bluuebunny/crossref_metadata_2025_split huggingface dataset:
Follicular lymphoma with marginal zone differentiation: cytogenetic findings in support of a high‐risk variant of follicular lymphoma
Authors: Goodlad J R , Batstone P J , Hamilton D , Hollowood K 
Published: December 2004

Aims:  The pathogenesis and clinical significance of marginal zone differentiation in follicular lymphoma remains to be determined, although genetic alterations are likely to be important determinants of both. We therefore report the cytogenetic findings in three cases of follicular lymphoma with marginal zone differentiation studied by routine karyotyping and in‐situ hybridization.Methods and results:  The morphology and immunophenotype of each case was typical of follicular lymphoma displaying marginal zone differentiation. Karyotyping, performed on GTL‐banded preparations of cell cultures derived from fresh lymph node tissue, revealed a complex karyotype in all three cases, including t(14;18)(q32;q21) and abnormalities associated with progression and/or transformation of follicular lymphoma. In addition, trisomy 3 was found in one case and translocations between the q27‐29 region of chromosome 3 and chromosome 2 in the other two cases; the latter was identified only in subclones derived from less complex stem lines possessing t(14;18). In‐situ hybridization, performed on sections cut from routinely processed paraffin‐embedded tissue blocks, localized cells possessing these abnormalities of chromosome 3 to both the follicular and marginal zone components of two lymphomas studied in this way.Conclusions:  Trisomy 3 and alterations involving the q27‐29 region of chromosome 3 are implicated in the pathogenesis of de novo marginal zone lymphoma. Their presence in the current cases indicates that they may also be responsible for marginal zone differentiation in follicular lymphoma when cells harbouring these genetic alterations are exposed to the appropriate microenvironment. Our findings are consistent with follicular lymphoma with marginal zone differentiation as a high‐risk variant of follicular lymphoma.
Excision biopsy findings of patients with breast needle core biopsies reported as suspicious of malignancy (B4) or lesion of uncertain malignant potential (B3)
Authors: Lee A H S , Denley H E , Pinder S E , Ellis I O , Elston C W , Vujovic P , Macmillan R D , Evans A J ,   for the Nottingham Breast Team
Published: December 2004

Aims:  The UK National Health Service Breast Screening Programme has proposed five categories for reporting breast needle core biopsies. The majority of cores are reported as benign (B1), normal (B2) or malignant (B5). The predictive value of the two borderline categories suspicious of malignancy (B4) and lesion of uncertain malignant potential (B3) was studied.Methods and results:  Over a 2‐year period a total of 3822 breast needle core biopsies were performed, with 2997 from symptomatic patients and 825 from women undergoing mammographic screening, including 43 B4 reports (40 patients) and 120 B3 reports (116 lesions in 115 patients). The frequencies of B4 (2.5% versus 0.7%) and B3 cores (7.3% versus 2.0%) were both higher in screening than in symptomatic patients. B4 was most commonly used for small fragments of atypical cells separate from the main core or focal atypical intraductal proliferations. The criteria for calling a core B3 were: atypical intraductal epithelial proliferations (including foci that in excision specimens would be classified as atypical ductal hyperplasia), lobular neoplasia, radial scar, papillary lesion, fibroepithelial lesion with cellular stroma and spindle cell proliferations. Excision biopsies were performed in 39 patients with B4 core and 96 with B3 core. Invasive carcinoma or ductal carcinoma in situ was seen in 33 of the patients with B4 (85%) and in 29 of those with B3 cores (25%). Some categories of B3 core were associated with a higher rate of malignancy (40% for atypical intraductal epithelial proliferations and 46% for lobular neoplasia).Conclusions:  The positive predictive value for carcinoma is high following a B4 core (86%). The lesion should be excised, but definitive cancer treatment is not appropriate. In some cases a definite diagnosis of malignancy can be made on repeat core. The B3 group is more heterogeneous and has a lower rate of malignancy on further biopsy (25%). The majority of B3 lesions require excision. All these patients should be discussed at multidisciplinary meetings.
Calibration of immunohistochemistry for assessment of HER2 in breast cancer: results of the French Multicentre GEFPICS* Study
Authors: Vincent‐Salomon A , MacGrogan G , Couturier J , Arnould L , Denoux Y , Fiche M , Jacquemier J , Mathieu M‐C , Penault‐Llorca F , Rigaud C , Roger P , Treilleux I , Vilain M‐O , Mathoulin‐Pélissier S , Le Doussal V 
Published: December 2004

Aims:  HER2 protein is over‐expressed in 15–30% of breast carcinomas. Immunohistochemistry (IHC) is a common and inexpensive method able to specifically detect HER2 protein. However, lack of standardization of IHC has been considered responsible for discrepancies in HER2 status assessment performed by IHC and fluorescence in‐situ hybridization (FISH). This prompted us to perform a multicentric IHC calibration test to achieve a maximum accuracy of HER2‐IHC compared with HER2‐FISH taken as the reference method.Methods and results:  Twelve French laboratories participated in this study, including 119 cases of invasive breast carcinomas for which both fixed and frozen tissues were available. HER2 expression was determined in fixed tissues by individual in‐house IHC techniques, using either CB11 (Novocastra, Newcastle, UK) or A0485 (Dako, Glostrup, Denmark) anti‐HER2 antibodies. Two cut‐off values were used: 10% and 60% of immunostained cells. In 116 of the 119 cases, HER2 gene status could also be determined by FISH on frozen sections, performed in a single laboratory. Results were centralized and compared. When suboptimal concordance between IHC and FISH was observed, IHC was calibrated and a second run was performed. The specificity, sensitivity and accuracy of IHC compared with FISH were noted before and after calibration. Forty‐four out of 116 (38%) tumours showed HER2 gene amplification. Accuracy of IHC was complete in the first run for 6/12 laboratories. Calibration, necessary for the six others, relied mainly on the combination of a heat‐induced epitope retrieval step with an increase of dilution of the primary antibody. In the second run, HER2 over‐expression was found in 46 (40%) and 44 (38%) of the 116 cases, using 10% or 60% of stained cells as cut‐offs, respectively. The corresponding accuracy rates were 93% and 95%.Conclusions:  This study showed that a high accuracy of IHC could be obtained for the determination of HER2 status in all laboratories using their in‐house IHC technique, provided that a calibration process was performed. Antigen retrieval procedure, high dilutions of anti‐HER2 antibody and the use of specific controls were crucial for HER2‐IHC calibration. A 95% accuracy rate of IHC, using FISH as gold standard, was obtained by considering immunolabelling HER2‐IHC results as a continuous variable, and taking 60% invasive stained cells as the cut‐off for HER2 over‐expression.
Concordance of FIGO grade of endometrial adenocarcinomas in biopsy and hysterectomy specimens
Authors: Mitchard J , Hirschowitz L 
Published: December 2004

Aims:  We compared the FIGO grade of endometrial adenocarcinomas in endometrial samples and subsequent hysterectomy specimens, between 1997 and 2000 in a general pathology department. Our aims were to assess concordance, and the influence of the sampling technique, patient age, reporting pathologist and interval between the biopsy and definitive surgery. In order that the study reflected working practice, the tumour grade given by the reporting pathologist was used whenever possible.Methods and results:  Endometrial samples and the subsequent hysterectomy specimens from 125 patients were studied. The comparative FIGO grades were analysed with reference to biopsy type, patient age, reporting pathologist and interval between biopsy and hysterectomy. Concordance was 45% for grade 1, 63.3% for grade 2 and 75.6% for grade 3 carcinomas, the overall concordance being 64.5%. The concordance for grade 3 tumours was significantly higher than for grade 1. The predictive accuracy was independent of biopsy type, patient age, the interval between biopsy and hysterectomy, and whether the same pathologist reported both specimens.Conclusions:  Irrespective of the sampling device used, patient age, time‐lapse between biopsy and hysterectomy, or whether the same pathologist reported both specimens, the grade of endometrial adenocarcinoma often differs in the initial biopsy sample from that in the final hysterectomy specimen. This may have important implications for patient management, especially for tumours that yield low‐grade biopsies.
Colorectal mass lesions masquerading as chronic inflammatory bowel disease on mucosal biopsy
Authors: Gupta J , Shepherd N A 
Published: December 2004

Aims:  We bring to the attention of diagnostic pathologists a further cause of mimicry of chronic inflammatory bowel disease on mucosal biopsy, namely intramural and subserosal colorectal mass lesions.Methods and results:  In a 10‐year prospective study in one centre, we describe 26 cases in which the initial colonoscopic biopsies suggested a diagnosis of chronic inflammatory bowel disease, whereas subsequent information indicated that the mucosal changes were due to underlying mass lesions, without evidence of chronic inflammatory bowel disease. These mass lesions included underlying primary adenocarcinoma, metastatic carcinoma, pneumatosis, endometriosis and complicated diverticular disease.Conclusions:  In the colon and rectum, intramural and subserosal mass lesions are a significant cause of chronic inflammatory bowel disease mimicry. Possible pathogenic mechanisms include mechanical effects, lymphatic obstruction by underlying tumour, relative mucosal ischaemia and mucosal prolapse. Since the changes seen on mucosal biopsies are a secondary phenomenon, we tentatively suggest that ‘secondary colitis’ may be an appropriate appellation.
Accuracy of magnetic resonance imaging in determining cause of sudden death in adults: comparison with conventional autopsy
Authors: Roberts I S D , Benbow E W , Bisset R , Jenkins J P R , Lee S H , Reid H , Jackson A 
Published: December 2004

Aim:  To determine the accuracy and define the limitations of post mortem magnetic resonance imaging (MRI) in determining the cause of sudden death in adults.Methods and results:  Sudden unexpected adult deaths in the community, reported to the Coroner (n = 10), excluding suspicious, violent or potentially drug‐related deaths, were submitted to whole body MRI, followed by full invasive autopsy. The MRI scans were reported independently by four radiologists, blinded to the autopsy findings; two had previous experience of post mortem MRI. An abnormality that related to the cause of death as identified at autopsy, was identified by at least one radiologist in eight cases. These were pulmonary consolidation (autopsy finding pneumonia) (n = 1), pneumoperitoneum (autopsy finding perforated peptic ulcer) (n = 2), left ventricular failure (autopsy finding ischaemic heart disease) (n = 4), and disseminated bronchial carcinoma (n = 1). However, in only one case were all radiologists able to provide a confident cause of death (disseminated bronchial carcinoma). In two cases, in which death occurred 2–6 days and 3–6 days before MRI, early decomposition prevented interpretation of the images. Severe coronary artery atheroma was detected at autopsy in 7/10, but these lesions were not detected by MRI. Previous experience in reporting post mortem MRI, without autopsy comparison, did not result in more accurate interpretation of the images.Conclusions:  This pilot study suggests that post mortem MRI can identify some abnormalities relating to the common causes of sudden death in adults, but there is a need for greater experience in correlating MRI with autopsy findings before a reliable cause of death can be made by MRI alone. Inability to image coronary artery lesions, differentiating thrombus from clot and pulmonary oedema from pneumonic exudates, are specific problems that may be corrected with greater experience and higher resolution scans.
Expression of maspin is up‐regulated during the progression of mammary ductal carcinoma
Authors: Umekita Y , Yoshida H 
Published: December 2004

Aims:  The tumour suppressor gene maspin is reported to inhibit the motility, invasiveness and metastasis of breast cancer cells. Maspin is expressed in normal mammary myoepithelial cells but is down‐regulated during the progression of ductal carcinoma. However, we recently reported that maspin expression was frequently observed in invasive ductal carcinoma (IDC) with an aggressive phenotype, and it was a strong indicator of a poor prognosis. To our knowledge, to date, there has been no report investigating maspin expression in a large series of ductal carcinoma in situ (DCIS).Methods and results:  To clarify whether there is down‐regulation during the progression of ductal carcinoma, we immunohistochemically investigated the expression of maspin in 145 DCIS, 92 invasive ductal carcinomas with a predominant intraductal component as well as 94 usual ductal hyperplasias and 27 atypical ductal hyperplasias. The expression of maspin in carcinoma cells was observed in 9.6% (14 of 145) of DCIS and 18.5% (17 of 92) of IDC with a predominant intraductal components. It significantly correlated with larger tumour size (P = 0.013; P = 0.042), higher histological grade (P = 0.015; P = 0.0003) and the presence of comedo‐necrosis (P = 0.000005; P = 0.0074) in DCIS and IDC with a predominant intraductal components, respectively. In epithelial cells, the expression of maspin was observed in only one case of usual ductal hyperplasia, and all cases of atypical ductal hyperplasia were negative.Conclusions:  These results and our previous investigation in which 27.4% of IDC were positive for maspin suggest that the expression of maspin in epithelial cells could be up‐regulated during the progression of ductal carcinoma, and that it could be correlated with the acquisition of an aggressive phenotype.
Cyclooxygenase‐2 expression in thyroid neoplasms
Authors: Ito Y , Yoshida H , Nakano K , Takamura Y , Miya A , Kobayashi K , Yokozawa T , Matsuzuka F , Matsuura N , Kuma K , Miyauchi A 
Published: December 2004

Aims:  Previous studies have demonstrated that cyclooxygenase‐2 (COX‐2) plays a role in carcinogenesis and carcinoma development. In this study, we investigated its expression in thyroid neoplasms in order to elucidate its role.Methods and results:  COX‐2 expression was studied immunohistochemically in 20 anaplastic (undifferentiated) carcinomas, 49 papillary carcinomas, 22 follicular carcinomas and 15 follicular adenomas. Positive staining was only occasionally seen in normal follicles or stromal cells. COX‐2 over‐expression was found in only 20.0% of follicular adenomas and 40.9% of follicular carcinomas. In papillary carcinomas, the incidence (81.3%) was significantly higher (P < 0.0001) than in follicular carcinomas, although COX‐2 expression was reduced in cases with old age (P = 0.0190), large size (P = 0.0028), advanced stage (P = 0.0225), satellite tumours (P = 0.0363), and the presence of solid, scirrhous or trabecular growth patterns (P = 0.0018). Undifferentiated carcinomas less frequently over‐expressed COX‐2 (P = 0.0004), with an incidence of 40.0%.Conclusions:  These results indicate that the up‐regulation of COX‐2 may contribute predominantly in the early phase of papillary carcinoma progression, whereas it plays a more adjuvant role in follicular carcinoma progression.
Cyclooxygenase‐2 is expressed frequently and early in Barrett's oesophagus and associated adenocarcinoma
Authors: Lagorce C , Paraf F , Vidaud D , Couvelard A , Wendum D , Martin A , Fléjou J‐F 
Published: December 2004

Aims:  To establish the prevalence of cyclooxygenase‐2 (COX‐2) expression in a large series of resected Barrett's adenocarcinoma and associated preneoplastic lesions and to correlate this expression with clinicopathological data and prognosis.Methods:  COX‐2 expression was assessed by immunohistochemistry in resected surgical specimens of 66 Barrett's adenocarcinomas and 32 cases of Barrett's mucosa (with dysplasia in 17 cases).Results:  Epithelial expression of COX‐2 protein was increased in Barrett's mucosa compared with normal oesophagus. Epithelial expression of COX‐2 was found in 91% of Barrett's specialized mucosa negative for dysplasia, 94% of Barrett's mucosa with dysplasia, and 97% of Barrett's adenocarcinoma. COX‐2 expression was significantly higher in the well‐differentiated adenocarcinomas when compared with the poorly differentiated tumours. There was no significant correlation between COX‐2 expression and the other pathological features of the tumours. Survival analysis showed no significant prognostic value for COX‐2.Conclusion:  Our results confirm up‐regulation of COX‐2 in Barrett's oesophagus—metaplastic and dysplastic—and in Barrett's adenocarcinoma. Increased COX‐2 expression did not differ during the progression from Barrett's oesophagus negative for dysplasia to Barrett's adenocarcinoma and is related to adenocarcinoma whose histology is well differentiated. This suggests that enhanced expression of COX‐2 may occur early during Barrett's‐associated neoplastic transformation.
Assessment of cell cycle state may facilitate the histopathological diagnosis of malignant mesothelioma
Authors: Sington J D , Morris L S , Nicholson A G , Coleman N 
Published: December 2004

Aims:  The differentiation of benign pleural conditions from malignant mesothelioma may be difficult, especially with a small biopsy. We have tested the hypothesis that assessment of the cell cycle status is of value in the histopathological diagnosis of such biopsies, by comparing 33 malignant mesotheliomas with 36 cases of reactive mesothelial hyperplasia and reactive pleural fibrosis.Methods and results:  Biopsies were investigated for proliferative status by immunostaining for a novel antibody, MCM2, all of which showed nuclear expression of MCM2 at higher frequency than Ki67 (P < 0.0001). Counts in areas of maximum tumour staining showed significantly higher labelling indices (LIMax) in epithelioid and sarcomatoid mesotheliomas compared with reactive mesothelial hyperplasia and reactive pleural fibrosis (P < 0.0001 for both). Average counts (LIAve) revealed a significant increase in epithelioid mesothelioma compared with reactive mesothelial hyperplasia (P < 0.0001).Conclusion:  We consider MCM2 to be a useful adjunct in the differential diagnosis of malignant mesothelioma.
Synovial sarcoma in older patients: clinicopathological analysis of 32 cases with emphasis on unusual histological features
Authors: Chan J A , McMenamin M E , Fletcher C D M 
Published: December 2004

Aims:  To analyse the clinicopathological features of synovial sarcoma presenting in patients over 60 years of age, an uncommon subset which have not been specifically studied.Methods and results:  Thirty‐two cases of primary synovial sarcoma in patients aged ≥60 years were retrieved from the authors' consultation files. These were analysed histologically and immunohistochemically and clinical follow‐up was obtained in 26 cases (median duration 41 months). Mean age at diagnosis was 71.6 years (range 60–84) with 19 females and 13 males. Anatomical sites were lower limb (n = 13), upper limb (n = 5), lung/pleura (n = 5), trunk (n = 4), head/neck (n = 3), mediastinum (n = 1) and scrotum (n = 1). Histologically, 23 were monophasic and nine were biphasic; 14 were poorly differentiated, of which five showed focally marked pleomorphism. Unusual features in two cases each included organoid nodules, granular cell change, squamous metaplasia and papillary architecture. Ten patients developed local recurrence and 11 developed metastases, of whom seven died. Large tumour size, poorly differentiated morphology and high mitotic rate correlated with poor outcome.Conclusions:  Less than 10% of synovial sarcomas occur in patients over 60, in which age group this diagnosis is often not considered. Despite inevitable bias in consultation material, it seems that these cases, when compared with younger age groups, more often show poorly differentiated histology and more often develop at unusual locations.
Prognostic indicators for gastrointestinal stromal tumours: a clinicopathological and immunohistochemical study of 108 resected cases of the stomach
Authors: Wong N A C S , Young R , Malcomson R D G , Nayar A G , Jamieson L A , Save V E , Carey F A , Brewster D H , Han C , Al‐Nafussi A 
Published: December 2004

Aims:  Whether immunohistochemical markers increase accuracy in predicting prognosis for gastrointestinal stromal tumours (GISTs) remains uncertain. However, past studies have used only small, heterogeneous patient groups. Our aim was to test previously studied and more novel morphological features as well as four immunohistochemical markers as prognostic indicators amongst a large cohort of surgically resected, gastric GISTs.Methods and results:  Tissues from 127 gastric mesenchymal tumours were collected retrospectively and subjected to repeat histological assessment and immunophenotyping. Further immunohistochemistry was performed for Ki67, p53, Bcl‐2 and cyclin D1. Complete follow‐up data were collected for 108 patients with immunophenotyped diagnoses of GIST (i.e. c‐kit+ tumours). At the census point, 52 patients were alive, 24 had died from their GISTs and the remainder of other causes. Univariate analysis showed the following predicted for shorter disease‐specific survival: size ≥50 mm; necrosis, no intratumoral lymphocytes; mitotic count ≥5/50 high power fields; Ki67 labelling index ≥5%; p53 immunopositivity. Of these variables, multivariate analyses showed only mitotic count and, to a lesser extent, Ki67 labelling to be independent prognostic indicators.Conclusions:  Mitotic count remains the best predictor of outcome following surgical resection of gastric GISTs. Ki67 immunohistochemistry does not provide better prognostication and p53, Bcl‐2 and cyclin D1 immunohistochemistry provide no additional prognostication.
Myxoglobulosis in oral extravasation mucocele: an entity?
Authors: Shah K A 
Published: December 2004

Aims:  Myxoglobulosis is a recognized variant of mucocele of the vermiform appendix. Myxoglobulosis has recently been reported in extravasation mucocele of the oral cavity. This morphological study was carried out to identify the prevalence and possible pathogenesis of this unusual feature.Materials and methods:  A retrospective review of archival material diagnosed as oral cavity mucocele was undertaken. This covered a period of 32 months and consisted of 76 cases. In accordance with the proposed traumatic origin of extravasation mucocele, histological changes were classified on the basis of mucin extravasation and cyst formation. Globular structures, as described in the reports of myxoglobulosis, were looked for, as were changes that could be ascribed to their formation.Conclusions:  Globular structures were noted in 22 (31%) of 71 cases of extravasation mucocele. They were present within cysts (11 samples) and in extraluminal connective tissue in the rest. They appeared to originate from alterations in connective tissue collagen following mucin extravasation. Their structure is different from that described in appendicial mucocele. When observed, they are best regarded as part of the normal sequence in the formation of oral cavity extravasation mucocele, without attaching special importance to them.