Comparing virtual with conventional microscopy for the consensus diagnosis of Barrett's neoplasia in the AspECT Barrett's chemoprevention trial pathology audit.

AIMS: To compare the diagnostic accuracy of conventional versus virtual microscopy for the diagnosis of Barrett's neoplasia. METHODS AND RESULTS: Sixty-one biopsies from 35 ASPirin Esomeprazole ChemopreventionTrial (AspECT) trial patients were given a Barrett's neoplasia score (1-5) by a panel of five pathologists using conventional microscopy. Thirty-three biopsies positive for neoplasia were digitized and rescored blindly by virtual microscopy. Diagnostic reliability was compared between conventional and virtual microscopy using Fleiss' kappa. There was substantial reliability of diagnostic agreement (κ = 0.712) scoring the 61 biopsies and moderate agreement scoring the subgroup of 33 'positive' biopsies with both conventional microscopy (κ = 0.598) and virtual microscopy (κ = 0.436). Inter-observer diagnostic agreement between two pathologists by virtual microscopy was substantial (κ = 0.76). Comparison of panel consensus neoplasia scores between conventional and virtual microscopy was almost perfect (κ = 0.8769). However, with virtual microscopy there was lowering of the consensus neoplasia score in nine biopsies. CONCLUSIONS: Diagnostic agreement with virtual microscopy compares favourably with conventional microscopy in what is recognized to be a challenging area of diagnostic practice. However, this study highlights possible limitations for this method in the primary diagnostic setting.

Current experience and attitudes to biomedical scientist cut-up: results of an online survey of UK consultant histopathologists.

AIMS: To assess the current utilisation of biomedical scientist (BMS) surgical specimen cut-up in the UK and attitudes of consultant histopathologists to the practice. METHODS: Email invitations were sent to all UK consultant histopathologists to participate in an online survey (SurveyMonkey) assessing attitudes to and utilisation of BMS surgical specimen cut-up. RESULTS: 463 individual replies were received (35% response rate) from 1320 invitations to participate, covering 181 UK histopathology departments. A majority of the respondents were either fully in favour of BMS cut-up (52.7%), or in favour but with some reservation (46.2%). Only five respondents (1.1%) were completely opposed to BMS cut-up. 267 (57.7%) respondents reported that their BMS staff loaded biopsies only. 148 (32%) reported BMS cut-up of more complex benign specimens, and 83 (17.9%) reported BMS handling of orientated skin specimens. Only 39 (8.4%) reported that BMS staff in their departments currently cut-up larger cancer resections. CONCLUSIONS: This survey is representative of current BMS cut-up practice in the UK. The majority of UK consultant histopathologists replying to this survey support BMS cut-up to some degree, but utilisation of BMS cut-up is rather limited and patchy at present. Cost, staffing constraints, perceived quality issues and individual consultant preferences are cited as reasons for limited uptake currently. Recognised benefits of promoting BMS cut-up include better use of consultant time, enhanced team working, BMS job satisfaction and career progression, and better adherence to standard operating procedures.

Fibroadenoma of the anogenital region.

Fibroadenoma of the anogenital region is a rare tumour histologically similar to fibroadenoma of the breast. Morphological and immunophenotypic features of a case with pseudoangiomatous stromal hyperplasia are presented here.

Characteristic Ber-EP4 and EMA expression in sebaceoma is immunohistochemically distinct from basal cell carcinoma.

AIMS: There is considerable overlap between the histological features of sebaceoma and basal cell carcinoma (BCC). The distinction between these two tumours is important due to the often more locally aggressive nature of BCC and the association of sebaceoma with the Muir-Torre syndrome. The aim of this study was to describe the immunohistochemical reactivity of the cells in sebaceoma to Ber-EP4 and epithelial membrane antigen (EMA) and investigate the utility of this panel to differentiate sebaceoma from basal cell carcinoma. METHODS AND RESULTS: Immunohistochemistry of 25 sebaceomas for Ber-EP4 and EMA revealed unequivocal negative expression of Ber-EP4 in 24 of 25 sebaceomas. A single case exhibited focal weak Ber-EP4 staining, predominantly in mature sebocytes and in < 10% of the tumour cells. EMA was not expressed in the germinative cells of sebaceoma, but was expressed strongly in approximately 50% of mature sebocytes in all cases and highlighted the cytoplasmic vacuoles. We reviewed the immunoreactivity of 51 cases of nodular BCCs and found moderate or strong BerEP4 expression in all cases with never less than 20% of the tumour staining. Expression of EMA was uncommon in BCC (moderate or strong in 8%) and was confined to keratotic or squamoid areas. CONCLUSION: The use of Ber-EP4 in combination with EMA, both widely used immunomarkers in histopathology, is a helpful aid in distinguishing sebaceoma from nodular BCC.

Subspecialisation in cellular pathology in the DGH setting: the Warwick experience.

A successful move towards subspecialised reporting in cellular pathology in the setting of a small to medium-sized district general hospital staffed by five consultant pathologists is described. This move has been facilitated by implementation of a prospective workload allocation system. Perceived benefits in service delivery and career progression are highlighted.

The Warwick system of prospective workload allocation in cellular pathology--an aid to subspecialisation: a comparison with the Royal College of Pathologists' system.

BACKGROUND: Guidelines on staffing and workload for histopathology and cytopathology departments was published by the Royal College of Pathologists (RCPath) in July 2003. In this document, a system is provided whereby the workload of a cellular pathology department and individual pathologists can be assessed with a scoring system based on specialty and complexity of the specimens. A similar, but simplified, system of scoring specimens by specialty was developed in the Warwick District General Hospital. The system was based on the specimen type and suggested clinical diagnosis, so that specimens could be allocated prospectively by the laboratory technical staff to even out workload and support subspecialisation in a department staffed by 4.6 whole-time equivalent consultant pathologists. METHODS: The pathologists were asked to indicate their reporting preferences to determine specialist reporting teams. The workload was allocated according to the "prospective" Warwick system (based on specimen type and suggested clinical diagnosis, not affected by final diagnosis or individual pathologist variation in reference to numbers of blocks, sections and special stains examined) for October 2003. The cumulative Warwick score was compared with the "retrospective" RCPath scoring system for each pathologist and between specialties. Four pathologists recorded their time for cut-up and reporting for the month audited. RESULTS: The equitable distribution of work between pathologists was ensured by the Warwick allocation and workload system, hence facilitating specialist reporting. Less variation was observed in points reported per hour by the Warwick system (6.3 (range 5.5-6.9)) than by the RCPath system (11.5 (range 9.3-15)). CONCLUSIONS: The RCPath system of scoring is inherently complex, is applied retrospectively and is not consistent across subspecialities. The Warwick system is simpler, prospective and can be run by technical staff; it facilitates even workload distribution throughout the day. Subspecialisation within a small-sized or medium-sized department with fair distribution of work between pathologists is also allowed for by this system. Reporting times among pathologists were shown by time and motion studies to be more consistent with Warwick points per hour than with RCPath points per hour.

The outcome of surgery in fulminant Clostridium difficile colitis.

BACKGROUND: The clinical presentation of Clostridium difficile infection ranges from asymptomatic carriage, colitis with or without pseudomembranes, to fulminant colitis. Although not common, fulminant C. difficile colitis can result in bowel perforation and peritonitis with a high mortality rate. Colectomy is often indicated in these cases. METHODS: We retrospectively analysed the outcome of 14 patients who underwent surgery for fulminant C. difficile colitis in the period 1996-2003 in our Unit. RESULTS: The indications for surgery were systemic toxicity and peritonitis (n = 10), radiological and clinical evidence of progressive toxic colonic dilatation (n = 3) and progressive colonic dilatation with bowel perforation (n = 1). C. difficile infection as the cause of colitis was diagnosed pre-operatively in seven (50%) patients, six of whom underwent a total colectomy and one a right hemicolectomy. Overall mortality in our series was 35.7%. Total colectomy was associated with a lower mortality rate of 11.1% (1/9) when compared with left hemicolectomy was 100% (4/4) (P = 0.01). One patient who underwent a right hemicolectomy (on the basis of deceptively normal external appearance of the rest of the colon intra-operatively) survived after a prolonged hospital stay. CONCLUSIONS: Early or pre-operative microbiological diagnosis of C. difficile infection can be difficult in patients with a fulminant presentation. Those patients with C. difficile colitis, who develop signs of toxicity, peritonitis or perforation, should undergo a total colectomy as the operation of choice.

Mucosal integrity and barrier function in the pathogenesis of early lesions in Crohn's disease.

Crohn's disease aetiology is multifactorial and remains enigmatic. However, animal models show that disease heterogeneity is probable, in that more than one defective mucosal mechanism can produce the same clinical phenotype. For example, Crohn's-like lesions are reported after compromise of mucosal integrity per se in the presence of an intact immune system, through altered expression of mucosal adhesion molecules, such as cadherins and tight junction proteins, highlighting the importance of the mucosal barrier in the disease process. Key to mucosal damage is the trigger of an inflammatory cascade after luminal antigen processing, a role classically ascribed to M cells in the surface follicle associated epithelium. Direct luminal antigen sampling has recently been proposed, however, by extension of dendritic cell (DC) processes through the intact gut epithelium, and it follows that early mucosal damage could result from de novo lymphoid recruitment. Cytokines, such as tumour necrosis factor alpha (TNFalpha), are known to drive inflammation, but emerging data suggest additional important roles for TNFalpha influencing mucosal barrier efficacy by altering adhesion molecule expression, influencing epithelial apoptosis, and affecting tight junction functionality.

Dermatofibrosarcoma protuberans treated by micrographic surgery.

Dermatofibrosarcoma protuberans is an uncommon cutaneous tumour which rarely metastasises. However, local recurrence following apparently adequate surgical excision is well recognised, presumably as a result of sub-clinical contiguous growth, for which micrographically controlled excision would be a logical treatment. A retrospective study of all patients treated by micrographic surgery, from April 1995-March 2000, at a tertiary skin oncology centre. Twenty-one patients (11 males), age 14 to 71 years with dermatofibrosarcoma protuberans on the trunk (10 patients), groin (four), head and neck (four), and limbs (three) were treated. In 15 patients one micrographic layer cleared the tumour, and four were cleared with two layers. For one patient the second stage was completed by conventional excision guided by positive margins. Another patient with a multiply recurrent perineal dermatofibrosarcoma protuberans, not cleared in one area after two layers, died from a pulmonary embolus before total clearance could be achieved. There was no correlation between tumour size and lateral excision margin. No recurrence was observed during the follow-up, from 21 to 80 months, median 47 months. The study provides further support for micrographic surgery as the treatment of choice for dermatofibrosarcoma protuberans.

Multiple cutaneous plasmacytomas following an autologous peripheral stem cell transplant.

We describe the unusual development of multiple cutaneous plasmacytomas following treatment of IgA lambda myeloma with myeloablative therapy and a peripheral blood stem cell autograft. Cutaneous metastatic spread was evident despite bone marrow remission. Treatment with an autograft may have contributed to the cutaneous relapse.

Aberrant P-cadherin expression is an early event in hyperplastic and dysplastic transformation in the colon.

BACKGROUND: Colorectal adenomatous and, probably, hyperplastic polyp development requires epithelial remodelling and stratification, with loss of E-cadherin expression implicated in adenoma formation. We have shown that P-cadherin, normally expressed in stratified epithelia and placenta, is aberrantly expressed in disturbed epithelial architecture associated with colitis. AIMS: (i) To investigate the role of P-cadherin in colonic polyp formation. (ii) To ascertain whether expression of P-cadherin is independent of or correlated with expression of its associated proteins--E-cadherin, beta-catenin, and gamma-catenin. (iii) To determine if P-cadherin is functional regarding catenin binding in polyps. METHODS: Expression and localisation of cadherins (E- and P-) and their associated catenins (beta- and gamma-) were determined in aberrant crypt foci (ACF), in polyps with hyperplastic morphology (hyperplastic polyps and serrated adenomas), and in adenomatous polyps by immunohistochemistry, western blotting, and mRNA in situ hybridisation. Assessment of cadherin-catenin binding was evaluated by co-immunoprecipitation. Adenomatous polyposis coli (APC) mutation was assessed in adenomatous polyps. RESULTS: P-cadherin was expressed from ACF through to hyperplastic and adenomatous polyps. Alterations in E-cadherin and catenin expression occurred later, with variant patterns in (i) ACF, (ii) hyperplastic polyps and serrated adenomas, and (iii) adenomatous polyps. P-cadherin present in adenomas was functional with regard to catenin binding, and its expression was independent of APC mutational status. CONCLUSIONS: P-cadherin is aberrantly expressed from the earliest morphologically identifiable stage of colonocyte transformation, prior to changes in E-cadherin, catenin, and APC expression/mutation. P-cadherin expression alone does not predict tissue morphology, and such expression is independent of that of associated cadherins and catenins.

Progressive nodular histiocytosis in a child with a hypothalamic tumor.

We report a 13-year-old girl with multiple cutaneous histiocytic lesions, precocious puberty, growth hormone deficiency and a hypothalamic tumour. We conclude that she has progressive nodular histiocytosis, but this case illustrates the difficulty in differentiating the type II histiocytoses.