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PF573,228 is a compound that targets focal adhesion kinase (FAK), a non-receptor protein kinase, which is over-expressed in various tumors. The aim of this study was to evaluate the effects of PF573,228 on the cells derived from mouse vascular tumors, namely, endothelioma cells. The treatment of endothelioma cells with PF573,228 reduced their growth with an IC50 of approximately 4.6 μmol L-1 and inhibited cell migration with an IC50 of about 0.01 μmol L-1. Microscopic studies revealed morphological attributes of apoptosis. These observations were confirmed by ELISA, which showed increased caspase-3 activity. PF573,228 also inhibited angiogenesis in a dose-dependent manner, with an IC50 of approximately 3.7 μmol L-1, and abrogated the phosphorylation of cell survival proteins, proline-rich Akt substrate (PRAS40) and S6 ribosomal protein (S6RP). Array data further revealed that PF573,228 induced caspase-3 activation, thus promoting apoptosis. Since all the processes inhibited by PF573,228 provide important support to tumor survival and progression, the drug may have a potential role in the treatment of vascular tumors.

Kaposiform hemangioendothelioma (KHE), a borderline tumor of endothelial origin, is associated with Kasabach-Merritt phenomenon, characterized by profound thrombocytopenia and consumptive coagulopathy resulting from the localized intravascular coagulation (LIC) in the tumor. Previous studies have suggested that the trapping of blood components, including platelets, may underlie the LIC in KHE. However, more evidence is needed to support this hypothesis. In this study, one case of a Chinese infant with a KHE in the left arm was complicated by Kasabach-Merritt phenomenon. The tumor was partially resected and the sample was used for ultrastructural observation and immunohistochemistry staining of Glut-1. Ultrastructural observation found the trapping of erythrocytes, platelets, macrophages, and lymphocytes in the slit-like channels of the tumor nodules, and phagocytic vesicles in the cytoplasm of neoplastic cells. Immunohistochemistry staining further showed numerous Glut-1(+) erythrocytes in the channels. In conclusion, our results provided compelling morphological evidence of the trapping of blood components in KHE, which may interpret the LIC in the tumor and subsequent consumptive coagulopathy.

Kaposiform hemangioendothelioma (KHE) is a rare vascular neoplasm of low malignant potential that mainly affects infants and adolescents. The tumor almost exclusively occurs in somatic soft tissue or the retroperitoneum. We report herein two cases of primary KHE occurring in a long bone without cutaneous changes with long-term follow up in young patients. The patients were a 9-year-old girl and 5-year-old boy presenting with lytic lesions of the femur and humerus, respectively, without cutaneous lesions. Histologically, the neoplasms were comprised of nodules of spindle- to oval-shaped cells growing in an infiltrative fashion. The neoplastic cells formed poorly canalized or slit-like blood vessels alternating with solid spindle areas. Immunohistochemical studies showed that the tumor cells expressed CD31, CD34 and Fli1, but not HHV8, LNA-1 or GLUT1. D2-40 stained the neoplastic spindle cells and lymphatic channels adjacent to vascular lobules. The girl remains well with 15 years and 6 months follow up after a second complete excision. The boy has no signs of recurrence or metastasis nearly 5 years after local complete excision. To our best knowledge, this is the first report in the English literature of primary long bone occurrences of KHE without cutaneous changes with long-term follow up., (© 2011 The Authors. Pathology International © 2011 Japanese Society of Pathology and Blackwell Publishing Asia Pty Ltd.)

Kaposiform hemangioendothelioma (KHE) is a rare tumor that occurs nearly exclusively during infancy and childhood. It has features common to both capillary hemangioma and Kaposi sarcoma and for that reason many terms have been used for these tumors including "Kaposi-like infantile hemangioendothelioma" and "hemangioma with Kaposi sarcoma-like features." KHE typically presents as an ill-defined, red to purple, indurated plaque and is often complicated by the Kasabach-Merritt phenomenon (KMP), a condition of severe thrombocytopenia and consumptive coagulopathy. Knowledge of the radiological findings of this uncommon tumor might be helpful for diagnosis. We present the MRI features of a case of KHE with neither typical skin lesions nor the Kasabach-Merritt phenomenon.

Spindle cell hemangioendothelioma is a rare vascular tumor which is presented with subcutaneous nodules and follows a benign indolent course but has a recurrent tendency, and is histologically resembling a cavernous hemangioma and Kaposi's sarcoma. We present a case of spindle cell hemangioendothelioma possessing clinical aggressiveness with painful bony erosion, histologic pleomorphism and mitoses. A 20-year-old man presented with a recurrent painful mass on the left ankle. The mass was dark brown and firm with irregular margins and measured 1.5 cm in diameter, which affected and eroded the underlying medial malleolus of the left tibia. Microscopically, the tumor was composed of cavernous endothelial-lined blood spaces and spindle cellular areas mimicking Kaposi's sarcoma. The spindle cells intermingled with plump epithelioid cells and showed a moderate degree of pleomorphism with occasional mitoses. Immunohistochemically, the spindle cells were focally positive for factor VIII-associated antigen and vimentin, and negative for S-100 protein, desmin, and epithelial membrane antigen.

Visualization and analysis of nucleolus organizer regions (NOR) by a silverstaining is a well accepted method in cytological and histological tumor diagnostic. For specific staining of the NOR the AgNOR-method developed by HOWELL and BLACK (1980) and PLOTON et al. (1986) is performed. One major disadvantage of the AgNOR-method is the instability of the reaction products and therefore the short durability of the slide preparations. A modification of the AgNOR-method, the PEG-Th-staining, leads not only to a longer durability of the reaction products but also to a better contrast within the sections. Main characteristic of the PEG-Th-staining is a postfixation of the specific silver precipitations for 5 min in a 5% sodium thiosulfate solution. It could be proven by image analysis that there is no significant difference between the morphometric parameters evaluated on AgNOR- and PEG-Th-stained sections. Therefore results evaluated on PEG-Th-stained sections are absolutely comparable to those obtained on sections stained with the AgNOR-method thus providing the advantage of a longer durability of the reaction products and easier evaluation.

Nine patients with cutaneous malignant hemangioendothelioma (CMHE) were reported in Okinawa. All the patients were elderly, between 75 and 93 years of age. Four patients were males and five were female. The onset of the disease ranged from 1 to 9 months before the first visit. Eight patients had lesions on the scalp, and one, on the face and cheek. The lesions were in the form of exudative erythematous purpura, erythematous purpuric ulcers, and tumors. One patient developed a systematic metastasis involving the lungs, heart and intestine, and two patients had local metastasis to the cervical lymph nodes. Histopathologically, the tumor vessels were proliferated irregularly and showed anastomosis. The lumens were lined by large and atypical endothelial cells. Most of the specimens were infiltrated with large numbers of red blood cells. By electron microscope, Weibel-palade bodies were found inside the tumor cells located at the peripheral part of the lesion. The patients were treated by irradiation, IL-2 injection, and/or surgery. They were treated for 3 months to 2 years. Eight patients died between 4 to 24 months after the onset of disease and one has survived. The prognosis was poor.

Background: Spindle cell hemangioendothelioma lesions are uncommon, affect a wide age range in both sexes, and show a predilection for skin and subcutaneous tissue of the extremities., Objective: To present three cases of spindle cell hemangioendothelioma and review the literature., Methods: Three cases of spindle cell hemangioendothelioma are presented., Results: Two of our cases first presented very early in life and progressed by local recurrences over many years. None of our cases showed evidence of metastases, but the lesions exhibited local aggressive and invasive behavior. Histologically, the lesions consist of alternating areas of dilated, thin walled cavernous vascular spaces and solid areas composed predominantly of spindle cells and clusters of epithelioid endothelial cells with intracytoplasmic vacuoles. That spindle cell hemangioendothelioma is a non-neoplastic lesion and not a neoplasm of borderline malignancy is suggested by the following observations from our cases: the repeated presence of organized intravascular thrombi in all cases, the early clinical presentation in two cases, and the presence of some degree of vascular malformation at the periphery of lesions., Conclusion: Both clinicians and pathologists should be aware of the existence of this lesion in order to diagnose and treat an affected patient correctly.

26 intraocular melanomas were studied histologically, ultrastructurally and morphometrically. For the first time the impregnation method was used for visualization of the nucleolar organizer (NO) in the cells of eye tumors using silver salts on the deparaffined sections. The efficiency and reliability of this method in the determination of the degree of malignancy of intraocular melanomas are demonstrated. A correlation existed between long-term postoperative results and the nucleolar organizer index (NO number/number of nuclei). The method can be practiced in any pathohistologic laboratory.

A 30-year-old woman was referred for evaluation of a small nodule of the clitoris. This was subsequently diagnosed as epithelioid hemangioendothelioma. This rare vascular tumor of intermediate malignancy has not been previously described in the vulva. The patient underwent a modified radical vulvectomy and bilateral inguinal lymph node dissection, and subsequently received photon therapy. She is alive with no evidence of disease 27 months after diagnosis.

A patient with spindle cell hemangioendotheliomas was followed from 1964 to the present time, allowing the authors the opportunity to examine the lesions in the early, mature, and old phases. Organizing thrombi of different stages associated with slit-like vascular proliferation were always observed, whereas cavernous vascular spaces predominated as the lesions became older. Each spindle cell hemangioendothelioma initially developed relatively rapidly and was sometimes painful but then persisted as a silent nodule for decades. Transmission and scanning electron microscopic studies revealed that endothelial cells tended to digitate into the slit-like proliferating channels, became attached to other cells by means of tight junctions, and thus obstructed the channels at sites where thrombi developed repeatedly. The vascular spaces, ranging in nature from slit-like to cavernous, were outlined further by a relatively sparse mantle of ramified or dendritic interstitial cells that corresponded to spindle cells. Most of the cells appeared simply to be fibroblasts, but they developed the features of pericytes when they were close to the endothelial lining of well-developed vascular lumens. Large vascular spaces and phleboliths were surrounded by smooth muscle cells. Approximately 20% of the interstitial cells were dendritic macrophages characterized by phagocytic activity, presence of many lysosomes, and Factor XIIIa expression. The long and characteristic clinical course, the histologic evidence that thrombosis and its organization was continually occurring within the lesions, and the ultrastructural finding that spindle cell hemangioendotheliomas were composed of different microvascular segments from capillaries to veins, suggest that spindle cell hemangioendotheliomas may develop from a cycle of recanalization after thrombosis that occurs repeatedly because of the unique endothelial growth that was noted. This is in contrast with the previous conception that they were low-grade angiosarcomas.

Ten cases of spindle cell haemangioendothelioma (SCH) were analysed clinicopathologically, including an immunohistochemical survey of seven cases and ultrastructural observations on one. There were seven females and three males, ranging from 16 to 76 years of age. All but one lesion developed on the extremities, predominantly on the hands and feet. Six of the ten patients presented multiple nodules or papules which gradually increased in size and number over a long duration. Among them, four patients had undergone operations twice or more, but no metastatic foci were recognized. Histologically, the lesions were composed of dilated vascular spaces and a proliferation of bland-appearing spindle cells and interspersed epithelioid endothelial cells. Ultrastructural and immunohistochemical studies demonstrated that the spindle cells were mainly made up of fibroblastic cells admixed with pericyte-like cells and macrophages. Smooth muscle cells and primitive mesenchymal cells were also present. The clinical and microscopic features suggest that SCH may be a benign vasoformative lesion of a heterochronological multicentric origin.

A 75-year-old female patient with neurological disturbances and numerous erythematous skin infiltrates is presented. Angioendotheliomatosis proliferans systematisata was diagnosed on histological detection of intravascular tumour cells in the cutaneous blood vessels. On immunohistochemistry and electron microscopy, the mononuclear tumour cells were identified as atypical B-lymphocytes. Our results provide further evidence that angioendotheliomatosis proliferans systematisata is a malignant angiotropic lymphoma with neurocutaneous manifestation.

Cellular hemangiomas of infancy, also known as "infantile hemangioendotheliomas," are benign tumors whose dense cellularity may lead to confusion with soft tissue sarcomas. Ultrastructural and immunohistologic study revealed considerable cellular heterogeneity in these lesions despite the monomorphous appearance revealed by routine histologic preparations. Pericytes and endothelial cells are predominant, but fibroblasts and mast cells are regularly present in these tumors. An interstitially located cell of uncertain identification, expressing factor XIIIa and a macrophage marker, not previously noted, comprises an important segment of the cell population. The cell composition reflects the dynamic potential of these lesions, whose natural tendency is to grow, then to become stable, and finally to involute.

A 66-year-old woman presented with a superior-anterior mediastinal mass that contained considerable calcification by computed tomography. Initial biopsy interpretation was inconclusive but suggested a giant cell sarcoma of soft parts because the tumor contained atypical epithelioid cells and osteoclastlike giant cells. After radiation and chemotherapy, the tumor was removed. It contained large epithelioid cells, pale chondroid areas, metaplastic bone, and osteoclastlike giant cells. Immunohistochemical and electron microscopic studies revealed the epithelioid cells to be factor VIII positive and to contain abundant intermediate filaments, micropinocytotic vesicles, Weibel-Palade bodies, basal lamina, and primitive cell-cell junctions. These epithelioid cells also stained for muscle-specific actin (HHF-35), yet were negative for desmin and cytokeratins (CAM 5.2 and AE1/3). The findings were most consistent with those reported to occur in epithelioid hemangioendothelioma.

Spindle cell haemangioendothelioma is an uncommon vascular lesion, of which 35 cases have been previously reported. A further 20 cases are reported herein. These lesions affected a wide age range in both sexes, and showed a predilection for the extremities. Twelve patients had multiple lesions and, in these cases, local progression over many years but no true recurrence was typical. None of the 20 patients developed metastases, but one later developed an angiosarcoma. Individual cases were associated with congenital lymphoedema. Klippel-Trenaunay syndrome and early-onset varicose veins. Histologically, in addition to the admixture of cavernous spaces and solid spindle cell/epithelioid cell areas, the presence both of irregularly distributed and perivascular smooth muscle cells and of malformed variably-sized vessels at the periphery of almost every lesion was noted in each case. Reticulin staining, immunohistochemistry and electronmicroscopy revealed the presence of primitive vessel formation and partial endothelial differentiation in the solid spindle cell areas. Combining these data with those from previously published series, it is suggested that spindle cell haemangioendothelioma is a non-neoplastic lesion (rather than a borderline malignancy as it is currently regarded) and that its development correlates with histological and/or clinical evidence of a malformed vasculature at the affected site.

Electron microscopic examination of an infantile hemangioendothelioma (IHE) type I of the liver, appearing in a five month old child, showed a high density of pericytes in the walls of the neoplastic vessels. These vessels, in part of the IHE patients, establish an important arteriovenous shunt leading to high output, congestive cardiac failure. It is unclear whether functions ascribed to pericytes, such as participation in microvascular contractility or as suppressors of endothelial cell proliferation are involved in two noteworthy aspects of the present case. The child exhibited no congestive heart failure and the multiple nodular lesions underwent spontaneous regression.

Intravascular lymphomatosis (IL) is a rare and potentially fatal multifocal intravascular proliferative disorder, most often involving the skin and the central nervous system. Originally considered an endothelial disorder, IL has recently been reclassified as an angiotropic lymphoma, most often of B-cell origin. We report immunocytochemical and ultrastructural findings in two patients with IL, both representing angiotropic T-cell lymphomas. In one patient, lesional tissue was examined by Southern blot analysis and monoclonal T-cell receptor rearrangement was found. As an additional feature in one patient, a myelosuppressive serum factor was demonstrated in peripheral blood progenitor cell cultures as the cause of underlying chronic anemia and leukopenia; this factor is thought to be a cytokine product of the lymphoma cells.

A case of epithelioid hemangioendothelioma of the anterior mediastinum in a 40-year-old woman is presented. It showed typical features described in such tumors, but in addition there were foci of osteoclast-like giant cells that were not previously reported in this lesion.

Film preparations, various histological stains, autohistoradiography and electron microscopy were used to study morphologic changes occurring in the course of formation of vascular kidney tumors in male CBA mice after subcutaneous injection of 1.2-dimethylhydrazine. Twenty-thirty animals were examined every 4 weeks up to 45-50 weeks. In mice, renal capsule (site of malignant hemangioendothelioma growth) is avascular. Blood vessels developed due to "formation of lumen" in bands of anastomosed cells. Endothelium of the newly formed vessels originated from multipotent mesenchymal cells. Also, intracytoplasmic formation of vascular lumens was observed. The initial neoplastic vascular structure (telangiectases) were registered after 20-30 weeks. They were composed of markedly atypical cells characterized by columnar shape, high nucleo-cytoplasmic ratio and high proliferative activity. Further progression was associated with the development of cavernous hemangioma-like tumors bearing cytologic signs of malignancy as well as well- and poorly-differentiated hemangioendotheliomas.

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.

Two autopsy cases of neoplastic angioendotheliomatosis (NAE) were presented. Both patients were elderly woman, characterized by an ascending progression of transverse myelopathy and abnormal brain shadows similar to metastatic tumor in computer tomographic examination in Case 1, and by typical clinical features of cerebral infarction in Case 2. Postmortem examinations of both cases revealed an exclusive intravascular distribution of large atypical cells in generalized organs, especially in the central nervous system, and associated multiple cerebral infarcts and, in Case 1, widespread demyelination of the spinal cord. There were no distinct lesions suggestive of a primary focus. In both cases only a few atypical cells were immunohistochemically positive for factor VIII-related antigen, likely due to non-specific absorption of serum factor VIII into the cells. On the other hand, almost all of the atypical cells were immunoreactive for LN-1, LN-2, and leukocyte common antigen, suggestive of lymphocytic (B cell) origin.

An untreated case of a malignant endothelial tumour of the thoracic aorta of a 67 year-old male is reported. A tumour, 7 x 6 x 1.5 cm in size occupied the lumen of the descending thoracic aorta and two daughter lesions, 0.5 cm in diameter, were located in the abdominal aorta and the left common iliac artery. Histologically, they were composed of a surface cellular lining and a underlying necrotic mass; the former was six to ten layers of bizarre epithelioid cells thick and the latter contained much nuclear debris. Innumerable tumour emboli of epithelioid tumour cells and producing ischaemic lesions were found in various organs and tissues. Ultrastructurally, tumour cells were arranged in acinar pattern with narrow lumena and immature basement membrane. There were ultrastructural appearances interpreted as Weibel-Palade bodies and immunohistochemically factor VIII related antigen and vimentin was seen in the tumour cells.

The histology and electron-microscopy of a malignant hemangioendothelioma of the esophagus wall appearing in a 42 year old male is presented. By light microscopy the tumor is composed of vessels and capillary-like structures of an anastomosing nature covered by atypical endothelial cells. These cells infiltrate the interstitial spaces growing into the posterior mediastinal area. Electron microscopy confirms the endothelial nature of the neoplastic cells, showing characteristics of the cell type, as is the presence of Weibel-Palade bodies, filaments and active pinocytosis. Hemangioendothelioma should be differentiated from other vascular tumors (angiosarcoma) as are hemangiopericytoma or hemangioblastoma, being composed exclusively of malignantly transformed endothelial cells.

The fine structure of crystalloid inclusions were found in the endothelial cells of capillary (strawberry) hemangiomas and cellular hemangiomas in nine infants. The inclusions measured from 0.5 to 2.0 microns in diameter and showed parallel lamellar bands with a regular periodicity of about 180 to 300 A. The presence of crystalloid inclusions and the absence of typical rod-shaped tubulated Weibel-Palade bodies suggest the immaturity and embryonic character of the endothelium present in the blood vessels of these kinds of hemangiomas.

Cells of a malignant angioendothelioma in pleural fluid were studied by light and electron microscopy. They occurred singly and clustered, with peripheral, pleomorphic nuclei containing finely particulate chromatin and one or two nucleoli. The cytoplasm was pale and finely vacuolated. Ultrastructural findings were those of endothelial cells: cytoplasmic pseudopodia, tight junctional complexes, cytoplasmic filaments and pinocytotic vesicles.

Three cases of malignant hemangioendotheliomas in elderly individuals are recounted. All of them died shortly after onset of the malignancies in spite of radical surgery in one; radical surgery, chemotherapy, and radiotherapy in another; and chemotherapy and radiotherapy in the third. Findings from studies of specimens of the malignancies by conventional microscopy, histochemistry, and electron microscopy are described.

Clinico-pathological data in a typical case are compared with those of 54 published reports of systemic angioendotheliomatosis. In this rare disease the lesions, characterized by clusters of abnormal cells in the small vessels, usually have multivisceral localizations, with chiefly cutaneous and encephalic manifestations and a rapidly fatal course. However cases are known with lesions restricted to the skin and a protracted if not regressive course; about half of these cases are associated with an endocarditis. In the case reported, the results of ultrastructural and histo-immunological studies (f. VIII, lysozyme, anti-protease, Ig) are in favour of the endothelial origin of the abnormal cells, a now widely accepted hypothesis.

A case of epithelioid hemangioendothelioma of the liver is reported. Both immunohistochemical and electron-microscopic examinations revealed the neoplastic cells to share many characteristics with endothelial cells. We discuss and compare this rare tumor, which represents a low-grade sclerosing hemangiosarcoma of the liver, with its pulmonary counterpart, which is known as intravascular bronchioloalveolar tumor (IVBAT).

A two-month-old female presented with hepatomegaly 5 cm below the right costal margin. Resection of a 6 cm hepatic mass demonstrated an infantile hemangioendotheliom (IHE). This documents for the first time the ultrastructural features of an IHE of the liver. Ultrastructural examination showed large numbers of vascular channels of varying sizes lined by abnormal endothelial cells. An incomplete basal lamina separated the endothelial cells from the extracellular material and there were no associated pericytes. The intervascular area contained abundant collagen fibers, fibrils, and cells ultrastructurally similar to fibroblasts. The relationship of structure to certain clinical features of this lesion is discussed.

Malignant hemangioendothelioma of the thyroid gland, which most often originates in a hemorrhagic nodule, is a well-known entity in European alpine regions with endemic goiter. In other parts of the world it very rarely has been diagnosed. This tumor may display considerable morphologic variation and often has been interpreted as a variant of undifferentiated carcinoma. In 13 out of 20 thyroid tumors, classified by light microscopy as malignant hemangioendothelioma, Factor VIII-related antigen, a marker for endothelial cells, was demonstrated in neoplastic cells with the help of immunohistochemical technics applied to conventional paraffin sections. In one case, in which material suitable for electron microscopy was available, Weibel-Palade bodies were found in tumor cells. These findings add strong support to the notion of an endothelial origin of this neoplasm.

A case of an epitheloid hemangioendothelioma of the skin and subcutaneous tissue of the scalp is described. Clinically and histologically a (metastatic) carcinoma had been considered in differential diagnosis. Of great help in recognition of the endothelial nature of this tumor was the immunohistochemical reaction with Factor-VIII associated antigen and Ulex europaeus antigen. Not only tumor cells in solid areas, but also intracytoplasmic vacuoles revealed positive staining. Thereby it could be shown, that this paranuclear vacuoles are actually compatible with developing capillary lumina. Only few tumor cells showed positive reaction with alpha-1-antichymotrypsin, pointing to a possible small histiocytic component of this tumor. Endothelial features of tumor cells and developing capillary lumina also could be demonstrated by electronmicroscopy.

Tumors of non-specialized gonadal mesenchyme have been reported only rarely. An intratesticular benign hemangioendothelioma from a 26-year-old man presented a diagnostic challenge due to the infrequency of well-defined vascular lumens. Electron microscopy was helpful in defining the vascular nature of the tumor. In spite of the cellularity of the neoplasm, there has been no recurrence or metastasis over a two and one-half year follow-up period. The histological features are compared with those of previously reported cases.

Two babies were found to have large hemangiomas. Histologically there were many islands of compactly packed mesenchymal cells in the deep dermis and subcutaneous tissue. Electron microscopically there was proliferation of immature endothelial cells and pericytes. Characteristic crystalline lamellae were in the endothelial cells. Our two cases seemed to be an independent entity from other benign angiomas because of the distinct clinical, histologic, and ultrastructural features. The suggested diagnosis was angioblastoma (Nakagawa; Miki and Matsumoto), hypertrophic hemangioma (Watson and McCarthy), and benign hemangioendothelioma (Stout).

Angiosarcoma of the colon with epithelioid and histiocytoid features, a malignant counterpart of epithelioid hemangioendothelioma, was observed in a 72-year-old man. The disease first manifested as a right cervical mass, with the histologic appearance of malignant, undifferentiated, large-cell epithelioid neoplasm. Light microscopy of the colonic tumor disclosed angiosarcoma, with active erythrophagocytosis and positive immunoperoxidase reactions to lysozyme, alpha-1-antitrypsin, and alpha-1-antichymotrypsin. Ultrastructural features of the tumor cells were those of intermediate between endothelial and histiocytic cells. The disease took a rapid fatal course with recurrence, peritoneal dissemination, and massive peritoneal hemorrhage. The cause remains unknown.

A malignant haemangioendothelioma of the nose has been examined with the electron microscope. The tumour is predominantly poorly differentiated with only little evidence of its vascular ancestry identified. The cells are polygonal with a wide spectrum of organelles, including microfilaments. A conspicuous feature was the presence of cytoplasmic fenestrae developing into intracytoplasmic vacuolated spaces. The satisfactory progress of this patient is noted, and the value of electron microscopy in enabling an early and accurate diagnosis of this tumour to be made is emphasised.

A 52-year-old woman presented with a solid spindle cell primary tumor of the lymph node. On light microscopic examination, mitoses and cellular atypia were absent. Electron-microscopic studies showed endothelial cell differentiation. Intracytoplasmic localization of Factor VIII-related antigen was demonstrated by the immunoperoxidase method, which confirmed the endothelial origin of the tumor. Seven-and-a-half years after the resection of this tumor, the patient is alive with no evidence of disease.

Epithelioid hemangioendotheliomas are uncommon vascular tumors, mainly observed in lung and soft tissues. Liver involvement is infrequent and, in contrast to the extrahepatic localizations of the tumor, has not been subjected to detailed ultrastructural analysis. This prompted us to report the results of the ultrastructural study of three cases of epithelioid hemangioendothelioma of the liver. Neoplastic proliferation was heterogeneous. Most of neoplastic cells presented features suggestive of endothelial differentiation, including presence of Weibel-Palade bodies and evidence of vasoformative properties demonstrated by formation of both intra- and extracellular vascular channels resembling the normal structures successively observed during embryogenesis and tissue regeneration. A minor cell population, unreported so far, exhibited ultrastructural characters resembling those of pericytes and presented organoid relationship to neoplastic endothelial cells. Tumor spreading along sinusoids induced pseudopeliotic dilatations and led to a progressive disruption of normal liver architecture. In conclusion, the three cases of hepatic epithelioid hemangioendothelioma examined in this work assume many organoid features mimicking the successive steps of normal angioformation and indicative of a high degree of morphological differentiation.

A case of epithelioid hemangioendothelioma that occurred in the mandible of a 4-year-old boy is reported, and the tumor's ultrastructural features are examined. The presence of small atypical vascular lumina, rounded or fusiform endothelial cells packed with intermediate-sized microfilaments, Weibel-Palade bodies, a small amount of distended rough endoplasmic reticulum, pinocytotic vesicles, and a basal lamina are shown. The remarkable finding of large, apparently "free" spaces within the cells that exhibit vesicle formation and sections of protrusions similar to those found in endothelial cells is discussed.

65 cases of hemangioendothelioma (HE) of the thyroid were accepted as such after control of slides of surgical or autopsy specimen or both. In a few of the more recent cases material could be examined by electron microscope and in some the search for factor VIII-related antigen (FVIIIRAG) was carried out. The demonstration of Weibel-Palade bodies in tumour cells in two cases and the evidence of FVIIIRAG in tumour cells of at least two cases, including primary tumour and distant metastasis, finally show, that the hemangioendothelioma of the thyroid is not simply an anaplastic carcinoma with some peculiar features; at least some of these tumours are true endotheliomas. The proposal that the term hemangioendothelioma be eliminated from the classification of thyroid tumours is therefore unfounded.

Five cases of hepatic hemangioendothelioma (HH) were seen in infants ranging from 2 days to 5 months of age. The cases were studied by clinical chemistry, immunohistochemical staining, and electron microscopic techniques. Serum alpha-fetoprotein (AFP) levels were elevated in each of the four patients in whom levels were obtained. The highest elevation was noted in a 2-day-old infant with a diffuse, unresectable lesion involving the right lobe. Two patients who underwent complete resections of their solitary HH had normalization of their AFP levels. This study suggests that AFP levels in patients with HH are closely related to the patients' age, with the youngest patient having the highest levels of AFP. Catecholamine by-products (VMA and HVA) were elevated in one of four patients in whom levels were obtained, this infant was 3 months old at the time of presentation. She also had an elevated AFP level, a diffuse unresectable lesion involving the entire liver, multiple pulmonary nodules, and cutaneous hemangiomas. Immunohistochemical study failed to demonstrate the source of AFP or the catecholamine by-products in the tumor of this patient, suggesting that the source of catecholamine by-products could be stress-induced catecholamine secretion.

Light and electron microscopic studies were conducted on the immature vascular tumors of two infants, containing various stages of differentiation of the blood vessels and both benign haemangioendotheliomas and haemangiopericytomas. We were able to confirm the existence of two kinds of hyperplastic, immature cells i.e. endothelial cells and pericytes in the same tumor. Presence of crystalloid inclusions in the endothelial cells and absence of the Weibel-Palade bodies, as well as a deficiency in factor VIII-related antigen and no tissue fibrinolytic activity, suggested that the endothelial cells in these lesions were immature. Electron microscopic studies appear more decisive in the diagnosis of heterogenous cellular vascular tumors than light microscopy and if available should be used to aid in the final diagnosis. The authors propose that the term cellular haemangioma would be more appropriate in describing this vascular entity.

Two cases of neoplastic angioendotheliomatosis are described. Both patients presented with subacute development of dementia punctuated by focal neurologic signs. Postmortem examination in both cases disclosed a vasculocentric distribution of neoplastic cells in many organs. Two characteristic histologic patterns were seen: (1) distension of vascular spaces by free-floating, intraluminal cells and (2) asymmetric, subendothelial tumor growth. Intravascular tumor and secondary vascular changes were associated with microinfarcts in involved organs. Immunohistochemical localization of factor VIII-related antigen in the neoplastic cells of one case provides evidence for their endothelial origin. The neoplastic cells in both cases exhibited similar but nonspecific ultrastructural features. In addition, dramatic fine structural changes including the acquisition of numerous pinocytotic vesicles and bundles of fine filaments with periodic densities were found in the non-neoplastic endothelial cells.