bluuebunny/crossref_metadata_2025 huggingface dataset:
Lectin binding and expression of blood group‐related antigens in carcinoma‐in‐situ and invasive carcinoma of urinary bladder
Authors: NAKANISHI K. , KAWAI T. , SUZUKI M.
Published: April 2007

To determine whether histochemical reactivities of carcinoma‐in‐situ of the urinary bladder differ from those of invasive transitional cell carcinoma, we tested a profile of eight different lectins and three antibodies directed against blood group‐related antigens for 15 cases of carcinoma‐in‐situ and 26 cases of non‐papillary (6 superficially and 20 deeply) invasive transitional cell carcinoma that had been diagnosed according to the histopathological criteria of the International Union against Cancer. For biotin‐labelled lectins and monoclonal antibodies to mouse blood group‐related antigens, the avidin–biotin peroxidase complex method was applied. Positive histochemical reactions of peanut agglutinin without neuraminidase treatment—PNA N(–)—in the 20 deeply invasive tumour cases were significantly higher than those in the 15 carcinoma‐in‐situ cases (P<0.05). In contrast, the reactions of blood group‐related antigens in the 20 deeply invasive tumour cases were significantly lower than those in the 15 carcinoma‐in‐situ cases or the 11 normal controls (P<0.05). The results confirm previously reported studies of the staining of PNA N(–) and blood group‐related antigens on carcinoma‐in‐situ and invasive tumours of urothelial organs. The application of lectins and blood group‐related antigens to the histopathology of urinary bladder cancer may be helpful in the differential diagnosis of carcinoma‐in‐situ from invasive cancer, but neither PNA N(–) nor blood group‐related antigens can be solely reliable in this.
Epitheliotropism in high‐grade lymphomas of mucosa‐associated lymphoid tissue
Authors: BATEMAN A. C. , WRIGHT D. H.
Published: April 2007

Low‐grade lymphomas of mucosa‐associated lymphoid tissue (MALT) characteristically show centrocyte‐like cells, plasmacytic differentiation, follicular colonization and lymphoepithelial lesions (epitheliotropism). High‐grade lymphomas of MALT are thought to lack these features and can only be identified as MALT lymphomas with confidence if they are admixed with residual low‐grade tumours. We studied 23 cases of MALT lymphoma of the thyroid. Six were predominantly low‐grade, 12 were predominantly high‐grade, and five contained both low‐ and high‐grade areas. All cases were stained for cytokeratin, epithelial membrane antigen and laminin using an immunoperoxidase technique. The low‐grade lymphomas all contained lymphoepithelial lesions, generally in the form of clusters of intra‐acinar centrocyte‐like cells. Eleven of the 12 high‐grade MALT lymphomas of the thyroid also showed lymphoepithelial lesions. These appeared in three forms: follicles or clusters of epithelial cells infiltrated by groups of centrocyte‐like cells, intra‐acinar clusters of blast cells, or irregular invasion of islands of epithelial cells by blast cells. The first pattern presumably represented residual low‐grade tumour over‐run by high‐grade lymphoma. The second two patterns indicated that the factors that result in epitheliotropism in low‐grade MALT lymphomas are also prsent in high‐grade tumours. Following this study we identified epitheliotropism in single examples of high‐grade MALT lymphomas of the bronchus and small intestine. Previous failure to recognize epitheliotropism in high‐grade MALT lymphomas of the gastrointestinal tract may be due to loss of the affected epithelium. The localization and relatively good prognosis of high‐grade MALT lymphomas may be related to retention of MALT characteristics including epitheliotropism.
Primary low‐grade B‐cell lymphoma of the conjunctiva: a mucosa‐associated lymphoid tissue type lymphoma
Authors: WOTHERSPOON A. C. , DISS T. C. , PAN L. X. , SCHMID C. , KERR‐MUIR M. G. , LEA S. HARDMAN , ISAACSON P. G. , S HARDMAN LEA , G ISAACSON P.
Published: April 2007

We describe the clinical presentation, morphology, immunophenotypic features and molecular biology of seven cases of conjunctival lymphoid infiltration. In five cases there was either immunophenotypic or molecular evidence of B‐cell lymphoma. Each of these cases showed the morphological, immunophenotypic and molecular feature of low‐grade B‐cell lymphoma of mucosa‐associated lymphoid tissue (MALT) type. The findings suggest that most conjunctival lymphomas are of this type and explains their uniformly favourable prognosis.
Divergent differentiation in small round‐cell tumours of the soft tissues with neural features—an analysis of 10 cases
Authors: PEARSON J.M. , HARRIS M. , EYDEN B.P. , BANERJEE S.S.
Published: April 2007

A series of 10 small round‐cell tumours, having in common evidence of neural differentiation, were investigated by immunohistochemistry and electronmicroscopy. In seven, evidence of divergent muscle and/or epithelial differentiation was found. This phenomenon thus appears more common than previously appreciated and suggests that there may be a continuous and overlapping phenotypic spectrum from Ewing's tumour of soft tissue to intra‐abdominal desmoplastic small cell tumour.
Reactive human bile ductules express parathyroid hormone‐related peptide
Authors: ROSKAMS T. , CAMPOS R.V. , DRUCKER D.J. , DESMET V.J.
Published: April 2007

Various cholestatic liver diseases as well as regeneration after submassive necrosis are accompanied by a striking increase in the number of bile ductules. These reactive bile ductules are thought to arise either from proliferation of pre‐existing bile ductules or bile ductule‐related facultative stem cells, or from ductular metaplasia of hepatocytes. Recently, we found that reactive bile ductules display neuro‐endocrine features, and speculated that the substance(s), produced in the neuro‐endocrine granules, might play a role in their growth and/or differentiation through an autocrine or paracrine pathway. Parathyroid hormone‐related peptide has been shown to be encoded by a growth factor‐regulated gene that may play a role in cell growth and differentiation. We studied the immunohistochemical expression of this peptide in human liver, including three normal biopsies, 11 cases of cholestatic liver disease, six cases of focal nodular hyperplasia and three cases of regenerating liver. In regenerating liver, primary biliary cirrhosis, primary sclerosing cholangitis and partial or intermittent obstruction, the majority of reactive ductular cells expressing neuro‐endocrine markers also expressed parathyroid hormone‐related peptide. In focal nodular hyperplasia, a smaller number of bile ductular cells expressed the peptide. These findings suggest that parathyroid hormone‐related peptide is localized in bile ductular cells and may indicate a role for this hormone in the growth and/or differentiation of human reactive bile ductules.
Expression of adhesion molecules in Langerhans' cell histiocytosis
Authors: RUCO L.P. , STOPPACCIARO A. , VITOLO D. , UCCINI S. , BARONI C.D.
Published: April 2007

Expression of adhesion molecules was investigated in six biopsy specimens of Langerhans' cell histiocytosis using immunocytochemistry. Cells with Langerhans' cell histiocytosis morphology were stained for ICAM‐1, for the beta‐1 integrins alpha‐4 (VLA‐4) and alpha‐5 (VLA‐5), and for the beta‐2 integrins LFA‐1, MAC‐1 and p150,95. This pattern of reactivity was different from that of epidermal Langerhans' cells of the normal skin which were not immunostained. A variable number of CD68+ multinucleated giant cells was present in five biopsies. They were less reactive than the cells of Langerhans' cell histiocytosis for alpha‐4 (VLA‐4) and LFA‐1, were positive for MAC‐1 and p150,95 and were characterized by prominent expression of the beta‐1 integrins alpha‐2 (VLA‐2), alpha‐3 (VLA‐3) and of VnR (alpha‐v/ beta‐3). The repertoire of adhesion molecules expressed by giant cells is indicative of profound cell‐matrix interactions, whereas that of Langerhans' histiocytosis cells suggests particularly active cell–cell interactions. Blood vessels of the lesions were stained for beta‐1 integrins, for vitronectin receptor and for molecules involved in adhesion and trans‐endothelial migration of circulating leukocytes, such as ICAM‐1, VCAM‐1 and E‐selectin. Additional findings were the observation of CD1a+ multinucleated giant cells in a single case, suggesting a possible lineage relationship with the histiocytosis cells, and the demonstration of some Ki‐67+ Langerhans' cell histiocytosis cells and CD1a+ mitotic figures in four of six cases, indicating local proliferation of Langerhans' histiocytosis cells.
Squamous cell carcinomas. An immunohistochemical study of cytokeratins and involucrin in primary and metastatic tumours
Authors: SUO Z. , HOLM R. , NESLAND J.M.
Published: April 2007

The expression of cytokeratins (CK) 1, 4, 5/6, 8, 13, 18, 19 and 20 and involucrin in 42 cases of squamous cell carcinomas from various locations was examined. The tumours expressed CK5/6 in 55%, CK8 in 76%, CK13 in 43% and CK19 in 95% of cases. The CK5/6‐positive primary tumours were from uterine cervix, head and neck, lung, skin, oesophagus is and urinary bladder, and the CK13‐positive primary tumours were from uterine cervix, lung and vulva. Metastatic squamous cell carcinomas from head and neck more frequently expressed CK5/6 and 13, 7/7 (100%) and 6/7 (86%) compared with 3/5 (60%) and 0/5 (0%) in the primary squamous cell carcinomas. Few cases were CK1, CK4 and CK18 immunoreactive, CK20 immunoreactivity was not observed. Involucrin was expressed in 71% of tumours, and most of the involucrin‐positive cells were located at the central parts of tumour cell clusters except for one case in which the peripheral cells around tumour cell clusters were positive. Thus, expression of the so‐called simple epithelial markers CK8 and CK19 occurs in the majority of squamous cell carcinomas. The absence of CK20 immunoreactivity may be helpful in differential diagnosis.
Papillary cystadenoma of the epididymis: a report of two cases with an immunohistochemical study
Authors: CALDER C.J. , GREGORY J.
Published: April 2007

Two cases of papillary cystadenoma of the epididymis are described. An immunohistochemical study demonstrates that these lesions have a similar pattern of immunostaining to the normal efferent epididymal ductules. This finding supports the theory that epididymal papillary cystadenomas originate from these ductules and are true epithelial tumours of the epididymis.
T‐cell‐rich B‐cell lymphoma presenting as liver disease
Authors: KHAN S.M. , COTTRELL B.J. , MILLWARD‐SADLER G.H. , WRIGHT D.H.
Published: April 2007

We describe a series of eight cases of T‐cell‐rich B‐cell lymphoma diagnosed on liver biopsy and collected over a period of 15 years. Of seven cases that were referred from elsewhere, in only one was the correct diagnosis of B‐cell lymphoma suggested. Common errors included misdiagnosis as inflammatory disease on histology, and misinterpretation as T‐cell lymphoma on immunohistochemistry. However, the cases had a distinct morphological appearance and immunohistochemical profile. They showed a lymphohistiocytic or granulomatous infiltrate, usually centred on portal tracts and containing abundant small T‐cells and scanty B‐cell blasts. All patients had an atypical clinical presentation which favoured non‐neoplastic liver disease. In seven cases liver involvement represented Stage IV disease and in one case disease was confined to the liver consistent with a primary hepatic lymphoma. Despite combination chemotherapy, the prognosis was poor with no patients surviving beyond 15 months from diagnosis. We believe T‐cell‐rich B‐cell lymphoma to be an under‐recognized subset of non‐Hodgkin's lymphoma that may mimic primary liver disease.
A histological morphometric study of nuclear size in benign and malignant neoplasms of the human cheek
Authors: JIN Y. , WHITE F.H. , YANG L.
Published: April 2007

This report describes the application of simple morphometric methods to generate quantitative data on nuclear size from tissue sections of normal, benign and malignant oral epithelium of the cheek. Measurements of nuclear areas of basal and spinous cells from cheek mucosa were made on haematoxylin and eosin‐stained sections using a Zeiss VIDAS image analyser. The lesions examined comprised benign squamous cell papillomas and islands of cells from invasive squamous cell carcinomas. Normal control epithelium was obtained from the biopsy margins of non‐neoplastic lesions. The nuclear areas (An) were obtained by direct measurement whereas the nuclear diameters (Dn) were determined automatically. In both basal and spinous strata, values for both these nuclear parameters were lowest in normal tissue and increased progressively through benign papillomas, with the highest values being found invariably in carcinomas. Statistically significant differences were detected between both normal and carcinoma and between papilloma and carcinoma. The morphometric parameters An and Dn are of value in distinguishing benign from malignant lesions of the human cheek.
The prognostic significance of the DNA content in Ewing's sarcoma: a retrospective cytophotometric and flow cytometric study
Authors: DIERICK A.M. , LANGLOIS M. , OOSTVELDT P. VAN , ROELS H.
Published: April 2007

The DNA content of the cell nuclei of Ewing's sarcoma was analysed by means of cytophotometry in situ with image analysis in Feulgen‐stained sections in 37 patients, and by retrospective flow cytometry according to the method of Hedley in 26 patients. Different histogram patterns were obtained: normal unimodal or bimodal DNA distributions and abnormal DNA distributions with one or two stem lines, or an abnormal DNA distribution with no stem lines. Both methods enabled us to make a distinction between two groups of Ewing's sarcomas with a different prognosis. All patients with aneuploid tumours died within 5 years after the initial diagnosis. Eleven of 19 (58%) patients with a normal DNA distribution in their tumour, as determined by cytophotometry, are still alive and in good health with a mean survival period of 7.5 years, ranging from 2 to 19 years. Of the group of patients in which flow cytometry revealed a normal DNA pattern, eight of 15 (53%) are still alive and in good health, with a mean survival period of 8 years. These results indicate that both techniques are reliable methods for obtaining prognostic information in Ewing's sarcomas. However, cytophotometry in situ yielded a better discrimination for the overall survival (P < 0.01) than did flow cytometry (P <0.05). In 19% of the cases there was a discrepancy between the DNA histograms obtained with the two techniques. In five of 26 cases the DNA distributions were classified as normal by one method and aneuploid by the other. Tumour cell representation or selective loss of cells during enzymatic treatment may be responsible for this discrepancy.
Gold in the dermis following chrysotherapy: histopathology and microanalysis
Authors: KEEN C.E. , BRADY K. , KIRKHAM N. , LEVISON D.A.
Published: April 2007

Paraffin‐embedded sections of skin from patients with rheumatoid arthritis treated with gold who had developed skin rashes were examined by light microscopy and scanning electronmicroscopy with microanalysis. Sparse, small, brown or black granules in plump, often elongated cells in the dermis were shown to contain gold by energy dispersive X‐ray microanalysis. These cells expressed some macrophage markers. The amount of gold present showed some correlation with the total gold dose. Gold was not confined to lesional skin. In one case where uninvolved skin was examined, more gold was found there than in lesional skin.
Detection of Epstein–Barr virus nucleic acid sequences and protein in nodal T‐cell lymphomas: relation between latent membrane protein‐1 positivity and clinical course
Authors: BRUIN P.C. DE , JIWA N.M. , VALK P. VAN DER , HEERDE P. VAN , GORDIJN R. , OSSENKOPPELE G.J. , WALBOOMERS J.M.M. , MEIJER C.J.L.M.
Published: April 2007

Forty‐six nodal T‐cell lymphomas, classified according to the updated Kiel classification, were investigated for the presence of Epstein–Barr virus (EBV) DNA by polymerase chain reaction (PCR), EBER 1 and 2 (EBER 1/2) and latent membrane protein‐1 (LMP‐1) expression. A combination of RNA in situ hybridization and immunohistochemistry was used to establish the phenotype of the Epstein–Barr virus harbouring cells. In 21 of 45 cases Epstein–Barr virus DNA sequences could be detected with the polymerase chain reaction. In 15 cases (14 of 21 EBV PCR positive cases), EBER 1/2 positive cells could be demonstrated. As judged by morphology, EBER 1/2 expression was found in non neoplastic and neoplastic lymphoid cells. Double staining revealed that more than 80% of the EBER 1/2 harbouring cells, lacked B‐, T‐ or histiocytic markers, suggesting down regulation of T‐ and B‐cell markers by Epstein–Barr virus. In eight of 15 cases some EBER 1/2 positive T‐cells (CD3, CD45RO, CD43) morphologically resembling tumour cells were found. In nine of 14 cases tested EBER 1/2 positive non‐neoplastic B‐cells (CD20) were seen. Based on in situ hybridization results, four patterns of EBER 1/2 positive cells were found, i.e. single cells (≤1 per medium power field (mpf), n= 3), scattered (1–25/mpf, n= 4), clustered (26–100/mpf, n= 5) and diffuse (≥100/mpf, n= 3). In eight of 15 cases a clustered or diffuse pattern of EBER 1/2 positive cells was found and these lymphomas were therefore considered to be strongly associated with Epstein–Barr virus. In these lymphomas LMP‐1 expression was found to be associated with an aggressive clinical course and hepatosplenomegaly.
Lipoblastoma and lipoblastomatosis: a clinicopathological study of 14 cases
Authors: MENTZEL T. , CALONJE E. , FLETCHER C.D.M.
Published: April 2007

The clinicopathological features of 14 cases of lipoblastoma and lipoblastomatosis are presented. The age of the patients at presentation ranged from 5 days to 6 years (mean 2.7 years); nine patients were male. Histologically, six cases were circumscribed (lipoblastoma) while eight were diffuse and ill‐defined (lipoblastomatosis). In both groups and in individual cases there was distinct lobulation, as well as a spectrum of adipocytic maturation. Cytologically, the 10 most mature lesions were composed of uniform adipocytes intermixed with only scattered lipoblasts and primitive mesenchymal cells. A notable feature in the other four cases was a prominent myxoid stroma producing a very close resemblance to myxoid liposarcoma. Mitotic figures were rare and always normal in appearance. Atypical nuclei were not evident. Follow‐up in eight patients revealed local recurrence in two. Liposarcoma in patients under 10 years is exceedingly rare, and, in myxoid form, may be almost impossible to distinguish histologically from lipoblastoma. Helpful clues are the lack of lobulation, variable growth pattern and increased nuclear atypia in liposarcoma.
Localized polyarteritis nodosa of breast—report of two cases and a review of the literature
Authors: NG W.F. , CHOW L.T.C. , LAM P.W.Y.
Published: April 2007

Two patients with localized polyarteritis nodosa involving the breast are reported. They presented with tender breast masses which were excised because of suspicion of carcinoma. The pathological features were similar with vasculitis of medium‐sized and small arteries. The medium‐sized arteries showed intimal fibroplasia, fragmentation of internal elastic lamina and inflammatory cellular infiltration. Fibrinoid vasculitis involving small arteries indicated a diagnosis of polyarteritis nodosa rather than giant cell arteritis. Both patients remain well. The differential diagnosis of these two arteritides and of Wegener's granulomatosis involving the breast is reviewed.
Immunocytochemical study of 12E7 in small round‐cell tumours of childhood: an assessment of its sensitivity and specificity
Authors: RAMANI P. , RAMPLING D. , LINK M.
Published: April 2007

12E7 is a monoclonal antibody to the MIC2 gene product and can be applied to formalin‐fixed, paraffin‐embedded tissue. The diagnostic utility of 12E7 as a marker of Ewing's sarcoma and peripheral neuroectodermal tumour was assessed. Immunocytochemical studies were performed on 120 small round‐cell tumours from children and adolescents. Immunoreactivity for 12E7 was seen in 13 of 15 Ewing's sarcomas, 14 of 15 peripheral neuroectodermal tumours, four of 14 embryonal rhabdomyosarcomas, seven of 11 T‐lymphoblastic lymphomas and one T‐cell acute lymphoblastic leukaemia. Immunoreactivity was located on the cell‐membrane of Ewing's sarcomas, peripheral neuroectodermal tumours and lymphoid tumours while rhabdomyosarcomas showed weak, cytoplasmic staining in differentiated rhabdomyoblasts. Studies on alveolar rhabdomyosarcomas (n= 10), acute myeloid leukaemias (3), B‐lymphoblastic lymphomas (8), blastema‐rich nephroblastomas (9), neuroblastomas (20) and retinoblastomas (10) as well as single examples of B‐cell acute lymphoblastic leukaemia, Ki‐1 anaplastic lymphoma of indeterminate phenotype and intra‐abdominal desmoplastic tumour with divergent differentiation were negative. 12E7 is a sensitive marker for the Ewing's sarcoma/peripheral neuroectodermal group of tumours and is useful in distinguishing them from neuroblastoma and blastema‐rich nephroblastoma. However, immunopositivity for 12E7 should be interpreted in conjunction with the results of neural and lymphoid markers.
Amyloidosis
Authors: TAN S.Y. , PEPYS M.B.
Published: April 2007

Amyloidosis is a heterogeneous group of disorders characterized by extracellular deposition of abnormal protein fibrils which are dérived from different proteins in different forms of the disease. Asymptomatic amyloid deposition in a variety of tissues is a universal accompaniment of ageing, and clinical amyloidosis is not rare. Intracerebral and cerebrovascular β‐protein amyloid deposits are a hallmark of the pathology of both sporadic and familial Alzheimer's disease, β2‐microglobulin‐derived amyloid is a common complication of long term haemodialysis, and islet amyloid polypeptide is the fibril protein in the universal islet amyloidosis of type II diabetes mellitus. New fibril proteins have lately been identified in hereditary amyloidosis, including variants of gelsolin, apolipoprotein AI, lysozyme and fibrinogen. The development of radiolabelled serum amyloid P component (SAP) scintigraphy has allowed amyloid to be diagnosed non‐invasively in vivo for the first time, provided unique insight into the distribution and size of amyloid deposits, and yielded novel information on the natural history and the effects of treatment. Amyloid deposits are in a state of dynamic turnover and can regress if new fibril formation is halted. The recent elucidation of the three dimensional structure of human SAP may enable the design of specific therapeutic agents.
Cytoplasmic c‐erbB‐2 protein expression correlates with survival in Dukes' B colorectal carcinoma
Authors: KAY E.W. , MULCAHY H. , WALSH C. BARRY , LEADER M. , O'DONOGHUE D.
Published: April 2007

The prognostic significance of c‐erbB‐2 expression was studied in paraffin wax embedded colorectal cancer tissue using a monoclonal antibody. One hundred and sixty‐four patients with Dukes' B disease were studied. Membranous staining was not detected in any case. Cytoplasmic c‐erbB‐2 staining was seen in 55 cancers (33.5%). Cytoplasmic taining was unrelated to patient age (P= 0.31), sex (P= 0.69), tumour site (P= 0.69), size (P= 0.57), histological grade (P= 0.42) or ploidy status (P= 0.21) but was found more frequently in obstructing cancers (P= 0.03). Mean follow up of the patient population was 6.3 years. Five‐year‐survival estimated by the Kaplan‐Meier life‐table method was 47% for those with cytoplasmic c‐erbB‐2 staining and 77% for those without (log rank analysis;P? 0.0001). Stepwise regression analysis identified c‐erbB‐2 staining (relative risk, 2.51;P= 0.0005) and bowel obstruction (relative risk, 1.99;P= 0.015) as independent predictors of survival. It is suggested that cytoplasmic c‐erbB‐2 expression may provide a useful marker of tumour behaviour in Dukes' B colorectal cancer.
Granular cell change in smooth muscle tumours of skin and soft tissue
Authors: MENTZEL T. , WADDEN C. , FLETCHER C.D.M.
Published: April 2007

Nine smooth muscle tumours, arising at a variety of sites and showing granular cell change of their cytoplasm, have been studied morphologically and immunohistochemically. The age of the patients ranged from 6 to 78 years (median 42 years); seven patients were female. Two tumours each arose in the dermis or subcutaneous tissue while the other five cases were situated in deeper soft tissue. Three of the lesions arose in the lower limbs, two in the pelvis and one each in the regions of the elbow, shoulder, breast and buttock. Follow‐up in eight patients was available and revealed local recurrence in three and pulmonary metastases in two cases. All cases showed at least focally the light microscopic features of a smooth muscle tumour and demonstrated moderate to strong positivity for α‐smooth muscle actin. Five were also HHF‐35 positive and three were desmin positive. Noteworthy was strong positivity for the ‘melanoma associated’ antigen NKI/C3 in all cases. Six cases stained also weakly positive for NSE, but all were S‐100 protein negative. The former is not specific but is the most reliable marker of lesions showing granular cell change. Granular cytoplasmic change represents simply a cytological phenotype, apparently representing a characteristic metabolic alteration, not exclusively associated with Schwann cell tumours. Tumours containing granular cells are best classified according to their line of specific cellular differentiation if possible.
Intravascular histiocytosis
Authors: O'GRADY J.T. , SHAHIDULLAH H. , DOHERTY V.R. , AL‐NAFUSSI A.
Published: April 2007

The majority of cases of intravascular lymphomatosis are B‐cell lymphomas with only the occasional case being of T‐cell type. We report a case of intravascular lymphomatosis in which the proliferating cells were of histiocytic type; the tumour has recurred following treatment.
The anaplastic variant of centrocytic lymphoma is marked by frequent rearrangements of the bcl‐1 gene and high proliferation indices
Authors: OTT M.M. , OTT G. , KUSE R. , POROWSKI P. , GUNZER U. , FELLER A.C. , MÜLLER‐HERMELINK H.K.
Published: April 2007

Ten cases of classic centrocytic lymphoma as defined in the Kiel classification system were investigated for their immunophenotype, their proliferation activity and by means of molecular diagnostics. The findings were compared to those obtained from a group of nine cases of anaplastic centrocytic lymphoma. Both groups showed virtually identical immunohistochemical characteristics with positivity for CD5 and negativity for CD10 and CD23. In the group of anaplastic centrocytic lymphoma, there were considerably higher proliferation indices as documented by staining for the Ki‐67 antigen, up to 80% of the tumour cells being positive. Moreover, the cases of anaplastic centrocytic lymphoma had bcl‐1 gene rearrangements in eight out of nine cases compared with three out of 10 cases of classic centrocytic lymphoma. DNA analysis was not able to detect bcl‐2 gene rearrangement in any case, pointing to a difference compared with lymphomas of germinal centre origin. The coincidence of anaplastic and sometimes blast‐like morphology of the tumour cells, high proliferation index and a rearranged bcl‐1 gene in nearly all cases of anaplastic centrocytic lymphoma support their classification as high‐grade malignant variants of centrocytic lymphoma and suggest a possible role for the bcl‐1 locus not only in the origin but also in the progression of centrocytic lymphomas.
Classification of primary cutaneous T‐cell lymphomas
Authors: WILLEMZE R. , BELJAARDS R.C. , MEIJER C.J.L.M.
Published: April 2007

The term cutaneous T‐cell lymphoma designates a group of neoplasms of skin homing T‐cells that show considerable variation in clinical presentation, histological appearances, immunophenotype and prognosis. The disadvantages of currently available histological classification schemes are discussed and a new classification is presented. This is based on a combination of clinical, histological and immunophenotypic criteria and it recognizes distinct clinico‐pathological entities within this group of diseases.
Evaluation of a histogenetic classification for thymic epithelial tumours
Authors: HO F.C.S. , FU K.H. , LAM S.Y. , CHIU S.W. , CHAN A.C.L. , MÜLLER‐HERMELINK H.K.
Published: April 2007

We reviewed 87 thymic epithelial tumours from Chinese patients and typed them according to the Marino and Müller‐Hermelink classification as updated by Kirschner and Müller‐Hermelink in 1989. Related categories were grouped for statistical analyses; group 1, medullary thymoma and mixed thymoma; group 2, cortical predominant thymoma; group 3, cortical thymoma and well‐differentiated thymic carcinoma; group 4, other thymic carcinomas; and group 5, unclassified. Group 3 tumours were more frequently associated with the myasthenia gravis syndrome compared with group 1 tumours (P=0.001). They also presented at a more advanced stage. Groups 1 and 2 showed an excellent prognosis (100% survival at 10 years). The 10‐year survival for groups 3 and 4 patients was 40% and 30% respectively. Pure medullary thymoma made up a higher proportion of our cases (10.3%) than those of a similar Caucasian study (5.3%). The eight thymic carcinomas (group 4) included two thymic lymphoepitheliomas. We conclude that the histogenetic classification evaluated shows a clear correlation with prognosis and clinical features, even when tested on separate geographic groups, where pathogenetic factors may be different. A common approach to classification of thymic epithelial tumours would greatly facilitate future studies on these possible differences.
Angiomyolipoma of the kidney. Immunoreactivity with HMB‐45. Light‐ and electron‐microscopic findings
Authors: KAISERLING E. , KRöBER S. , XIAO J.‐C. , SCHAUMBURG‐LEVER G.
Published: April 2007

Immunoreactivity with HMB‐45 has recently been described in renal angiomyolipoma, a tumour of smooth muscle cells. HMB‐45 is a monoclonal antibody that reacts specifically with melanosomes. In order to determine whether the tumour cells contain melanosomes and synthesize melanin, seven tumours were studied by light microscopy and immunohistochemically with the antibodies HMB‐45, KP1 (CD68), PG‐M1 (CD68), Ki‐M1P, anti‐lysozyme, anti‐smooth‐muscle actin, anti‐vimentin, anti‐S100 protein and KL1 (anti‐keratin). Two tumours were also studied by electronmicroscopy and one by immuno‐electronmicroscopy. Histochemical investigation for dopa oxidase was performed on cryostat sections. The tumours contained varying numbers of HMB‐45‐positive muscle cells. Reactivity was noted in lysosomal granules and rough endoplasmic reticulum. Typical premelanosomes were found in the tumour cells by electronmicroscopy. Groups of tumour cells stained for dopa oxidase. The tumour cells were not reactive for lysozyme, but reacted with KP1, PG‐M1 and Ki‐M1P. Immuno‐electronmicrosopy showed that reactivity for KP1 was located within lysosomal granules. The findings show that the tumour cells of renal angiomyolipoma contain premelanosomes and that they are able to synthesize melanin, because they contain dopa oxidase. Immunoreactivity with KP1, PG‐M1 and Ki‐M1P can be attributed, in the absence of staining for lysozyme, to the large number of lysosomal granules. The tumour cells were not found to be related to macrophages or myeloid cells.
The extracellular matrix in pigmented skin lesions: an immunohistochemical study
Authors: DUINEN C.M. VAN , FLEUREN G.J. , BRUIJN J.A.
Published: April 2007

In recent years the interaction between tumour cells and the surrounding extracellular matrix in the process of tumour development, invasion and metastasis has been a focus of interest. We studied frozen sections of nine naevocellular naevi (junctional, compound and intradermal), 40 dysplastic naevi, six pagetoid in situ melanomas and 12 superficial spreading melanomas in order to determine the expression of: the basement membrane proteins collagen type IV and laminin, the interstitial collagen types I, III and VI, and fibronectin and tenascin. An indirect immunoperoxidase technique was used. In the various stages of melanocytic tumour progression we observed: 1 loss of type IV collagen and laminin within dermal melanocytic cell nests; 2 de novo expression of basement membrane type IV collagen and increased expression of the interstitial collagen types I, III and VI, as well as tenascin and fibronectin in the dermal stroma surrounding dysplastic naevus cells and melanoma cells; 3 presence of extracellular matrix components in close association with intra‐epidermally located invading atypical melanocytes. These data demonstrate the complex alterations of the composition of the extracellular matrix from bland naevi through lesions with progressive atypia to invasive melanoma. The changes described result in a molecular environment which melanocytes with an altered adhesion molecule profile are able to invade.
Primary breast lymphoma with skin involvement arising in lymphocytic lobulitis
Authors: ROONEY N. , SNEAD D. , GOODMAN S. , WEBB A.J.
Published: April 2007

Primary breast lymphoma is a rare tumour which has recently been associated with pre‐existing lymphocytic lobulitis. We report a patient with lymphocytic lobulitis in whom the lymphoma recurred in the contra‐lateral breast 5 years after the initial presentation, to be followed shortly afterwards by skin involvement. This progression ilustrates the relationship between extra‐nodal lymphomas and underlying autoimmune disease and the homing of lymphomas to related sites.
Melanoses of the gastrointestinal tract
Authors: GHADIALLY F.N. , WALLEY V.M.
Published: April 2007

Electronmicroscopy and electron probe energy dispersive X‐ray analysis studies have substantially contributed to our understanding of the various gastrointestinal tract melanoses. The nature of the pigment granules which occur in the various melanoses is discussed; their pattern of distribution in melanosis coli, melanosis ilei, melanosis duodeni and melanosis oesophagi is summarized and current knowledge of the aetiology and pathogenesis of these conditions is reviewed. Brief mention is also made of other examples of lipofuscin pigmentation, and a case of haemosiderosis ilei is described.
Immunohistochemical detection of bcl‐2 protein in liver lesions: bcl‐2 protein is expressed in hepatocellular carcinomas but not in liver cell dysplasia
Authors: ZHAO M. , ZHANG N‐X. , ECONOMOU M. , BLAHA I. , LAISSUE J.A. , ZIMMERMANN A.
Published: April 2007

A proto‐oncogene, bcl‐2, encodes a protein that inhibits programmed cell death (apoptosis) and may play a role in cell and tissue differentiation. As bcl‐2 appears to be involved in the turn‐over of stem or precursor cells, it is thought to be operational in carcinogenesis pathways. However, apart from certain lymphomas, only limited data are available on the frequency of its expression in solid tumors. Immunohistochemical analysis with an antibody specific for bcl‐2 protein was used to detect the protein in hepatocellular carcinomas and in one of the putative precursor lesions, liver cell dysplasia. We detected bcl‐2 protein in 5 of 37 hepatocellular carcinomas. Immunoreactivity was not related to type, grade, or extent of PCNA staining of the tumours. No bcl‐2 protein staining was observed in three types of liver cell dysplasia. Thus, bcl‐2 is abnormally expressed in some hepatocellular carcinomas but not in potential tumour precursor cells.
The extent of apoptosis in different types of high grade prostatic carcinoma
Authors: GAFFNEY E.F.
Published: April 2007

Apoptosis is the genetically mediated mechanism by which individual cells are deleted from living tissues. The extent of apoptosis in human tumours has not been examined in detail. In this study, apoptotic indices were assessed semi‐quantitatively by light microscopy in routine haematoxylin and eosin (H & E) stained sections of 15 high‐grade carcinomas of the prostate by light microscopy, using the 40x objective, counting 2000–2500 tumour cells per case. The mean apoptotic index for nine solid undifferentiated carcinomas was 1.7% (range 0.2–2.4%), for three small cell undifferentiated carcinomas 25.2% (range 10–37%), and for three secondary transitional cell carcinomas of the prostate 5.5% (range 2.4–9.1%). In general, apoptosis was easily identified, using the 40x objective. There were minor variations in apoptosis from field to field in each tumour, and greater variability in the apoptotic index was observed among the small cell undifferentiated carcinomas and transitional cell carcinomas. In conclusion, assessment of apoptosis in routine H & E sections of human tumours is feasible, but it remains to be determined whether the extent of apoptosis correlates with other determinants of biological behaviour.
Goseki grading in gastric cancer: comparison with existing systems of grading and its reproducibility
Authors: DIXON M.F. , MARTIN I.G. , SUE‐LING H.M. , WYATT J.I. , QUIRKE P. , JOHNSTON D.
Published: April 2007

A novel grading method which utilises intra‐cellular mucin content and tubular differentiation (the Goseki grade) has been applied to 181 gastric cancers removed in potentially curative resections, and compared to conventional tumour grading (well, moderate, poor differentiation) and the Lauren, Ming and WHO classifications. The Goseki grade is significantly related to patient survival and, unlike the existing approaches, remains so after allowing for tumour stage in multivariate analyses. Potential relationships between the Goseki grade, direct tumour spread, lymph node involvement and survival have been investigated. Prognosis is particularly related to mucin content; 55% of patients with mucin‐rich tumours dying within 5 years compared to 29% of those with mucin‐poor cancers. A smaller proportion of mucin‐poor cancers show lymph node involvement (N1 and N2) than mucin‐rich tumours (52%v. 73%) and a smaller proportion of cancers showing good tubular differentiation exhibit widespread lymph node involvement (N2) than tubule‐poor cancers (11%v. 28%). However, these differences did not achieve statistical significance. When compared to the existing classification or grading methods, the Goseki grade was found to be highly significantly correlated with the WHO and Lauren classifications and to conventional grading, but not to the Ming classification. These inter‐relations are largely dependent upon tubular differentiation. There was no relationship between Goseki grade and the lymphocytic response around the tumour margin. Inter‐observer agreement on the WHO type and the Lauren, Ming and Goseki grading methods was tested on 70 randomly selected cases. Only moderate agreement was achieved with any of these approaches (pairwise kappa values ranging from 0.485–0.565), but when the two‐category situation ‘mucin‐rich’ versus ‘mucin‐poor’ was examined a higher level of reproducibility was achieved (agreement = 81%; K= 0.605) indicating that pathologists can distinguish these prognostically important categories. It seems likely, therefore, that the strength of the association between tumour cell mucin content and survival will outweigh discrepancies introduced by observer variation.
Recent developments in soft tissue tumours
Authors: GOODLAD J.R. , FLETCHER C.D.M.
Published: April 2007

This article reviews the clinicopathological features of several recently described soft tissue tumours, namely ossifying fibromyxoid tumour, angiomyofibroblastoma, epithelioid angiosarcoma, retiform haemangioendothelioma, intra‐abdominal desmoplastic small cell tumour, spindle cell liposarcoma and low grade fibromyxoid sarcoma. Conceptual changes are also discussed. These include the relationship between Ewing's sarcoma and peripheral primitive neuroectodermal tumour, the proposed use of the term atypical lipoma for a subset of well differentiated liposarcomas, and the occurrence at a wide variety of sites of inflammatory myofibroblastic lesions of uncertain biological potential. In addition, advances in the study of soft tissue lesions at the molecular and cytogenetic levels are outlined, with particular emphasis on the recent identification of tumour‐specific karyotypic abnormalities in a wide variety of sarcomas.
Low‐grade B‐cell lymphomas of the splenic marginal zone: a clinicopathological and immunohistochemical study of 14 cases
Authors: PAWADE J. , WILKINS B.S. , WRIGHT D.H.
Published: April 2007

We have studied 14 cases of low‐grade, splenic marginal zone, B‐cell non‐Hodgkin's lymphoma. The clinical presentation in all cases was with splenomegaly and, in 10 cases, circulating neoplastic lymphoid cells in the peripheral blood with involvement of bone marrow. In all cases the splenic white pulp was hyperplastic with expansion of marginal zones and varying degrees of infiltration of germinal centres by neoplastic cells. The cells were a mixture of medium sized lymphocytes with moderate amounts of cytoplasm and finely dispersed nuclear chromatin, together with occasional blast cells with small nucleoli. Satellite red pulp aggregates of tumour cells centred on small epithelioid cell clusters were seen in all cases. These appear to be a characteristic and diagnostically important feature of splenic marginal zone lymphoma. The tumour cells expressed CD20, CD45RA, bcl‐2 and the antigens detected by MB2. All cases expressed IgM with light chain restriction. In addition, IgD was expressed in four cases. The follicular dendritic cell network was disrupted in those follicles which were infiltrated by tumour cells. A network of stromal myoid cells, at the periphery of the marginal zone, identified by expression of α‐smooth muscle actin, was preserved. Alpha‐smooth muscle actin positive dendritic cells were also seen within and around satellite tumour nodules in the red pulp.
Cytokeratin 20 expression by non‐invasive transitional cell carcinomas: potential for distinguishing recurrent from non‐recurrent disease
Authors: HARNDEN P. , ALLAM A. , JOYCE A.D. , PATEL A. , SELBY P. , SOUTHGATE J.
Published: April 2007

Although approximately 50% of patients with non‐invasive (Ta) papillary transitional cell carcinoma show no recurrence of their disease, current histopathological approaches cannot distinguish this sub‐group from those patients in whom the disease will recur. In this 5 year retrospective study, we have shown that cytokeratin 20 (CK20) was expressed in 19 of 29 (65.5%) of non‐invasive papillary tumours of grades 1 or 2. CK20 expression patterns were predictive of disease non‐recurrence in a sub‐group of eight patients, representing 51.7% of patients with non‐recurrent disease. In normal bladder mucosa, CK20 expression was restricted to the terminally‐differentiated superficial cell. In eight CK20‐positive tumours which showed no recurrence at 5 years, CK20 expression was either restricted to, or most intense in, the luminal cells of the papillae. This pattern of expression was not seen in any of the 15 tumours from the recurrent group. Disruption of normal CK20 expression was highly significantly correlated with recurrent tumours. These results suggest that changes in the expression of differentiation‐associated antigens, such as CK20, may be useful in predicting benign versus malignant behaviour and may, therefore, be useful in defining treatment strategies.
Diffuse leiomyomatosis of the uterus
Authors: MULVANY N.J. , ÖSTÖR A.G. , ROSS I.
Published: April 2007

The clinical and pathological features of four cases of the rare entity diffuse leiomyomatosis of the uterus are described. The patients, who ranged in age from 28 to 35 years, presented with a six month to ten year history of abnormal uterine bleeding, dysmenorrhoea and an enlarged uterus. Hysterectomy in each case revealed a symmetrically enlarged uterus containing numerous small ill‐defined leiomyomatous nodules. On microscopic examination the nodules were composed of compact fascicles and interweaving bundles of plump uniform benign smooth muscle cells. The nodules blended with each other and merged imperceptibly with the surrounding less cellular normal myometrium. The four patients are alive and well without further treatment. The follow‐up period ranged from six months to twelve years.
Intraosseous secondary calcium salt crystal deposition: an artefact of acid decalcification
Authors: KEEN C.E. , CROCKER P.R. , BRADY K. , BUK S.J.A. , LEVISON D.A.
Published: April 2007

We previously observed, in decalcificated bone specimens, intraosseous crystal deposits with morphological and analytical similarity to calcium pyrophosphate dihydrate. We have now been able, by a combination of more detailed morphological studies of these and similar cases, and by infrared spectroscopy in three cases, to show that this is, in fact deposition of the secondary calcium salts brushite and monetite, occurring as an artefact during formic acid decalcification. Our earlier postulate of bone as an additional primary crystallization site for calcium pyrophosphate dihydrate is effectively disproved. This artefact deserves wider recognition.
Aneurysmal benign fibrous histiocytoma: clinicopathological analysis of 40 cases of a tumour frequently misdiagnosed as a vascular neoplasm
Authors: CALONJE E. , FLETCHER C.D.M.
Published: April 2007

Forty cases of the distinctive but poorly recognized aneurysmal variant of cutaneous fibrous histiocytoma are described. These tumours presented most commonly in middle‐age adults, with a slight predilection for females. Anatomical distribution was wide with most cases occurring in the lower limb/limb girdle (50%), upper limb/limb girdle (20%) and trunk (17%). Lesional size ranged from 0.5 cm to 4 cm. Haemorrhage accounted for the rapid clinical growth of some lesions and the frequent clinical confusion with a cyst, a melanocytic lesion or a haemangioma. Five (19%) of the twenty‐six cases with follow‐up (mean duration 2.5 years) recurred locally, twice in two cases. One of these cases had involvement of a regional lymph node in the second recurrence, most likely as a result of direct local extension. Distinctive histological features were prominent blood‐filled spaces, varying from artefact‐like clefts to cystic areas mimicking cavernous vascular channels but devoid of an endothelial lining, prominent haemosiderin deposition, numerous siderophages and giant cells, and a moderate mitotic rate. Despite the presence of prominent secondary changes due to haemorrhage, all cases showed cellular polymorphism, hyalinized collagen bundles surrounded by tumour cells in the periphery of the lesion and 88% showed some degree of epidermal hyperplasia, as seen in common fibrous histiocytoma. Immunohistochemistry (ABC method) revealed only vimentin and, rarely, focal smooth muscle actin positivity. CD68 was positive in some reactive macrophages only. Stains for CD31, CD34, desmin and factor XIIIa were negative in all cases tested. Emphasis is placed on differential diagnosis since these lesions are commonly confused with benign and malignant vascular tumours including angiosarcoma, Kaposi's sarcoma and spindle cell haemangioendothelioma, and with angiomatoid malignant fibrous histiocytoma.
Benign regressing histiocytosis of the liver
Authors: FOSCHINI M.P. , MILANDRI G.L. , DINA R.E. , USELLINI L. , MACCHIA S. , SPONGANO P.
Published: April 2007

A case of benign regressing histiocytosis of the liver is reported. The patient, an adult male, presented with fever and diarrhoea and on abdominal echography multiple nodules were present in the liver. Histologically and immunohistochemically the lesions had features of Langerhans' cell histiocytosis. The nodules regressed within four months, without therapy, and the patient is free of disease 29 months after presentation.