los hamartomas vasculares puede ser lesiones solitarias o formar parte de enfermedades complejas determinadas genéticamente. La clasificación de los tumores vasculares no está ampliamente conocida en la clínica y el comportamiento biológico de algunas neoplasias es aún controversial. Los tumores vasculares son frecuentes en el tracto uveal, órbita y párpados y menos frecuente en retina y nervio óptico. Los linfangiomas son muy poco frecuentes. En el momento actual los nuevos métodos diagnósticos de gabinete facilitan el diagnóstico clínico. El tratamiento debe ser quirúrgico y conservador cuando sea posible y las radiaciones en las neoplasias benignas se deben evitar.

Progressive growth in immunodeficient mice and host cell recruitment by mouse endothelial cells transformed by polyoma middle-sized T antigen: implications for the pathogenesis of opportunistic vascular tumors.

A retroviral construct encoding polyoma middle-sized T antigen was used to generate transformed endothelial cell lines from heart (H5V), brain (B9V), and whole-embryo (E10V) of C57BL/6 mice. When injected into syngeneic recipients, H5V and the less studied B9V and E10V cells caused vascular tumors which, depending on the number of cells inoculated, regressed or progressed, leading to death of the host. When H5V cells were injected into immunodeficient mice, tumors were observed with inocula which did not form lesions in immunocompetent recipients and regression did not occur. Treatment with anti-LFA-1, anti-Thy-1.2, and anti-CD8 antibodies abolished rejection; anti-CD4 was a somewhat less effective inhibitor of resistance. Animals with progressive tumors exhibited secondary lesions in various organs with prominent skin involvement in nude mice. Histologically, the tumors had the appearance of a hemangioma, with areas resembling Kaposi sarcoma. Cells lining vascular lacunae had the morphological features of injected H5V cells. The lesions were characterized by prominent neovascularization and mononuclear cell infiltration. Southern blot hybridization analysis revealed that approximately 5% of the cells in the tumor mass were transplanted H5V cells. Thus, the H5V transformed endothelial line causes vascular lesions that are sustained to a large extent by recruitment of host cells and manifests full malignant behavior only in immunocompromised hosts. The hypothesis of a tumor sustained by a minute proportion of transformed cells, which recruit host elements and express full malignant behavior only in immunodeficient hosts, would account for several features of some vascular neoplasms in man.

Vascular transformation of sinuses in lymph nodes. A study of its morphological spectrum and distinction from Kaposi's sarcoma.

Vascular transformation of lymph node sinuses (VTS) is characterized by conversion of nodal sinuses into capillary-like channels, often accompanied by fibrosis. A detailed study of this entity, based on 76 cases, showed that the morphologic spectrum was much broader than that originally described. The vasoproliferative process caused variable expansion of the subcapsular, intermediate, and medullary sinuses of the lymph nodes and involved single or multiple lymph nodes in a diffuse or segmental fashion. The proliferated vessels formed anastomosing narrow clefts, rounded spaces of different sizes, plexiform channels, or solid spindled to plump cellular foci and often were associated with variable degrees of sclerosis. The vascular spaces were empty, filled with lymph-like fluid, congested with blood, or occasionally thrombosed; extravasation of red cells was common. Several patterns were commonly observed in an individual case. Less common features included perivascular fibrin deposition and the presence of eosinophilic globules. Vascular thrombosis was identified only rarely in extranodal vessels available for histologic assessment. The more cellular forms of this vascular transformation may be mistaken for Kaposi's sarcoma, but can be distinguished from it by the pure sinusoidal distribution, a lack of well-formed spindle cell fascicles, the associated fibrosis, the maturation of the spindle cells into well-formed vascular channels toward the capsular aspect, and the failure of this process to involve the capsule itself, which is frequently affected by Kaposi's sarcoma.

[Histogenesis of Kaposi's sarcoma]. / O gistogeneze sarkomy Kaposhi.

The origin of Kaposi's sarcoma from the endothelium and fibroblast-like cells of a vascular wall is proven on the basis of complex pathomorphological, immunomorphological, autoradiographic and electron microscopical investigation of tumour biopsies. Depending upon the predominating cell type of origin, the tumour in its different parts, may form the structures of either different variants of angiomas or fibrosarcomas.

Brown tumors associated with secondary hyperparathyroidism of chronic renal failure.

Two cases of brown tumors associated with secondary hyperparathyroidism and chronic renal failure are reported. Both patients underwent excision of the tumor because of mechanical interference. Subsequent parathyroidectomy has substantially improved the general status of the patients.