Systemic reactive angioendotheliomatosis-like syndrome in a steer presumed to be persistently infected with bovine viral diarrhea virus.

Unusual proliferative intravascular lesions were seen in multiple organs of a 2-year-old Corriente steer presumed to be persistently infected with bovine viral diarrhea virus (BVDV), based on widespread immunohistochemical detection of BVDV antigen. Proliferations of spindle cells, which were immunohistochemically positive for von Willebrand factor-related antigen, partially-to-completely occluded vessel lumens and were supported by cells that were immunohistochemically positive for smooth muscle actin. Distribution and character of the intraluminal proliferations are strikingly similar to those described in feline systemic reactive angioendotheliomatosis, a rare entity of unknown cause. The presence of occasional intravascular thrombi suggests that the proliferative vasculopathy was associated with an underlying thrombotic process with immunohistochemical similarities to thrombotic thrombocytopenic purpura of humans. Death of the steer was due to hemorrhage from a castration wound, which may indicate thrombocytopenia or platelet dysfunction. The role of persistent BVDV infection in the formation of the intravascular lesions is unknown.

Absence of HHV-8 DNA in hobnail hemangiomas.

BACKGROUND: Hobnail hemangioma (HH) is a rare subtype of hemangioma that shares the morphological feature of hobnail endothelia with retiform hemangioendothelioma (RHE) and has to be considered in the differential diagnosis of Kaposi sarcoma. Since DNA of the human herpesvirus type 8 (HHV-8) has been detected in more than 90% of Karposi sarcomas and could recently be demonstrated in RHE, we sought to detect HHV-8 DNA in HH. METHODS AND RESULTS: DNA from 12 HH was extracted and subjected to polymerase chain reaction analysis for HHV-8 DNA using two independent protocols with a single set of primers and a nested PCR approach, respectively. PCR amplification was performed using the LightCycler as well as using a thermocycler. HHV-8 DNA could not be detected in HH, although each sample contained DNA adaequately preserved for PCR reactions, as determined by amplification of the beta actin gene. CONCLUSIONS: HHV-8 appears to play no rule in the pathogenesis of HH. Absence of HHV-8 DNA in HH might be important in the differential diagnosis to other vascular tumours, in particular Kaposi sarcoma.

Studies on the pathology, especially brain hemorrhage and angioendotheliomas, induced by two new mos-containing viruses.

Recombinant virus 7 (R7), a spontaneous deletion mutant of SV7, which is itself a molecular clone of Moloney murine sarcoma virus 124 (MoMuSV 124), induces brain lesions and tumors of the subcutaneous tissue and spleen in all infected mice. In contrast, SV7 only induces tumors of the spleen and subcutaneous tissues. One of the genetic differences between R7 and SV7 is that R7 encodes a Gag-Mos protein whereas SV7 encodes an Env-Mos protein. To investigate whether the novel R7 gag-mos oncogene is required for brain lesion induction, two viruses (SV7d1 and SVM1) were constructed in which the R7 gag-mos sequences and the adjacent 53 bp of the 5' noncoding sequence were replaced by either the SV7 or myeloproliferative sarcoma virus (MPSV) env-mos oncogenes, respectively. Like R7, SV7d1 and SVM1 induced brain lesions and tumors in the spleen and subcutaneous tissues. A prominent component of R7-, SV7d1-, and SVM1-induced tumors of the brain, subcutaneous tissues, and spleen was the presence of abnormally enlarged cells with eccentric nuclei lining vessels, scattered singly or in small clusters. Their size, localization to the luminal surface of distended vessels, and binding to Bandeiraea simplicifolia (BS-1) lectin, an endothelial cell (EC) marker, suggest that they are most likely transformed ECs. Our findings therefore indicate that the induction of brain lesions is not limited to the expression of the R7 Gag-Mos protein. However, our findings also indicate that expression of the different forms of the Mos protein results in differences in the relative abundance of ECs in brain angioendotheliomas and subcutaneous and spleen tumors induced by these viruses.

Retiform hemangioendothelioma: another tumor associated with human herpesvirus type 8?

Retiform hemangioendothelioma is a rare low-grade angiosarcoma of the skin. It shares some clinical characteristics with Kaposi's sarcoma, a tumor with known human herpesvirus 8 (HHV-8) association. We report a case of retiform hemangioendothelioma in which we detected HHV-8 DNA sequences.

Juvenile hemangioma (infantile hemangioendothelioma) of the parotid gland associated with cytomegalovirus infection.

A case of parotid juvenile hemangioma associated with cytomegalovirus infection is reported. A growing lobulated mass, measuring 30 x 20 mm, was extirpated from the left parotid gland in a 4-month-old male. Histologically, the tumor consisted of cellular plump endothelial cells, stromal cells and residual ductal and acinar elements of the parotid gland. Numerous intranuclear and cytoplasmic inclusions were observed in the ductal cells of the whole parenchymal part of the parotid gland and the residual part of the tumor. Immunohistochemically, some nuclei of the ductal cells possessing these inclusions were positive for the anti-cytomegalovirus antibody but there were no positive findings in the endothelial or stromal cells. Although the present lesion may suggest that the human cytomegalovirus plays some role in the etiology of juvenile hemangioma, it is unknown whether or not this association is incidental.

Studies on the pathology, especially brain lesions, induced by R7, a spontaneous mutant of Moloney murine sarcoma virus 124.

We have recently isolated R7, a spontaneous Moloney murine sarcoma virus (MoMuSV) 124 variant. Molecular cloning and sequence analysis showed that, relative to MoMuSV 124, R7 has an extra repeat in each enhancer and a truncated mos gene in frame with the truncated gag coding sequence. This report presents a detailed study on the pathology induced by R7. R7 induced not only sarcomas with well developed angiomatous components but also brain lesions. Brain lesions were observed in all less-than-48-hour-old BALB/c mice inoculated with greater than 2 x 10(5) R7 focus-forming units (FFUs). R7 was detected in all brains examined by day 9 after inoculation, and brain lesions were observed in two of four mice examined by day 14 after inoculation. Light microscopy of brains revealed that approximately 15% of the lesions were unenclosed blood pools of varying sizes containing red blood cells and inflammatory cells spreading into surrounding brain tissues. The remainder of the brain lesions had tumor cells. These lesions ranged from a few enlarged vascular endothelial cells intermixed with blood cells to large circumscribed lesions consisting of well developed tangled masses of vessels surrounded by blood pools. Activated astrocytes surrounded and infiltrated the tumors. In addition, the thymus of R7-infected mice regressed significantly and precipitously due to apoptosis (especially of cortical thymocytes) at the end stage of the disease.

Diagnostic implication of Kaposi's sarcoma-associated herpesvirus with special reference to the distinction between spindle cell hemangioendothelioma and Kaposi's sarcoma.

OBJECTIVE: To assess the diagnostic utility of recently identified Kaposi's sarcoma-associated herpesvirus (KSHV, also referred to as human herpesvirus 8) in distinction between Kaposi's sarcoma (KS) and other types of vascular lesion, especially spindle cell hemangioendothelioma (SCH). DESIGN: We conducted a polymerase chain reaction analysis of KSHV in 93 cases of benign and malignant vascular lesions, using DNA extracted from archival specimens. RESULTS: All five cases of Kaposi's sarcoma examined, including cases related and cases unrelated to acquired immunodeficiency syndrome, were positive for KSHV. Vascular lesions other than KS, including 6 SCH, 1 kaposiform hemangioendothelioma, 8 angiosarcomas, 46 hemangiomas (15 cavernous, 12 capillary, 7 venous, 6 intramuscular, 2 sinusoidal, 2 epithelioid, 1 microvenular, 1 glomeruloid), and 7 glomus tumors were consistently negative, except for 1 of the 20 pyogenic granulomas examined. CONCLUSIONS: Our data support the previous finding that KSHV is confined almost exclusively to KS, irrespective of human immunodeficiency virus infection, and suggest that KSHV is a reliable diagnostic marker to differentiate KS from other vascular lesions, including those with KS-like morphology, such as SCH.

No role for human herpes virus 8 in the etiology of infantile capillary hemangioma.

Infantile capillary hemangiomas are vascular neoplasms that can appear quite infiltrative histologically and that are characterized by cords of cells with areas of marked cellularity. These lesions have been shown to contain a population of rapidly proliferative endothelial cells. Given the recent association between the presence of human herpes virus 8 (HHV8) and another proliferative vascular lesion, Kaposi's sarcoma, we used polymerase chain reaction technology to examine a series of 16 biopsy specimens from 15 infantile capillary hemangiomas for the presence of HHV8 DNA. We were unable to detect HHV8 DNA in any of the lesions studied. All of the cases were examined in parallel with a case of Kaposi's sarcoma that was known to be positive for HHV8 DNA and a series of negative controls. In all of our cases, amplification of beta-globin gene DNA demonstrated adequate preservation of DNA in the tissue studied. These findings suggest that not all endothelial cell proliferations can be attributed to HHV8 and that the etiology of some of these conditions remains unclear.

Absence of Kaposi's sarcoma-associated herpesvirus-like DNA sequences in malignant vascular tumors of the serous membranes.

Reports connect Kaposi's sarcoma-associated herpesvirus (KSHV) with various types of Kaposi's sarcoma (KS) and body-cavity-based lymphomas (primary effusion lymphomas). KSHV DNA sequences have also been detected in a few non-KS malignant vascular tumors. To determine whether KSHV is associated with malignant vascular tumors involving the body cavities, 11 primary vascular tumors of the serous membranes (4 angiosarcomas, 7 hemangioendotheliomas) were tested for KSHV sequences by polymerase chain reaction and Southern blot hybridization. The tumors were from patients who were not known to be immunocompromised. KSHV sequences were detected in the penile KS control but were absent in all 11 specimens studied. Our results were consistent with previous reports that KSHV sequences were rarely detected in non-KS vascular lesions. The results also suggested that although KSHV sequences might be present in primary effusion tumors such as primary effusion lymphoma, they might not be found in other tumors related to body cavities or to serous membranes.