Intravascular papillary endothelial hyperplasia of the breast--report of a case with scanning electron microscopic observations

A 65-year-old woman noticed a left breast mass and underwent excisional biopsy. The excised mass measured 1.7 cm in diameter. Histologically, the tumor-like mass revealed irregular vascular channels with occasional thrombi and many papillary projections of fibrous stalks lined with a layer of flat endothelial cells. A small cavernous hemangioma was present adjacent to the lesion. Scanning electron microscopic observation revealed disorderly oriented thin and thick cords forming branches and meshworks in the lumina. The luminal wall and cords were covered with flat endothelial cells. Light and scanning electron microscopic differences between intravascular papillary endothelial hyperplasia and angiosarcoma are discussed.     

Cavernous hemangioma mimicking a cystic renal cell carcinoma

A 69-year-old man was hospitalized for treatment of a left renal tumor. The tumor had originally been demonstrated as a simple renal cyst 4 years before. However, the size of the tumor decreased, and at the time of hospitalization, the tumor showed a solid, papillary component that was enhanced by contrast medium on computed tomography (CT) and had high signal intensity on T2-weighted magnetic resonance imaging (MRI). We diagnosed this tumor as a cystic renal cell carcinoma of the left kidney, cT1aN0M0, arising from the epithelium of a renal cyst, and performed a left partial nephrectomy. The pathological diagnosis was cavernous hemangioma of the left kidney. Generally, it is difficult to diagnose a cavernous hemangioma of the kidney preoperatively. This case is unusual because the configuration of this tumor changed within a few years. When we find a renal cyst with a solid component, renal cavernous hemangioma arising from the cyst wall should be considered in the differential diagnosis, and a conservative surgical approach should be considered.     

Human endothelial cells expressing polyoma middle T induce tumors

The middle T oncogene of murine polyomavirus (PymT) rapidly transforms and immortalizes murine embryonic endothelial cells (EC), leading to the formation of vascular tumors in newborn mice, by recruitment of host, non-transformed EC. These tumors are reminiscent of human vascular tumors like cavernous hemangioma, Kaposi's sarcoma or those characterizing Kasabach-Merrit syndrome. Here we investigate the in vitro and in vivo behavior of human primary umbilical cord vein EC expressing PymT. While PymT has been unable to transform human fibroblasts in earlier experiments or controls done here, mT expressing EC (PymT-EC) derived by infection with pLX-PymT retrovirus induce hemangiomas in nu/nu mice. These tumors contain not only human cells but also recruited mouse EC as shown by the presence of human and murine CD31 positive EC. In vitro analysis shows that PymT-EC retain endothelial specific markers like CD31, Von Willebrand factor, and VE-cadherin, and reach the confluence without signs of overgrowth. They are also responsive to vascular endothelial growth factor-A. However, their proliferation rate is increased. The balance between urokinase-type plasminogen activator and plasminogen activator inhibitor-1 is modified; RNA and catalytic activity for the former are elevated while PAI-1 RNA is reduced. In contrast with murine model, where the PymT EC cells become immortal, the effects induced by PymT in human EC are transient. After 12-15 passages, human PymT EC stop proliferating, assume a senescent phenotype, and lose the ability to induce hemangiomas. At the same time both the amount of middle T protein and the level of activation of pp60c-src lower.     

Pulmonary sclerosing hemangioma of the lung. A type II pneumocytoma by immunohistochemical and immunoelectron microscopic studies

Three cases of pulmonary sclerosing hemangioma were studied by immunohistochemical and immunoelectron microscopic methods using a panel of antibodies. Six cases of adenocarcinoma of the lung, three cases of normal mesothelium, and three cases of mesothelioma were used as controls. The cytoplasm of some of the sclerosing hemangioma tumor cells was positive for the anti-lung surfactant apoprotein monoclonal antibody (PE-10). These cells were the pale cells of the solid areas, the cells covering the papillary projections, and the cells lining the cleft-like spaces. These cells also were positive for conventional epithelial cell markers. Some cells also were positive for vimentin. Electron microscopic study showed that the predominant cell was a poorly differentiated pneumocyte. Immunoelectron microscopic study also demonstrated that PE-10 existed in the rough endoplasmic reticulum of some of the cells in the solid areas, in the same way as normal type II pneumocytes. We concluded that the sclerosing hemangioma is an epithelial tumor with differentiation towards type II pneumocytes.     

端粒体逆转录酶在婴幼儿血管瘤中的表达及意义

目的 通过检测不同时期血管瘤、血管畸形组织中端粒体逆转录酶(TERT)的表达情况,了解血管瘤、血管畸形内皮细胞的生物学特性,进一步探讨血管瘤的生长、演变机制.方法 对手术切除的40例血管瘤、15例血管畸形病理标本和11例正常皮肤组织标本,用免疫组织化学染色方法检测内皮细胞标志物CD31、端粒体逆转录酶TERT及核增殖抗原Ki-67在血管瘤、血管畸形及正常皮肤组织中的表达情况.同时,观察其血管内皮细胞的形态学和组织学特征.结果 增殖期血管瘤组织中TERT及Ki-67的表达明显高于消退期血管瘤、血管畸形和正常皮肤组织(P＜0.01).血管畸形和正常皮肤组织的血管内皮细胞间TERT、Ki-67的表达无显著差异性(P＞0.05).血管瘤中TERT和Ki-67间存在直线正相关关系(r=0.965,P＜0.01).结论 血管瘤内皮细胞的生物学特性不同于血管畸形和正常皮肤组织,血管瘤内皮细胞在增生期具有较高的增殖活力,消退期细胞增殖活力下降.而血管畸形的内皮细胞与正常皮肤血管内皮细胞在细胞增殖活性方面无明显区别,属于正常血管内皮细胞.     

Morphology of experimental malignant hemangioendothelioma]

Various histological stains, histoautoradiography and electron microscopy were used to study the morphologic features of 77 malignant hemangioendotheliomas induced in CBA mice with subcutaneously injected 1,2-dimethylhydrazine. The histologic and cytologic structure of those tumors proved similar to those of malignant hemangioendothelioma in man. The ability of tumor cells to form vascular structures and degree of their neoplastic atypia were used to identify three types of neoplasia: "cavernous hemangioma" with cytologic signs of malignity and well- and poorly--differentiated malignant hemangioendotheliomas. Due to high rate of tumor development and inevitable growth in the renal capsule which makes tumor easy to detect at early stage, the model offers promise for evaluating morphogenesis of malignant hemangioendothelioma.     

Histiocytoid hemangioma of the heart with peripheral eosinophilia

A histiocytoid hemangioma of the heart is reported, which was found incidentally in a man with unusually high eosinophilia. The eosinophilia subsided dramatically following removal of the tumor. The "histiocytoid" or the "epithelioid" appearance of the tumor cells and the presence of vacuolated cells were the characteristic microscopic features. The endothelial origin of this tumor was verified by positive immunostaining for factor VIII-related antigen and ultrastructural demonstration of intracytoplasmic lumen formation, abundant cytoplasmic filaments, pinocytotic vesicles, and prominent basal lamina. The presence of mitotic activity, cellular pleomorphism, and tumor necrosis raised the possibility of its malignant potential. The occurrence of this tumor in the heart may be mistaken for a myxoma clinically and a metastatic carcinoma pathologically.     

A case of intravascular papillary endothelial hyperplasia (Masson's tumor) arising from renal sinus

A 55-year-old woman had a right renal tumor incidentally diagnosed by ultrasonography. CT revealed a perirenal low density mass 3 cm in diameter. Dynamic CT showed peripheral enhancement of the tumor in early phase and internal homogeneous enhancement in delayed phase. Since hemangioma was considered most likely, we performed tumor resection and spared the right kidney. The tumor was supplied by the superior ureteral artery from the right main renal artery which was considered to be derived from the renal sinus. The tumor was diagnosed as intravascular papillary endothelial hyperplasia (Masson's tumor). This is the first report of intravascular papillary endothelial hyperplasia existing in the perirenal space. Although preoperative diagnosis of intravascular papillary endothelial hyperplasia is difficult, intra-operative pathology and kidney-sparing treatment should be considered in such a case.      

Histiocytoid hemangioma of the skin and scapula. A case report with electron microscopy and immunohistochemistry

This report presents the interesting case of a 50-year-old white man with an unusual benign tumor composed predominantly of a proliferation of atypical endothelial cells combined with a variable inflammatory response. This case represents an instance of the recently renamed entity "histiocytoid hemangioma" in which two organ systems are involved. Both skin and bone showed typical lesions. No physical connection jointed the separate lesions. The results of examination by light microscopy, electron microscopy, and immunoperoxidase examination for lysozyme and Factor VIII are reported. The significance of this case is that it supports the concept of classifying similar vascular lesions, despite varied organ system origin, into a single entity, the histiocytoid hemangioma.     

Sclerosing hemangioma of the lung: an ultrastructural study.

A well-circumscribed nodular mass was excised from the lingula of the left lung of a 40-year-old-female. The lesion was discovered on routine chest x-ray examination and corresponded to a typical "sclerosing hemangioma" described by Liebow and Hubbell. Electron microscopic study revealed unequivocal epithelial cells in both the irregular spaces and the solid areas of the tumor; some of these cells were identical to granular pneumonocytes. The true vascular component was sparsely distributed. We concluded that "sclerosing hemangioma" was a misnomer because we were dealing with an essentially epithelial lesion.     

Disruption and inactivation of the PP2A complex promotes the proliferation and angiogenesis of hemangioma endothelial cells through activating AKT and ERK

Hemangioma is a benign vascular neoplasm of unknown etiology. In this study, we generated an endothelial-specific PyMT gene-expressing transgenic mouse model that spontaneously develops hemangioma. Based on this transgenic model, a specific binding between PyMT and the core AC dimer of protein phosphatase 2A (PP2A) was verified in hemangioma vascular endothelial cells. The binding between PyMT and the PP2A AC dimer resulted in dissociation of the B subunit from the PP2A complex and inactivation of PP2A phosphatases, which in turn activated AKT and ERK signaling and promoted cell proliferation, migration and angiogenesis in vitro and tumorigenesis in vivo. Consistent with the in vitro findings, decreased PP2A phosphatase activity and disruption of the PP2A heterotrimeric complex were also observed in both primary transgene-positive TG(+) mouse hemangioma endothelial cells (TG(+) HEC cells) and human proliferating phase hemangioma endothelial (human HEC-P) cells, but not in transgene-negative TG(−) mouse normal vascular endothelial cells (TG(−) NEC cells) and human involuting phase hemangioma endothelial (human HEC-I) cells. Further, it was observed that in human hemangioma cells, endoglin could compete with the PP2A/A, C subunits for binding to the PP2A/B subunit, thereby resulting in dissociation of the B subunit from the PP2A complex. Treatment of Tie2/PyMT transgenic mice with the PP2A activator FTY720 significantly delayed the occurrence of hemangioma. Our data provide evidence of a previously unreported anti-proliferation and anti-angiogenesis effect of PP2A in vascular endothelial cells, and show the therapeutic value of PP2A activators in hemangioma.     

肝原发性血管肉瘤临床病理分析

 目的 探讨肝原发性血管肉瘤（PHA）的临床病理学与免疫组织化学特点。方法 采用HE和免疫组织化学SP法染色对3例PHA进行研究，观察PHA的临床病理学、免疫组织化学特点。结果 患者年龄2～68岁，男∶女为2∶1；临床症状和实验室检查无特异性。1例为多个结节，2例为单个结节；肿瘤直径平均大小为7.2（5～11.3）cm，有出血和坏死。病理学特征：肿瘤细胞呈梭形和不规则形，大小不一。胞质较少，嗜酸性，淡染,边界不清，核较大，卵圆形或梭形，染色深，核仁大小不一，可见少数核分裂象，瘤细胞部分排列成索状，片状，较密集，与周围肝组织界线不清，部分区域可见大而不规则的血管腔隙，局部肿瘤细胞集聚成团，呈乳头状突入血管腔内，相互吻合，内衬不典型性细胞。不规则血管腔样结构广泛弥漫分布于肝实质内，伴局部出血。免疫组化因子Ⅷ和（或）CD34阳性。结论 PHA极少见，为高度恶性，预后差。临床和病理上均易误诊为肝血管瘤、肝上皮样血管内皮瘤、肝细胞癌等；根据PHA的组织学和免疫组化特点，可作出明确的病理诊断。     

RCAS/SCL-TVA animal model allows targeted delivery of polyoma middle T oncogene to vascular endothelial progenitors in vivo and results in hemangioma development.

PURPOSE: To recapitulate the generation of cancer stem cells in the context of an intact animal using a retroviral vector capable of in vivo delivery of oncogenes to primitive endothelial and hematopoietic stem cells. EXPERIMENTAL DESIGN: Targeting of these progenitors was achieved using transgenic mice in which the avian TVA retroviral receptor was placed under the control of the stem cell leukemia (scl/tal-1) gene promoter and SCL +19 enhancer. RESULTS: Injection of an avian retrovirus encoding polyoma middle T (PyMT), an oncogene that transforms endothelial cells, caused rapid lethality in all SCL-TVA mice but not in control TVA(-) littermates. The infected animals exhibited hemorrhagic foci in several organs. Histopathologic analysis confirmed the presence of hemangiomas and the endothelial origin of the PyMT-transformed cells. Surprisingly, the transformed endothelial cells contained readily detectable numbers of TVA(+) cells. By contrast, normal blood vessels had very few of these cells. The presence of TVA(+) cells in the lesions suggests that the cells originally infected by PyMT retained stem cell characteristics. Further analysis showed that the tumor cells exhibited activation of the phosphatidylinositol 3-kinase/Akt and S6/mammalian target of rapamycin pathways, suggesting a mechanism used by PyMT to transform endothelial progenitors in vivo. CONCLUSIONS: We conclude that this experimental system can specifically deliver oncogenes to vascular endothelial progenitors in vivo and cause a fatal neoplastic disease. This animal model should allow the generation of endothelial cancer stem cells in the natural environment of an immunocompetent animal, thereby enabling the recapitulation of genetic alterations that are responsible for the initiation and progression of human malignancies of endothelial origin.     

So-called gastric carcinosarcoma--a case of chondrosarcomatous undifferentiated in the metastatic foci

A case of so-called gastric carcinosaroma in a 70-year-old man was presented. The primary tumor measuring 5.6 X 5.4 cm was located in the gastric antrum and had the appearance of Borrmann 2 type. A massive metastatic tumor was found in the pyloric lymph nodes. Histologically, the primary tumor was predominantly composed of papillary adenocarcinoma invading to the muscle layer with lymphatic and vascular involvements. Atypical spindle cells occasionally intervened between carcinoma nests. The metastatic tumor consisted of mixed papillary adenocarcinoma and well differentiated chondrosarcoma with transitional areas by atypical spindle cells. Therefore, it was suggested that sarcomatous components in the present case were derived from carcinoma cells by undifferentiated. Three cases of gastric carcinosarcoma reported in Japan were reviewed, and their histogenesis was discussed as compared with the present case.     

Combretastatin A4 phosphate induces programmed cell death in vascular endothelial cells

Combretastatin A4 phosphate (CA4P) is currently undergoing clinical trials as a tumor vascular-targeting agent. Here, we defined the antivascular effect and programmed cell death (PCD) induced by CA4P in vascular endothelial cells. CA4P induced time- and dose-dependent antiproliferative activities against human umbilical vein endothelial cells (HUVECs), and caused G2/M arrest accompanied with DNA fragmentation. The in vitro wound assay and tube formation assay indicated that CA4P potently inhibited migration of endothelial cells and tube formation. The apoptosis and autophagy marker microtubule-associated protein light chain 3 (LC3)-II was induced in CA4P-treated HUVECs. The current study demonstrates that CA4P is a promising antivascular agent with potent PCD-inducing activities. CA4P may be useful in the treatment of cancer and hemangioma.     

Effects of chemotherapeutic drugs on platelet and metastatic tumor cell-endothelial cell interactions as a model for assessing vascular endothelial integrity

An in vitro assay for examining the sublethal effects of chemotherapeutic agents on vascular endothelial integrity is described. Using vascular endothelial cell monolayers, the kinetics of binding of radiolabeled platelets or metastatic tumor cells were altered when endothelial cells were pretreated for 2 hr with low, clinically relevant concentrations of certain drugs. Electron microscopic examination by scanning electron microscopy revealed that these same drugs caused endothelial cell retraction and exposure of subendothelial matrix. Platelets and tumor cells were found bound only to the exposed areas of subendothelial matrix. Some drugs (bleomycin, 1,3-bis(2-chloroethyl)-1-nitrosourea, vincristine) induced rapid endothelial cell retraction and increased platelet and tumor cell binding to exposed subendothelial matrix, while one of the drugs tested (Adriamycin) caused delayed (1 to 3 days after a 2-hr drug treatment) endothelial cell retraction and increased cell binding. Of the drugs tested, only 5'-fluoro-2'-deoxyuridine which interferes with DNA replication failed to induce endothelial cell retraction and increased tumor cell and platelet binding. The results suggest that certain drug effects on the vascular endothelium can be assessed using the vascular endothelial cell monolayer model.     

Hemorrhagic epithelioid and spindle cell hemangioma: a newly recognized, unique vascular tumor of bone

BACKGROUND: Epithelioid vascular tumors of bone are uncommon and include epithelioid hemangioma, epithelioid hemangioendothelioma, and epithelioid angiosarcoma. It is important to distinguish among them because they have significantly different biologic potential and require different forms of therapy. In the current study the authors describe six cases of a distinct benign epithelioid and spindle cell vascular tumor of bone that, because of their unusual morphology, were confused with aggressive vascular neoplasms. METHODS: Cases were retrieved from the surgical pathology files of the Department of Pathology or from the consultation files of one of the authors. Hematoxylin and eosin stained slides were examined. Immunohistochemistry was performed on two cases and electron microscopy was performed on one case. RESULTS: The tumors arose in the small bones of the hands and feet and the tibia. Three patients had multifocal bone disease at the time of presentation. Histologically, all lesions were comprised of lobules of spindle cells that grew focally in a fascicular pattern and were associated with abundant hemorrhage. Plump epithelioid cells were intermixed and were present focally in the interlobular areas as well, in which they lined larger, more well developed vascular spaces, often protruding into the vascular lumen in a "tombstone" fashion. Immunohistochemically and ultrastructurally the neoplastic cells had features of endothelium. One case was treated by amputation, one by resection, three by curettage, and one by curettage plus radiation therapy. None of the lesions was locally aggressive nor did any metastasize. CONCLUSIONS: The authors believe that hemorrhagic epithelioid and spindle cell hemangioma of bone is a histologically benign bone tumor. It should be distinguished from malignant epithelioid vascular tumors of bone, which have metastatic potential and need to be treated more aggressively.     

Cell culture and its application. Application of cultured vascular endothelial cells to the in vitro assay for the invasion of cancer cells through endothelium-matrix membrane system]

Usefulness of cultured human vascular endothelial cells for the in vitro assay of cancer invasion was reviewed. Selective isolation procedures for the vascular endothelial cells from the different types of vascular tubes were described. Human umbilical cord vein is one of the most useful sources for the isolation of fresh normal endothelial cells. The cells are isolated by perfusing trypsin solution through the umbilical cord vein and successively subcultivated up to 80 population doubling levels as in vitro life span. In case of human thoracic aorta, endothelial cells were removed from endothelium layer of aorta ring by a jet flow of collagenase solution through a needle. Purity of these cells as endothelial cells can be determined by indirect staining of the cytoplasma with anti-endothelin antibody. Usefulness of these cultured endothelial cells has been proved in the studies of regulation of endothelin biosynthesis, ageing of vascular cell, isolation of some new growth factors, interaction with other blood cells, etc. In addition to these studies, we consider that interaction of tumor cells with endothelial cells plays an important role in tumor metastasis. So we established in vitro invasion assay system through the interaction with endothelial cells to examine the invasion and adhesion of tumor cells. Human umbilical cord endothelial cells (HUVEC) were cultured on porous membranes coated with laminin (LN). HT1080 fibrosarcoma cells were seeded onto HUVEC, and HT 1080 cells passed through the membrane were counted. HUVEC were easily distinguished from tumor cells by specific staining of endothelial cells with UEA-1 lectin. Using scanning electron microscopy, we confirmed that HT1080 cells invaded between HUVEC. Roles of adhesion molecules induced by some cytokines on invasion of cancer cells through the endothelial cells-matrix membrane system were discussed.     

20例肺硬化性血管瘤临床病理分析

目的寻找肺硬化性血管瘤(Pulmonary sclerosing hemangioma,PSH)的诊断和鉴别诊断方法。方法  回顾性分析20例PSH临床症状、CT和冰冻切片诊断、组织学及免疫组织化学染色特点。结果  女性18例,平均年龄55岁。右肺11例,双肺1例,左肺8例。CT检查19例表现为孤立性肺结节,1例双肺分别见有结节;CT诊断肺癌17例,食管癌伴有肺转移2例,错构瘤1例。有10例进行术中冰冻检查, 2例诊断为类癌,2例细支气管肺泡癌,1例描述性诊断PSH,5例炎性假瘤等良性病变。常规切片中同时具有实性区、乳头区、硬化区、血管瘤样区4种结构的11例,并可见圆形和立方形两种肿瘤细胞, HE切片诊断PSH。9例结合免疫组织化学染色,中央圆形细胞EMA、TTF-1、Vimentin弥漫强阳性,AE1/AE3阴性,被覆立方细胞AE1/AE3和TTF-1阳性,而Vimentin阴性等做出诊断。结论  PSH是常发生于中老年女性的少见肿瘤,多表现为孤立性肺结节,CT和术中冰冻切片检查均易误诊,前者极易误诊为肺癌,后者虽然在判断性质方面较前者准确性高,但是多数PSH仍然很难确诊,术后常规切片辅以免疫组织化学检查是诊断和鉴别诊断的有效方法。     

脾脏硬化性血管瘤样结节性转化1例临床病理观察并文献复习

目的:报道1例少见的脾硬化性血管瘤样结节性转化(SANT),以提高对该病变的认识。方法:对1例SANT的临床、病理特征、免疫组化表达及术后随访情况进行分析并复习文献。结果:脾SANT具有众多由环靶状纤维组织围绕的肉芽肿样结节,伴有结节间不同程度硬化的间质。肉芽肿样结节内细胞呈卵圆形、短梭形,胞质相对丰富,部分细胞胞质内可形成含红细胞的腔隙,细胞间还穿插有衬覆肥胖内皮细胞的枝芽状毛细血管及相对扩张的窦隙样血管腔隙。免疫组化显示结节内不同血管样结构有3种不同的免疫组化表达。结论:SANT是脾具有特征性改变的一种良性病变,临床上易与脾脏恶性肿瘤混淆,病理上易与炎性假瘤、错钩瘤等混淆,诊断依靠病理组织学表现及免疫组化特点。行脾切除术可治愈,预后良好。