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A total of 85 patients with paratesticular tumours were diagnosed over a period of 36 years at this hospital; 66 patients (78%) had benign tumours, usually either an adenomatoid tumour or a lipoma. Of the remaining 19 malignant cases, 10 were primary neoplasms and 9 were metastases. A rare mucin-secreting epididymal adenocarcinoma was the only primary malignant epithelial tumour, the others being of mesenchymal origin. In 4/9 metastatic cases the initial presentation of a paratesticular swelling led to the discovery of the occult primary neoplasm following histological examination. Clinical features of a painful or painless mass, with or without an accompanying hydrocele, do not help to distinguish a benign from a malignant lesion. The prognosis of malignant tumours of mesenchymal origin depends mainly on the histological grade. Surgical resection remains the mainstay of treatment and adjuvant therapy significantly improves the chances of survival only in young patients with paratesticular rhabdomyosarcomas. Older patients with high grade tumours usually succumb to their disease despite chemotherapy and/or radiotherapy.

The majority of primary bladder neoplasms are known to arise within the mucosa around the ureteric orifices and bladder base. This may be due to the mucosa in this area being more susceptible to carcinogens than other areas of the bladder. Deficiency in the nucleotide salvage pathway enzyme thymidine kinase (TK), and especially its TK1 isozyme, has been shown to predispose cell lines to increased mutagenesis. Total TK and TK1 activities were measured in mucosal samples taken adjacent to the ureteric orifices and dome in 32 normal bladders and both total TK and TK1 were shown to be significantly decreased in the mucosa adjacent to the ureteric orifices. This may explain why primary bladder neoplasms occur more commonly in this site.

EDITOR, - T G Ashworth was correct when he predicted that his views would incur the displeasure of some of his peers.1 In the interest of job satisfaction and economy he advocates that medical laboratory scientific officers should undertake the gross examination of surgical specimens and the microscopical examination of some unspecified tissues. He states that, for 50 years, his laboratory has entrusted the selection of tissue for embedding and microscopy to medical laboratory scientific officers and he knows of no instance in which this practice has led to diagnostic error. Without the aid of external audit what is this statement worth? Undoubtedly, medical laboratory scientific officers could be trained to describe and dissect many surgical specimens and to select appropriate tissues for histological examination, but they do not have the appropriate background for this. Is it cost effective to train staff for jobs for which they have inadequate background experience and education? While the medical laboratory scientific officers are undertaking these tasks who does the skilled work for which they have been trained? If a medical laboratory scientific officer misses an early neoplasm in a specimen (for example, an adenocarcinoma in a distorted fibrotic sigmoid colon resected for diverticulosis) who will be responsible? Finally, this separation of gross from microscopical examination increases the chances of diagnostic error. Gross examination is an integral part of diagnostic histopathology, and the findings on gross examination not infrequently modify the interpretation of the microscopical appearances. With respect to the reporting of microscopical examinations, I am not sure what Ashworth means when he says, “All histopathologists know the lesions to which I am referring, those that require simple, objective answers and which can be easily verified.” Does he mean appendixes and gall bladders, when the debate often revolves around whether they should be …

OBJECTIVE--To investigate the extent to which the detection of antibodies to gliadin, endomysium, and jejunum predicts the eventual diagnosis of coeliac disease according to the revised ESPGAN diagnostic criteria in a group of patients in whom there is a high suspicion of coeliac disease. DESIGN--Clinical assessment and laboratory analysis of patients with suspected coeliac disease. SETTING--Gastroenterology department of teaching hospital. PATIENTS--96 adults with suspected coeliac disease attending for jejunal biopsy. MAIN OUTCOME MEASURES--Diagnosis of coeliac disease with the revised criteria of the European Society of Paediatric Gastroenterology and Nutrition in patients with and without antibodies associated with coeliac disease. RESULTS--28 patients had a clinical diagnosis of coeliac disease, seven of other gastrointestinal diseases, and 12 of miscellaneous diseases; 49 had no diagnosis. Gliadin IgA detected by ELISA was found in all patients with coeliac disease and none of those without, giving a sensitivity, specificity, positive and negative predictive values, and predictive efficiency of 100% for diagnosing coeliac disease within the group. Endomysial IgA was found in 25 (89%) patients with coeliac disease and jejunal IgA in 21 (75%); neither IgA was found in patients without coeliac disease. CONCLUSION--Detection of gliadin IgA by ELISA and to a lesser extent the endomysial IgA should allow better selection of patients for jejunal biopsy and thus make diagnosing coeliac disease simpler and more efficient.

Eighteen patients with a variety of non-gastrointestinal symptoms were incidentally found to have circulating antireticulin antibody and on subsequent testing were also positive for antigliadin antibody. They prospectively underwent jejunal biopsy to determine whether or not they had coeliac disease. Their age range was 21-79 years (mean 42 years). Enteropathy was present in 13 (72 per cent) and was always associated with circulating IgA antigliadin antibody. Enteropathy was not present in the five cases who had only IgG antibody. Clinical improvement occurred in eight of 11 patients who complied with a gluten-free diet and was paralleled by an improvement in the mucosal histology in seven of eight who were re-biopsied. The most remarkable cases were two patients who presented with severe debility and no apparent haematological or biochemical abnormalities, and who subsequently made a dramatic recovery on a gluten-free diet. It is concluded that antireticulin antibody detected by routine autoantibody screening and confirmed to have IgA antigliadin antibody specificity is a useful indicator of an otherwise undiagnosed enteropathy. This serves to emphasize that the condition can sometimes be associated with atypical features and significant morbidity.

Eighteen patients with a variety of non-gastrointestinal symptoms were incidentally found to have circulating antireticulin antibody and on subsequent testing were also positive for antigliadin antibody. They prospectively underwent jejunal biopsy to determine whether or not they had coeliac disease. Their age range was 21-79 years (mean 42 years). Enteropathy was present in 13 (72 per cent) and was always associated with circulating IgA antigliadin antibody. Enteropathy was not present in the five cases who had only IgG antibody. Clinical improvement occurred in eight of 11 patients who complied with a gluten-free diet and was paralleled by an improvement in the mucosal histology in seven of eight who were re-biopsied. The most remarkable cases were two patients who presented with severe debility and no apparent haematological or biochemical abnormalities, and who subsequently made a dramatic recovery on a gluten-free diet. It is concluded that antireticulin antibody detected by routine autoantibody screening and confirmed to have IgA antigliadin antibody specificity is a useful indicator of an otherwise undiagnosed enteropathy. This serves to emphasize that the condition can sometimes be associated with atypical features and significant morbidity.

AIMS: To assess c-erbB-2 immunostaining in relation to morphological type of in situ and invasive breast carcinoma. METHODS: Formalin fixed, wax embedded archival tissue was used. Invasive carcinomas comprised 50 infiltrating ductal (NOS); seven medullary, 10 tubular, 15 mucinous and 24 classic invasive lobular. In situ carcinomas comprised 48 ductal (DCIS) and 10 cases of lobular (LCIS). The antibodies used were pAB1 (polyclonal) which stains cell lines that over express the c-erbB-2 oncogene, and ICR 12 (monoclonal) which stains sections of breast carcinoma known to show c-erbB-2 amplification. RESULTS: Immunostaining consistent with c-erbB-2 overexpression was found in 10 out of 50 cases of infiltrating ductal carcinoma (NOS), one of 24 infiltrating lobular carcinomas and one of seven medullary carcinomas only. Seventy per cent of ICR 12 positive cases of infiltrating ductal carcinoma also had extratumoral DCIS. Forty six per cent of pure DCIS lesions also showed strong membrane staining for c-erbB-2 protein, confined to large cell types. CONCLUSIONS: Immunostaining for c-erb B-2 oncoprotein occurs mainly in large cell DCIS and infiltrating ductal carcinoma NOS, especially those with an extratumoral DCIS component. There is a low incidence in other types of breast cancer, including those associated with a better prognosis. Different biological mechanisms may be responsible for histologically distinct types of breast carcinoma.

The clinical, microscopical, immunocytochemical and ultrastructural features of five cases of benign mesenchymal proliferative lesions of the urinary bladder, mimicking sarcoma, are presented. Four of the five patients are alive and disease-free following diagnosis, an interval ranging from 9 months to 9 years, mean 4 years. A fifth patient, who had a pseudosarcomatous stromal response adjacent to a urinary transitional cell carcinoma, now has invasive transitional cell carcinoma. The lesions revealed a striking microscopical, immunocytochemical and ultrastructural similarity to nodular fasciitis, suggesting the lesions represented a bizarre mesenchymal proliferative response to inflammation.

Between 1954 and 1988 only a total of twenty five cases of primary adenocarcinoma of the small bowel (excluding periampillary tumours) were recorded at the Department of Histopathology, Belfast City Hospital. Of these, 14 tumours were located in the jejunum: the remainder arose in the ileum. The average age at presentation was 61.3 years and a slight female to male preponderance of 1:7:1 was noted. The adenocarcinoma arose from a preexisting villous adenoma in six cases. The overall prognosis was poor, with a five year survival of 15.7%. All the survivors had tumours located in the jejunum. The single most important prognostic indicator was the depth of tumour invasion or stage at the time of diagnosis. Tumour size and grade did not seem to correlate well with survival. It is concluded that the rarity of these tumours and their inaccessibility hinder detection and treatment and that surgical resection is more effective than chemotherapy.

Lymphangiomas are rare tumours of lymphatic vessels, most commonly found in children. We present the unusual case of small bowel obstruction caused by benign lymphangioma in a middle aged woman.

A clinical, enzymatic, and pathological study of an infant with the acute form of hereditary tyrosinaemia is presented. Treatment with a diet low in methionine, tyrosine, and phenylalanine was unsuccessful. A selection of specific and nonspecific hepatic enzymes, obtained at necropsy within one hour of the infant's death at 9 1/2 weeks, were studied to try to throw light on the basic defect. The major pathological findings were those of a peculiar hepatic fibrosis associated with bile retention and an abnormal grouping of hepatocytes, islet-cell hyperplasia of the pancreas, and dilatation of the proximal renal tubules. Death was precipitated by bronchopneumonia and liver failure. The difficulty in diagnosing the acute form of tyrosinaemia is pointed out, especially in differentiating it from hereditary galactosaemia (transferase deficiency) and hereditary fructosaemia. All three may present with the same clinical symptoms and liver lesions, and the distinction must be made by enzyme studies and by therapeutic trial.

The presence of misplaced mucosal epithelium was studied in the colectomy specimens from 30 patients with Crohn's disease, 30 patients with ulcerative colitis, 15 patients with ulcerative colitis complicated by carcinoma and 30 patients with non-colitic colorectal carcinoma. Misplaced epithelium was present in 21 (70%) of the resection specimens with Crohn's disease, 20 (66.7%) with ulcerative colitis and 12 (80%) with ulcerative colitis complicated by carcinoma. None of the specimens with non-colitic colorectal adenocarcinoma showed misplaced foci of epithelium. Two pathogenetic mechanisms for epithelial misplacement are proposed: (1) the effects of mucosal inflammation and repair; and (2) muscular abnormalities in inflammatory bowel disease. The proposed mechanisms and patterns of epithelial misplacement are discussed and illustrated. The importance of its recognition is emphasized because, when associated with mucosal dysplasia, difficulties in interpretation arise in distinguishing it from 'early' invasive adenocarcinoma. Epithelial misplacement is common in patients with longstanding ulcerative colitis and may be a factor in increasing the significance of pre-existing mucosal dysplasia and promoting the development of adenocarcinoma. This may explain the unusual growth pattern encountered in ulcerative colitis, of submucosal cancer underlying a flat, non-dysplastic mucosa.

The presence of mucosal hyperplasia and sialomucin goblet cell secretion (transitional mucosa) was assessed in various benign, premalignant and malignant colorectal tissues. Transitional mucosa was seen in diverticular disease, solitary ulcer syndrome of the rectum, ischaemic and irradiation colitis and other diseases including pneumatosis coli, endometriosis, haemorrhoids and a colostomy margin. Adenocarcinomas had a sulphomucin or mixed secretion pattern with transitional features in the adjacent mucosa mucosa (18/27). Premalignant adenomatous polyps showed mixed secretion with transitional glands incorporated in the stalk and sometimes in the adjacent mucosa. Epithelium showing dysplasia secreted sulphomucins and in amounts related to its degree of differentiation. Transitional mucosa may not be a primary premalignant phenomemon. The conclusion and unifying concept is that it is a secondary event related to goblet cell immaturity. This can occur, secondary to proliferation in mucosal inflammation, ischaemia and prolapse or as a phenotypic expression of growth derived from underlying dysplastic epithelium.

Images Figs. 1-4 Figs. 5-7,9 Figs. 8,10-12

The clinicopathological details of eight cases of ulcerative colitis complicated by carcinoma of the colon are described. There was a total of 14 primary colonic cancers, six of which were not detected before pathological examination of the resection specimens. The reason for this may be related to atypical tumour growth patterns. Three occurred in flat mucosa, one in a mucosal plaque lesion, and another in polypoidal mucosa. The occurrence, distribution, and morphology of mucosal dysplasia were noted in both resection specimens and biopsies taken at varying stages before resection. Tumour was associated with normal and adjacent dysplastic mucosa of varying grades. The extent and grade of dysplasia were not reliable indicators of tumour differentiation or subsequent clinical outcome. Only two cancers were poorly differentiated. In five cases a total of 23 mucosal biopsies were taken, all less than 12 months before resection. Three rectal biopsies were graded positive for dysplasia and three colonic biopsies indefinite for dysplasia. The subsequent resection specimens showed both dysplastic and carcinomatous changes. Three rectal and 14 colonic biopsies were graded negative for dysplasia despite positive findings in the subsequent resection specimens. This anomaly is partly attributed to the patchy nature of dysplasia in colitic mucosa. Two cases illustrate the possibility of dysplasia pursuing a rapidly progressive course. The mucosal changes of ulcerative colitis were assessed using a recently introduced and standardised international classification.

Summary Fifty-one cases of solitary rectal ulcer syndrome diagnosed over the past 10 years have been studied. The syndrome, of which solitary ulceration was a feature in only 35 per cent of cases, included patients with multiple ‘solitary’ ulcers (22 per cent), broad-based polypoid lesions (25 per cent) and patchy granular hyperaemic rectal mucosa (18 per cent). The syndrome was found to be strongly associated with abnormal rectal descent. Full-thickness prolapse to or beyond the anal verge was present in 59 per cent of patients while a further 32 per cent had lesser degrees of rectal descent. In only 9 per cent was no such abnormality demonstrated. Treatment with high roughage diet supplemented with bulking agents benefited two-thirds of 27 patients so treated. Ivalon sponge rectopexy has been performed in 6 patients with associated complete rectal prolapse, and in the first 3 of these (followed for a sufficient period) the results have been satisfactory.

Although there have been previous reports of cases (Haskell and Rovner 1965, Wayte and Helwig 1967) which in retrospect fit into the classification of the solitary rectal ulcer syndrome, it was only in 1969 that this syndrome was first clearly described (Madigan and Morson 1969). This terminology has persisted for want of a better name even though rectal ulceration is not always solitary and, on occasion, macroscopic rectal ulceration is not the major manifestation (Martin et al. to be published). At this stage aetiology is unclear and treatment is generally considered difficult (Goligher 1980).

Right atrial laceration is described as a complication of external cardiac massage in two patients. In each there was a pre-existent cause of weakness of the atrial wall. There was pronounced right atrial dilation with attenuation of the wall in one case, and in the other there was a granulomatous myocarditis involving the atrial wall. The significance of atrial laceration as a complication of traumatic injuries to the heart is discussed.

A STATISTICAL analysis of consecutive routine autopsy reports was carried out in an attempt to clarify the epidemiological and clinical importance of coincident cerebral and cardiac infarction. Three thousand five hundred and thirty two autopsies fulfilled our basic criteria, being performed on subjects over 20 years of age and dying from natural causes. These were examined and only those in whom macroscopic recent infarcts of the brain and heart were found were accepted for the study. Therefore only infarctions which could produce unambiguous clinical symptoms were analysed. Out of a total 906 infarctions 282 were cerebral alone, 532 cardiac alone and 92 coexisted in both the heart and brain.

Two monoclonal antibodies were applied to benign, dysplastic, and malignant human colorectal tissues using immunohistochemical techniques on formalin fixed paraffin embedded material. RAP-5 antibody is directed against a synthetic peptide, reflecting an amino acid sequence of the ras oncogene p21 protein product. Despite using several different techniques and antibody dilutions differential staining between the various epithelial populations was not obtained. RAP-5 also showed other tissue components such as plasma cells, histiocytes, fibroblasts, smooth muscle and vascular endothelium. CA19-9 antibody recognizes an epithelial surface carbohydrate antigen originally derived from a human colorectal carcinoma cell line: it did not stain normal colorectal mucosa or adenomatous polyps, but showed focal expression of variable strength in regenerative, dysplastic, and cancerous mucosa in ulcerative colitis, and in non-colitic colorectal carcinoma. Neither antibody was found to be a reliable marker of the evolution of malignant mucosal changes, although CA19-9 may be of limited use in confirming adenocarcinoma of gastrointestinal origin.

In a twenty-year period 19 appendicectomy specimens were diagnosed as primary Crohn's disease. This represents 4.9% of the total number of both resection specimens and mucosal biopsies diagnosed as Crohn's disease during that time. This is a review of the main histopathological features found in these appendices and their subsequent clinical outcome. The predominant feature is transmural inflammation characterised by fibrosis and giant cell epithelioid granulomata. An accompanying spectrum of acute imflammatory changes is also seen. One patient progressed to more widespread ileal and caecal disease 17 months later. One patient developed perianal fistulae and chronic non-specific proctitis 24 months later. This represents a proven recurrence of one case in a study population of 19. The conclusion is that primary Crohn's disease of the appendix is usually an isolated phenomenon but rarely it may forewarn of more widespread bowel disease in the future. A discussion regarding the differential diagnosis of granulomatous appendiceal lesions is included.

Two rare complications of coeliac disease are described in patients who presented as acute abdominal emergencies. One of the patients had both oesophageal and small intestinal obstruction produced by an ulcerative process involving these portions of the gastro-intestinal tract. The other, a patient with long standing dermatitis herpetiformis, perforated his small intestine at a site involved by both a lymphoma and partial villous atrophy.

Mucin secretion was assessed in Crohn's colitis, in ulcerative colitis with regeneration, dysplasia and carcinoma and in non-colitic adenocarcinoma. The high iron diamine-alcian blue (HID-AB) and periodate borohydride-saponification periodic acid Schiff (PB-KOH-PAS) techniques were used to demonstrate sulphomucins and sialomucins, and O-acylated sialomucins respectively. There was mucosal hyperplasia and increased sialomucin secretion in Crohn's disease, quiescent and active ulcerative colitis. In colitis with carcinoma inflamed mucosa away from the tumour had increased sialomucins as had colitis with dysplasia. They did not differ statistically from each other or from colitic controls without cancer. Dysplastic crypts frequently secreted sulphomucins and the increased sialomucins were in transitional-like glands in the surface fronds or adjacent to the dysplasia. A comparative study of the HID-AB technique gave total correct qualitative allocation of individual quantitatively assessed crypts. Routine HID-AB staining did not aid the recognition of dysplasia in ulcerative colitis. With the PB-KOH-PAS technique colorectal adenocarcinoma showed a significant diminution in O-acylated sialomucins compared with its adjacent mucosa. Mucosal dysplasia in ulcerative colitis displayed a similar trend in O-acylated sialic acid variants, differing with respect to age-and sex-matched colitic controls. The PB-KOH-PAS technique may be of help in assessing mucin secretion in ulcerative colitis as a guide to the evolution of malignancy.

Summary Pathogen-free CD1 mice were experimentally infected with mouse hepatitis virus (MHV3), and half of them were also given daily doses of cortisone. Ultrastructural examination of the splenic white pulp revealed viral particles, corresponding in size, shape and structure to MHV3, within small lymphocytes as well as extracellularly. Virus formation within the lymphocytes was associated with proliferation of the rough endoplasmic reticulum and budding of viral particles from these membranes. Intracellular viral particles were readily seen only in the cortisone-treated mice, possibly because of the stabilising effect of cortisone on intracellular membranes. It is suggested that the lymphoid necrosis of MHV3 infection is attributable to the virus replication within the lymphocytes.

Atherosclerosic agents can promote the proliferation of smooth-muscle cells in the arterial intima (Stout, 1984). These cell colonies readily accumulate lipid, probably derived from plasma cholesterol and lipoproteins (Kramsch & Hollander, 1973). As the disease develops lipid deposits are also formed extracellularly and are retained in a loose network of connective tissue (Hajar et al., 1980). In the developed lesion, plaques, ulcerations and lipid-filled foam cells are characteristic features (Ross, 1981). The luminal surface of the aorta consists of a monolayer of endothelial cells, which covers a connective tissue containing smoothmuscle cells and elastic lamellae. Endothelial integrity is altered by the developing atheromatous lesion and permits entry to the connective tissue of plasma components that would normally be excluded. Access of elastase and plaque lipids could accelerate the degradation of the elastin component of the lamellae (Elliott & Darling, 1985). The lipid composition of the arteries from several species has been examined (Kramsch et al., 1971 ; Jacotot et al., 1973; Claire et al., 1976; Noma et al., 1979; Santillan et al., 1980). Chloroform/methanol (2 : 1, v/v) is the most commonly used solvent for the extraction of lipids (Folch et al., 1957). Homogenization is usually employed to obtain rapid quantitative extraction (Radin, 1969). An alternative lipid extraction process, using successive extractions of acetone and butan-1-01, has been used to de-lipidate elastin (Robert & Hornebeck, 1976). In the present work the aim was to remove the lipid from the aorta, yet avoid causing mechanical damage to the elastic lamellae. A lOcm segment of the thoracic aorta obtained during post-mortem examination had remaining adherent tissue removed with a scalpel before cutting into O.5cm wide bands. Twelve bands were washed in 0.9% (w/v) saline, at 4"C, and half of the samples dehydrated to constant weight in a vacuum desiccator. The samples, six dehydrated (D) and six hydrated (H), were allocated to three extraction methods (A, B and C). Each method used 6 x 24h extractions at 4°C in closed and stirred containers. Method A : initial extraction was acetone followed by butan-1 -01. The sequence of acetone then butan1-01 was repeated twice, a total of six extractions. Material solubilized by extraction was recovered by removal of the solvent, with a rotary vacuum evaporator. Method B used chloroform/methanol (2 : I , v/v) under the same conditions as described in method A, and six extracts were recovered. Method C used a combination of methods A and B in the sequence acetone, butan-1-01. chloroform/methanol; this was repeated to give six extracts. The experiment produced a total of 36 lipid residues (Fig. I ) , each of which was solubilized in 3ml of chloroform for subsequent analysis. The total lipid in each extract was estimated by the phosphovanillan assay (Bauer, 1982). The lipid obtained from the aorta by the three extraction methods is shown in Fig. I(a). Lipid content has been expressed as a percentage of the initial wet weight of the tissue. The acetone/butan-I01 extraction yielded significantly less lipid than the chloroform/methanol extraction. There was no difference in lipid recovery between dehydrated and hydrated aorta samples, within the same extraction method. The quantity

This paper describes an elderly patient who developed an acute attack of porphyria cutanea tarda symptomatica. Autopsy revealed a primary hepato-carcinoma. There have been two previous reports of porphyria in association with primary hepatic tumours in the elderly.