SUMMARY A review of histopathology reports on 2046 patients in the large bowel cancer project showed considerable observer variation in histological grading, Dukes staging, and lymph node harvest. These parameters have a well-established relationship to prognosis, but, if they are to be applied for both clinical and research purposes, they must be assessed consistently. A minimal level of information which should be recorded from a resection specimen is suggested, with a description of the methods by which this information can be obtained.The large bowel cancer project was initiated in 1976, and currently specimens are sent to the 22 histopathology departments from the 84 participating surgeons. Although many departments have more than one histopathologist to deal with these specimens, they have been treated as 22 observers for this analysis.The objective of this part of the study was to assess the consistency of reports on the histopathology of the resected specimens. We anticipated that there might be considerable observer variation in histological grading, which is a subjective process, but we did not expect significant differences in the staging of local tumour spread, which is an objective assessment with sharp delineation between subgroups, or in lymph node harvest. We report here the results on 2046 resected tumours. We found clinically important and statistically significant differences between histopathology departments in the reporting of these specimens. Differences between hospitals have been calculated using the x2 test for independent samples. (Fig. 1). The difference between observers was statistically significant (p < 0-001). Some lack of uniformity is inevitable in grading, but the order of difference shown can be due only to different techniques of assessment. In the present study of 2046 specimens 26 0 were well, 58% moderately, and 16% poorly differentiated;however, the proportion placed in each grade by the different observers varied widely: well-differentiated 3-93 %, moderately 8-82 %, and poorly 5-30 %

A multi-centre study is described in which thirty-five adult patients with papillary IgA dermatitis herpetiformis (DH) were compared with forty-two patients with linear IgA deposits, of whom thirty-four had homogeneous-linear (HL) and eight had granular-linear (GL) IgA deposits. The three groups were similar with regard to age of onset, presence of circulating immune complexes and auto-antibodies, incidence of spontaneous remission, histology of lesional skin and response to dapsone. There was a female predominance in the HL group in contrast to the male predominance in the other two. It was not possible to diagnose the HL group clinically. Some patients had a rash typical of DH whilst others resembled pemphigoid. In the majority, however, no specific diagnosis could be made with confidence. The GL group clinically resembled the DH group. The incidence of positive potassium iodide patch tests was greater in the DH group than in the other two. An associated enteropathy was found in 24% of patients in the HL group, 30% of patients in the GL group and 85% of patients in the DH group. Fifty-six percent of HL patients had HLA-B8 compared with 50% in the GL group and 88% in the DH group. Patients with linear IgA deposits may not be a uniform group, but until they can be divided into specific subgroups (e.g. by ultrastructural localization of the deposit or by response to a gluten-free diet) we propose that the term adult linear IgA diseases should be used to distinguish these patients from those with papillary IgA deposits.

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SUMMARY The cytoplasmic bodies in hepatocytes thought to indicate possession of the Z allele for a1-antitrypsin deficiency were found at necropsy in 10 of 64 adults with cirrhosis, four of nine with hepatic fibrosis, and four of 15 with hepatocellular carcinoma. They were also found in six of 76 adults with severe panacinar emphysema, and in four of a control series of 110 adults with neither emphysema nor liver disease. The association of the bodies with each of the three liver diseases was statistically significant, but the association of the bodies with emphysema was not. It is considered probable that heterozygous (PiMZ) a,-antitrypsin deficiency is associated with an increased incidence of cirrhosis, hepatic fibrosis, and hepatocellular carcinoma. 28 June 1976 records were examined for cases of hepatic fibrosis, hepatoma, and cirrhosis other than that due to large duct obstruction: 64 cirrhotic livers (11 with hepatocellular carcinoma), nine fibrotic livers (1 with hepatocellular carcinoma), and three livers with hepatocellular carcinoma but neither cirrhosis nor fibrosis were found; blocks of non-neoplastic liver were available from all cases (76), and blocks of hepatocellular carcinoma from the 15 cases with hepatocellular carcinoma. The control series consisted of blocks of liver from 110 consecutive adult necropsies in which there was neither clinical nor pathological evidence of liver disease or emphysema.All the liver blocks were formalin-fixed and paraffin-embedded. Sections were cut at 4 ,um: one section from each case was stained with haematoxylin and eosin, one for reticulin, and one with periodic acid Schiff after diastase. The diagnosis on the liver was checked and confirmed in each case. The characteristic acx-antitrypsin bodies were not stained in the haematoxylin and eosin preparation but were seen as rounded, sharply-defined, solid bodies staining strongly with periodic acid Schiff after diastase, in the cytoplasm of hepatocytes, predominantly in the periportal cells. Bodies up to at least 3 ,um diameter were found in each positive case, and frequently bodies up to 15,um diameter were present. In addition, sections were cut at 4 ,um from the liver blocks of all cases with cirrhosis, hepatic fibrosis or hepatocellular carcinoma, of all cases showing cxlantitrypsin bodies on periodic acid Schiff staining, and of 27 cases of emphysema randomly selected from those without cti-antitrypsin bodies oa periodic acid Schiff staining: these were mounted on albumin-132

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