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This paper published in 1989 comes number 8 in the most cited papers in the Journal of Clinical Pathology in this 70th anniversary of the Journal and cited some 631 times in the 27 years since it was published. In this paper, the French–American–British (FAB) group studied specimens from 110 patients who were well characterised with clinical and laboratory studies including electron microscopy.1 They looked at peripheral blood films, bone aspirate and trephine specimens and some lymph node biopsy specimens. On the basis of cytology and membrane phenotype, the disorders were defined. Immunological techniques used included distinguishing between B and T lymphocytes using membrane (SMIg) and cytoplasmic (CyIg) immunoglobulin and rosette tests with sheep erythrocytes and monoclonals against cell surface epitopes. In a series of meetings over 18 months, the group met and reviewed and discussed the cases and agreed on the classification. The technologies used were the state-of-the-art methods of the time. Morphology, the long-standing foundation of haematology, is the initial technique used. However, it is recognised that morphological appearances in certain entities can be highly variable. In this paper, the experts agree and define the appearances of the different types of chronic leukaemias and in the illustrations give clear examples of the morphology. However, at the time of …

A simple method for the collection of blood specimens on filter paper for serology of Helicobacter pylori was devised. Blood was freshly applied to small Whatman 3 mm filter paper and allowed to dry. Serological activity, as measured by reactivity to H pylori antigens (AMRAD, Australia), was retained after storage for one month at both room temperature and at 4 degrees C. This technique eliminates formal venepuncture, separation of sera, and arduous packaging of specimens to be sent to the laboratory.

A new method of detecting urease activity in Enterobacteriaceae was developed. An 8.5 cm filter paper disc impregnated with 20% urea and 0.5% bromocresol purple was placed on the surface of a glucose fermentation plate after inoculation with a multipoint replicator and overnight incubation. This method was compared with the commercially prepared Mast urea agar (Multipoint) and Fuscoe's Urea Plate Medium. A total of 240 routine isolates of Enterobacteriaceae were tested for urease activity using the three methods. Sixty five isolates were positive by the three methods while 33 isolates gave differing results. The urea disc method was more sensitive for detecting urease activity in isolates of Klebsiella species, Morganella morganii, and Yersinia enterocolitica. It also overcame the problem associated with the other two media of diffusion of alkali end products through the medium.

In celebration of the Platinum Jubilee, the current Editor-in-Chief, Professor Tahir Pillay, has reflected on the past 70 years, especially the best cited papers that have appeared in the Journal of Clinical Pathology ( JCP ).1 For the journal to have endured and remained relevant for this length of time, clearly it must have published good work consistently. The second most cited paper in the Journal is a superb review by Bosch and colleagues on human papillomavirus (HPV) and uterine cervical cancer.2 Data measurement on impact and relevance in publishing is now de rigueur and the yardstick by which a piece of work is judged. There are several repositories and search engines such as Google Scholar …

From time to time, while signing out our surgical pathology cases, my colleagues and I have noted how certain pathological entities have been described either fairly recently, or at least since we entered the medical field. The best example of such a new disease is, of course, AIDS. In histopathology, lesions such as aggressive angiomyxoma, solid aneuysmal bone cyst, anaplastic large cell lymphoma and gastrointestinal stromal tumour are four lesions that we now see, but which would have been signed out quite differently in a different era. This, and my interest in history of medicine and pathology got me thinking: which are the 20 most important landmark papers/concepts in surgical pathology over the past 50 years, 1957–2007? I refer to papers which have changed the practice of surgical pathology in one respect or the other. I asked, by e-mail, 83 pathologists around the world what their choice of such papers would be. Of course, the list was likely to be subjective, given that there are obviously much more than 20 important papers. Further, many of those receiving the mail had specialty interests and quite a few have described some of those entities. There was only one condition: the papers must be for the time period 1957 to 2007. Respondents could choose papers which have radically changed the practice of pathology in any respect, or simply their favourite paper (for whatever reason—it may have been elegantly written, it may have had a major impact on their field or changed a concept entirely, it may have been related to the first paper that they had published, etc). Respondents were asked to try and include papers from beyond their current area of interest or specialisation and to state why they had included them in the list, if it were …

A simple paper chromatographic method was found to be effective for the study of phenylketonuria and tyrosyluria. It proved to be much more reliable than conventional tests for the detection of abnormal amounts of ketoacids in urine and was suitable and convenient for following the effects of dietary variations on the excretion of these compounds. Information obtained about ketones other than those of primary importance to the conditions studied included confirmation of the excretion of p-hydroxyphenylpyruvic acid in phenylketonuria. A modification of the method applicable to histidinaemia was devised.

A method for the determination of urinary normetadrenaline and metadrenaline is described whereby these 3-O-methoxy metabolites of noradrenaline and adrenaline are separated by paper chromatography before estimation by Pisano's method. Results in 80 normal subjects are given.

Simple paper chromatography of urine obtained in the Figlu test has been found satisfactory for determining excess excretion of the imidazole metabolites of histidine. It has been confirmed that examination for these in addition to formiminoglutamic acid is necessary for a full assessment of this test. When excretion of the latter is not abnormal in folic-acid and/or vitamin B(12) deficiency, that of urocanic acid, a glycine conjugate of urocanic acid and/or imidazole propionic acid, is usually raised. An abnormally high excretion of hydantoin-5-propionic acid after histidine has also been found in these deficiencies, and its estimation may be of additional use in the evaluation of the Figlu test.

The protein and lipid electrophoresis patterns of lymph and various body fluids have been examined. Chylous fluids produce a characteristic lipid pattern with a dense deposit at the origin and a lipid trail. The value of centrifuging turbid fluids at high speed before electrophoresis is stressed.

Because they are cumbersome, tests to determine the quantitative susceptibility of organisms to antimicrobial drugs are not performed routinely in many diagnostic laboratories. This paper describes a simple method of incorporating the antimicrobial drug in agar. It is an adaptation of the Rolinson and Russell technique which allows the determination of minimum inhibitory concentrations (MIC) of antimicrobial drugs for a large number of organisms. Results are comparable with those obtained when the standard agar dilution method is used. Strains of aerobic Gram-negative bacilli were tested by both methods using ampicillin (86 strains), cephaloridine (72 strains), trimethoprim (72 strains), and gentamicin (72 strains). Of the 302 tests thus performed, a difference in MIC of more than one double dilution was noted in only 11 tests. With one strain of Pseudomonas aeruginosa, however, it was not possible to detect ampicillin resistance by the method described in this paper.

Materials for wrapping surgical dressings were studied by a method which measured the recontamination rate in packs stored for periods of up to several weeks. Of the materials tested a thick crepe paper was better than calico and balloon cloth fabrics. Dressings wrapped in paper were not significantly contaminated after storage in dusty places for periods of up to three weeks. For added protection during handling and for convenience in transport and storage, paper packs may be sterilized and kept in paper-lined cartons. The shelf life in good storage conditions would be many weeks at least.

Filter paper blood samples were used to measure complement-fixation antibody in 34 children with sore throats. The method was satisfactory and should be particularly useful to minimize trauma in general practice and to conserve reagents in developing countries.

Paper tests for occult blood were assessed on faecal specimens from adults. An orthotolidine/sodium perborate and a modified orthotolidine/peroxide test were found to be reasonably satisfactory. The Hematest and Occultest tablets and a paper guaiac test were unsatisfactory.A large number of false positive results was obtained in children and infants. It is suggested that this might be due to meat derivatives reaching the faeces more easily in the young. Red cells labelled with either Cr(51) or Fe(59) were swallowed by human volunteers. Although between 45% and 73% of the red cell iron reappeared in the faeces, the peroxidase activity of the labelled material dropped six-fold on passage through the alimentary canal.

A homogeniser (Stomacher 400) which does not damage bacteria has been used to produce an homogenate of spore papers, from which it was possible to make quantitative assessments of viable spores recoverable from such papers before and after exposure to sterilising procedures.

Aim—To compare anticardiolipin (ACL) and anti-s2 glycoprotein 1 (s2gp1) enzyme linked immunosorbent assays (ELISAs) in the diagnosis of antiphospholipid syndrome (APS) and to incorporate these results into a meta-analysis of published data. Method—Three representative commercial ACL ELISAs and an in house s2gp1 assay were optimised and then assessed on 124 sera from normal donors, patients with infection, or patients with APS. A Medline search was screened for papers meeting defined criteria to conduct a meta-analysis. The performance of the assays used in this study was included. Results—A non-quantitative ACL assay performed at least as well as the anti-s2gp1 assay in the diagnosis of APS. Meta-analysis confirmed that neither assay is perfect, although the anti-s2gp1 assay had a higher specificity and lower sensitivity than the ACL assay. Conclusions—The pooled data suggest that the ACL assay is used to investigate thrombosis without overt underlying pathology and that the improved specificity of the anti-s2gp1 assay is exploited where infection, connective tissue disease, or atheroma are present. Key Words: antiphospholipid syndrome • anticardiolipin antibodies • anti-s2 glycoprotein 1 • sensitivity

Viral uveitis and retinitis, usually caused by herpesviruses, are common in immunosuppressed patients. The diagnosis of viral anterior uveitis and retinitis is usually clinical. The polymerase chain reaction (PCR) has been used for the diagnosis of some viral infections, especially those caused by herpesviruses. This paper reports the use of PCR in the diagnosis of viral retinitis in vitreous samples from Brazilian patients.PCR was used for the diagnosis of necrotising retinitis in vitreous samples from patients from the Hospital São Geraldo, Universidade Federal de Minas Gerais, Brazil. The vitreous samples were collected by paracentesis and stored until analysis. Samples were analysed by PCR using specific primers designed to amplify herpes simplex virus 1 (HSV-1), varicella zoster virus (VZV), or human cytomegalovirus (HCMV). In a case of anterior uveitis, PCR was performed with a sample from the anterior chamber.Herpesvirus DNA was amplified in 11 of 17 samples. HCVM DNA was detected in nine samples but DNA from HSV-1 and VZV were detected only once each.These results strongly suggest that PCR could be used for a rapid complementary diagnosis of viral uveitis and retinitis. A prospective study to evaluate the PCR results, clinical evolution, and treatment is imperative to corroborate the real value of PCR in diagnosis and how it could help the clinicians' approach.

Aims—The use of the H score (involving the assessment of intensity and distribution of positivity) on sections stained for the oestrogen receptor (ER) by immunocytochemistry (ICC) allows diVerent samples to be compared and detailed correlations to be made between hormone receptor expression and morphology. This study assessed the reliability of core biopsy in predicting ER expression in the same tumour excised later at treatment. The distribution of ER within excised tumours was investigated. Methods—The distribution of ER positivity was investigated in 51 diagnostic core biopsies and across the diameter of 51 subsequently excised tumours in a field by field (magnification, ×40; field diameter, 0.4 mm) assessment using the semiquantitive H scoring system. Results—The ER H score in diagnostic core biopsy was significantly higher (p = 0.05, paired rank test; overall mean, 130; n = 51) than the mean in the corresponding excised tumour (mean, 110; n = 51). There was a significant downward trend in ER positivity from the periphery of tumours towards the centre (p = 0.001). The reduction of ER positivity was 6 H score units (2%)/mm. If core biopsies were orientated with the tumour edge at one end no change in ER positivity with field number along the length of the core could be demonstrated. Conclusions—ER estimation in core biopsies correlated well with expression in tumours but ER expression was higher in the core biopsies than in the excised tumours. ER expression was higher at the periphery of tumours than at the centre. The higher ER expression in cores may reflect the higher chance of sampling the peripheral part of a tumour using a needle core. (J Clin Pathol 2001;54:951‐955)

Aims—To investigate whether MUC1 mucin, a high molecular weight transmembrane glycoprotein, also known as epithelial membrane antigen (EMA), differs in its expression and degree of glycosylation between anaplastic large cell lymphoma (ALCL) and classic Hodgkin’s disease (HD), and whether MUC1 immunostaining can be used to diVerentiate between CD30 positive large cell lymphomas. Methods/Results—Using five diVerent monoclonal antibodies (E29/anti-EMA, DF3, 139H2, VU-4H5, and SM3) that distinguish between various MUC1 glycoforms, high MUC1 expression (50‐95% of tumour cells positive) was found in 13 of 17 anaplastic lymphoma kinase (ALK) positive systemic nodal ALCLs, and in one of 20 cases of classic HD. Scattered or focal staining (< 25% of tumour cells) was seen in two additional ALK positive systemic ALCLs, two additional classic HD cases, and in three of 20 cases of ALK negative systemic nodal ALCL. Primary cutaneous ALCL showed no staining with the anti-MUC1 antibodies. Antibodies detecting hypoglycosylated MUC1 were found to be absent in all lymphomas (SM3) or present in only six of 15 ALK positive ALCLs (VU-4H5). Conclusions—MUC1 is preferentially expressed by a subtype of systemic nodal ALCL, characterised by ALK expression, but is found in only a few cases of classic HD and ALK negative ALCL. Therefore, although MUC1 could be used in a panel of markers for CD30 positive lymphomas, it is probably not a valuable tool to diVerentiate between ALK negative CD30 positive large cell lymphomas. Finally, the degree of MUC1 glycosylation in lymphomas is relatively high, compared with the aberrant hypoglycosylation found in adenocarcinomas. (J Clin Pathol 2001;54:933‐939)

Aims—To clarify p21waf1/cip1 expression in sinonasal lesions. Methods—Archived surgical specimens from 38 patients were investigated by means of immunohistochemistry. p21waf1/cip1 staining was evaluated in the different layers of the epithelium. In addition, human papillomavirus (HPV) infection and p53 protein overexpression were assessed and correlated with p21waf1/cip1 expression. Results—p21waf1/cip1 staining was negative in non-papillomatous nasal mucosa. HPV infection and p53 protein overexpression were not seen. Sixteen of 20 inverted papillomas showed p21waf1/cip1 expression. HPV infection was found in 16 cases and p53 protein overexpression was present in 13 specimens. Expression of p21waf1/cip1 was restricted to surface cells in five cases, but involved basal/parabasal cells in 11 specimens. Immunoreactivity for p21waf1/cip1 in basal/parabasal cells colocalised with p53 protein overexpression. Enhanced expression rates for p21waf1/cip1 were seen in transitional and squamous epithelium compared with columnar epithelium. p21waf1/cip1 expression involved only surface cells in cylindrical cell papillomas. HPV infection and p53 protein overexpression were detected in all specimens. One of five squamous cell carcinomas showed p21waf1/cip1 expression. HPV infection was seen in two cases, and all carcinomas showed p53 protein overexpression. Conclusions—Expression of p21waf1/cip1 is associated with terminal differentiation in surface cells in inverted papillomas and cylindrical cell papillomas, but not in non-papillomatous nasal mucosa. Overexpression of p53 protein colocalises with p21waf1/cip1 expression in basal/parabasal cells in inverted papillomas but not in cylindrical cell papillomas. Expression of p21waf1/cip1 in squamous cell carcinomas involves a subset of tumours with p53 protein overexpression. Key Words: p21waf1/cip1 • nasal mucosa • sinonasal papillomas • squamous cell carcinomas

Aims —Although frequent reduction or loss of DCC (deleted in colorectal carcinomas) has been demonstrated in gliomas, the association with cell kinetics and survival is still unclear. Methods —A total of 119 astrocytomas, comprising 39 grade IV, 36 grade III, and 44 low grade tumours, were immunohistochemically investigated, along with 26 normal adult brain samples and two fetal brains. The results were compared with p53 abnormalities, Ki-67 labelling index (LI), mitotic index (MI), apoptotic index (AI), and survival. Results —In normal adult and fetal brain tissues, DCC expression was detected in mature and terminally differentiated neuronal cells but not glial elements. In astrocytomas, whereas DCC expression was still clearly shown with low grade malignancy, DCC scores were significantly decreased in high histological grade malignancy, along with an increase in cell kinetics determined by AI, MI, and Ki-67 LI values. In addition, p53 LI values were significantly increased, although a direct link between DCC scores and p53 LI values was not evident. Univariate analysis revealed that high DCC scores and low p53 LI values were closely related to a favourable outcome for astrocytoma, although only the AI was an independent prognostic factor. Conclusions —The loss of DCC expression may be closely related to changes in cell kinetics and tumour phenotype in astrocytomas, independent of p53 abnormalities.