Aims: Although they are non specific, minimal intestinal lesions are at the end of the coeliac histological damage spectrum. To investigate whether minimal intestinal lesions in patients without endomysial antibodies are due to coeliac disease, we studied not only their prevalence and causes but also their risk of evolving into frank coeliac disease.

Methods: From Jan-2000 to Dec-2005, 645 duodenal biopsies were performed. In 209 patients, duodenal biopsies were performed independently of endomysial antibody results. Clinical data and HLA-typing of all the patients negative to endomysial antibodies but with minimal mucosal lesions were re-evaluated. Three years later, they were offered to be seen again and further investigations were proposed.

Results: 14 out of 209 patients had minimal mucosal lesions and negative endomysial antibodies. Two patients were lost to follow-up; in 7/12 patients, symptoms and histological lesions were due to a different condition, not related to coeliac disease. In 11/12 patients, HLA-typing made diagnosis of coeliac disease very unlikely. Only one patient was on a gluten-free diet because of gluten-sensitive symptoms and was DQ2+/DQ8+.

Conclusions: Minimal duodenal lesions in patients negative to endomysial antibodies are rare and are likely to be due to conditions unrelated to coeliac disease.

The gross examination is critical to making accurate diagnoses on placental specimens. An orderly evaluation of the cord, membranes and villous tissue allows maximal opportunity to recognize abnormalities. Many lesions have a pathognomonic gross appearance while other processes are best seen on histology. Quantitation of the volume of placental tissue involved in by an abnormal process is necessary to distinguish normal variation from significant pathology. Histologic sections must include cord, membranes and central villous tissue.

Solid pseudopapillary tumours (SPT) of the pancreas are uncommon, but with widespread and increased imaging several of these lesions are coming to light incidentally and are subject to needle biopsies. On limited material and especially the solid or clear cell variants of SPT can morphologically mimic most notably pancreatic neuroendocrine tumours and even metastatic renal cell carcinoma or melanoma. In this context, immunohistochemistry is important and useful in helping to reach the correct diagnosis.

Several antibodies have been used in the immunohistochemical evaluation of SPT. As with most tumours, no one marker is specific but rather a core panel is advocated. Recently, both β-catenin and E-cadherin have shown to be of value in SPT. Nuclear and cytoplasmic decoration of tumour cells by β-catenin is seen almost 100% of cases. This protein relocalization from the cell membrane is underscored by mutations of the β-catenin gene. Mutations of the E-cadherin gene are very uncommon in SPT but the immunohistochemically-detected changes to the protein are consistent and present in 100% of cases. Using an E-cadherin antibody to the extracellular domain of the molecule results in complete membrane loss, while the antibody directed to the cytoplasmic fragment produces distinct nuclear staining of the tumour cells. In addition, there is concordance of staining abnormalities between the two antibodies. When combined with CD10 and progesterone receptor positivity, a diagnosis of SPT can be rendered with confidence even in small biopsy samples.

Pancreatic intraductal papillary mucinous neoplasms (IPMNs) are mucin producing neoplasms with frequent papillary architecture that arise within the pancreatic ducts and are increasingly being recognized. Because they exhibit a spectrum of dysplasia ranging from low grade to high grade and may also have associated invasive carcinoma, and because they are clinically detectable, they are now intensively studied. There is marked overlap between IPMNs and pancreatic intraepithelial neoplasia (PanIN), such that the distinction between these two lesions is nearly impossible in certain cases. In addition, IPMNs sometimes can be confused with other primary cystic lesions of the pancreas. As a result, the correct diagnosis of IPMN can be challenging. This review addresses the clinical and pathological features of IPMNs, emphasizing their diagnostic criteria, differential diagnosis, and biologic behavior. Problematic issues in the pathologic evaluation of IPMNs are discussed.

Assessment of the Clinical Significance of Intestinal Spirochaetosis.

Introduction: Spirochaetes are well known causative agents of diarrhoea in veterinary medicine. However to date there is no agreement as to whether or not they have any clinical significance in humans.

Objectives: The objective of our study is to assess the symptoms associated with intestinal spirochaetosis, their response to treatment and the natural history of untreated cases.

Methods: A retrospective review of all cases of intestinal spirochaetosis identified within an eight year period in a single university teaching hospital was performed. A chart review and follow up telephone interview was performed to assess the indications for colonoscopy that led to the diagnosis, treatment received, duration and nature of the symptoms.

Results: 18 cases were identified. The indications for colonoscopy were diarrhoea in 50% and rectal bleeding in 16.7%; also investigation of constipation, anaemia, abdominal pain and in two cases re-assessment of chronic proctitis. Two subjects were treated with metronidazole and two were treated with aminosalycilates. 69% had complete resolution of symptoms at follow up, 15% had persistent symptoms and 15% had intermittent symptoms. Of the two patients treated with metronidazole one had resolution of symptoms and one has persistent abdominal pain.

Conclusion: Symptoms do not appear to parallel spirochaete persistence or eradication and therefore it seems appropriate to adopt a wait and see approach to treatment of patients in whom spirochaetes are identified, giving a trial of antimicrobial treatment only in those who have severe or persistent symptoms. Careful consideration of both host and pathogen should be undertaken.

Aims:Most staphylococci grown from blood cultures are contaminants. Since they are microscopically indistinguishable from non-contaminants, considerable time and resources may be spent following up all patients with positive blood cultures before the identification is made the following day. Since there is no formal guidance or standard available in this area, we surveyed practice in our region.

Methods: Telephonic interview using a standardized questionnaire. Results were analysed using descriptive techniques.

Results: The majority of microbiologists did not communicate all presumptive staphylococci but waited for identification in some cases.

Conclusion: There is a range of practice in our laboratories due to conflicting pressures: limited time, fear of criticism if results are not phoned, fear of causing confusion with provisional information, and lack of clarity concerning what is ‘good practice’. From this survey, we concluded that a decision not to telephone every presumptive staphylococcus in blood cultures on Day 1 is reasonable.

There have been recent major advances in obstetric ultrasound, both regarding technologies and expertise, such that high-resolution antenatal structural imaging, determination of maternal and fetal blood flow parameters and 3D and 4D ultrasound, are part of routine practice. This has resulted in changes in the way antenatal and obstetric care is now delivered. For example, antenatal and obstetric management of pregnancies complicated by intrauterine growth restriction (IUGR) and pre-eclamptic toxaemia (PET) is now dependent on several sonographic techniques including Doppler indices of the umbilical cord and maternal uterine arteries, hence ultrasound findings have become an increasingly common indication for placental pathological examination. The quality of specialist surgical pathology reports is related to pathologist expertise and, regarding the placenta, it has been reported that about 40% of placental diagnoses made by non-specialist pathologists were incorrect on specialist review, 90% being errors due to unrecognised lesions and 10% erroneous diagnoses,1 many of these differences possibly being related to pathologist unfamiliarity with current obstetric technologies. This review aims to provide an overview of relevant obstetric ultrasound techniques and their clinical relevance to the diagnostic pathologist, primarily focussing on conditions with specific placental implications. There are several detailed texts regarding histological findings and their implications of placental pathological lesions,2-4 and therefore this review will specifically discuss the pathological correlates of sonographic findings, with details of the specific histological entities being found elsewhere. The aim of pathological examination of the placenta is to determine the pathological basis for the clinical findings and advance understanding of the pathophysiology of pregnancy complications.

Microsatellite analysis is an important tool in clinical research and molecular diagnostics, because microsatellite instability (MSI) occurs frequently in various types of cancer. Approximately 10-15% of colorectal, gastric or endometrial carcinomas are associated with MSI, which has an impact on clinical prognosis.

The microsatellite loci Bat25, Bat26, D2S123, D5S346, and D17S250, recommended by the Bethesda guidelines, were analysed by microfluidic-based on-chip electrophoresis in 40 cases of colon carcinoma with known MSI status. In all cases, microfluidic separation of the PCR amplicons resulted in highly resolved, distinct patterns of each of the five microsatellite loci. Detection of MSI could be demonstrated by microsatellite loci-associated, well-defined deviations in the electropherogram profiles of tumour and non-tumour material and confirmed the classification of MSI cases performed by conventional technology.

In conclusion, microfluidic chip technology is a simple and reliable approach for MSI detection, which allows label-free and very fast analysis of microsatellite amplicons.

Background: The relationship between tumefactive lesions classified as sclerosing mesenteritis and IgG4-related sclerosing disorders (e.g. lymphoplasmacytic sclerosing pancreatitis/autoimmune pancreatitis) remains uncertain.

Aims: In this study, lesions coded as "sclerosing mesenteritis" were reviewed for findings in keeping with IgG4-related sclerosing disorders.

Methods: Inclusion in the study required available paraffin blocks for IgG4 staining and documentation of a mass lesion.

Results: A total of nine mesenteric lesions ranging from 3-14 cm were identified in 6 male and 3 female patients. On hematoxylin and eosin-stained sections, all were characterized as loosely marginated fibroinflammatory processes with variable amounts of fat necrosis. Lymphocytic venulitis/phlebitis was identified in 8 of 9 cases. IgG and IgG4 expression in lesional plasma cells was assessed by immunohistochemistry (IHC). IgG4-positive plasma cells were counted in the areas of greatest density in ³ 3 high power fields (HPFs). The highest number per HPF was recorded and a score assigned based on the following scale: <5/HPF- none/minimal; 5-10/HPF-mild; 11-30/HPF- moderate; >30/HPF- marked. The relative proportion of IgG4-reactive plasma cells to total IgG-positive plasma cells was assessed. IgG4-reactive plasma cells ranged from 0 to >100 in the most dense zones (3 cases- none/minimal, 4 cases- moderate, 2 cases- marked).

Conclusions: Although this study is limited by small numbers, our findings suggest that some tumefactive lesions regarded as sclerosing mesenteritis may be a subset of IgG4-related sclerosing disorders.

Aim: The clinical and biological significance of syncytial giant cell change of hepatocytes in hepatitis C (HCV) infection is poorly understood. We investigated the clinical and histological correlates of giant cell transformation in the setting of HCV mono-infection and co-infection with HCV and human immunodeficiency virus (HIV).

Methods: The prevalence of hepatocyte giant cell transformation was determined and serological, biochemical and histological findings were examined.

Results: Amongst 856 liver biopsies, 22 cases (2.6%) showed giant cell transformation, representing 18 individuals. The median serum ALT was 37 IU, AST 49 IU, and alkaline phosphatase 97 IU. Eleven cases had HCV RNA loads available, with a median HCV RNA of 5.52 log IU/mL. Twelve of 17 individuals with available test results were also HIV positive (71%), compared to 46% of controls, p= 0.08. Giant cell transformation was found exclusively in zone 3 hepatocytes and the accompanying histological findings were otherwise typical of chronic HCV. The hepatic giant cells typically had a cytoplasmic appearance that resembled smooth endoplasmic reticulum proliferation. Most cases had only mild inflammation and fibrosis, with a median MHAI grade of 3/18 and a median MHAI stage of 1/6. Three individuals had follow-up biopsies and all continued to have giant cell change.

Conclusion: In conclusion, giant cell transformation occurs most commonly in the setting of HCV/HIV co-infection, but can also be seen in chronic HCV infection alone. Histologically, giant cells were located in zone 3 hepatocytes, were persistent over time, and do not appear to be a marker of aggressive hepatitis.

Hereditary breast cancer accounts for up to 5-10% of all breast carcinomas. Recent studies have demonstrated that mutations in two high penetrance genes, namely BRCA1 and BRCA2, are responsible for about 16% of the familial risk of breast cancer. Even though subsequent studies have failed to find another high-penetrance breast cancer susceptibility gene, several genes that confer moderate to low risk of breast cancer development have been identified; moreover, hereditary breast cancer can be part of multiple cancer syndromes. In this review we will focus on the hereditary breast carcinomas caused by mutations in BRCA1, BRCA2, Fanconi Anaemia (FANC) genes, CHK2 and ATM tumour suppressor genes. We describe the hallmark histological features of these carcinomas compared with non-hereditary breast cancers and show how an accurate histopathological diagnosis may help improve the identification of patients to be screened for mutations. Finally, novel therapeutic approaches to treat patients with BRCA1 and BRCA2 germline mutations, including cross-linking agents and PARP inhibitors, are discussed.

Aims: BRCA1-related breast cancer is associated with a basal-like phenotype, and is frequently estrogen receptor and HER2-negative. The expression of EGFR has been considered to be one component of the basal-like phenotype, but no standard criteria exist. We have studied the relationship between EGFR expression, BRCA1 status and basal markers with respect to clinico-pathological associations and prognosis, in addition to an evaluation of different criteria for EGFR assessment by immunohistochemistry.

Methods: A tissue microarray comprising 230 available cases from our series of primary invasive breast cancer diagnosed in Ashkenazi Jewish women during 1980-1995, was stained for EGFR using the Dako PharmDX kit, and evaluated by Webslide virtual microscopy.

Results: EGFR was positive in 9-19% according to different criteria. Expression was associated with BRCA1 carrier status and basal-like markers as negative ER, positive CK 5/6 and positive P-cadherin staining. EGFR was prognostically significant by univariate and multivariate analysis within the group carrying germ-line BRCA1 mutations. Histological grade, axillary lymph node status and P-cadherin status had significant independent value in the final multivariate model including all cases, whereas EGFR was not significant in this model. All five scoring systems gave comparable results concerning clinico-pathological associations and patient outcome, although the most restrictive criteria (EGFR-HI) tended to be most sensitive in predicting BRCA1-status, a basal phenotype, and patient prognosis.

Conclusions: EGFR expression, being present in 9-19% of the cases, was prognostically significant among BRCA1 mutated cases only. In multivariate survival analysis of all cases, no independent effect was seen. Still, EGFR immunostaining might be relevant to predict the response to targeted therapy, and this should be studied further.

MYCN is the most commonly amplified gene in human neuroblastomas. This proto-oncogene has been overexpressed in a mouse model of the disease in order to explore the role of MYCN in this tumour.

Aims: To report the histopathological features of neuroblastomas from MYCN transgenic mice.

Methods: 27 neuroblastomas from hemizygous transgenic mice and 4 tumours from homozygous mice were examined histologically, and Ki67 and MYCN immunocytochemistry performed in 24 tumours.

Results: Tumours obtained from MYCN transgenic mice resembled human neuroblastomas, displaying many of the features associated with stroma-poor neuroblastoma including heterogeneity of differentiation (but no overt ganglionic differentiation was seen), low levels of Schwannian stroma and a high mitosis karyorrhexis index. The tumours had a median Ki67 labelling index of 70% and all tumours expressed MYCN with a median labelling index of 68%. The most striking difference between the murine and human neuroblastomas was the presence of tingible body macrophages in the transgenic mouse tumours reflecting high levels of apoptosis. To our knowledge this has not previously been described in human or other murine neuroblastoma models.

Conclusions: These studies highlight the histological similarities between tumours from MYCN transgenic mice and human neuroblastomas, and reaffirm their role as a valuable model to study the biology of aggressive human neuroblastoma.

Aims: To analyse the distribution of Nestin expression in different breast tumours and to determine the prognostic impact of Nestin expression.

Methods: Nestin expression was immunohistochemically analysed in a cohort of 245 invasive breast cancer patients treated with therapeutic surgery followed by anthracycline-based chemotherapy using a semi-quantitative scoring system.

Results: Nestin was exclusively expressed in grade III breast carcinoma and preferentially expressed in basal-like and triple negative cancers. Nestin-positive tumours displayed high proliferation rates and p53 nuclear expression. Lymph-node positive patients with Nestin-positive cancers had a shorter breast cancer specific survival; however Nestin was not an independent prognostic factor on multivariate analysis.

Conclusions: Nestin expression is preferentially found in basal-like and triple negative breast carcinomas. Further studies are warranted to define the biological role played by Nestin in these subgroups of breast cancers.

Disseminated Cryptococcosis is an uncommon occurrence in immunocompetent populations and occurs mainly in immunocompromised patients. We describe the first reported case of Cryptococcus meningitis and skin lesions in a 4 year old confirmed HIV negative boy who presented with fever, meningism and skin lesions. On examination he was confused, uncooperative, had neck stiffness and raised skin lesions. A septic screen, including skin scraping, was performed and he was on an empiric stat dose of Penicillin and Ceftriaxone for suspected meningococcal meningitis. The cerebrospinal fluid revealed normal protein, glucose and chloride levels; yeasts were observed on Gram stain from the CSF and skin scraping. The India ink stain and Cryptococcus neoformans latex agglutination test on the CSF were both positive. Bacterial culture of the skin biopsy, CSF and blood culture specimens was negative. He was treated with Amphotericin B based on preliminary results and had a gradual, recovery with no neurological sequelae. He continued oral Fluconazole.

Background: Endoscopy and biopsy are used to diagnose celiac disease. There are however, observer dependent interpretations of the degree of villous atrophy in biopsies. We performed a pilot study using quantitative image processing procedures to quantify the degree of villous atrophy in patients with celiac disease.

Method: The degree of villous atrophy in duodenal biopsy images was quantified by calculating the ratio of villous edge to piecewise arc length (E/P ratio) and this value was compared to the blinded assessment of Marsh score for degree of villous atrophy.

Results: Mean E/P ratios for N=32 biopsy images: 2.76±0.44 (Marsh IIIa), 1.91±0.50 (Marsh IIIb) and 1.18±0.22 (Marsh IIIc) were significantly different (p=0.006). Based on nonparametric tests, E/P ratios were inversely correlated with the Marsh scores (Spearman’s coefficient = ­0.798, Kendall’s = -0.681; p<0.0001).

Conclusions: Biopsy images quantified by image analysis correlated exceedingly well with the histopathologic grade of villous atrophy. Since quantified measurements are real-numbered values and lack observer bias, measurement of villous atrophy based on image analysis lends itself to standardization of histologic grading.

Mucins are high molecular weight glycoproteins with complex oligosaccharide side-chains attached to the apomucin protein backbone by O-glycosidic linkage, found both in crude mucus gels that protect epithelial surfaces in the major tracts of the body and as trans- membrane proteins expressed on the apical cell surface of glandular and ductal epithelia of various organs. Changes in the sequence of glycosylation of mucins in different settings generate a variety of epitopes in the oligosaccharide side-chains of mucins, including newly expressed blood-group antigens, distinguishing between normal and diseased states. Tumour-associated epitopes on mucins and their antigenicity make them suitable as immuno-targets on malignant epithelial cells and their secretions, creating a surge of interest in mucins as diagnostic and prognostic markers for various diseases, and even influencing the design of mucin-based vaccines. In this review, I discuss the emerging roles of mucins such as MUC1 and MUC4 in cancer and some other diseases and stress how under-glycosylated and truncated mucins are exploited, both as markers of disease and to monitor widespread metastasis, making them useful in patient management. Furthermore the type, pattern and amount of mucin secreted in some tissues have been considered in the classification and terminology of neoplasia and in specific organs such as the pancreas. These factors have been instrumental in pathologic classification, diagnosis and prognostication of neoplasia.

The incidence of placenta accreta, defined as the abnormal adherence of the placenta to the uterine wall, has been increasing alarmingly in the developed as well as the developing world. There is considerable maternal morbidity and mortality related to the condition. The pathophysiology focusses on the balance between decidualisation on the one hand and trophoblast invasion on the other. Pathological diagnosis relies on the finding of placental villi in direct apposition to myometrium, either in hysterectomy specimens or in placental basal plates.

Background: There is an increasing necessity to extract the maximum amount of information, beyond even a cancer diagnosis, from prostate biopsies. Thus, maintaining site-specific information regarding individual biopsy cores might be critical.

Aim: To evaluate the applicability of employing tissue ink to maintain the identity of individual prostatic biopsy cores.

Method: In this ongoing study, 12 core prostate biopsy specimens are sent to the laboratory in individual pots labelled according to anatomical site. The biopsies are placed in two separate multi-compartment cassettes. They are inked with different colours to identify the site of origin from each lobe. The cassettes are then processed with a single paraffin block for each side and the six cores from each side can be mounted on a single slide.

Results: The different colours used adhere well to the biopsy cores, thus maintaining the identity of each core. Six cores from each side are embedded in a single paraffin block and examined on a single slide, making it cost-effective, while maintaining high quality, accurate histopathological information.

Conclusion: Differential inking of prostate biopsy cores is an easily applicable method that is cost-effective and provides tumour location information. Prostate biopsy data archived to maintain individual core information might be used to determine applicability of such information to determine extra-capsular extension by correlating with imaging and radical prostatectomy findings, and for treatment planning.

Placental examination in obstetric cases complicated by maternal or fetal disorders can provide insight into chronicity and etiology. This review considers two common complications of pregnancy, pre-eclampsia toxemia and intrauterine growth restriction and describes the placental pathologic features often present.

We report a case where displaced non-neoplastic ovarian granulosa cells within the fallopian tube mimicked a small cell carcinoma. This peculiar phenomenon of displaced granulosa cells has been described previously in the ovary as a rare diagnostic pitfall which may be misinterpreted as metastatic carcinoma. To the best of our knowledge, this is the first documentation of its occurrence in the fallopian tube. Awareness of this rare phenomenon and immunostaining for markers of sex cord differentiation assist in diagnosis and in preventing a false positive diagnosis of malignancy.

Aims: Two different forms of vulvar intraepithelial neoplasia (VIN) are recognized: usual type (bowenoid) VIN which is related to high-risk papillomavirus infection, and differentiated (simplex) VIN which is associated with chronic inflammation. In this study, we aimed to examine the presence of chromosome 3q26 gains in the spectrum of precancerous lesions and invasive squamous carcinomas of the vulva.

Methods: 3q26 gains were analysed using fluorescence in situ hybridisation (FISH) in a series of usual type VINs, VINs of the differentiated type and invasive squamous cell carcinomas. In addition, all cases were examined for HPV-DNA, p53 mutations as well as p16 and p53 protein expression.

Results: Gains of chromosome 3q26 were present in all VIN of the differentiated type and in 50% of the usual type VIN lesions. 81% of SCC were positive for 3q26 gains irrespective of the HPV status and of the associated precursor lesion. HPV-associated lesions exhibited the typical, strong cytoplasmic p16 accumulation while mutated p53 was only detected in HPV-negative VINs or SCCs and was associated with an overexpression of p53 protein.

Conclusions: Immunohistochemical evaluation of p16 and p53 expression aids in the differential diagnosis of squamous cell alterations of the vulva. However, detection of 3q26 imbalances is of additional diagnostic value in difficult cases of HPV-unrelated usual type VINs and VINs of the differentiated type.

Aim: To determine if human papilloma viruses (HPVs) play a role in the histogenesis of adenosarcomas of the uterine cervix.

Methods: Nine archival cases of primary cervical adenosarcoma were studied. The HPV status of the 9 histologically proven tumours was investigated by non-isotopic in situ hybridisation (NISH) and the polymerase chain reaction (PCR). NISH was performed using digoxigenin labelled probes to HPV types 6, 11, 16, 18, 31 and 33. PCR employed GP5+/GP6+ primers to the HPV L1 gene.

Results: Neither the benign epithelial components nor the malignant stromal components of the 9 neoplasms harboured nuclear NISH signals for the HPV types investigated. Amplimers of the HPV L1 gene were not detected by PCR in any of the tumours studied.

Conclusion: HPVs do not appear to play an aetiological role in cervical adenosarcomas. This suggests that a different histogenetic pathway for this rare tumour type must exist.

Abstract We experienced a patient of Legionella pneumophila pneumonia with rhabdomyolysis-induced acute tubulointerstitial nephritis (ATIN) and prolonged renal dysfunction. The case was a 54-year-old man, admitted to our hospital for high-grade fever, ataxia and muscle dysfunction and his chest roentgenogram showed multilobular infiltrations. As L. pneumoniae was detected in his sputum and urine, either by the PCR as well as by culture,he was diagnosed as L. pneumophila pneumonia. Despite the anitmicrobial therapy to Legionella, he further developed renal failure and rhabdomyolysis. The renal biopsy revealed ATIN, by showing the presence of myoglobin casts that occluded the distal tubuli and tubulointerstitial nephritis, leading to the diagnosis of rhabdomyolysis-induced ATIN. Later, the renal function was improved into the normal range, after he discharged on foot. To our knowledge, this is the first pathological evidence that confirmed the involvement of rhabdomyolysis in legionellosis-associated ATIN.

Aims: The objective of this study is to determine the incidence of PSA relapse in patients with low volume prostate cancer following radical prostatectomy.

Methods: Between 1993 and 2001, 50 of 717 patients had total tumor volumes of less than 0.5 cc following radical prostatectomy. Biochemical recurrence was defined as two consecutive values of serum PSA levels of 0.2 ng/mL or greater.

Results: Median follow-up of the 50 patients was 58 months. In five of the 50 patients (10%), PSA recurrence was observed. All of these five cases had Gleason score of 3+3 (well and /or moderately differentiated), organ confined and surgical margin negative tumors. In three of the five cases, capsular incision resulted in benign glands extending into the surgical margin.

Conclusions: Five of 50 cases had PSA failure. In three of the five patients, benign glands located in the margin could explain the "PSA recurrence". However, in the other two patients, none of the pathological parameters correlated with measurable PSA levels. The explanation for their PSA failure is unclear.

NUT midline carcinoma (NMC) is a rare, highly lethal cancer that occurs in children and adults of all ages. NMCs uniformly present in the midline, most commonly in the head, neck, or mediastinum, as poorly differentiated carcinomas with variable degrees of squamous differentiation. This tumor is defined by rearrangement of the Nuclear protein in testis (NUT) gene on chromosome 15q14. In most cases, NUT is involved in a balanced translocation with the BRD4 gene on chromosome 19p13.1, an event that creates a BRD4-NUT fusion gene. Variant rearrangements, some involving the BRD3 gene, occur in the remaining cases. NMC is diagnosed by detection of NUT rearrangement by fluorescence in situ hybridization or RT-PCR. Due its rarity and lack of characteristic histologic features, most cases of NMC currently go unrecognized.

There are approximately 30 serum complement proteins (15% of the globulin fraction), excluding cell surface receptors, and regulatory proteins. Many are manufactured in the liver, and reduced complement is a feature of severe liver failure. Complement proteins contribute to the acute phase response, and high levels are seen in chronic untreated inflammation (e.g. rheumatoid arthritis). Once activated, complement is strongly pro-inflammatory. Indeed, almost half of the complement system proteins / receptors play regulatory roles, reflecting the importance of controlling inappropriate activation. This review focuses on disease states arising as a direct consequence of complement deficiency or dysfunction.

Brucella spp. is an uncommon class 3 pathogen isolated in laboratories serving nonendemic areas. We report four recent cases of brucellosis diagnosed at five different London laboratories which highlights the need to maintain a high index of suspicion for brucellosis in patients with a history of travel to and/or consumption of unpasteurised foods from endemic areas. We propose a protocol for risk categorisation, and describe the strategy adopted for serological follow-up of exposed staff and use of postexposure prophylaxis.

Background: Loss of control of mucosal crypt cell proliferation resulting in a hyperproliferative field change occurs early in the adenoma-carcinoma sequence. Ki-67, the current gold-standard marker of cellular proliferation, is a cell cycle protein that may lack sensitivity in demonstrating altered mucosal crypt cell dynamics. Minichromosome maintenance protein 2 (MCM2) has a specific role in DNA replication and has been proposed as a new marker for screening for colorectal cancer. Aim: To compare the expression of Ki-67 with MCM2 in colorectal mucosa associated with colorectal cancer. Methods: Ki-67 and MCM2 immunostaining was performed on serial sections taken from formalin-fixed, paraffin-embedded specimens. Labelling indices (LI’s) were calculated by counting the proportion of positively stained nuclei in representative areas of adenocarcinoma, and in equivalent superficial, middle, and basal crypt compartments of mucosa sampled 1cm from the tumour (Ca1) and 10cm from the tumour (Ca10). Results: Specimens were obtained from 43 patients. Most nuclei in specimens of adenocarcinoma stained positively for MCM2 and Ki-67. In Ca1 and Ca10 samples significantly greater staining was seen in all crypt compartments with MCM2 compared with Ki-67. Receiver operator characteristic curve analysis suggested that proliferation changes (assessed either by MCM2 or by Ki-67) in Ca10 but not Ca1 mucosa significantly predicted for origin from a carcinoma-associated colon. Conclusions: MCM2 was more sensitive than Ki-67 in identifying colorectal mucosal proliferation. Increased proliferation (assessed either by MCM2 or Ki-67) in mucosa at 10 cm but not at 1 cm from the carcinoma, significantly predicted for origin from a carcinoma-associated colon.

A previously healthy male with subacute onset right leg weakness is suspected to have an astrocytoma after a lesion is demonstrated via imaging. However a subsequent biopsy demonstrated the presence of foamy macrophages containing periodic acid-Schiff staining granules, suggesting Whipple’s disease as a possible diagnosis. We here present the case and the report on the patient’s current clinical status.

This review will focus on patients with genetic defects predisposing to infections with poorly pathogenic mycobacteria [Bacillus Calmette-Guerin and environmental Non-Tuberculous Mycobacteria (NTM)] as well as Salmonella species. Mycobacteria and Salmonella are facultative intracellular pathogens capable of surviving and multiplying within mononuclear phagocytes. Host defense against these pathogens depends on the action of cell-mediated immunity (CMI), effected by interactions between T cells and macrophages. The principal effector mechanism responsible immunity against these pathogens is the activation of infected macrophages by type 1 cytokines, particularly interferon- (IFN-) and Tumor necrosis factor alpha (TNF-)[1].

Result of the immunohistochemical reactions routinely used in diagnostic surgical pathology should be properly interpreted, since false results, related to technical and interpretative pitfalls may lead to incorrect diagnosis. We review of the main sources of such pitfalls, analytically described and related to different steps (fixation, tissue processing and embedding, decalcification, antigen retrieval) which may affect the accuracy of immunohistochemistry. In addition, presence of endogenous enzyme activity, improper binding of avidin to endogenous biotin, incorrect use of antibodies, chromogen and detection system, as well as incorrect interpretation may produce unreliable data. The high frequency and extension of such pitfalls make mandatory the use of internal and external controls and adoption of cross-validation programs. The present study, supported by an extensive review of the related literature is intended as a guideline leading to proper interpretation of immunohistochemical data, an essential component of the diagnostic process. Our experience on the antigen retrieval procedures for different antigens is also presented.

We present a broad overview, with examples, of the potential pitfalls encountered in the clinical immunology laboratory. Illustrative examples and cases are provided from autoimmunity, immunochemistry and cellular immunology, looking both at technical and interpretative pitfalls.

Background: In the United States, the lack of processes standardization in histopathology laboratories leads to less than optimal quality, errors, inefficiency, and increased costs. The effectiveness of large scale quality improvement initiatives rarely has been evaluated.

Aim: To measure the effect of implementation of a Lean quality improvement process on the efficiency and quality of a histopathology laboratory section.

Methods: We performed a non-concurrent interventional cohort study from January 1, 2003 to December 31, 2006 and implemented the Lean process on January 1, 2004. We also compared the productivity of the Lean histopathology section to a sister histopathology section that did not implement Lean processes. We measured pre- and post-Lean specimen turn-around time and productivity ratios (work units/full time equivalents). For 200 Lean interventions, we used a 5-part Likert scale to assess the impact on error, success, and complexity.

Results: In the Lean laboratory, the mean monthly productivity ratio increased from 3,439 and 4,074 work units/full time equivalents (P < 0.001) as the mean daily histopathology section specimen turn-around time decreased from 9.7 to 9.0 hours (P = 0.01). The Lean histopathology section had a higher productivity ratio compared to a sister histopathology section (1,598 work units/full time equivalents, P < 0.001) that did not implement Lean processes. The mean impact, success, and complexity of interventions were 2.4, 2.7, and 2.5, respectively. The mean number of specific error causes affected by individual interventions was 2.6.

Conclusion: We conclude that Lean process implementation improved histopathology section efficiency and quality.

This third best practice review examines four series of common primary care questions in laboratory medicine: (i) 'minor' blood platelet count and haemoglobin abnormalities, (ii) diagnosis and monitoring of iron deficiency anaemia , (iii) secondary hyperlipidaemia and hypertriglyceridaemia and (iv) HbA1c and microalbumin use in diabetes. The review is presented in question-answer format, referenced for each question series. The recommendations represent a précis of guidance found using a standardised literature search of national and international guidance notes, consensus statements, health policy documents and evidence-based medicine reviews, supplemented by MEDLINE EMBASE searches to identify relevant primary research documents. They are not standards but form a guide to be set in the clinical context. Most are consensus rather than evidence-based. They will be updated periodically to take account of new information.