Neoadjuvant chemoradiation therapy (CRT) is an increasingly used therapeutic strategy for rectal cancer. Clinically, it remains a major challenge to predict therapeutic response and patient outcome after CRT. Rsf-1 (HBXAP), a novel nuclear protein with histone chaperon function, mediates ATPase-dependent chromatin remodelling and confers tumour aggressiveness and predicts therapeutic response in certain carcinomas. However, the expression of Rsf-1 has never been reported in rectal cancer. This study examined the predictive and prognostic impacts of Rsf-1 expression in patients with rectal cancer following neoadjuvant CRT.
Rsf-1 immunoexpression was retrospectively assessed for pre-treatment biopsies of 172 rectal cancer patients without initial distant metastasis. All of them were treated with neoadjuvant CRT followed by surgery. The results were correlated with the clinicopathological features, therapeutic response, tumour regression grade and metastasis-free survival (MeFS), local recurrent-free survival and disease-specific survival.
Present in 82 cases (47.7%), high-expression of Rsf-1 was associated with advanced pre-treatment tumour status (T3, T4, p=0.020), advanced post-treatment tumour status (T3, T4, p<0.001) and inferior tumour regression grade (p=0.028). Of note, high-expression of Rsf-1 emerged as an adverse prognosticator for diseases-specific survival (p=0.0092) and significantly predicted worse MeFS (p=0.0006). Moreover, high-expression of Rsf-1 also remained prognostic independent for worse MeFS (HR 2.834; p=0.0214).
High-expression of Rsf-1 is associated with poor therapeutic response and adverse outcome in rectal cancer patients treated with neoadjuvant CRT, which confers tumour aggressiveness and therapeutic resistance through chromatin remodelling and represents a potential prognostic biomarker in rectal cancer.
To increase the diagnostic yield in pulmonary diseases, histopathology, imprint cytology and brushing cytology are assessed in combination during flexible bronchoscopy. However, the individual diagnostic discrimination of the three methods is unclear.
The authors performed the three sampling techniques in 102 consecutive patients with suspected pulmonary pathologies and compared the definitive diagnosis with those of histopathology, imprint and brushing cytology for their diagnostic values regarding evidence of malignancy.
33.3% of all histopathological specimens, 31.4% of all imprints and 26.5% of brush biopsy specimens were positive for malignancy. The values for sensitivities were 94% for histopathology, 89% for imprint cytology and 75% for brushing cytology, respectively. Although brushing cytology had limited sensitivity, in two cases a malignant lung tumour was only diagnosed from cytological examination of brushing.
In conclusion, routine imprint cytology does not increase the diagnostic sensitivity, whereas routine brushing cytology should be used in combination with histopathology to obtain the highest diagnostic rate of yield.
To study the HER2 gene amplification or overexpression in patients with advanced gastric cancer (GC) and their association with patient characteristics and patient survival.
Tumour tissue samples from 148 patients with advanced GC were studied for HER2 by immunohistochemistry (IHC), fluorescence in situ hybridisation (FISH) and dual colour silver enhanced in situ hybridisation (dc-SISH) methods. Clinicopathological data from all patients were collected. Progression free survival and overall survival were also analysed.
Mean age was 67 (33–83) years; 75% were male subjects, and 51% had intestinal histological type. HER2+ rates were 10.1% (15/148) by IHC, 18.2% (27/148) by FISH+ or 21.6% (32/148) by dc-SISH+. There were significant differences in HER2+ rates according to histological type when FISH (intestinal, 23%; no intestinal, 4%; p<0.0001) or dc-SISH (intestinal, 26%; no intestinal, 6%; p<0.0001) amplification techniques were used. Median overall survival was significantly longer in HER2+ patients despite the determination technique used: IHC (21.4 vs 9.8 months, HR 0.42; p=0.005); FISH (19.6 vs 9.7 months, HR 0.49; p=0.007) or dc-SISH (19.6 vs 9.7 months, HR 0.53; p=0.009). Factors associated with favourable survival in the multivariate analysis were intestinal type and Her2+ determination by IHC, FISH or dc-SISH.
HER2 gene amplification is significantly associated with patient survival. HER2 gene amplification approaches might be an optimal HER2/neu testing strategy for the selection of HER2+ GC patients who are candidates to be treated with anti-HER2 therapies.
Clinical data were obtained from 39 patients with primary MPM between 1997 and 2009. The...]]>
The pathogenesis of thyroid-associated orbitopathy (TAO) remains unclear. The aim of this study is to elucidate the gene expression profile of orbital fat from patients with active, but untreated, TAO.
A case–control gene expression study was conducted using test samples of orbital fat from TAO patients and control orbital fat specimens; apart from drugs to control thyrotoxicosis, the TAO patients had received no treatment for orbital disease. cDNA expression analysis was performed using the Affymetrix GeneChip Human Genome U133 Plus 2.0 platform and validated using quantitative PCR.
The highest-ranked differentially expressed genes were dominated by IGF-1 signalling genes. These include IGF-1, IGF-1 receptor binding/signalling genes, such as SOCS3 and IRS2, and downstream signalling and transcriptional regulators, such as SGK (PDK/Akt signalling) and c-JUN. Our microarray data also demonstrate dysregulation of wingless-type MMTV (Wnt) signalling gene expression, including Wnt5a, sFRPs and DKK.
Altered Wnt signalling confirms previous array findings. Further investigation of the role of Wnt signalling in TAO pathogenesis is warranted. These data also provide the first evidence of dysregulation of IGF-1 pathway genes in TAO tissue, further strengthening the evidence for the role of IGF-1 signalling in the pathogenesis and potential treatment of TAO.
Complex or composite adnexal tumours of the skin (CATS) are unusual neoplasms composed of two or more histopathologically distinct subtypes of appendageal neoplasms coexisting in a single cutaneous lesion. The authors report three examples of CATS, review literature and discuss their probable histogenesis.
Of the three tumours described, one tumour showed a mixture of a proliferating pilar tumour and syringocystadenoma papilliferum, the second lesion was composed of a proliferating pilar tumour and tubulopapillary hidradenoma and the third tumour exhibited a syringocystadenoma papilliferum and tubulopapillary hidradenoma in combination.
CATS are rare tumours. The authors reported three unique cases in addition to the 10 other reported cases. These three cases further strengthen the hypothesis of a ‘folliculosebaceous apocrine’ unit as the most likely point of origin of CATS.
In this study, the authors investigated a panel of invasion-associated markers in a series of EPC and compared their expression with control groups of non-papillary ductal carcinoma in situ (DCIS) and conventional invasive carcinomas. The expression pattern of four matrix metalloproteinases (MMP-1, MMP-2, MMP-7 and MMP-9), transforming growth factor receptor beta, vascular endothelial growth factor (VEGF) and E-cadherin were assessed in the tumour cell and/or stromal tissue, and the results were analysed.
EPC showed higher expression levels of both MMP-1 and MMP-9 compared with DCIS, and no significant differences were observed between EPC and invasive carcinoma. Expression of MMP-2 and MMP-7 levels were similar in EPC and DCIS, but both showed lower levels compared with invasive tumours. EPC showed higher expression of E-cadherin and transforming growth factor receptor ß1 compared with both DCIS and invasive cancer. No difference in the stromal expression of MMPs or tumour expression of VEGF was detected.
EPC exhibits an expression pattern of invasion-associated markers, which is intermediate in nature between DCIS and invasive cancer, providing further support of the unique biological features of EPC, and which may explain its clinically indolent behaviour.
The indicated patient was referred to our hospital with the suspicion of constrictive pericarditis. His medical history reported pericardial calcifications of unknown aetiology. Furthermore, there was a suspicion of asbestos exposure in occupational setting. Cardiac...]]>
The class III histone deacetylase SIRT1 is a nicotinamide adenine dinucleotide (NAD+)-dependent deacetylase, and has been reported to serve diverse roles in various biological processes, such as caloric restriction, apoptosis, neuronal protection, cell growth, differentiation and tumourigenesis. With respect to tumourigenesis, there have been conflicting data supporting whether SIRT1 act as a tumour promoter or as a tumour suppressor.
SIRT1 protein expression, determined by immunohistochemistry, was investigated in human normal colonic mucosa, adenoma, adenocarcinoma and metastatic tissue samples.
All normal colonic mucosa showed SIRT1 expression with no exception, and 42 (80.8%) of 52 adenomatous polyps were positive for SIRT1. However, only 208 (41.9%) of 497 colorectal adenocarcinomas were positive. Moreover, 45 (35.7%) of 126 metastatic tissues were positive. Collectively, the SIRT1 expression was gradually decreased during carcinogenesis and tumour progression. The associations between SIRT1 expression and clinicopathological parameters revealed that loss of SIRT1 expression was associated with proximal tumour location, mucinous histology and defective mismatch repair protein expression. This suggests that loss of SIRT1 expression is associated with the microsatellite instability phenotype of colorectal adenocarcinoma. In survival analyses, the loss of SIRT1 expression was significantly associated with overall survival (p=0.027, log-rank test) in univariable analysis, but multivariable analysis failed to achieve significance.
SIRT1 expression was gradually decreased during the normal–adenoma–adenocarcinoma–metastasis sequence, suggesting a possible role of SIRT1 in tumour suppression in the colorectum, and a probable link to the microsatellite instability pathway.
The developmental mechanisms of breast neuroendocrine carcinoma (B-NEC) have not been sufficiently analysed and are not well understood.
To investigate NE cells in the background tissues surrounding B-NECs.
Three cases (four breasts) having many NE cells in the background tissues of multifocal B-NECs were identified at the University of Yamanashi Hospital and St Luke's International Hospital, Japan. These patients were, respectively, 28-, 31- and 38-year-old women with no familial history of NE tumour. The totally-resected breasts were serially studied by immunohistochemistry for specific NE markers (chromogranin A/synaptophysin) and the morphologies and/or localisation of NE cells were investigated.
Immunohistochemical examination showed extensively-distributed NE cells in the background mammary ducts/lobules of the NECs in all breasts. These NE cells were classifiable into three emerging patterns: isolated/scattered, clustered and circumferential. Their distributions were intermingled and were not clearly related to B-NEC foci. NE cells were morphologically polygonal, oval or columnar with sometimes eosinophilic and/or fine-granular cytoplasm and round-to-ovoid nuclei lacking atypia. Some cells were located between epithelial and myoepithelial cells. Apical snouts were occasionally observed in NE cells forming luminal structures.
Benign-appearing NE cells in the parenchyma of a breast with NEC could be regarded as hyperplastic from their emerging patterns and distribution; this NE cell hyperplasia may be associated with the histogenesis of B-NEC as a precancerous condition. These observations might raise questions about the treatment for B-NEC.
To systematically compare different approaches for evaluating mucosal proliferative activity regarding their diagnostic role for delineating flat lesions of the bladder mucosa.
32 carcinoma in situ (CIS) and 31 flat non-CIS conditions (low-grade dysplasia and reactive atypia) of the bladder mucosa were assessed by two independent pathologists in two rounds in terms of their proliferative activity assessed by the mitotic counts on H&E-stained sections (mitoses per mm2) and immunohistochemically using the MIB-1 antibody and the mitosis marker phosphohistone H3 (PHH3). Two different approaches for immunoscoring (percentage of stained nuclei vs dichotomised height of mucosal staining considering lower half vs full-thickness marker expression) were applied. statistics were used to evaluate interobserver and intraobserver reproducibility.
Scoring the percentage of Ki67 expressing cell nuclei seems to be superior to dichotomisation of the height of mucosal staining as well as to PHH3 immunostaining and conventional mitotic counts in terms of delineating CIS from flat non-CIS conditions. This approach shows substantial (=0.62–0.65; p<0.001) interobserver and substantial to almost perfect (=0.67–0.83; p<0.001) intraobserver reproducibility.
The MIB-1 antibody is a useful adjunct in the differential diagnosis of conventionally challenging flat lesions of the bladder mucosa. In particular, 16% or more Ki67 positive cell nuclei favours CIS over flat non-CIS conditions, whereas 15% or less Ki67 positive cell nuclei is supportive of non-CIS conditions. However, due to some important limitations of MIB-1 staining, the MIB-1 antibody should be used as a component of a panel.
Gilbert syndrome is an inherited disease characterised by mild unconjugated hyperbilirubinaemia caused by mutations in UGT1A1 gene which lead to decreased activity of UDP-glucuronosyltransferase 1A1. The most frequent genetic defect is a homozygous TA dinucleotide insertion in the regulatory TATA box in the UGT1A1 gene promoter.
182 Polish healthy individuals and 256 patients with different types of hereditary haemolytic anaemias were examined for the A(TA)nTAA motif. PCR was performed using sense primer labelled by 6-Fam and capillary electrophoresis was carried out in an ABI 3730 DNA analyser. The frequency of the (TA)7/(TA)7 genotype in the control group was estimated at 18.13%, (TA)6/(TA)7 at 45.05% and (TA)6/(TA)6 at 36.26%. There was a statistically significant difference in the (TA)6/(TA)6 genotype distribution between healthy individuals and patients with glucose-6-phosphate dehydrogenase deficiency (p=0.041). Additionally, uncommon genotypes, (TA)5/(TA)6, (TA)5/(TA)7 and (TA)7/(TA)8 of the promoter polymorphism, were discovered.
Genotyping of the UGT1A1 gene showed distinct distribution of the common A(TA)nTAA polymorphism relative to other European populations. Because of a greater risk of hyperbilirubinaemia due to hereditary haemolytic anaemia, the diagnosis of Gilbert syndrome in this group of patients is very important.
Ring 20 syndrome is a rare condition still not well characterised both at the genetic and clinical levels. It was described for the first time by Borgaonkar and Bolling
Extramural venous invasion (EVI) is an important predictor of haematogenous metastasis in colorectal cancer (CRC). However, remarkable discrepancies in incidence rates indicate major problems regarding EVI assessment. The present prospective study applies tangential vessel preparation to CRC resection specimens and correlates results of EVI with metachronous haematogenous metastatic (MHM) spread.
Stage II CRC diagnosed at the Institute of Pathology, University Teaching Hospital Feldkirch, Austria over a period of 30 months were analysed and tangential sectioning of the pericolonic tissue was performed. Confirmation, or exclusion of MHM, as assessed by computerised tomography, sonography or biopsy, was recorded.
In 50/79 (63%) cases EVI was detected. In 13/50 (26%), MHM developed. Of the 29/79 (37%) patients without EVI, only one (3.5%) developed MHM. Statistically, the rate of MHM for patients with EVI was independent of adjuvant chemotherapy.
Tangential sectioning of the tumour periphery in CRC stage II yields a high rate of histologically evaluable extramural veins and permits proper assessment of EVI. Absence of EVI is significantly associated with metastasis-free survival, a finding of potential therapeutic value. On the other hand, one-third of the patients with EVI and circumferential tumour growth develop MHM, a setting in which the option for adjuvant chemotherapy should be considered. This study emphasises the importance of tangential sectioning of the invasive tumour front in CRC compared with the recommended perpendicular technique. The sensitivity and specificity of this method regarding MHM are characterised.
The earlier detection of breast cancer through mammographic screening has resulted in a shift in stage distribution with patients who are node-positive tending to present with a lower number of positive lymph nodes (LN). This study aims to assess the prognostic value of absolute number of positive nodes in the pN1 TNM stage (1–3 positive LN) and whether the prognostic value of the number of nodes in this clinically important stage justifies its consideration in management decisions.
This study is based on a large and well-characterised consecutive series of operable breast cancer (3491 cases), treated according to standard protocols in a single institution, with a long-term follow-up.
LN stages and the absolute number of LN are associated with both breast cancer specific survival (BCSS) and distant metastasis free survival (DMFS). In the pN1 stage, patients with three positive LN (14% of pN1) show shorter BCSS (HR=1.9, (95% CI 1.3 to 2.6)) and shorter DMFS (HR=2.2, (95% CI 1.6 to 2.9)) when compared with one and/or two positive nodes. This effect is noted in the whole series as well as in different subgroups based on tumour size (pT1c and pT2), histological grade (grade 2 and 3), vascular invasion and oestrogen receptor status (both positive and negative). Multivariable analyses showed that three positive LN, compared with one and two positive LN, are an independent predictor of shorter BCSS and DMFS.
The number of LN in the pN1 stage yielded potentially informative risk assignments with three positive LN providing an independent predictor of poorer outcome.
β5t is a recently discovered proteasomal β subunit expressed exclusively in thymic cortical epithelial cells in both humans and mice.
Spindle cell lesions of the breast represent an interesting diagnostic challenge as they comprise a wide range of tumours that are rare. Differentiating dermatofibrosarcoma protuberans (DFSP) from other dermatofibromas using CD34 immunohistochemistry alone is difficult; therefore, fluorescence in situ hybridisation (FISH) analysis is often employed to identify typical COL1A1–PDGFB fusion or gene rearrangement. Although molecular confirmation of diagnosis is unnecessary in the majority of DFSP cases, the detection of chromosomal rearrangement is valuable in tumours that show unusual clinicopathological features as in this study the authors report a case of DFSP of breast that did not show any typical known molecular features.
Morphological and immunohistochemical study was highly suggestive of the diagnosis of DFSP. To further investigate this case, DNA copy number alterations were investigated by the 250 K Affymetrix SNP Mapping array. DNA analysis did not show any of the known translocations reported in DFSP or any known solid tumour category. However, in addition to copy number changes on chromosome 1, amplification of chromosome 7p which contains the epidermal growth factor receptor (EGFR) gene was observed. Results from EGFR FISH showed an increase in EGFR gene to chromosome 7 ratio (3:1) suggesting amplification of the EGFR gene.
This case of an unusual DFSP demonstrates that genomic interrogation provides additional potential targets such as a therapeutic avenue with anti-EGFR therapies and shows the power of molecular characterisation of unusual tumours for a personalised medicine approach.
To report the exceedingly rare occurrence of oligodendroglioma in the glial component of ovarian teratomas.
Six cases of oligodendrogliomas arising in the glial component of ovarian teratomas were studied and the literature was reviewed. Immunohistochemistry was performed by the Flex technique.
The ages of the patients ranged from 12 to 28 years (mean 21 years). Four tumours were located in the right and one in the left ovary. The size of the ovarian cysts ranged from 7 cm to 29 cm (mean 19.6 cm). Four cases arose in immature and two cases in mature teratomas. In all cases, oligodendroglioma was WHO grade II. On immunohistochemistry, glial fibrillary acidic protein stain was positive in all cases. The Mib 1 (Ki 67) proliferative index was low and the tumour cells were negative for synaptophysin. Follow-up was available in five patients and ranged from 1 to 42 months. Two patients died of disease after 1 and 36 months of diagnosis, respectively. In both these cases oligodendroglioma arose in an immature teratoma. The remaining three patients are alive with a follow-up of 4–42 months.
Oligodendroglioma arising in the glial component of ovarian teratomas is exceedingly rare. Ovarian teratomas should be extensively sampled and carefully evaluated to rule out the possibility of a glial tumour. This is the single and largest series of oligodendrogliomas arising in ovarian teratomas. The prognosis is good for oligodendrogliomas arising in mature teratomas compared with those arising in immature teratomas, although long-term follow-up is needed to determine the exact behaviour.
The biopsy specimen showed papillary lesions with abundant stromal proliferations. Under low-power magnification, the nodular lesion appeared to be invasive. On the other hand, under high-power...]]>
Two years previously, she had been investigated in her local hospital for pancytopenia (haemoglobin 10.9 g/dl, mean cell volume (MCV) 79 fl, platelet count 111x109/l and white blood cell (WBC) 2.9x109/l). Systemic enquiry revealed that she had bony aches and pains and menorrhagia. She was known to have uterine fibroids but there was no other medical or family history of note.
Clinical examination indicated moderate splenomegaly and her spleen measured 22 cm on a CT scan. A blood film was unremarkable but testing for JAK-2V617F by standard allele-specific PCR was positive. Bone marrow aspiration yielded a hypercellular sample but films did not show characteristic features of a myeloproliferative neoplasm (MPN). Histology of a bone marrow trephine specimen examined in parallel was initially interpreted likewise.
At this stage, she was referred to...]]>
This study was performed to determine systematically whether KRAS mutational analysis in biopsy tissue is a reliable indicator of KRAS status in subsequent corresponding resection specimens.
30 colorectal cancer (CRC) patients with biopsy and corresponding subsequent surgical resection specimens were studied. KRAS mutational analysis was performed on each biopsy sample as well as two separate samples from each resection specimen by PCR and Sanger sequencing.
Overall, KRAS mutations were identified in 12/30 (40%) of the tumours. There was 100% correlation between biopsy and resection specimens regarding the presence or absence of KRAS mutations. In fact, the same point mutation was identified in both biopsy and corresponding resection specimens in 12/12 (100%) cases. In addition, in two cases, there were two different point mutations detected within the same biopsy specimen.
This study shows perfect correlation between KRAS mutation status in biopsy and resection specimens from an individual patient, and suggests that biopsy material is adequate for KRAS mutational analysis in CRC patients.
The adequacy of lung cancer diagnosis with sputum cytology depends on duration of sputum sampling. The aim of this methodological study was to determine whether the hypermethylation detection rate of RASSF1A, adenomatous polyposis coli (APC) and cytoglobin (CYGB) is influenced by the duration of sputum collection.
Prospective sputum samples were collected from 53 lung cancer patients and 47 chronic obstructive pulmonary disease patients as controls. Subjects collected spontaneous sputum at home during nine consecutive days in three canisters I, II and III (ie, days 1–3, days 4–6, days 7–9, respectively). Quantitative methylation-specific PCR was performed to assess gene promoter methylation status of RASSF1A, APC and CYGB.
Analysis of each canister separately showed hypermethylation of RASSF1A, APC and/or CYGB in samples I, II and III, in 43%, 40% and 47% of cases, respectively. In control samples, these numbers were 4%, 2% and 4%, respectively. Cumulative analysis for days 1–6 and days 1–9 revealed an increase in sensitivity to 53% and 64%, and specificity of 94% and 91%, respectively.
Sputum collected over multiple successive days results in a gain in sensitivity for the detection of lung cancer, at the expense of a small loss in specificity.
Assessment of hypermethylation sensitivity of biomarkers in sputum collected over a prolonged period for the detection of lung cancer resulted in a promising gain in sensitivity, at the expense of a small loss in specificity.
To assess the prevalence of acquired diverticulum of the appendix (DA), including incipient forms and its possible significance as a marker of local/regional neoplasms.
The pathology database at Hvidovre Hospital was searched for appendix specimens, received between 2001 and 2010, coded for DA or for a space-occupying lesion. Slides were reviewed to determine DA status and the nature of lesions possibly causing DA.
Among 4413 appendix specimens, DA were identified in 39 (0.9%, CI 0.6% to 1.2%) cases, 17 (43.6%, 28.0% to 59.2%) of which additionally harboured an appendiceal neoplasm/neoplastic precursor, whereas this figure was 1.2% (CI 0.9% to 1.6%) for non-DA specimens (p<0.0001). Six of the 39 DA specimens comprised incipient DA, three of which coexisted with appendiceal neoplasms. In addition, local/regional non-neoplastic lesions (six cases) and colorectal carcinomas (four cases) coexisted with DA.
DA has significance as a putative marker of local/regional neoplasms. Therefore, a DA specimen proved significantly more likely to harbour a neoplastic growth than a non-DA counterpart. Submission for microscopy of the entire DA specimen, whether transmural or only incipient, and a comment in the pathology report on the occasional concurrence of local/regional neoplasms in this setting seem appropriate. The observation of DA may thus provide a valuable contribution in the diagnostic process.
To evaluate the significance of non-deletional α gene variants identified in neonates during newborn screening for sickle cell disorders.
1534 newborn babies were screened in the last 2 years for sickle cell disease using a targeted screening approach. Investigations included a complete blood count, high performance liquid chromatography analysis, cellulose acetate electrophoresis (pH 8.9), heat stability test, restriction digestion and Amplified Refractory Mutation System for confirmation of sickle haemoglobin (Hb S), α genotyping by multiplex PCR and DNA sequencing.
Three non-deletional α gene variants, Hb Fontainebleau, Hb O Indonesia and Hb Koya Dora, were identified in heterozygous condition in newborns. This is the first report of Hb Fontainebleau in association with Hb S. The baby had anaemia at birth (Hb 11.4 g/dl) with no cyanosis, icterus or need for transfusion. She had occipital encephalocoele and was operated on day 24 to remove the mass. The baby diagnosed with Hb O Indonesia in combination with Hb S also had a low haemoglobin level of 12.7 g/dl.
Newborn screening for sickle cell disorders also enabled us to identify three α globin chain variants. Two babies who inherited Hb Fontainebleau and Hb O Indonesia along with Hb S had reduced Hb levels at birth and need to be followed up.
Tubular carcinoid is a rare variant of appendiceal well-differentiated neuroendocrine tumour. Although considered benign lesions, the small infiltrating tubules that characterise the tumour may raise concern for metastatic adenocarcinoma. To our knowledge, the cytokeratin 7 (CK7)/cytokeratin 20 (CK20) expression profile of these neoplasms remains unexplored.
The authors characterised the CK7/CK20 immunophenotype and Ki-67 expression of the eight available tubular carcinoids seen at their institution from 1991 to 2011.
CK7 and CK20 staining was variable, ranging from none to focal staining for either or both CK7 and CK20, to diffuse expression of CK7 or CK20.
The CK7/CK20 expression profile is of limited value when the differential diagnosis includes primary tubular carcinoid and well-differentiated metastatic adenocarcinoma. In such cases, careful attention to the location of the neoplasm, mitotic count and presence or absence of an associated classic carcinoid component are more useful for arriving at the correct diagnosis.
An external positive control section is included in each immunohistochemical analysis as a well recognised and validated technique for standardising results. The method is time-consuming and expensive. On the contrary, internal controls are warranted and inexpensive, but their use is only feasible in selected diagnoses. The aim of this work is to show how the method of the authors allows improving the interpretation and cuts costs in the immunohistochemical analysis of bone marrow specimens.
A paraffin-embedded tonsil tissue cylinder was sampled from a donor block using an automated sampler and included as an ‘internal control’ together with a bone marrow biopsy in a recipient block, avoiding the use of external tonsil tissue control. To validate this technique, the authors compared the quality of immunohistochemistry, the workload and costs with routine external control in 50 consecutive bone marrow biopsies.
Processing simultaneously the sample and the tissue control in the same block, 60 external positive control tests were spared. Only a few minutes were taken for the preparation of the recipient blocks, and no particular technical skill was required. Considering that the volume of antibodies used for the analysis of each sample was not increased, a considerable amount of the disposable material was saved. The workload of technicians was decreased and some potential technical bias was avoided. The time required for pathologists to interpret the slides was also reduced.
In conclusion, this seems to be a feasible, cost-cutting and quality-improving technique, not limited to haematopathology but potentially extensible to other fields of pathology.
Incident reporting (IR) refers to systematic documentation of adverse incidents to facilitate their appropriate investigation and institution of corrective or remedial actions, and provide data to identify risk trends for recurrent problems. Minimisation of errors and reduction in process variation is recognised as an important goal of quality management and is an essential part of continuous quality improvement. Published data on the role IR plays in cellular pathology remains scanty.
In this study, the authors collected and analysed all incidents and adverse events reported in their department over a 2-year period.
584 incidents were reported (0.5% of all cases processed). The majority (59%) occurred in the pre-analytical phase of the laboratory process with 23% in the analytical and 18% in the post-analytical phases. Booking-in and specimen labelling-related incidents were the largest single group (56% of all incidents), prompting further root cause analysis, but no other obvious patterns or trends were identified, and most incidents were followed by corrective actions on an individual basis. Most incidents (79%) posed potential harm, as opposed to causing actual harm to the service or patients. Only 78 cases (14%) posed a major risk to patients, such as specimen loss or mix-up, whereas 27% were associated with moderate risk and 59% with minor or insignificant risk.
Major risk incidents are relatively rare in the cellular pathology laboratory. IR should be included as an important component of a risk management strategy and clinical governance framework.
This study compared the perfomance of the RNA-based EndoPredict multigene test on core biopsies and surgical breast cancer specimens and analysed the influence of biopsy-induced tissue injuries on the test result.
80 formalin-fixed paraffin-embedded samples comprising paired biopsies and surgical specimens from 40 ER-positive, HER2-negative patients were evaluated. Total RNA was extracted and the EndoPredict score was determined.
RNA yield was considerably lower in core biopsies, but sufficient to measure the assay in all samples. The EndoPredict score was highly correlated between paired samples (Pearson r=0.92), with an excellent concordance of classification into a low or high risk of metastasis (overall agreement 95%).
The measurements are comparable between core biopsies and surgical sections, which suggest that the EndoPredict assay can be performed on core biopsy tissue. Inflammatory changes induced by presurgical biopsies had no significant effect on the RNA-based risk assessment in surgical specimens.
Automated scanning devices and image analysis software provide a means to overcome the limitations of manual semiquantitative scoring of immunohistochemistry. Common drawbacks to automated imaging systems include an inability to classify tissue type and an inability to segregate cytoplasmic and nuclear staining.
Immunohistochemistry for the membranous marker α-catenin, the cytoplasmic marker stathmin and the nuclear marker Ki-67 was performed on tissue microarrays (TMA) of archival formalin-fixed paraffin-embedded tissue comprising 471 (α-catenin and stathmin) and 511 (Ki-67) cases of prostate adenocarcinoma. These TMA were quantitatively analysed using two commercially available automated image analysers, the Ariol SL-50 system and the Nuance system from CRi. Both systems use brightfield microscopy for automated, unbiased and standardised quantification of immunohistochemistry, while the Nuance system has spectral deconvolution capabilities.
Overall concordance between scores from both systems was excellent (r=0.90; 0.83–0.95). The software associated with the multispectral imager allowed accurate automated classification of tissue type into epithelial glandular structures and stroma, and a single-step segmentation of staining into cytoplasmic or nuclear compartments allowing independent evaluation of these areas. The Nuance system, however, was not able to distinguish reliably between tumour and non-tumour tissue. In addition, variance in the labour and time required for analysis between the two systems was also noted.
Despite limitations, this study suggests some beneficial role for the use of a multispectral imaging system in automated analysis of immunohistochemistry.
This pilot study of the direct observation of practical skills (DOPS) assessment of histopathology trainees is needed in the absence of existing information on histopathology in the UK. The aim of the study was to explore the experiences and perceptions of trainers in using the DOPS tool with histopathology trainees.
A qualitative approach was taken using paper-based questionnaires to consultants in a single teaching hospital histopathology department.
DOPS was perceived by all trainers as a valid form of assessment. There was a spread of opinion regarding its feasibility, with some respondents raising concern about its impact on time. 28% of respondents were doubtful about the formative nature of DOPS. All stated the assessment was fair.
Themes that have emerged include concerns about impact on trainer time, whether DOPS is used in a formative manner and concerns about the amount of guidance provided to trainers. Further research is required to expand on these points.
To determine whether Ki-67 immunoexpression in penile squamous cell carcinoma (PSCC) has a prognostic value and correlates with lymph node metastasis, human papillomavirus (HPV) infection and patient survival.
148 formalin-fixed paraffin-embedded PSCC samples were tissue-microarrayed, including 97 usual-type SCCs, 17 basaloid, 15 pure verrucous carcinomas, 2 warty and 17 mixed-type tumours. All samples were immunostained for Ki-67 protein. HPV DNA was detected with INNO-LiPA assay. Follow-up data were available for 134 patients.
Ki-67 was strongly expressed in 57/148 (38.5%) of PSCCs. Different cancer subtypes showed significant difference in Ki-67 expression (p<0.0001) with highest positivity in basaloid, 16/17 (94%), followed by usual type, 38/97 (39%) and lack of Ki-67 positive cases within verrucous tumours, 0/15. Ki-67 positively correlated with high-risk HPV (p<0.0001) and showed good specificity (84%) but low sensitivity (61%) for high-risk HPV detection. Ki-67 protein strongly positively correlated with tumour grade (p<0.0001) but not with stage (p=0.2193), or lymph node status (p=0.7366). Ki-67 showed no prognostic value for cancer-specific survival (HR=1.00, 95%, CI 0.99 to 1.02, p=0.54) or overall survival (HR=1.00, 95%, CI 0.99 to 1.02, p=0.45). High tumour stage, lymph node metastasis, high tumour grade and age at diagnosis were all independent prognostic factors for cancer-specific survival and overall survival.
Ki-67 is only a moderate surrogate marker for HPV infection in PSCC. It does not show prognostic value for cancer-specific survival and overall survival in PSCC.
CUL-4 plays a critical role in DNA replication in Caenorhabditis elegans, and interacts with p53 and p21 proteins in cell cycle regulation and response to genomic instability. However, the role of CUL-4 in human carcinomas is widely unknown.
To investigate the expression of CUL-4 protein and its association with p53 and p21, and to determine its prognostic relevance in invasive ovarian carcinoma.
CUL-4, p53 and p21 protein expression was determined retrospectively by immunohistochemistry in 140 specimens of human epithelial ovarian tumours (98 invasive carcinomas and 42 tumours of low malignant potential; LMP).
Overexpression of CUL-4 was observed in 41 (41.8%) of carcinoma samples and in 10 (23.8%) LMP tumours. CUL-4 was significantly more often overexpressed in invasive carcinomas compared with LMP tumours (p=0.042, 2 test, OR 2.302, 95% CI 1.018 to 5.203). In invasive carcinoma, CUL-4 overexpression was found to be a prognostic factor for overall (p=0.017, Cox regression, HR 2.387, 95% CI 1.17 to 4.869) and disease-free survival (p=0.005, Cox regression, HR 3.5, 95% CI 1.465 to 8.365), respectively. In subgroup analysis, CUL-4 was only of prognostic relevance in carcinomas without p53 expression.
These data indicate for the first time that CUL-4 might play a relevant role in the development and progression of ovarian carcinoma, warranting further investigations. Degradation of wild-type p53 might be a key mechanism to explain why CUL-4 leads to more aggressive clinical behaviour. Not only CUL-4 itself, but also its associated proteins might represent targets for novel, selective therapeutic strategies.
The nuclear factor B (NF-B) family comprises transcription factors that promote the development and progression of cancer. The NF-B pathway is induced by radiation therapy and may be related to tumour radioresistance. The aim of this study was to evaluate the expression of NF-B as a predictor of the response to radiotherapy and its value as a prognostic marker.
A retrospective analysis was performed in a series of 32 individuals with stage IB2 and IIB cervical cancer who underwent radiotherapy, followed by radical hysterectomy, from January 1992 to June 2001. NF-B-p65 and NF-B-p50 expression was examined by immunohistochemistry in biopsies from all patients before radiotherapy and in 12 patients with residual tumours after radiotherapy.
16 (50%) patients had residual disease after radical hysterectomy. The median follow-up time was 73.5 months, and the 5-year overall survival was 66.5%. Before radiotherapy, cytoplasmic expression of NF-B-p65 and NF-B-p50 was noted in 91% and 97% of cases, respectively, versus 59% of cases with nuclear expression of these subunits. Cytoplasmic expression of NF-B-p65 and NF-B-p50 in the residual tumours after radiotherapy was observed in 50% of cases; 75% of cases with residual tumours had nuclear expression of NF-B-p50 versus none with NF-B-p65. NF-B-p65 and NF-B-p50 did not correlate with the risk of residual tumours after radiotherapy or recurrence or death.
These data suggest that NF-B does not predict the response to radiotherapy and does not correlate with poor outcomes in advanced cervical cancer.
A 31-year-old woman (gravida 0, para 0) was noted to have high-grade squamous intraepithelial lesion at routine two-yearly cervical smear. At colposcopy, three separate acetowhite areas were seen. The colposcopic impression was of low-grade squamous intraepithelial lesion and chronic inflammatory change. A Lletz biopsy of the cervix was performed. The patient had been on microgynon 50, which she had ceased before the last period. The last menstrual period was 3 weeks prior to the colposcopy. No significant gynaecological or medical history was noted.
The gross specimen consisted of an intact Lletz biopsy of cervix measuring 17x10 mm and resected to a depth of 15 mm. The tissue was transected and blocked in toto. Histologically, high-grade squamous intraepithelial lesion (CIN 2) and associated koilocytosis consistent with human papillomavirus was seen. Background changes of moderate chronic cervicitis and associated squamous metaplasia were present. An additional finding noted were three circumscribed foci of cribriform glandular...]]>
For small specimens, such as skin excisions, 15 ml nail varnish pots have proved to be ideal. Empty nail varnish pots are available for <£1 each (http://www.naio.co.uk). For larger specimens, we use small specimens pots with a hole made in the lid using either a soldering iron or a heated Allen/hex key....]]>
Forkhead Box P1 (FOXP1) has been described as both a tumour suppressor candidate and a potential oncogene. The aim of this study is to identify new prognostic biomarkers and therapeutic target structures for the diagnosis and treatment of hepatocellular carcinoma (HCC).
The expression of FOXP1 mRNA in HCC was characterised using real-time PCR and 20 pairs of fresh frozen HCC tissues and corresponding non-cancerous tissues. FOXP1 protein expression in HCC was confirmed using immunohistochemistry on a tissue microarray chip. Finally, FOXP1 expression was correlated with conventional clinicopathological features of HCC and patient outcome.
The expression of FOXP1 mRNA and protein in HCC cells was much higher than in normal hepatic cells (Z=2.315, p=0.021 and 2=28.071, 95% CI 0.233 to 0.480, p<0.001, individually). The comparison of clinicopathological characteristics and immunohistochemistry by 2 test analysis showed that the high expression of FOXP1 in HCC was related to large tumour diameter (2=6.210, p=0.013), high serum α-fetoprotein levels (2=6.920, p=0.031) and later stage grouping with tumour node metastasis classification (2=6.714, p=0.035). Kaplan–Meier survival and Cox regression analysis showed that high FOXP1 expression (HR=2.182, 95% CI 1.146 to 4.154, p=0.018) and regional lymph node metastasis (HR=2.326, 95% CI 1.037 to 5.217, p=0.041) were independent prognosis factors.
From this investigation the authors elucidated for the first time that the correlation of high FOXP1 expression correlates with an aggressive malignant phenotype and may constitute a novel prognostic factor for HCC. These results also support a role for FOXP1 as an oncogene in HCC.
This article highlights the important aspects of structure, function, mutations and role in cancer that are of relevance to the practicing pathologist. For more detailed information on these aspects the reader should refer to recently published articles.
The PTEN gene, mapped to 10q23.3, contains nine exons and encodes a 47 kD protein with 403 amino acids. Exons 1–6 code for the N-terminal domain, which consists of the...]]>
At the age of 45 years, the patient was diagnosed with primary polycythaemia based on haemoglobin (Hb) 22 g/dl, histological appearances of the bone marrow (
To evaluate the impact of decision support on the proportion of troponin I (cTnI) tests and associated costs over the period 2000–7 for patients presenting with chest pain in an emergency department (ED) setting.
A longitudinal study using linked data for patients presenting with chest pain from the ED and laboratory information systems of a metropolitan teaching hospital in Melbourne, Australia. The study period was divided into a pre-intervention period (2000–2), which contained no decision support; an initial post period (2003–4) after the introduction of a quality improvement initiative (utilising a paper-based guideline, education, audit and feedback) about cTnI test ordering and the incorporation of the guideline as a decision support feature of the computerised provider order entry system; followed by a post-modification period (2005–7) after the electronic decision support feature was modified to allow clinicians to bypass viewing the complete guideline.
There was a significant fall in the proportion of cTnI tests ordered per patient presentation across the three periods—pre (2000–2), post (2003–4) and post-modification (2005–7)—from 7.3% to 4.1% and 2.8%, respectively. Analysis of costs showed significant reductions in the mean costs for cTnI tests per patient presentation from $A9.28 to $A8.54 and $A8.18, respectively, which amounted to a modest saving of $A13 251 since the initiation of decision support in 2003.
Decision support systems are often part of multifaceted implementations undertaken over time. They require continuous monitoring and modifications to ensure optimal performance.
To extend the biomedical scientist (BMS) cut-up role to include gastrointestinal category D colorectal cancer resection specimens, and to address issues of quality and safety by presenting performance data from the first 50 BMS cut-up specimens in comparison with national guidelines and pathologist performance over the same timeframe.
Close mentoring and consultant supervision was carried out for every case with adherence to standard operating procedures and following colorectal cancer dataset guidelines as published by the Royal College of Pathologists. Performance targets were audited including anticipated spread of Dukes' stage, targets for mean lymph node harvest, percentage extramural vascular invasion and serosal involvement, and mean tumour blocks sampled. Histological pre-reporting of 20 cases was encouraged, and time spent by BMS and consultant at all stages of specimen reporting was noted.
Performance targets were all exceeded by the BMS and compared favourably with pathologist performance. A measure of consultant cut-up and histology reporting time saved was identified.
Benefits of extending the BMS role to category D specimens may include BMS professional advancement, efficient use of consultant time and the development of a team approach to cancer reporting. The achievement of colorectal cancer performance targets and favourable comparison with pathologist performance implies there was no perceived detrimental effect on quality or safety and thus patient management.
Epidermal growth factor receptor (EGFR) gene mutation at the kinase domain and EGFR gene amplification are reported to be predictors of the response to EGFR tyrosine kinase inhibitors in lung cancer cases. In malignant mesothelioma (MM), the role of EGFR is less clear.
Thirty-eight MM specimens were submitted to EGFR mutation evaluation, and compared with the results of immunohistochemical staining and fluorescence in situ hybridization (FISH) analysis. DNA was extracted from paraffin blocks and PCR was performed to amplify exon regions 18–21 of the EGFR gene. Direct sequencing of the purified PCR products was performed.
Five EGFR missense mutations were detected in six of the 38 patients (16%); two of these mutations were novel, two were originally detected in non-small cell lung carcinoma, and one resembled a location previously noted for malignant peritoneal mesothelioma.
As far as the authors are aware there has been no report of the EGFR mutation of MM in Japanese cases, but in this study EGFR missense mutations were detected in some cases. EGFR mutation results were not related to immunohistochemical and FISH analysis.
Currently more than 200 types of human papillomaviruses (HPV) have been classified, where the low-risk ones are those that are not capable of developing into cancer while the high-risk ones are.
In 1978, WHO defined leukoplakia as a white plaque of oral mucosa, not removable by scraping, which cannot be characterised clinically or pathologically as any other disorder.
Persistently elevated antiphospholipid antibodies and positive lupus anticoagulant (LAC) are associated with an increased risk of thrombosis. The objective of this study was to explore whether antiphospholipid antibody and/or LAC positivity were associated with the traditional risk factors for thrombosis or with medication use in patients without autoimmune diseases hospitalised with arterial or venous thrombosis.
Cross-sectional study.
Montefiore Medical Center, a large urban tertiary care centre.
270 patients (93 with deep vein thrombosis (DVT) or pulmonary embolism (PE), and 177 with non-haemorrhagic stroke (cerebrovascular accident (CVA)) admitted between January 2006 and December 2010 with a discharge diagnosis of either DVT, PE or CVA, who had LAC and antiphospholipid antibodies measured within 6 months from their index admission. Patients with lupus or antiphospholipid syndrome were excluded.
The main dependent variable was antiphospholipid antibodies of 40 units or greater (antiphospholipid antibody positivity) and/or LAC positivity. Independent variables were traditional thrombosis risk factors, statin use, aspirin use and warfarin use.
31 (11%) patients were LAC positive and/or antiphospholipid antibody positive. None of the traditional risk factors at the time of DVT/PE/CVA was associated with antiphospholipid antibody positivity. Current statin use was associated with an OR of 3.2 (95% CI 1.3 to 7.9, p=0.01) of antiphospholipid antibody positivity, adjusted for age, ethnicity and gender. Aspirin or warfarin use was not associated with antiphospholipid antibody levels.
If statin therapy reflects the history of previous hyperlipidaemia, high levels of antiphospholipid antibodies may be a marker for earlier endothelial damage caused by hyperlipidaemia.
Eligibility for anti-human epidermal growth factor receptor 2 (HER2) treatments in breast cancer requires a correct HER2 status assessment. Testing guidelines recommend fluorescence in-situ hybridisation (FISH) for samples scored as 2+ by immunohistochemistry. This study investigates the correlation between pathological features and FISH amplification in HER2 2+ breast cancer cases.
480 HER2 2+ breast cancer samples were included. The association between tumour grade, hormone receptor status, proliferation index (Ki67) and FISH amplification, using both US Food and Drug Administration (ratio ≥2) and American Society of Clinical Oncologists/College of American Pathologists cut-offs (ratio >2.2) was evaluated.
90.2% of the samples were hormone receptor positive. The median Ki67 value was 23.5%; 311 (64.8%) samples showed a Ki67 value of 15% or greater. Tumour grade was evaluable in 421 cases (87.7%), 268 (55.8%) being grade 3. FISH amplification rates were 27.5% (ratio ≥2.0) and 20.8% (ratio >2.2). Grade 3 tumours were more frequently amplified than grades 1–2 tumours: 34% versus 18% (ratio ≥2.0, p<0.001) and 27% versus 9% (ratio >2.2, p<0.001). Samples with Ki67 of 15% or greater showed higher amplification rates than low Ki67 samples: 31% versus 21% (ratio ≥2.0, p=0.022) and 25% versus 12% (ratio >2.2, p=0.003). The OR for FISH amplification was significant in the case of grade 3 and high Ki67 with both cut-offs.
In this study, high tumour grade and high Ki67 significantly predicted FISH amplification in 480 HER2 2+ breast cancer samples.
To analyse postmortem cases of myocardial infarction (MI) with normal coronary arteries in terms of patient characteristics, features of the MI and risk factors.
This retrospective non-case controlled study was carried out at a specialist cardiac pathology department at a tertiary cardiac referral centre. Cases of histologically confirmed MI and normal coronary arteries during the period 1996–2010 were identified and analysed for the presence of risk factors.
Nineteen cases of histologically confirmed MI and normal coronary arteries were identified with a similar gender ratio 1:1.1 (male:female) and mean age of 33±12 years (range 14–58). All patients died suddenly. The location of the infarct was variable, with left anterior descending artery territory being the single most prevalent (47%). Risk factors were identified in the majority of cases (n=14), with some cases experiencing more than one association, including alcohol and/or predominately class A drug use (n=7), including cocaine, inflammation (n=2), hypercoagulable state (n=3) and exertion (n=2).
Current data regarding prognosis in MI with normal coronary arteries suggests a favourable outcome in the context of major cardiovascular events. No large series of fatal cases have been reported. This study highlights that this entity can be fatal and its prognosis may be less favourable than currently considered. This autopsy series also demonstrates that the causation of MI with normal coronary arteries is complex and multifactorial, including a history of alcohol and/or drug use. It also highlights the importance of accurate epidemiological data from referring pathologists.
In many institutions, initial handling of bloody aspirates, which can be voluminous, entails expressing the specimen into preservative or fixative liquid media. Later recovery of cellular particles is achieved by either clotting or centrifugation.
We recently discovered a simple and effective alternative method for the initial handling of a large volume of blood...]]>
A patient with hypertension, ischaemic heart disease, atrial fibrillation and recurrent strokes was admitted for acutely worsening abdominal distension and breathlessness. There was a history of persistent abdominal distension and diarrhoea, which were treated conservatively. Endoscopy done had shown reflux oesophagitis, peptic ulceration and right-sided ischaemic colitis. Per-rectal examination revealed blood clots mixed with mucus. CT of the abdomen and pelvis showed no evidence of mesenteric vascular occlusion or masses.
The patient subsequently became hypotensive and underwent emergency laparotomy. Intraoperatively, ischaemic changes of left colon and patchy oedema of the mesentery were noted. Left hemicolectomy with colostomy was performed. Postoperatively, the patient was found...]]>
We had previously reported similar findings of primary ovarian mucinous carcinomas having the highest prevalence of HER2 genomic amplification and protein overexpression among the various EOC histological subtypes and had proposed that ovarian mucinous carcinomas represent a...]]>
The medical regulator in the UK, the General Medical Council, requires curricula and assessments for postgraduate training to be blueprinted to its regulatory statement, Good Medical Practice. A similar document, Tomorrow's Doctors (2009), covers undergraduate education and training. Good Medical Practice, originally designed to regulate medical practice, is not optimally worded as an educational document. The Royal College of Physicians and Surgeons of Canada's physician competency framework known as CanMEDS is designed with education more centrally in mind.
The wordings of Good Medical Practice and Tomorrow's Doctors (2009) were compared with CanMEDS using ‘word clouds’, a textual analysis tool which provides a display of word frequency, revealing the emphasis in the wording of documents.
Good Medical Practice places much greater emphasis on the regulatory rather than the educational aspects of medical practice when compared with CanMEDS and is therefore less suitable for blueprinting curricula, especially in disciplines with high science content such as pathology.
Good Medical Practice is less suitable for an educational role and the General Medical Council should consider developing a more specific educational document around these principles.
Lymphoepithelioma-like carcinoma (LELC) of the liver is extremely rare. To our knowledge, only 16 cases of pure LELC or LELC with ordinary adenocarcinoma arising in the hepatobiliary tract have been reported in the English literature.
After reviewing 207...]]>
The book is divided into 10 anatomical sections: nasal cavity and paranasal sinuses, pharynx (nasal, oro-, hypo-), larynx and trachea, oral cavity, salivary glands, jaw, ear and temporal bone, neck (soft tissue and lymph nodes), thyroid gland and parathyroid glands along with an antibody index. These sections are subdivided into their...]]>
A 73-year-old woman who presented with anaemia and gastroscopy revealed a 30 mm firm ulcer with raised edges at the lesser curve of the stomach. A CT scan revealed features within the ulcer that were suspicious for malignancy. She was treated with a proton pump inhibitor and sucralfate but the ulcer failed to heal over a 1-year period. Three sets of biopsies from the ulcer edge during this time revealed benign changes only. There was no history of non-steroidal anti-inflammatory drug usage and urinary salicylate estimation was negative. The serum gastrin concentration was not raised. Her medical history included insulin-dependent diabetes mellitus and ischaemic heart disease. There was no history of a systemic inflammatory disorder. Due to the continued concern of occult malignancy she proceeded to laparotomy with partial gastrectomy, after which she made an uneventful recovery.
Macroscopic examination of the resection specimen revealed a 30 mm mucosal ulcer with slightly raised...]]>
A persistent problem in gynaecological differential diagnosis is the differentiation of primary ovarian mucinous carcinoma from metastatic disease either in the ovary or disseminated throughout the abdomen and pelvis from extragenital organs. Traditionally, there has been a tendency to vary treatment depending on a perception of origin in the ovary, secondary müllerian system
Further, the distinction between a primary ovarian mucinous carcinoma arising in either the background of borderline change or as a carcinoma within a teratoma, although admittedly both are unusual, and a metastasis, for example, from a bowel...]]>
Ovarian cancer represents the fifth most common cancer to affect women in the UK, with approximately 6700 cases diagnosed annually. The majority of ovarian cancers are serous epithelial ovarian cancers (sEOCs), with mucinous epithelial ovarian cancers (mEOCs) forming around 12% of diagnosed cases, and hence comparatively rare.
Evolving evidence has demonstrated distinct histopathological and clinical contrasts between mEOC and sEOC, as discussed further in this issue, leaving oncologists questioning the current blanket approach to their treatment. Loco-regionally advanced sEOC and mEOC (the most prevalent presentation) is treated with a combination of chemotherapy and debulking surgery. However, there is evidence to suggest that mEOCs may be less sensitive to platinum based chemotherapy and the low prevalence of mEOC patients within randomised controlled trials...]]>
Although traditionally regarded as the second most common type of primary ovarian carcinoma following serous carcinoma, recent studies have illustrated that primary ovarian mucinous carcinomas are rather uncommon neoplasms representing approximately 3% of primary malignant ovarian epithelial tumours.