J Clin Pathol

Differential expression of CD44v6 in metastases of intestinal and diffuse types of gastric carcinoma.

Year 1998
Castella EM. Ariza A. Pellicer I. Fernandez-Vasalo A. Ojanguren I.
Department of Pathology, Hospital Germans Trias I Pujol, Autonomous University of Barcelona, Spain.
AIMS: To assess whether standard and variant isoforms of CD44 (CD44s, CD44v5, and CD44v6) have a differential expression profile in early versus advanced gastric adenocarcinoma of the diffuse and intestinal types and their metastases. METHODS: Immunohistochemical expression of CD44s, CD44v5, and CD44v6 was evaluated in 14 early gastric cancers (nine intestinal and five diffuse) and 37 advanced adenocarcinomas (21 intestinal and 16 diffuse) as well as in 18 cases of perigastric lymph node metastasis. Ten normal and five metaplastic gastric mucosa samples were also included in the study. RESULTS: Although no significant association was found between the degree of invasion and the CD44 expression profile, CD44v6 positivity was detected more frequently in metastases of intestinal-type carcinomas (66%) than in metastases of diffuse-type neoplasms (11%) (p < 0.05). Weak CD44s, CD44v5, and CD44v6 expression was observed focally in both normal and metaplastic gastric mucosa samples. CONCLUSIONS: These data suggest that CD44v6 expression may be involved in the production of lymph node metastases in intestinal-type gastric carcinoma but not in the diffuse-type disease, the metastatic potential of which is most likely unrelated to the CD44 family of adhesion molecules.

Chronic cryptosporidiosis in patients with AIDS: stable remission and possible eradication after long-term, low dose azithromycin.

Year 1998
Dionisio D. Orsi A. Sterrantino G. Meli M. Di Lollo S. Ibba Manneschi L. Trotta M. Pozzi M. Sani L. Leoncini F.
Infectious Diseases Unit, Careggi Hospital, Florence, Italy.
AIMS: To investigate the effectiveness of long term, low dose azithromycin treatment for chronic cryptosporidiosis in patients with AIDS. METHODS: Azithromycin was administered as initial daily treatment to 13 patients with AIDS: 6 patients received 500 mg for 30 to 40 days (mean 35); 3 patients received 1000 mg for 21 to 50 days (mean 37); and 4 patients received 1500 mg for 20 days. Nine of the 13 patients were also given low dose maintenance treatment with different schedules of azithromycin for 30 to 360 days (mean 129). Patients were monitored, during and after treatment, for parasite shedding in stool and for daily stool frequency and body weight. All but one patient had severe immunodeficiency. RESULTS: Long term, low dose maintenance treatment was associated with major clinical and parasitological benefits: there was probable eradication of infection in 2 patients, and 7 patients showed a complete response with persistent high decrease (5 patients) or clearance (2 patients) of parasite in stool. The drug was well tolerated, and there was no relapse either during treatment or during follow up (up to 21 months). These results were more impressive than those observed after the short term initial course of azithromycin, which was unable at any tested dose to achieve parasite clearance in stool (except in the patient with less advanced immunodeficiency) or to prevent relapse in 3 patients who discontinued treatment. Reversible side effects occurred with the 1500 mg daily dose. CONCLUSIONS: Long term, low dose azithromycin is well tolerated and may induce stable remission of chronic cryptosporidiosis in patients with AIDS. It may lead to probable eradication of the infection in some patients, even those with severe immunodeficiency.

Use of PCR in resolving diagnostic difficulties potentially caused by genetic variation of hepatitis B virus.

Year 1998
van Deursen FJ. Hino K. Wyatt D. Molyneaux P. Yates P. Wallace LA. Dow BC. Carman WF.
Institute of Virology, University of Glasgow, UK.
AIMS: To assess the relevance of genetic variants of hepatitis B virus (HBV) and to demonstrate the usefulness of the polymerase chain reaction (PCR) in cases of HBV diagnostic difficulty. METHODS: Five serum samples from patients that presented diagnostic difficulty in routine laboratories were sent to a research laboratory for PCR, and if appropriate, S gene sequencing, in vitro expression, and antigenic analysis. RESULTS: The demonstration of HBV in serum by PCR allowed a definitive diagnosis of current infection. One serum sample with poor reactivity in a diagnostic assay had a minor hepatitis B surface antigen (HBsAg) variant and another with very poor reactivity had multiple variants of HBsAg. Transient HBsAg reactivity was observed in a recently vaccinated patient. A hepatitis Be antigen (HBeAg) false positive reaction was noted in a patient from a well defined risk group for HBV. One patient who was strongly HBsAg/HBeAg positive, but anti-hepatitis B core antibody negative, was viraemic. CONCLUSIONS: PCR may become the gold standard for the diagnosis of current HBV infection. HBV variants are responsible for a proportion of diagnostically difficult cases. Modification of commercial assays is necessary to increase the sensitivity of detection of such variants.

How many lymph nodes to stage colorectal carcinoma?

Year 1998
Mainprize KS. Kulacoglu H. Hewavisinthe J. Savage A. Mortensen N. Warren BF.
Department of Colorectal Surgery, John Radcliffe Hospital, Oxford, UK.
This study aimed to establish the number of cassettes that should be filled with lymph nodes to stage a colorectal carcinoma as Dukes's stage C. The records from the Oxford Colorectal Cancer database of all patients diagnosed with Dukes's stage C cancer from late 1988 to early 1993 were reviewed. Each slide of lymph nodes was examined to determine how many slides needed to be looked at to find the first positive lymph node. The resected specimens were not fat cleared but dissected manually in a routine fashion. One hundred and eight slides were retrieved. The mean total lymph node harvest was 8.44 for each patient. Ninety eight patients (90.7%) had positive lymph nodes on the first slide with an average of 3.42 lymph nodes on each slide, of which a mean of 1.82 were positive. For nine patients, two slides were required to make a diagnosis of lymph node involvement, and for one patient the first three slides needed inspection to establish Dukes's stage C. In conclusion, using a routine technique to obtain lymph nodes from colorectal cancer specimens 99% of Dukes's stage C colorectal carcinoma can be found by filling two cassettes with lymph nodes.

Increased expression of proliferating cell nuclear antigen in autoimmune hepatitis in a patient with raised serum concentration of CA19-9.

Year 1998
Sohda T. Iwata Y. Shijo H. Egashira Y. Egashira K. Okumura M.
First Department of Internal Medicine, School of Medicine, Fukuoka University, Japan. hh038131@msat.fukuoka-u.ac.jp
A 52 year old woman had autoimmune hepatitis and an increased concentration of serum carbohydrate antigen 19-9 (CA19-9). The origin of the raised CA19-9 was studied using immunohistochemistry. Liver biopsy section showed chronic active hepatitis with large numbers of proliferated bile ductules. Immunohistochemical analysis revealed that the proliferated bile ductule cells were positive for proliferating cell nuclear antigen (PCNA) and for CA19-9. It is speculated that the raised serum CA19-9 concentration was derived from proliferated bile ductule cells and these cells, which are positive for PCNA, may be able to produce high concentrations of CA19-9.

A case of systemic pseudo-pseudoxanthoma elasticum with diverse symptomatology caused by long-term penicillamine use.

Year 1998
Coatesworth AP. Darnton SJ. Green RM. Cayton RM. Antonakopoulos GN.
Department of Thoracic Surgery, Birmingham Heartlands Hospital, UK.
A 47 year old man presented with a two year history of increasing cervical dysphagia, dyspnoea, and cutaneous signs. He had been diagnosed 27 years previously with Wilson's disease and was treated with penicillamine (1.5 g daily). Systemic abnormality of elastic fibres was confirmed by light and electron microscopy following biopsy of skin, lung, oesophageal muscle, gum, pharyngeal tissue, and cervical connective tissue. Dysphagia was relieved by cricopharyngeal myotomy. Substitution of trientene dihydrochloride for penicillamine relieved cutaneous and systemic manifestations. This is possibly the first case demonstrating an association between prolonged penicillamine use and biopsy proved systemic pseudo-pseudoxanthoma elasticum. The presenting symptoms may have resulted from the abnormal numbers and properties of elastic fibres, and the changes were caused by penicillamine use, rather than by idiopathic, inherited pseudoxanthoma elasticum.

Expression of proliferation associated antigens and detection of numerical chromosome aberrations in primary human liver tumours: relevance to tumour characteristics and prognosis.

Year 1998
Nolte M. Werner M. Nasarek A. Bektas H. von Wasielewski R. Klempnauer J. Georgii A.
Institute of Pathology, Medizinische Hochschule Hannover, Hannover, Germany.
AIMS: To assess cell proliferation and the presence of numerical chromosome aberrations involving chromosomes 1 and 8 in benign and malignant liver tumours. METHODS: Cell proliferation was studied immunohistochemically in paraffin wax embedded material from 62 primary liver tumours (20 hepatocellular carcinomas, 16 cholangiocellular carcinomas, 15 liver cell adenomas, 11 focal nodular hyperplasias), and the results were compared with histological characteristics and clinical data. Copy numbers of chromosomes 1 and 8 were assessed by interphase fluorescence in situ hybridisation (FISH) with satellite probes in fresh tumour material. RESULTS: The expression of proliferation associated antigen Ki67, using the monoclonal antibody MIB-1, and proliferating cell nuclear antigen (PCNA), using the antibody PC10, was found to be significantly higher in malignant versus benign liver tumours. Neither Ki67 nor PCNA expression were independent prognostic parameters. However, there was a tendency for a worse outcome (survival < 12 months) for patients with a high MIB-1 labelling index (> 20%) compared with patients having the same tumour stage and a low MIB-1 index. Aneusomy for chromosomes 1 and 8 was demonstrated by FISH in malignant tumours (six of seven hepatocellular carcinomas, four of five cholangiocellular carcinomas) but not in benign tumours (none of nine) or non-neoplastic liver (none of nine). CONCLUSION: Both the determination of the proliferating cell fraction and FISH analysis are useful for distinguishing hepatocellular carcinoma from liver cell adenoma or focal nodular hyperplasia; high fractions of proliferating cells are predictive of an early relapse.

Clinical and histological associations of cagA and vacA genotypes in Helicobacter pylori gastritis.

Year 1998
Warburton VJ. Everett S. Mapstone NP. Axon AT. Hawkey P. Dixon MF.
Department of Pathology, University of Leeds, UK.
AIMS: To determine the relation among the cytotoxin associated gene (cagA) and vacuolating cytotoxin gene (vacA) status of Helicobacter pylori isolates, the associated clinical diseases, and the severity and pattern of chronic gastritis. METHODS: Helicobacter pylori was cultured from gastric biopsies obtained from dyspeptic patients. DNA was extracted from the isolates and the cagA and vacA status determined by the polymerase chain reaction (PCR). The prevalence of the different cagA and vacA genotypes in three clinical groups, duodenal ulcer, gastric ulcer, and non-ulcer dyspepsia was compared. The histological features in sections from two antral and two corpus biopsies were graded by one blinded observer. The grades were compared with age and sex matched groups with different cagA and vacA genotypes, and with duodenal ulcers, or non-ulcer dyspepsia. RESULTS: Isolates from 161 patients were included. One hundred and nine (68%) harboured a cagA+ strain and 143 (89%) harboured a vacA s1 strain. The prevalence of cagA+ strains in duodenal ulcer patients (94%) was highly significantly greater than in those with non-ulcer dyspepsia (56%). However, of the patients infected with a cagA+ strain, almost equal numbers had non-ulcer dyspepsia or peptic ulceration. Chronic inflammation, polymorph activity, surface epithelial degeneration, atrophy, and intestinal metaplasia were all significantly more severe in the cagA+ than in the cagA- group, whereas only corpus epithelial degeneration was significantly more severe in the vacA s1 group compared with the vacA s2 group. Patients infected with cagA+ strains were almost four times more likely to have antral intestinal metaplasia than cagA- patients. An antral predominant gastritis was present in duodenal ulcer patients compared with matched non-ulcer dyspepsia patients, but this was not attributable to cagA or vacA status. CONCLUSIONS: Helicobacter pylori strains showing cagA positively and the vacA s1 genotype are associated with more severe gastritis but these virulence factors do not appear to determine the overall pattern. The pattern is closely linked to clinical disease. Therefore, it is likely that the nature of the disease complicating chronic infection is determined by host and environmental factors, while bacterial factors determine the magnitude of the risk of developing such disease.

Sequential malt lymphomas of the stomach, small intestine, and gall bladder.

Year 1998
Stephen MR. Farquharson MA. Sharp RA. Jackson R.
Department of Pathology, Royal Infirmary, Glasgow, UK.
Low grade lymphomas of mucosa associated lymphoid tissue (MALT) are indolent neoplasms that, although tending to remain localised for many years, may spread to other mucosal sites. A 53 year old woman treated by total gastrectomy for low grade MALT lymphoma of the stomach developed a recurrence in the small bowel 18 years later, and a further recurrence involving the gall bladder after three years in complete clinical remission after chemotherapy. In situ hybridisation showed that the small intestine and gall bladder recurrences had the same pattern of light chain restriction. Tumour from all three sites was shown to be derived from a single clone by the demonstration of an identical immunoglobulin heavy chain gene rearrangement by the polymerase chain reaction. The case illustrates the propensity of MALT lymphomas to "home" to mucosal sites and gives an insight into their behavior over an extended follow up.

Familial pancreatic lymphoma.

Year 1998
James JA. Milligan DW. Morgan GJ. Crocker J.
Department of Haematology, Birmingham Heartlands Hospital, UK.
Non-Hodgkin's lymphoma is not commonly a familial condition. This is believed to be the first two cases of primary pancreatic lymphoma within a single family. The two cases, a brother and sister, both presented in their 60s and were diagnosed histologically as having high grade B cell lymphoma affecting the pancreas, an uncommon primary site. Both responded well to treatment with chemotherapy and were in remission at the time of writing. On further investigation it was found that their mother also presented with a malignant lymphoma of cervical nodes 30 years earlier and subsequently died of the disease.