In vivo image-guided (1)H-magnetic resonance spectroscopy of the serial development of hepatocarcinogenesis in an experimental animal model.

Histology on a core or open biopsy is considered the gold standard for the diagnosis of tumours. While the non-invasive technique of magnetic resonance imaging can direct some of the decision diagnostic making, it has limitations and disadvantages, that can be partly overcome with the use of in vivo magnetic resonance spectroscopy (MRS). In vivo MRS is able to provide a specific biochemical profile on tumour tissue, compared with normal tissue. The capability of this technique is demonstrated here by the long-term development of hepatocellular carcinoma in an animal model. It allows the observation of the biochemical changes that occur in tumour tissue during its progression from preneoplastic nodules to hepatocellular carcinoma. Specifically the changes in the lipid profiles of tumour tissue at various stages of development are observed with proton ((1)H) MRS. Significant increases occurred in the lipid acyl chain methylene and methyl hydrogens during the early developmental stages of hepatocarcinogenesis, whereas during later stages associated with tumour development there was a significant increase in the levels of olefinic acyl chain hydrogens from unsaturated lipids. It is anticipated that this model will precede the application of the same technology to the non-invasive diagnosis and grading of human hepatocellular carcinoma.

Evidence that portal tract microvascular destruction precedes bile duct loss in human liver allograft rejection.

In liver allograft rejection, interlobular bile ducts are thought to be the main target of rejection. In contrast, in other organ allografts the capillary bed of the graft appears to be the primary target. To determine whether portal tract microvasculature is destroyed in liver allografts during rejection, we have identified portal tract microvasculature in 11 normal livers and 38 liver allograft biopsy specimens using monoclonal antibodies to capillary endothelium in immunohistochemical staining. E1.5, CD31 and EL-4 antibodies identified portal microvascular endothelium in normal liver that had the morphology of capillaries. In allograft biopsies the number of microvascular structures per portal tract was reduced markedly in acute cellular rejection to 1.1 +/- 0.6 (n = 25) and to 0.65 +/- 0.9 (n = 15) in chronic ductopenic rejection compared with nonrejecting allografts (2.8 +/- 0.6) (n = 4) or normal liver (3.8 +/- 0.7) (n = 11). To determine whether loss of microvascular structures preceded bile duct destruction in rejection, sections were double-stained to identify both microvasculature and bile ducts. The number of microvascular structures per bile duct was significantly lower in acute cellular rejection (0.5 +/- 0.4) (n = 18) or chronic rejection (0.3 +/- 0.4) (n = 8) compared with normal liver (2.3 +/- 0.6) (n = 7) (P < 0.0001), demonstrating that components of the portal vasculature are destroyed prior to bile ducts. There was a correlation between the severity of rejection and the loss of microvascular structures per bile duct (P < 0.001). In conclusion, in common with other allografted organs, the microvasculature of liver allografts appears to be an early target of rejection.

Vascular endothelial growth factor expression in human chronic renal allograft rejection.

BACKGROUND: Chronic renal allograft rejection is characterized by interstitial fibrosis and vasculopathy. Vascular endothelial growth factor (VEGF) is an endothelial mitogen with increased expression in inflammation and vasculopathy. METHODS: Renal tissue from 17 patients with chronic rejection was examined for VEGF protein and the presence of CD 68-positive macrophages, and compared to biopsies from patients with temporary allograft dysfunction, acute rejection, and native kidneys with thin membrane disease. RESULTS: In the chronic rejection group, there was markedly increased expression of VEGF protein in the interstitium (P<0.0001). In serial sections, VEGF colocalized with the expression of CD 68-positive macrophages. Significantly more macrophages were in the tubulointerstitium in tissue with chronic rejection than in those with temporary allograft dysfunction (P<0.005). Additionally, VEGF protein expression in the glomeruli and the vascular compartment of patients with chronic rejection was increased. CONCLUSION: The up-regulation of VEGF in chronic renal allograft rejection may be important in inflammation and development of fibrosis.

Early up-regulation of macrophages and myofibroblasts: a new marker for development of chronic renal allograft rejection.

BACKGROUND: Increased numbers of macrophages and myofibroblasts are observed to occur in chronic renal allograft rejection (CR). The aim of this study was to examine the expression of cellular markers for the macrophage and myofibroblast in early renal transplant biopsy specimens and correlate these findings with allograft outcome. METHODS: The first postengraftment biopsy specimens from 53 patients who underwent renal transplantation between January 1993 and December 1995 were studied using immunohistochemistry with antibodies to alpha-smooth muscle actin, which identifies myofibroblasts and CD68, a marker for monocytes and macrophages. Patients were followed until December 1998 (mean follow-up 4.7+/-1.2 years). RESULTS: Nine patients had progressed to CR by the time of the study, whereas 44 patients continued to have stable renal function. A marked increase in both macrophages (P=0.02) and myofibroblasts (P=0.04) was noted in the first biopsy specimen obtained after engraftment in the patients who developed CR compared with those with stable allograft function. There was a positive correlation between alpha-smooth muscle actin and collagen expression (P=0.0001). CONCLUSION: Significant increases in macrophages and myofibroblasts occur in the first renal biopsy specimen in those patients who later develop CR.

The pathological assessment of ovarian neoplasms V: The germ cell tumours.

All neoplasms of the ovary encountered in a 25-yr study period of King George V Memorial Hospital were classified according to the World Health Organisation (WHO) Histological Classification of Ovarian Tumours. Of just fewer than 1700 tumours, 467 fell into the category designated as germ cell tumours: 4 dysgerminomas, one endodermal sinus tumour, one primary choriocarcinoma, 6 immature and 454 mature teratomas and one mixed malignant germ cell tumour. Two additional cases of gonadoblastoma with associated dysgerminoma were encountered and included for discussion. A detailed histological assessment is presented and the major clinical correlates are documented.

Teratomas in childhood.

Of 107 teratomas in children, 86 were benign and 21 malignant. Sacrococcygeal and pelvic teratomas predominated (51 cases) and these fell into 3 groups: post sacral, dumb-bell and presacral. The 34 purely posterior tumours were always congenital and benign, whilst the incidence of malignancy in dumb-bell and presacral teratomas increased as the tumour became more internal. Malignant teratomas were carcinomas, usually containing glandular, papillary and clear-cell areas, and metastases were similar. Immature tissues in benign teratomas were usually neural or connective tissue. They did not give rise to neuroblastomas or sarcomas, and did not indicate a worse prognosis. Only 2 originally benign teratomas later developed malignancy.

Histopathological prediction of hepatitis B recurrence in liver allografts.

The aim of this study was to review the clinical, serological and histopathological features of 20 patients who underwent orthotopic liver transplantation for hepatitis B virus (HBV) related liver disease in an attempt to identify factors which predict recurrence of HBV infection, pattern of disease and disease severity. Hepatitis B recurrence occurred in 11 patients (55%). Positive immunoperoxidase staining for HBsAg and HBcAg of the hepatectomy specimen were shown to have a sensitivity (82% and 64% respectively) and specificity (55% and 66%) in predicting recurrence. This was comparable to serological markers such as HBV DNA (36% sensitivity and 89% specificity). The staining for HBcAg in some cases was weak, focal and had a reticular pattern. Therefore, examination of multiple blocks with a high magnification was necessary to detect HBcAg staining. Negative staining of multiple sections for HBsAg and HBcAg were shown to have a good correlation with clearing of HBV infection (5 out of 6 patients). If recurrence occurred, the range of histological and clinical patterns of HBV recurrence was varied, with severe disease occurring in 5 patients. Neither pre-transplant serology nor hepatectomy immunoperoxidase staining characteristics were shown to be of value in predicting the pattern or the severity of disease once HBV recurrence had occurred. This study indicates that lack of staining for HBV antigens on multiple sections of the native liver may predict a subgroup of HBsAg positive transplant patients who will not suffer from recurrent disease. Once disease did occur however, markers for severity of recurrence were not identified.

Hepatocellular carcinoma metastasizing to the orbit diagnosed by fine needle aspiration cytology.

Hepatocellular carcinoma (HCC) rarely metastasizes to the orbit. We report a case of a 78-year-old man with a past history of HCC, who presented with a periorbital mass, which was diagnosed as metastatic HCC by fine needle aspiration cytology (FNAC) and subsequently confirmed on excision biopsy. The cytological, histopathological and immunohistochemical findings are presented and the differential diagnosis is discussed. To our knowledge there has been no previously reported case of HCC metastatic to the orbit diagnosed by FNAC.

Synovial osteochondromatosis of the temporomandibular joint. An historical review with presentation of 3 cases.

Loose bodies in joints have long held the fascination of surgeons and their recognition clearly enjoys a most distinguished antiquity (Pare, 1558; Haller, 1764; Barwell, 1876; Halstead, 1895) despite the rarity of their occurrence. This paper presents an historical review of the subject in conjunction with a report of three cases operated upon by one of the authors (JdeBN). The results have been critically reviewed by pathologists with a catholicity of experience in the field. The condition is singularly uncommon in the jaw joint, and must rank with synovial cyst and para-articular chondroma as an unusual cause of a swelling of firstly the temporomandibular joint and secondly the parotid gland. Earlier workers recognized the value of comparative pathology to illustrate the nature of a genus of tumours and it is educative to read the following: "A good physiological type for the loose cartilaginous bodies which infest joints is furnished by the temporomandibular joint of the skate. A recess communicating with this articular cavity usually contains a collection of smooth cartilaginous bodies, in contour and size like melon seeds." Bland-Sutton (1907).

A case of AIDS presenting as intra-oral malignant lymphoma.

A range of oral manifestations in a patient who was subsequently confirmed as infected with the human immune deficiency virus are presented. Most of these lesions have been previously reported in the literature, and represent opportunistic infection changes resulting from immune deficiency. The rare occurrence of a malignant large cell lymphoma intra-orally in this patient is also reported. The need for clinicians to treat all oral lesions as potentially infective and to wear gloves routinely is stressed.

Hyperplasia of the mandibular condyle. A historical review of important early cases with a presentation and analysis of twelve patients.

Thirteen patients with condylar hyperplasia have been examined and twelve operated upon in a nine year period ending December 1979. A further eight patients with facial asymmetry, considered to be the sequelae of condylar hyperplasia, had extra condylar osteotomies carried out. As no specimens are available for histopathological examination, they have been excluded from the series. There appears to be a similarity between the histological findings of osteochondromata of the mandibular condyle and coronoid processes, active condylar hyperplasia and the changes noticed in the region of the costo-chondral junction of the acromegalic rib.

Teratomas in childhood.

Of 109 teratomas in children 86 were benign and 23 malignant. Sacro-coccygeal and pelvic teratomas predominated 52 cases, and these fell into three groups, post-sacral, dumb bell and pre-sacral. The 34 purely posterior tumours were always congenital and benign whilst the incidence of malignancy in dum bell and pre-sacral teratomas increased as the tumour became more internal. Other sites affected in order of frequency were: the gonads, head and neck, retroperitoneal anterior mediastinum and the central nervous system. Malignant teratomas were carcinomas usually containing glandular, capillary and clear cell areas, and metastases were similar. Immature tissues in benign teratomas were usually neural or connective tissue. They did not give rise to neuroblastomas or sarcomas and did not indicate a worse prognosis. Only two originally benign teratomas later developed malignancy.

Hepatic infarction and nodular regenerative hyperplasia of the liver with associated anticardiolipin antibodies in a young woman.

An 18-year-old woman developed acute congestive hepatic infarction in the presence of a circulating anticardiolipin antibody. She subsequently developed nodular regenerative hyperplasia of the liver (NRHL) with associated portal hypertension. Unlike previously reported cases of NRHL, this case offers a prospective follow-up of the development of NRHL. Its occurrence following an episode of hepatic venous impairment in an otherwise normal liver supports the hypothesis that NRHL may develop as a consequence of diminished hepatic venous drainage.

Post-transplant quasispecies pattern remains stable over time in patients with recurrent cholestatic hepatitis due to hepatitis C virus.

BACKGROUND/AIMS: Several studies have shown that cholestatic recurrent hepatitis is associated with very high HCV RNA loads in liver transplant recipients. The aim of this study was to investigate whether a correlation exists between cholestatic hepatitis post-transplant and the population of viral quasispecies. METHODS: One hundred and nine serial sera samples were tested from 15 recurrent HCV patients. Four of these patients showed severe cholestatic recurrent hepatitis, 11 patients demonstrated non-cholestatic recurrent hepatitis post-transplant. Quasispecies were detected by RT-PCR amplification of the HVR1 followed by single-stranded conformational polymorphism analysis. RESULTS: Forty-one samples from four cholestatic patients were tested. All four patients showed very stable quasispecies patterns post-transplant. One cholestatic patient also showed a stable quasispecies band pattern following retransplantation, again associated with severe cholestatic hepatitis. Sixty-eight samples were tested from the 11 non-cholestatic patients. In contrast, these patients showed significantly more quasispecies bands than the cholestatic patients. The noncholestatic patients also displayed fluctuating band patterns post-transplant. Serial samples were tested after retransplantation in one non-cholestatic patient, with a fluctuating pattern again seen. There was a negative correlation between the HCV RNA load in serum and the number of quasispecies bands. CONCLUSIONS: Stable hepatitis C viral quasispecies associated with persistently high viral load in post-transplant cholestatic hepatitis suggest that viral escape from immune pressures may play a role in the pathogenesis of this condition.

Nonspecificity of monoclonal antibody Tordji-22 for the detection of hepatitis C virus in liver transplant recipients with cholestatic hepatitis.

Detection of hepatitis C virus (HCV) antigens in liver tissue provides important diagnostic and pathological information. Limited studies have been performed on tissue taken after liver transplantation for HCV. In this study, serial post-liver transplantation biopsy tissue from patients with recurrent HCV was tested, with particular interest in patients showing severe cholestatic hepatitis. HCV-related antigens were detected using the commercial monoclonal antibody, Tordji-22. Initial results were promising, showing intense positive staining, especially in areas of hepatocyte ballooning. HCV-negative donor tissue was consistently negative by staining. However, as a final control for the level of tissue damage, HCV negative posttransplantation biopsy tissue showing hepatocyte ballooning was examined. These tissues also showed positive staining. All attempts to eliminate this nonspecific interaction failed. In conclusion, Tordji-22 was associated with nonspecificity in this posttransplantation population, and care is warranted when using this monoclonal antibody.