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Aims-To examine the vascular changes occurring in three archival cases of acute multiple sclerosis, and to provide immunohistochemical evidence of early endothelial cell activation and vascular occlusion in this condition. Methods-Central nervous system tissues from three cases of acute active multiple sclerosis and six non-inflammatory controls were stained using the following methods: haematoxylin and eosin, Luxol fast blue, cresyl violet, Bielschowsky's silver, and reticulin. Tissues were also inmunostained with specific antibodies against collagen type IV, factor XIIIa, class II antigens, glial fibrillary acidic protein, and fibrinogen. Results-Early vascular endothelial cell activation which may progress to vasculitis and vascular occlusion including class II antigen expression and fibrin deposition were identified. The vascular changes were seen prior to cerebral parenchymal reaction and demyelination, and were not seen in control cerebral tissues.Conclusion-It is proposed that vascular endothelial cell activation may be an early and pivotal event in the evolution of multiple sclerosis, and that demyelination may have an ischaemic basis in this condition. The vascular endothelium may contain an early element in the evolution of multiple sclerosis. (J Clin Pathol 1994;47:129-133) Academic

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Aphthoid ulceration has been regarded as an early macroscopic feature of Crohn's disease, yet the cause ofthis mucosal lesion is unknown. Examination of areas of apparently normal and non-inflamed bowel in Crohn's disease has allowed the identification of mucosal changes which occur before macroscopic and microscopic ulceration. Thirty five resection specimens from patients with Crohn's disease were compared with 12 specimens from patients with ulcerative colitis and 13 controls. Specimens were fixed either by immersion in formalin in the routine way or by perfusion fixation with formalin at mean arterial pressure. Immunostaining for macrophages, vessel wall, and blood constituents allowed identification of small mucosal capillaries which were not apparent otherwise. In Crohn's disease damage and rupture of these small capillaries occurred before infiltration of the lamina propria by inflammatory cells. Loss of the overlying epithelium seemed to follow this vascular damage.

Aims: To determine if massive pulmonary platelet thromboembolism is a common cause of peroperative death following liver transplantation; and to compare the incidence of this event with patients dying after non-transplantation procedures. Methods: Necropsy tissues from all patients dying within 10 days of operation during the past three and a half years were studied (six liver transplantations and 13 unrelated operations). Haematoxylin and eosin stained sections of all tissues were examined. Additional sections of lung tissue were immunostained for constituents of thrombus (fibrin and platelets). Results: At necropsy the lungs from all six liver transplant recipients were heavy with a rubbery texture and little oedema fluid. Those from non-transplantation patients appeared normal or very oedematous. Microscopic examination showed that there were numerous platelet aggregates occluding pulmonary capillaries in all six transplant recipients, but in only three of the non-transplant patients. These thrombi were numerous in patients dying during surgery and the number was underestimated in routine sections because of the surrounding capillary congestion. Detection was improved by immunostaining for platelets with factor XIIIA and platelet glycoprotein IIIa. Conclusions: Massive platelet thromboembolism is a likely cause of death in patients dying unexpectedly following recent liver transplantation. Non-transplantation patients dying during surgery who show similar appearances usually have conditions known to have a high risk of thrombosis or embolism (cement hypotension syndrome and disseminated intravascular coagulation). The cause of this extensive platelet activation in liver transplant recipients is uncertain and may be multifactorial. The unusual rubbery consistency of the lungs on macroscopic examination could alert the pathologist to the underlying condition. Immunostaining for platelets improves the detection microscopically. Liver transplantation is performed with considerable success in many centres throughout the world. In over 100 adult orthotopic liver transplantations carried out at the Royal Free Hospital there have been minimal surgical complications but three patients died unexpectedly during the operation. At necropsy numerous platelet aggregates were found occluding pulmonary capillaries. Similar platelet thrombi were recently described in the lungs of children dying during liver transplantation. ' Although pulmonary microembolism is a recognised complication of several conditions including disseminated intravascular coagulation (DIC), multiple trauma and major orthopaedic and vascular surgery,23 an association with transplantation has not been widely established. It is also unknown if platelet thrombi are found more commonly in liver transplant recipients who make a poor recovery and die soon after operation.We have reviewed all perioperative deaths in adults up to the tenth postoperative day to determine if such platelet thrombi are a common finding in transplant related deaths or if the...

Factor XIIIA is the active subunit of plasma factor XIII that is responsible for cross linking fibrin into a stable clot. Sixteen patients with Crohn's disease were studied prospectively from relapse (Crohn's disease activity index >150) into remission. Plasma factor XIIIA concentrations were significantly lower in active disease (median 63 (95% CI 46-72) U/dl) than remission (median 90 (95% CI 60-112) U/dl; p=0002). Plasma factor XIIIA concentrations correlated positively with the activity index (p=0005) and platelet count (p=0003), and negatively with serum albumin (p=0 006). In five patients with persistent aggressive disease, the factor XIIIA concentration remained below the lower range of normal despite apparent clinical improvement in response to medical treatment. Tissues from three patients who underwent surgical resection during the study were immunostained for factor XIIIA. Gut mucosal and submucosal macrophages stained strongly for factor XIIIA. In one patient, capillary thrombi near superficial mucosal erosions immunostained for factor XIIIA in macroscopicaily normal mucosa. Similar changes were identified in more severely inflamed sections ofintestine from the other two patients. The demonstration of significantly low plasma factor XIIIA concentrations in active Crohn's disease, and the immunostaining of factor XIIIA in capillary thrombi in the bowel wall, suggest that activation of coagulation may be involved in the pathogenesis of Crohn's disease. The plasma factor XIIIA concentration may prove a useful laboratory marker of disease activity.

Kaposi's sarcomas are seen more commonly in routine histopathology laboratories since the advent of the more widespread and aggressive variant of the disease associated with HIV infection. Distinguishing nodular lesions from other spindle cell and vascular tumours can sometimes be difficult. Immunohistochemistry has been disappointing as a diagnostic aid, often requiring special fixation or frozen tissue and even then, staining of spindle cells has been variable. We describe the use of the new IgG1 mouse monoclonal antibody raised against human placental endothelial cells, QBEnd/10, on routine formalin-fixed, paraffin-embedded tissue. A retrospective study was performed on 22 Kaposi's sarcomas of skin including patch, plaque, and nodular lesions and compared with 38 other vascular and spindle cell tumours from skin. All sections were stained with haematoxylin and eosin, QBEnd/10, Ulex europaeus agglutinin 1 (UEA-1) and for factor VIII-related antigen (FVIIIRAg). The results demonstrate that spindle cells in lesions from Kaposi's sarcomas, but not other vascular or spindle cell tumours, immunostain clearly with QBEnd/10. Immunostaining for FVIIIRAg shows only weak and irregular positivity of the spindle cells, whilst staining with UEA-1 is consistently negative. We find that immunostaining with QBEnd/10 aids the diagnosis of Kaposi's sarcomas and allows their distinction from other spindle cell neoplasms of skin in routinely processed material.

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