The finding of epithelioid cell granulomas within liver biopsies is a not uncommon occurrence. We undertook this study to investigate the underlying conditions responsible for a diagnosis of granulomatous hepatitis in Northern Ireland during the thirteen year period 1980-1992. One hundred and sixty-three patients with hepatic granulomas were identified, accounting for 4% of all liver biopsies undertaken during the period of the study. In 145 cases (89%) a definite clinical diagnosis was established. The most common clinical diagnoses were primary biliary cirrhosis which accounted for 90 cases (55%) and sarcoidosis which accounted for 30 cases (18%). Other less common conditions associated with hepatic granulomas included tuberculosis (3 cases), Crohn's disease (3 cases), chronic active hepatitis (2 cases), drug hypersensitivity (2 cases) and extra-hepatic biliary obstruction (2 cases). Six patients were identified with a clinical diagnosis of psoriasis. Other miscellaneous conditions accounting for single examples of granulomatous inflammation were schistosomiasis, gout, Hodgkin's disease, secondary adenocarcinoma, collapse and necrosis of tumour following radiotherapy and chemotherapy, granulomatous inflammation within the wall of an abscess cavity and idiopathic cirrhosis. Only eighteen cases (11%) remained idiopathic with no definite diagnosis established after detailed investigation. The findings confirm the wide range of clinical conditions which can result in hepatic epithelioid cell granulomas. This has been emphasised in several previous major studies which are reviewed in this paper.

There is compelling evidence for the central role of the p53 pathway in human neoplasia but, despite an enormous literature, the clinical utility of assessing this pathway remains ambiguous. Even simple questions about the assessment of p53 status in clinical samples remain unanswered and the literature is confusing and often contradictory. The p53 pathway is certainly complicated and the biochemical mechanisms for regulating the function of p53 and its downstream consequences are rabbinical in complexity. This perspective considers this complexity and the reasons why establishing the true utility of clinical assessment of p53 has proven to be so difficult. Indeed, recent observations regarding the existence of alternate splice variants of p53, the complexity of p53 regulation, and the existence of allelic variants of p53 and its regulators with distinct functionality makes the situation even more complex. Problems with the available assays are considered and the need to consider an array of methodological issues is emphasized. Newer strategies including analysis of the expression of downstream targets of p53 and the use of threshold strategies to measure p53 protein may provide more robust measures of the p53 pathway in clinical settings, perhaps coupled with cheap sequencing-based approaches for mutation (and polymorphism) detection. However, progress will only be made if these methodological issues are resolved and robust assays are performed in the context of appropriately powered studies in clinical trial settings.

McCluggage WG, Lioe TF, McClelland HR, Lamki H. Rhabdomyosarcoma of the uterus: Report of two cases, including one of the spindle cell variant. Int J Gynecol Cancer 2002;12:128-132. Most uterine sarcomas fall into the category of leiomyosarcoma, endometrial stromal sarcoma, or undifferentiated sarcoma. Pure rhabdomyosarcomas are extremely rare, although a rhabdomyosarcomatous element may be present as a component of an adenosarcoma or carcinosarcoma (malignant mixed müllerian tumor). This report describes two uterine rhabdomyosarcomas in 28-and 67-year-old women. These were of spindle cell and pleomorphic types, respectively. At presentation the pleomorphic rhabdomyosaroma was stage IV, exhibiting massive pelvic and abdominal dissemination that mimicked an ovarian neoplasm. The spindle cell rhabdomyosarcoma was stage I, being confined to the uterus. Grossly, both uterine tumors had a polypoid appearance. Immunohistochemically, tumor cells were positive with the skeletal muscle markers sarcomeric actin, myoglobin, and myoD1. The patient with stage IV disease died within a short time of diagnosis and the other patient is alive and well at 2 years' follow-up. This report adds to the published literature on uterine rhabdomyosarcomas. This is the first reported uterine case of the spindle cell variant of embryonal rhabdomyosarcoma. Based on these cases and the published literature, rhabdomyosarcoma, especially the pleomorphic variant, appears to be a very aggressive neoplasm with an extremely poor prognosis. Immunohistochemical demonstration of skeletal muscle differentiation is necessary for a definitive diagnosis.

No abstract