Biomedical subjects
Publications and source records attributed to J M Geraghty.
Intraneural synovial sarcomas are extremely rare in the main nerve trunks of the upper limb. We report on a 16-year-old youth who presented with a painless mass on the flexor aspect of the wrist with the clinical appearance of a ganglion. At operation there was a tumour of the median nerve that was shown on histology to be an intraneural synovial sarcoma.
Colorectal tumorigenesis in familial adenomatous polyposis (FAP) results from somatic mutation of either the normal APC allele or another growth control gene in epithelial cells bearing a germline APC defect. The rate at which tumors develop is therefore dependent on the somatic mutation frequency; it is not known whether this is normal or elevated in FAP. We aimed to quantify stem cell somatic mutation in FAP, comparing it with hereditary nonpolyposis colorectal cancer (HNPCC) and Crohn's disease (CD). Stem cell somatic mutation frequency was studied in 47 FAP patients, 5 HNPCC patients, and 13 CD patients, all younger than 49 years, by quantifying crypt-restricted loss of O-acetyltransferase activity in sections of morphologically normal colonic mucosa from individuals heterozygous for this monogenically inherited polymorphism. Median stem cell somatic mutation frequency was significantly higher in FAP than HNPCC (4.2 x 10(-4) v 1.4 x 10(-4), Mann-Whitney U, P < .02). The level in CD (4.0 x 10(-4)) was similar to FAP. Mutated crypts occurred in groups more frequently in FAP (22%) than HNPCC (12%) or CD (10%), suggesting an increase in stem cell division associated with crypt fission in FAP. We conclude that stem cell somatic mutation frequency is raised in non-neoplastic colorectal mucosa in FAP. This is probably related to increased stem cell proliferation and contributes to the high rate of tumor formation in this condition.
Hereditary non-polyposis colorectal cancer (HNPCC) has recently been linked to germline defects of DNA repair genes. Colorectal tumours in HNPCC frequently show DNA microsatellite instability, but it is not certain whether this mutator phenotype occurs throughout the morphologically normal colonic mucosa. We have previously used the mPAS histochemical technique in human colorectal mucosa to identify a polymorphism for O-acetyltransferase activity that shows monogenic inheritance and to show that crypt-restricted loss of O-acetyltransferase activity in heterozygotes is due to somatic mutation. We have now used this histochemical technique to measure the somatic mutation frequency in the uninvolved colon of 12 heterozygous patients with HNPCC, 15 with ileocaecal Crohn's disease and 16 with sporadic colorectal cancer (CRC). HNPCC patients showed a significant increase in mutation frequency with age (Mann-Whitney U, P = 0.02). In HNPCC patients aged < 49 years the mean stem cell mutation frequency was significantly lower than in the slightly younger group of patients with Crohn's disease (0.8 +/- 0.9 x 10(-4) vs 3.5 +/- 3.3 x 10(-4), P < 0.01), probably reflecting an increased mutation rate relating to chronic mucosal damage in Crohn's disease. Although not statistically significant, the stem cell mutation frequency was slightly less in HNPCC patients > 50 years than in sporadic CRC cases (4.9 +/- 3.4 x 10(-4) vs 5.9 +/- 3.6 x 10(-4), P > 0.5). We conclude that germline defects in HNPCC do not result in a generalised increase in liability to mutation in normal colonic mucosa but that a second, somatic, event is required. We postulate that this second event occurs in crypt stem cells at low frequency, giving rise to scattered individual crypts composed of mutation-prone cells. The cells in these crypts are then at high risk of acquiring the mutations that lead to adenomas, and to rapid progression to carcinoma.
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The development of naevus spilus-like hyperpigmentation at sites of resolving plaques of psoriasis has been reported previously. Although the mechanism is not understood, PUVA therapy has been implicated in most cases. We report an additional case in which lentigines, confined to sites of resolving psoriasis, occurred following oral PUVA. We also describe similar clinical features in two patients who had not received PUVA, which strengthens the observation that this treatment is not a prerequisite for development of this unusual pattern of pigmentation.
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AIMS: To investigate the histopathological changes in the livers of patients undergoing cholecystectomy and to relate these changes to the underlying biliary tract pathology. METHODS: Liver changes in 67 patients undergoing cholecystectomy were investigated. Sixty three had gall stones, one cholesterolosis only, and there were three cases of acute acalculous cholecystitis. RESULTS: Only 34% of the patients had completely normal liver biopsy specimens. The most clinically important pathology was found in 11 of the 14 patients with choledocholithiasis: three of these had cholangitis and eight had features of large bile duct obstruction (four also had chronic cholestasis and portal-portal linking fibrosis). Non-specific reactive hepatitis was the most common abnormality in the remaining 53 patients with cholecystitis alone, and was found in 18. A further four patients had chronic cholestasis without fibrosis and early primary biliary cirrhosis was a coincidental finding in another. Clinical symptoms were poorly correlated with gall bladder and liver pathology apart from an association between jaundice and choledocholithiasis. Liver function tests of obstructive pattern were noted in 23 of 58 patients, most of whom had choledocholithiasis or non-specific reactive hepatitis. Bile cultures were positive in 10 of 42 patients, predominantly in cases of cholangitis and acute cholecystitis. CONCLUSIONS: Cholangitis and extensive fibrosis associated with large bile duct obstruction are common findings in patients with choledocholithiasis. The liver disease may progress to secondary biliary cirrhosis if the obstruction is not relieved, emphasising the need for early surgery. A peroperative liver biopsy may be useful to exclude cirrhosis in these patients, but is unlikely to be informative in those with cholecystitis alone.
Glomus tumours are benign vascular tumours, usually located in the skin. Intra-oral glomus tumours are rare. A glomus tumour of the palate is reported, only the fifth such case out of a total of 14 intra-oral glomus tumours in the world medical literature.
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We reviewed the pathology of 81 malignant colorectal polyps in 80 patients treated by endoscopic polypectomy and assessed the importance of carcinomatous invasion of veins in the stalk (submucosa). All the patients were followed up for at least five years. Venous invasion was present in 30 of the polyps (37%). The histological features of lymphatic invasion were considered too subjective to be of value. Most of the tumours were well or moderately differentiated adenocarcinomas, one was poorly differentiated, and one was a signet ring cell carcinoma. Seventy one patients were treated by polypectomy alone, and 58 of these were alive and well five years later, with no evidence of recurrence. Nine died of unrelated causes within five years, but four died of carcinomatosis: one with recurrent tumour, one with a possible metachronous caecal cancer, and in two patients there was late development of malignancy of uncertain nature. The remaining nine patients underwent surgical resection after initial endoscopic polypectomy because of incompleteness of excision, poor differentiation of the tumour, or a decision by the surgeon. Tumour was not present in the resection specimens apart from a single lymph node deposit in the patient with signet ring cell carcinoma. These nine patients were alive and well without evidence of recurrence five years later. The results reemphasize the necessity of good cooperation between endoscopist and pathologist, meticulous laboratory technique, strict histopathological criteria including examination of resection margins and degree of differentiation of the tumour, and regular endoscopic follow up. Endoscopic polypectomy of pedunculated and sessile malignant polyps is adequate treatment if the lesion can be removed in one piece, the tumour is well or moderately differentiated, and local excision is judged complete by endoscopic and histological criteria. Patients with histologically incompletely excised polyps, containing well or moderately differentiated carcinoma, can be safely managed by conservative treatment provided the endoscopist is certain there is no residual tumour. Venous invasion by tumour is a common finding in malignant colorectal polyps and seems to have no prognostic importance.
Diversion of the faecal stream by ileostomy or colostomy leads to inflammation in the defunctioned segment, known as diversion colitis. The affected bowel is rapidly restored to normality by reanastomosis. Diversion colitis should not be mistaken for inflammatory bowel disease, for which reanastomosis would be inappropriate. Studies of biopsy material from patients with diversion colitis have shown a variety of histological features, but no consistent pattern. The histology in resection specimens of defunctioned large bowel from 15 patients with no pre-existing inflammatory bowel disease was studied. Nine patients had symptoms of abdominal pain or rectal discharge of blood or mucus that developed between 9 months and 17 years after diversion procedure. The histology was abnormal in all. Findings were similar in 14 patients, regardless of the duration of faecal diversion, and comprised diffuse mild chronic inflammation with or without mild crypt architectural abnormalities, crypt abscesses, or follicular lymphoid hyperplasia. One patient had more severe changes, resembling active ulcerative colitis. These features in biopsy specimens are unlikely to be diagnostic but should provide useful information in avoiding a mistaken diagnosis of inflammatory bowel disease in these patients.
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