bluuebunny/crossref_metadata_2025_split huggingface dataset:
Loss of E‐cadherin expression in early gastric cancer
Authors: Blok  , Craanen  , Dekker  , Tytgat  
Published: March 2003

AimsReduction or loss of E‐cadherin expression was examined in early gastric carcinomas and precursor lesions with the following aims: (1) to assess overall E‐cadherin expression in various stages of gastric carcinogenesis; (2) to correlate E‐cadherin expression with the Lauren type, the grade of differentiation and the type of growth pattern of the tumours; and (3) to correlate E‐cadherin expression with lymph node metastasis and overall prognosis.Methods and resultsForty‐five paraffin‐embedded gastrectomy specimens from early carcinomas were examined for the presence of various precursor lesions. The Lauren type, the grade of differentiation and the type of growth pattern were reassessed for all early carcinomas. E‐cadherin expression was examined using antibody HECD‐1. Whereas E‐cadherin was strongly and evenly expressed in the gastric foveolar epithelium, intestinal metaplasia and early gastric carcinomas showed a lower expression. A significant difference in E‐cadherin expression was found between the Lauren types (P < 0.0001). Moreover, an inverse correlation was found between E‐cadherin expression and histological grade (P < 0.0001). Neither a difference in E‐cadherin expression between the various growth types nor an association with lymph node metastasis and overall prognosis was found.ConclusionsThe Lauren types differ in E‐cadherin expression, although reduced E‐cadherin expression in all probability rather reflects poor differentiation than a diffuse growth pattern ‘genotype’. Moreover, E‐cadherin expression does not underlie the difference in biological behaviour of early carcinomas with different types of growth pattern. Finally, E‐cadherin expression is not associated with lymph node status and 5‐year survival rate, at least not in early gastric carcinomas.
Small cell carcinoma of urinary bladder is differentiated from urothelial carcinoma by chromogranin expression, absence of CD44 variant 6 expression, a unique pattern of cytokeratin expression, and more intense γ‐enolase expression
Authors: Iczkowski K A , Shanks J H , Allsbrook W C , Lopez‐Beltran A , Pantazis C G , Collins T R , Wetherington R W , Bostwick D G 
Published: March 2003

AimsSmall cell (neuroendocrine) carcinoma of the urinary bladder is clinically more aggressive than urothelial (transitional cell) carcinoma. We have investigated the immunohistochemical markers most useful in diagnosing small cell carcinoma in bladder.Methods and resultsWe evaluated the expression of chromogranin A, CD44 variant 6 (CD44v6), cytokeratin (CAM 5.2), gamma‐enolase, synaptophysin, and CD45 in 46 small cell carcinomas of the bladder. Small cell and urothelial carcinoma were mixed in 21 (46%) cases. The two immunohistochemical markers with best ability to discriminate between small cell and urothelial carcinoma were chromogranin A and CD44v6. Chromogranin A had 97% specificity for small cell carcinoma, staining 65% of cases with 2+/3+ mean intensity; only one case (5%) of urothelial carcinoma was weakly (1+/3+) positive. CD44v6 was 80% specific for urothelial carcinoma, with immunoreactivity in 60% of cases, compared with 7% of small cell carcinoma cases. In cases positive for CD44v6, the mean percentage of reactive urothelial carcinoma cells was 75% (range 10–100%), greater than the 12% of cells in three cases of small cell carcinoma (P = 0.31); further, the pattern of immunoreactivity was membranous vs. focal cytoplasmic, respectively. All small cell carcinomas stained with one of the three neuroendocrine markers tested; 76% of cases were reactive for synaptophysin and 93% for gamma‐enolase, with specificities of 86% and 73% in comparison to urothelial carcinoma. γ‐enolase staining of small cell carcinoma was more intense (P = 0.01) than for urothelial carcinoma. Cytokeratin CAM 5.2 stained a mean 47% of cells in small cell carcinoma, always in a punctate perinuclear pattern, and 75% in urothelial carcinoma, in a membranous pattern.ConclusionsCD44v6, chromogranin A, and possibly gamma‐enolase and cytokeratin (CAM 5.2) help differentiate small cell carcinoma from urothelial carcinoma.
High‐grade extraskeletal myxoid chondrosarcoma: a high‐grade epithelioid malignancy
Authors: Lucas  , Fletcher  , Adsay  , Zalupski  
Published: March 2003

AimsExtraskeletal myxoid chondrosarcoma is typically a low‐to‐intermediate grade sarcoma that is associated with a prolonged clinical course. High‐grade forms are rare and not well characterized. In this series we report the clinicopathological, immunohistochemical and ultrastructural findings in four cases of high‐grade extraskeletal myxoid chondrosarcoma.Methods and resultsThe patients were three men and one woman (ages 34–73 years) with tumours located in the thigh (two cases), paraspinal soft tissue and perineum. Three patients had metastases, one at 12 weeks, one at 10 months, and one at presentation of recurrent tumour. In the latter case the original tumour was low grade and became high grade when it recurred 3.5 years later. All three patients died of disease. One patient was lost to follow‐up. The most striking histological feature in all four tumours was the presence of numerous large epithelioid cells. These cells were arranged in cords within myxoid matrix and in sheets devoid of matrix. Two tumours had areas of conventional extraskeletal myxoid chondrosarcoma intermixed with the high‐grade areas. One tumour showed transition to high‐grade spindle cell sarcoma. One tumour had cells with rhabdoid features. Immunohistochemically, two tumours focally expressed S100 protein, and one focally expressed EMA. All were negative with cytokeratin, desmin, smooth muscle actin, HMB45, CD31 and CD34. Ultrastructural features in three cases were compatible with chondrosarcoma; one tumour had aggregates of microtubules within rough endoplasmic reticulum, a characteristic feature of this tumour.ConclusionsHigh‐grade extraskeletal myxoid chondrosaroma is a rare and aggressive soft tissue sarcoma, and should be included in the differential diagnosis of other epithelioid malignancies.
Genotypic and phenotypic alterations in Epstein–Barr virus‐associated lymphoma
Authors: Ohshima  , Suzumiya  , Kanda  , Haraoka  , Kawasaki  , Shimazaki  , Kikuchi  
Published: March 2003

AimsEpstein–Barr virus (EBV) is associated with numerous reactive and neoplastic lymphoproliferative disorders. In vitro, EBV infection can transform B‐lymphocytes and induce phenotypic alterations. This study presents the clinicopathological features of four cases with malignant lymphoma, which showed phenotypic and/or genotypic alterations during the course of the disease.Methods and resultsTo determine the type of EBV genotype, we performed polymerase chain reaction (PCR) for lymphocyte‐defined membrane antigen (LYDMA) of EBV, subtype A/B and latent membrane protein (LMP)‐1 deletion. In addition, we analysed the terminal repeat (TR) band of EBV and receptor genes (T‐cell receptor gene, TCR; immunoglobulin gene heavy chain, IgH) for EBV‐infected cell clonality. Double staining of cell markers (B, T‐lymphocytes; histiocytes), and in‐situ hybridization (ISH) for EBV were performed using tissues obtained during the course of the disease. The first case showed genotypic and phenotypic alterations of T‐cell type to B‐cell type. The first TCR rearrangement and T‐cell markers (CD3+, CD4+, CD8−) were lost and IgH rearrangement and B‐cell markers (CD19+, CD20+) were identified. During the course of the disease, EBV‐TR bands changed in size; however, the EBV genotype type B, LMP1 deletion type, and single LYDMA band remained the same. The initial T‐cell lymphoma clone was considered to be different from the latter B‐cell lymphoma clone. The second case showed phenotypic alterations. The first B‐cell marker (CD19+, CD20+, CD68−) changed to histiocytic markers (CD19−, CD20−, CD68+). However, IgH rearrangement and EBV‐TR bands remained the same throughout the course of the disease and EBV genotype type A, LMP1 deletion type, and single LYDMA band remained unchanged. The third case showed phenotypic alterations. The B‐cell marker (CD20+) was lost; however, IgH rearrangement of PCR and EBV genotype remained the same. In the second and third cases, the initial lymphoma clones were considered to be same as the latter clones. The last case showed lineage alterations from Hodgkin's disease to natural killer (NK) cell leukaemia. However, EBV genotype did not change. The second case and Hodgkin's disease showed LMP expression, but the first and third cases showed no LMP, and EBNA2 was not detected in all cases.ConclusionsWe report the genotypic and/or phenotypic alterations in four patients with EBV‐associated lymphoma/leukaemia. However, EBV genotype did not change in all four. These findings suggest that EBV might induce the cell marker and lineage alteration in vivo, as in vitro.
Spinal melanotic schwannoma: a tumour with poor prognosis
Authors: Vallat‐Decouvelaere  , Wassef  , Lot  , Catala  , Moussalam  , Caruel  , Mikol  
Published: March 2003

AimTo clarify the prognosis of melanotic schwannoma. This is a rare tumour which is generally considered as a benign lesion, reported in many cases with a short follow‐up only.Methods and resultsFive cases of spinal melanotic schwannoma were retrospectively studied. The tumours were examined using standard histological, immunohistochemical and ultrastructural methods. No features of malignancy (high mitotic count, atypia or necrosis) were found in the primary tumours. The follow‐up period ranged from 3 to 7 years. Malignant clinical behaviour was clear‐cut in four cases: three patients died from metastases to various sites and one presented several discrete spinal tumours of the same type seven years after the first operation. Only one patient presented no recurrence and was free of disease 6 years after initial diagnosis. The review of 57 cases of the literature (including our cases), showed that 15% of the cases had recurrences and 26.3% were complicated by metastasis. Only 53% of the cases followed for more than 5 years, were free of disease vs. 67.5% of the cases with shorter follow‐up. Twenty additional cases had no follow‐up.ConclusionAppropriate long‐term follow‐up is required for all melanotic schwannomas, as it may recur or metastasize after more than 5 years, even in the absence of overt malignant histological features.
A neural network approach to the biopsy diagnosis of early acute renal transplant rejection
Authors: Furness  , Levesley  , Luo  , Taub  , Kazi  , Bates  , Nicholson  
Published: March 2003

AimsTo develop and test a neural network to assist in the histological diagnosis of early acute renal allograft rejection.Methods and resultsWe used three sets of biopsies to train and test the network: 100 ‘routine’ biopsies from Leicester; 21 selected difficult biopsies which had already been evaluated by most of the renal transplant pathologists in the UK, in a study of the Banff classification of allograft pathology and 25 cases which had been classified as ‘borderline’ according to the Banff classification in a review of transplant biopsies from Oxford. The correct diagnosis for each biopsy was defined by careful retrospective clinical review. Biopsies where this review did not provide a clear diagnosis were excluded. Each biopsy was graded for 12 histological features and the data was entered into a simple single layer perception network, designed using the MATLAB neural network toolbox. Results were compared with logistic regression using the same data, and with ‘conventional’ histological diagnosis. If the network was trained only with the 100 ‘routine’ cases, its performance with either of the other sets was poor. However, if either of the ‘difficult’ sets was added to the training group, testing with the other ‘difficult’ group improved dramatically; 19 of the 21 ‘Banff’ study cases were diagnosed correctly. This was achieved using observations made by a trainee pathologist. The result is better than was achieved by any of the many experienced pathologists who had previously seen these biopsies (maximum 18/21 correct), and is considerably better than that achieved by using logistic regression with the same data.ConclusionA neural network can provide a considerable improvement in the diagnosis of early acute allograft rejection, though further development work will be needed before this becomes a routine diagnostic tool. The selection of cases used to train the network is crucial to the quality of its performance. There is scope to improve the system further by incorporating clinical information. Other related areas where this approach is likely to be of value are discussed.
Variation in the histological pattern of nodal involvement by gamma/delta T‐cell lymphoma
Authors: Charton‐Bain  , Brousset  , Bouabdallah  , Gaulard  , Merlio  , Dubus  , Rostaing  , de Roux  , Weiller  , Hassoun  , Xerri  
Published: March 2003

AimsGamma‐delta (γδ) T‐cell non‐Hodgkin's lymphomas (NHLs) usually present with liver, spleen and marrow infiltration. Lymph node involvement by γδ T‐cell NHL has been rarely documented so far; its histological pattern needs to be further defined.Methods and resultsTwo cases of nodal γδ T‐cell NHL are reported: case 1, a 44‐year‐old man, presented with cytomegalovirus retinitis and superficial lymphadenopathies. Histological analysis of an inguinal lymph node showed complete destruction by a diffuse pleomorphic lymphoid proliferation, which was positive for CD2, CD3, CD43, CD45, TIA‐1 and granzyme B, and displayed a γδ phenotype (δTCR1+, Vδ1+, Vδ2−, Vδ3−, βF1−). Bone marrow was normal. Case 2, a male 24‐year‐old patient with a history of renal transplantation, presented with hepatosplenomegaly and supraclavicular lymph node enlargement. Lymph node architecture was globally preserved. Peripheral sinuses contained scattered nests of medium‐sized irregular lymphoid cells. Bone‐marrow was infiltrated. Phenotype showed positivity for CD2, CD3, CD45 and TIA1 and expression of γδ TCR (δTCR1+, δV1+, δV2−, δV3−, βF1−). Both patients died a short time after diagnosis.ConclusionsThese observations suggest that at least two forms of nodal γδ T‐cell NHL may be encountered: one mimicking classical αβ T‐cell NHL, with diffuse pleomorphic cell proliferation, and one displaying sinusoidal neoplastic infiltration suggesting a close relationship with hepatosplenic γδ T‐cell NHL.
Association of Helicobacter pylori‐dependent gastritis with gastric carcinomas in young Japanese patients: histopathological comparison of diffuse and intestinal type cancer cases
Authors: Koshida Y , Koizumi W , Sasabe M , Katoh Y , Okayasu I 
Published: March 2003

Aims : The causal relationship of H. pylori gastric colonization with gastric cancer development has not as yet been fully elucidated. The prevalence of H. pylori infection increases with age in the asymptomatic population in Japan, and reaches a high plateau in those older than 40 years. The objective of this study was to assess the link between H. pylori and gastric carcinomas in patients younger than 40 years. Methods and results : Detection of H. pylori and assessment of background mucosa based on the Sydney system was performed histopathologically for 40 Japanese gastric cancer cases younger than 40 years and compared with 40 age‐ and sex‐matched controls. H. pylori infection in gastric mucosa was detected significantly more frequently (P < 0.001) in patients with cancer (29/40; 72.5%) than in controls (11/40; 27.5%). Additionally, by histopathological comparison between intestinal (18 cases) and diffuse (70 cases) types of young gastric cancer patients, mucosal atrophy and intestinal metaplasia were found to coexist with acute and chronic inflammation in the background mucosa of both intestinal and diffuse types, being significantly more prevalent than in young controls. Conclusions : As well as the high prevalence of H. pylori in young subjects with gastric cancer, it is clear that persistent infection induces mucosal damage, resulting in atrophy and intestinal metaplasia. Thus, acute/chronic gastritis could play an essential role in the early development of neoplasia in the stomach.
Anti‐mesothelial markers in sarcomatoid mesothelioma and other spindle cell neoplasms
Authors: Attanoos R L , Dojcinov S D , Webb R , Gibbs A R 
Published: March 2003

AimsTo undertake a comparative evaluation of three antimesothelial markers (thrombomodulin, cytokeratin 5/6 and calretinin) with broad spectrum cytokeratin (AE1/AE3) in differentiating between sarcomatoid mesothelioma and a spectrum of spindle cell neoplasms.Methods and resultsThirty‐one malignant sarcomatoid mesotheliomas were studied. Calretinin expression was focally identified in 12 (39%) tumours and thrombomodulin and cytokeratin 5/6 immunoreactivity was seen in nine (29%) cases. In comparison there was strong diffuse cytoplasmic reactivity with the broad spectrum cytokeratin (AE1/AE3) in 24 of 31 (77%) tumours. Thirty mixed spindle cells neoplasms were studied. No calretinin expression was identified in any case. Thrombomodulin immunoreactivity was identified in four (16%) cases (two angiosarcomas, two high‐grade sarcomas, not otherwise specified). Cytokeratin 5/6 expression was seen in one high‐grade pulmonary sarcoma originally termed malignant fibrous histiocytoma. None of the antimesothelial markers was expressed in the four spindle cell carcinomas studied. In contrast, broad spectrum cytokeratin was diffusely expressed in all four spindle cell carcinomas (three pulmonary, one renal), both synovial sarcomas, both malignant mixed Müllerian tumours, one of three pulmonary leiomyosarcomas and two of nine sarcomas, not otherwise specified.ConclusionsImmunohistochemistry has a more limited role in the diagnosis and distinction of sarcomatoid mesothelioma from other spindle cell neoplasms. The combination of a broad spectrum cytokeratin with calretinin combines both high sensitivity (77% for AE1/AE3) with high specificity (100% for calretinin) for sarcomatoid mesothelioma and can be diagnostically useful. The mesothelial markers, thrombomodulin and cytokeratin 5/6, are not useful alone in the diagnosis of sarcomatoid mesothelioma as each shows insufficient antibody sensitivity, although together they complement calretinin.
Changing patterns of histological subgroups during therapy of Ph1+ chronic myelogenous leukaemia
Authors: Thiele J , Kvasnicka H M , Schmitt‐Graeff A , Leder L D , Schaefer H E 
Published: March 2003

AimsBone marrow histopathology reveals a striking heterogeneity at diagnosis of Philadelphia chromosome positive (Ph1+) chronic myelogenous leukaemia (CML). Based on semiquantitative evaluations of the number of megakaryocytes and the content of fibres, various histological subtypes have been postulated. However, little information exists on whether these groups represent stable categories of the different classification systems and whether therapeutic regimes exert any influence on the putative shift of histological patterns.Methods and resultsA retrospective clinicopathological study was performed on 396 bone marrow biopsies derived from 173 patients. There were at least two representative trephines taken at diagnosis and at median intervals of 16 months. Processing of the specimens involved immunostaining with CD61 (megakaryopoiesis) and Ret40f (erythropoiesis) and Gomori's silver impregnation technique. Based on morphometric analysis and in accordance with the general appearance of bone marrow histology three different histological subtypes were distinguished. These consisted of a granulocytic (51 patients), a predominantly megakaryocytic (73 patients) and a myelofibrotic pattern (49 patients). Follow‐up biopsies revealed that a significant transition of histological groups occurred and that, independently of treatment modalities, the myelofibrotic category was associated with an unfavourable prognosis. Of the 124 patients without myelofibrosis at onset, 42% later transformed into the myelofibrotic subtype. However, these patients showed no prevalence of either a pre‐existing granulocytic or megakaryocytic growth. Myelofibrotic changes were significantly associated with interferon (IFN) and busulfan (BU) therapy. On the other hand, a transition of a myelofibrotic into a nonfibrotic subtype was detectable in 17 of the 49 patients under study and related to hydroxyurea (HU) treatment.ConclusionsHistological classification systems of bone marrow features in CML do not represent stable patterns, but may be significantly altered by therapy, in particular IFN and HU.
Borrelia burgdorferi‐associated cutaneous marginal zone lymphoma: a clinicopathological study of two cases illustrating the temporal progression of B. burgdorferi‐associated B‐cell proliferation in the skin
Authors: Goodlad J R , Davidson M M , Hollowood K , Batstone P , Ho‐Yen D O 
Published: March 2003

A relationship between Borrelia burgdorferi and primary cutaneous B‐cell lymphoma (PCBCL) has recently been confirmed following demonstration of the organism in lesional skin of patients with PCBCL. We report herein two cases of B. burgdorferi‐associated PCBCL which strengthen this association by demonstrating the organism in cutaneous B‐cell infiltrates present at sites in which PCBCL subsequently developed.All studies were performed on formalin‐fixed paraffin‐embedded tissues. These were examined by routine light microscopy and immunohistochemically by a standard streptavidin–biotin–complex technique. Genotypic studies were also undertaken using semi‐nested polymerase chain reaction (PCR) for immunoglobulin heavy chain gene rearrangement, and nested PCR for B. burgdorferi flagellin gene. Both patients presented with erythematous skin lesions, biopsy of which showed dense perivascular infiltrates comprising small T‐lymphocytes and collections of B‐blasts. Primary cutaneous marginal zone lymphoma (MZL) developed subsequently in both cases at the same site. PCR for B. burgdorferi flagellin gene was positive in the perivascular lymphocytic infiltrates and the succeeding lymphomas in both patients.These results show that, at least in some instances, PCBCL arises from chronically stimulated lymphoid tissue acquired in the skin in response to B. burgdorferi infection. This may have significant therapeutic implications and warrant further studies on the extent of this association.
Expression of CD44 and its variant isoform v3 has no prognostic value in gastric cancer
Authors: Setälä L , Lipponen P , Tammi R , Tammi M , Eskelinen M , Alhava E , Kosma V‐M 
Published: March 2003

To study the controversial role of transmembrane glycoprotein CD44 as a moderator of tumour spread and as a prognostic factor in gastric cancer.The expression of all CD44 forms and that with exon v3 was assessed in 198 stage I‐IV gastric adenocarcinomas using immunohistochemistry. CD44 expression was found in 72% and CD44v3 in 55% of the cases. The intensity of CD44 expression was associated with the level of invasion and with hyaluronan expression, while the frequency of CD44 positive cells was not significantly related to any of the clinical or histological features of the tumours. CD44v3 expression failed to show any association with the clinical or histological variables examined. Neither total CD44 nor CD44v3 expression affected survival. The most important prognostic factors in this cohort were the level of invasion, lymph node status, tumour size and vascular or perineural invasion.Changes in CD44 or CD44v3 expression level do not predict tumour spread or patient survival in gastric cancer.