bluuebunny/crossref_metadata_2025 huggingface dataset:
Hyaline globules in ovarian tumours
Authors: AL‐NAFUSSI A.I. , HUGHES D.E. , WILLIAMS A.R.W.
Published: April 2007

Hyaline eosinophilic globules have so far been described in a restricted variety of tumour types. We have noted their presence in a variety of gynaecological malignancies, in particular mixed Müllerian tumours and other epithelial ovarian tumours. We therefore studied their incidence and distribution in a series of malignant, borderline and benign epithelial ovarian tumours, and endometrial and endocervical adenocarcinomas. Hyaline eosinophilic globules were found in all 30 mixed Müllerian tumours from various sites in the female genital tract, 22 of 30 clear cell carcinomas, seven of 30 serous, two of 30 mucinous, and one of 30 endometrioid carcinomas examined, and were also seen in metastases from these tumours. They were present in only two of 25 borderline serous, one of 25 borderline mucinous tumours, and in four of 50 benign serous and one of 50 benign mucinous tumours. The globules were not found in any of 25 Brenner tumours examined, nor in 30 endometrial or 30 endocervical adenocarcinomas. The globules were periodic acid–Schiff positive after diastase, stained positively with PTAH, and were immunoreactive for α‐1‐antitrypsin. This study therefore demonstrates that eosinophilic globules are not specific for any particular tumour. However, their frequency in malignant mixed Müllerian tumours suggests that this diagnosis should be carefully excluded whenever these globules are present in epithelial tumours of the female genital tract.
Cutaneous epithelioid angiosarcoma: a clinicopathological study of four cases
Authors: PRESCOTT R.J. , BANERJEE S.S. , EYDEN B.P. , HABOUBI N.Y.
Published: April 2007

Four cases of cutaneous epithelioid angiosarcoma are described together with the potential diagnostic trap of mistaking these tumours for poorly differentiated carcinoma or malignant melanoma. The immunophenotypic profile using four endothelial markers showed positive staining in all cases for factor VIII related antigen in a predominantly paranuclear dot‐like fashion and for CD31 (JC70); in three cases for CD34 (QB‐END/10) and in two cases with UEA‐1. All four cases were cytokeratin (CAM 5.2 and AE1/AE3) negative in contrast to the positive staining reported at non‐cutaneous sites. Aberrant S‐100 protein expression was seen in one case. In two cases subsequent recurrences showed better differentiation than the original tumour. Electronmicroscopy confirmed the absence of non‐endothelial lines of differentiation but failed to reveal Weibel‐Palade bodies.
Differentiation of adenocarcinoma of the lung and malignant mesothelioma: predictive value and reproducibility of immunoreactive antibodies
Authors: SKOV B.G. , LAURITZEN A.F. , HIRSCH F.R. , SKOV T. , NIELSEN H.W.
Published: April 2007

A panel of antibodies against keratins, epithelial membrane antigen (EMA), epithelial antigen (Ber‐EP4), carcinoembryonic antigen (CEA), tumour‐associated glycoprotein (B72.3), vimentin and LeuM1 was applied to sections of adenocarcinoma of the lung and malignant mesothelioma in a randomized design. The proportion of stained tumour cells within each section was estimated independently in five categories by three pathologists (no positive tumour cells, 1–10%, 11–33%, 34–66% and more than 67% positive tumour cells). The kappa values representing the chance corrected interobserver agreement for the different antibodies in such a five group assessment were between 0.38 and 0.72. In two group assessment the kappa values were between 0.53 and 0.94. Nosological sensitivity and nosological specificity were calculated for all antibodies, and diagnostic sensitivity and diagnostic specificity (predictive values) were calculated for the Ber‐EP4, CEA, B72.3, LeuM1 and vimentin. The difference between nosological sensitivity and nosologic specificity and the clinically relevant predictive values of positive and negative tests were demonstrated. In respect of the reproducibility and the diagnostic power defined by the predictive values, we demonstrated that a panel of antibodies, including CEA, Ber‐EP4 and B72.3 and, to a lesser degree, LeuM1 and vimentin is applicable for the histopathological distinction between adenocarcinoma of the lung and malignant mesotheliomas. Before introduction of new diagnostic tests, including new antibodies, the prevalence of the tested tumours should be estimated. Nosological sensitivity and nosological specificity should be converted to predictive values.
Immunohistochemical detection of p53 in differentiated, poorly differentiated and undifferentiated carcinomas of the thyroid
Authors: SOARES P. , CAMESELLE‐TEIJEIRO J. , SOBRINHO‐SIMÕES M.
Published: April 2007

In an attempt to find whether or not p53 immunoreactivity in the thyroid gland is restricted to undifferentiated carcinomas and to evaluate the putative prognostic usefulness of its detection, we investigated p53 immunoreactivity in a series of 14 benign thyroid lesions and 65 thyroid carcinomas (12 papillary; six minimally invasive follicular; four widely invasive follicular; 31 poorly differentiated and 12 undifferentiated tumours). Unequivocal nuclear immunostaining for p53 was observed in two widely invasive follicular carcinoma (20.0%), five poorly differentiated carcinomas (16.1%) and in 10 undifferentiated carcinomas (83.3%). The percentage of immunoreactive cells was much smaller in the former groups than in undifferentiated carcinomas. Despite a trend to a more aggressive behaviour of the p53 immunoreactive cases no significant differences in the outcome of patients with positive and negative tumours was found when the comparison was made within each category of carcinomas. We conclude that p53 immunoreactivity can be detected both in undifferentiated carcinomas and in some differentiated and poorly differentiated thyroid carcinomas. Larger series of cases are necessary to evaluate the prognostic usefulness of this finding.
p53 immunostaining suggests that uterine carcinosarcomas are monoclonal
Authors: MAYALL F. , RUTTY K. , CAMPBELL F. , GODDARD H.
Published: April 2007

The histogenesis of carcinosarcomas has intrigued pathologists for a long time and remains unresolved. Two main theories have been put forward, one suggesting that they are monoclonal, another suggesting that they are biclonal. Our study examined p53 immunostaining in 17 uterine carcinosarcomas (mixed Müllerian tumours) and found positivity in five (30%). There was no disparity in immunostaining between the epithelial and the stromal components in any of the 17 tumours. This concordance in every tumour would be very unlikely if carcinosarcomas are biclonal. However, it would be expected if carcinosarcomas are monoclonal.
Keratinocyte induced chemotaxis in the pathogenesis of Paget's disease of the breast
Authors: POTTER C.R. DE , EECKHOUT I. , SCHELFHOUT A.‐M. , GEERTS M‐L. , ROELS H.J.
Published: April 2007

In Paget's disease of the breast, the epidermis contains large clear neoplastic cells. To explain the pathogenesis of this disease, the immunohistochemical characteristics of these cells were investigated in 25 patients. The cytoplasmic presence of low molecular weight cytokeratin and the absence of high molecular weight cytokeratin in all cases confirmed the glandular origin of the Paget cells. Membrane over‐expression of the neu‐protein was established in 96% of cases. It was hypothesized that epidermal keratinocytes release a chemotactic factor which attracts neu‐over‐expressing breast carcinoma cells by chemotaxis into the epidermis. The biological assays showed that normal keratinocytes release one or more chemotactic factor(s) into their conditioned medium, which induced spreading and motility of neu‐over‐expressing SK‐BR‐3 human breast cancer cells. The conditioned medium of keratinocytes also attracted the SK‐BR‐3 cells by chemotaxis in a modified Boyden chamber. Furthermore, MCF‐7 human breast cancer cells, which do not over‐express the neu‐protein, were not attracted by chemotaxis of conditioned medium of human keratinocytes. The involvement of the neu‐protein in spreading, motility and chemotaxis is further indicated by the inhibition of these processes by monoclonal antibodies against the extracellular domain of the neu‐protein. We conclude, therefore, that the Paget cells spread through the epidermis due to the motility induced by a chemotactic factor, which is released by epidermal keratinocytes and whose influence is mediated by the neu‐protein.
Atypical carcinoid tumour of the thymus: a study of eight cases
Authors: VALLI M. , FABRIS G.A. , DEWAR A. , CHIKTE S. , FISHER C. , CORRIN B. , SHEPPARD M.N.
Published: April 2007

Atypical carcinoids of the thymus are rare neoplasms of uncertain prognosis. We have studied eight cases (six male, two female; age range 48–60 years, mean 55 years), none with evidence of a paraneoplastic neuroendocrine syndrome. Tumour size was large and ranged from 7.5 to 10 cm. Microscopically, all had a nesting/insular or trabecular pattern, eosinophilic cytoplasm, round nuclei with fine chromatin and small nucleoli. No small cell features were evident. Mitotic activity ranged from 2 to 21 per 1.52 mm2. Focal necrosis was seen in all cases. All were positive for cytokeratin (AE1/AE3, CAM 5.2) and the neuroendocrine markers NSE, synaptophysin and chromogranin; five cases were positive for calcitonin. On electronmicroscopy all contained dense core granules, often numerous. Three cases were stage I and five stage III (infiltrating lung or chest wall). Follow‐up information was available in four cases (one stage I and three stage III): the stage I tumour had local recurrence and metastasis to the lung within a year whilst the three patients with stage III tumours died of liver, bone and brain metastases within 3 years.
Pagetoid spread into the rete testis by testicular tumours
Authors: LEE A.H.S. , THEAKER J.M.
Published: April 2007

Germ cell neoplasia of the testis can spread into the rete testis in a pagetoid manner, but this is less often recognized than vascular invasion or direct spread into the tunica albuginea. The rete testis was studied in 71 orchidectomy specimens: 47 with an untreated germ cell tumour, 18 with germ cell neoplasia after treatment with chemotherapy, and six with other tumours. Pagetoid spread into the rete testis was seen in 14 of the 47 cases of germ cell tumour. The cytology of the infiltrating cells was that of intratubular germ cell neoplasia. Hyperplasia of the rete testis was seen in six cases. In three of the four testes with untreated germ cell neoplasia and hyperplasia of the rete, neoplastic cells were seen in the hyperplastic rete epithelium. The two testes with extensive pagetoid involvement of the rete testis by intratubular germ cell neoplasia both had associated hyperplasia of the rete testis. Two of the 18 testes with germ cell neoplasia after chemotherapy had focal hyperplasia. Pagetoid involvement of the rete testis by intratubular germ cell neoplasia is common and may be a cause of hyperplasia of the rete testis.
M‐cells are damaged and increased in number in inflamed human ileal mucosa
Authors: CUVELIER C.A. , QUATACKER J. , MIELANTS H. , VOS M.DE , VEYS E. , ROELS H.J.
Published: April 2007

Ileocolonoscopy and biopsies of patients with spondylarthropathy reveal gut inflammation in 62% of cases. In order to better understand the pathogenetic mechanisms of spondylarthropathy‐related gut inflammation, the follicle‐associated epithelium was examined. Biopsies from nine controls and 18 patients with spondylarthropathy were studied by electronmicroscopy. Membranous (M) cells were investigated in normal and inflamed ileum. In normal mucosa, M‐cells were scarce whereas in inflamed mucosa their number was increased (up to 24% of follicle‐associated epithelial cells). They showed a thin rim of cytoplasm covering groups of lymphocytes. In chronic ileitis, necrotic M‐cells, rupture of M‐cells and lymphocytes entering the gut lumen were observed. The bursting of M‐cells at the top of the lymphoid follicles leads to interruption of the gut epithelial lining and gives the luminal content access to the lymphoid tissue. This pathogenetic mechanism may cause aphthoid ulcers.
Proliferation centres in B‐cell malignant lymphoma, lymphocytic (B‐CLL): an immunophenotypic study
Authors: SCHMID C. , ISAACSON P.G.
Published: April 2007

Proliferation centres, also known as pseudofollicles, are present in approximately 90% of lymphocytic lymphomas (B‐CLL). They consist of loosely arranged larger cells that often contain prominent nucleoli. In contrast to true B‐cell follicles, which may be found entrapped within the small lymphocytic infiltrate in sections of B‐CLL, proliferation centres are said not to contain follicular dendritic cells, although their presence has been occasionally recorded. We have carried out an immunohistochemical study of proliferation centres from 30 lymph node specimens of known cases of B‐CLL, classified according to the Kiel classification, in six of which fresh frozen in addition to paraffin embedded tissue was available. We have compared proliferation centres with the surrounding small lymphocytic infiltrate and reactive B‐cell follicles with respect to the presence of follicular dendritic cells and their associated network of IgM and complement, the cell proliferation fraction, the concentration of T‐cells and the expression of bcl‐2 protein. Most proliferation centres contained a delicate follicular dendritic cell network which was associated with IgM and complement, and showed a higher proliferation fraction than the surrounding small lymphocytic infiltrate. The proliferation centres contained more T‐cells than the surrounding infiltrate and showed decreased expression of bcl‐2 protein. Entrapped reactive B‐cell follicles contained a much denser network of follicular dendritic cells, associated with much stronger expression of IgM and complement, and exhibited a very high proliferation fraction; they contained many T‐cells and expressed very little bcl‐2 protein. These results show that proliferation centres share many properties with reactive B‐cell follicles and suggest that they may be centres of antigen driven proliferation.
Melanocytic lesions of the palm and sole
Authors: FALLOWFIELD M.E. , COLLINA G. , COOK M.G.
Published: April 2007

Pigmented lesions of palmar and plantar skin may cause diagnostic problems, partly because they are infrequently excised and also because some features of benign lesions in these sites may raise the suspicion of melanoma if considered alone. We have examined a series of benign melanocytic lesions and compared them with melanomas from these sites. The presence of severe melanocytic atypia was the most valuable feature in distinguishing between naevi and melanomas. Pagetoid infiltration of the epidermis by single atypical cells, or small groups of cells with abundant pale cytoplasm was seen only in melanomas, while transepidermal elimination of well‐circumscribed nests was present only in benign lesions. A lymphocytic infiltrate was present in the dermis in 13 of 14 malignant lesions, but only two of the 26 naevi showed a sparse infiltrate: we suggest that the presence of a lymphocytic infiltrate should prompt a careful search for other features of malignancy. Other features examined, including elongation of rete ridges, pattern of melanocyte distribution at the dermo‐epidermal junction, dermal sclerosis, and pigment in the stratum corneum or in the dermis, were seen in both naevi and melanomas and were not found to be useful in distinguishing benign from malignant lesions.
Waldeyer ring lymphomas. A clinicopathological study of 79 cases
Authors: MENÁARGUEZ J. , MOLLEJO M. , CARRIÓAN R. , OLIVA H. , BELLAS C. , FORTEZA J. , MARTIN C. , RUIZ‐MARCELLÁAN C. , MORENTE M. , ROMAGOSA V. , CUENA R. , PIRIS M.A.
Published: April 2007

Waldeyer ring lymphomas belong to a category of tumours which has not yet been fully defined. Their relation to mucosa‐associated lymphoid tissue (MALT) and other extranodal lymphomas remains largely unknown. We performed a clinicopathological retrospective study of 79 patients, and compared them with a series of MALT and nodal lymphomas. Tumours from the nasopharynx and palatine tonsil showed similar histological profiles, with a predominance of large B‐cells. Centroblastic lymphomas constituted the largest group (n= 45), followed by those of centrocytic type (9) with smaller groups of centroblastic‐centrocytic (5) and Hodgkin's lymphomas (2). Three monocytoid B‐cell lymphomas were identified. Only one case could be classified as MALT lymphoma. The frequency of bcl‐2 expression in large B‐cell tumours of Waldeyer's ring has an intermediate range between large B‐cell lymphomas occurring in mucosal and nodal locations. Epitheliotropism was present in all low‐grade cases, and was therefore not a useful marker in the identification of potential MALT lymphomas in contrast with other mucosal sites. Comparative survival studies showed significant overall differences between Waldeyer ring lymphomas, MALT and nodal cases. These disappeared after taking stage and histological grade into account. We conclude that Waldeyer ring lymphomas show distinctive features, mainly in terms of histological distribution and immunophenotype. The key factor determining their behaviour could be their different spreading capability. These findings suggest that extranodal lymphomas are heterogeneous, and indicate the need for additional efforts to clarify this.
Expression of BCL‐2 in the developing human fetal and infant breast
Authors: NATHAN B. , ANBAZHAGAN R. , CLARKSON P. , BARTKOVA J. , GUSTERSON B.
Published: April 2007

The expression of BCL‐2 protein was analysed in 10 fetal and 45 infant breast specimens by immunocytochemical staining of methacarn‐fixed, paraffin‐embedded tissue. In the developing fetal breast bud, BCL‐2 was expressed in the basal cell layer and in the surrounding mesenchyme. Basal cells of epithelial buds destined to become hair follicles also expressed BCL‐2 while the basal cell layer of the epidermis was negative. In infant breasts studied (aged 0–2 years), there was heterogeneous staining of the luminal epithelial cells of the ducts and lobules and no staining of myoepithelial cells or fibroblasts. The intensity of staining had a strong positive correlation with the age of the infant. Although the function of the bcl‐2 gene in epithelial cells is unknown, these findings suggest that bcl‐2 has a role in the morphogenesis of the human breast, and may help to sustain active epithelial‐mesenchymal interaction by inducing longevity of certain cells.
High frequency of Epstein–Barr virus in Chinese peripheral T‐cell lymphoma
Authors: ZHOU X.G. , HAMILTON‐DUTOIT S.J. , YAN Q.H. , PALLESEN G.
Published: April 2007

Forty‐two cases of Chinese T‐cell lymphoma were studied for expression of Epstein–Barr virus (EBV) encoded RNA (EBER‐1) and EBV latent membrane protein‐1 (LMP‐1) using in situ hybridization and immunohistochemistry, respectively. EBV was detected in tumour cells in 24/39 peripheral T‐cell lymphomas (62%), comprising 18/27 pleomorphic, medium and large cell lymphomas (67%), 4/6 angioimmunoblastic lymphadenopathy‐like lymphomas (67%), 2/2 Lennert's lymphomas, 0/2 anaplastic large cell lymphomas, and 0/2 T‐zone lymphomas. EBV was not found in three T‐lymphoblastic lymphomas. EBV was associated with 12/24 nodal (50%) compared with 12/15 extranodal (80%) peripheral T‐cell lymphomas. In EBV positive nodal lymphomas, 9/12 cases (75%) contained less than 10% EBER positive tumour cells. In EBV positive extranodal lymphomas, 9/11 cases (82%) showed EBV gene expression in more than 50% of the tumour cells, and in five of these almost all tumour cells were positive. Lymphomas of the nasopharynx (mainly midline granuloma‐type) showed EBER‐1 expression in nearly all tumour cells. LMP‐1 was detected in 19/23 EBER positive peripheral T‐cell lymphomas (83%). Our results show that EBV is strongly associated with peripheral T‐cell lymphomas in Chinese. An important role for the virus is suggested in lymphomas of the nasopharynx. The significance of EBV in T‐cell lymphomas that contain only a minor population of virally infected tumour cells is currently unclear.
Hamartomas of the breast: six novel diagnostic features in three‐dimensional thick sections
Authors: DAVIES J.D. , KULKA J. , MUMFORD A.D. , ARMSTRONG J.S. , WELLS C.A.
Published: April 2007

Fifteen hamartomas of the breast have been studied by dissecting microscopy of thick sections at a depth of 1.0 to 2.5 mm, and by conventional 5 μm deep sections. This combined approach has revealed six distinctive features, three in the parenchymal structure and three in the connective tissue components. Ducts (invariably of penetrating or arcuate configuration) and discrete lobules, neither of which are seen in lesions accepted as fibroadenomas, were invariably found. In one‐third of hamartomas, up to 10% of the surface area was occupied by Heräti‐style nodules composed of concentric rings of epithelium. In the hyaline interlobular connective tissue characteristic drifts of caraway seed‐like fibrocytes, encasement of adipocytes by hyaline collagen, or spider‐naevus vascular abnormalities were found in approximately half of the mammary hamartomas when examined in thick sections. Hitherto the positive diagnosis of hamartomas of the breast has relied on a combined clinical, radiological and pathological assessment. We suggest that the additional features described here, taken in conjunction with those already known, may facilitate the recognition of mammary hamartomas by histopathological examination alone.
c‐erbB‐3 protein expression in human breast cancer: comparison with other tumour variables and survival
Authors: QUINN C.M. , OSTROWSKI J.L. , LANE S.A. , LONEY D.P. , TEASDALE J. , BENSON E.A.
Published: April 2007

c‐erbB‐3 protein expression was investigated immunohistochemically in a series of 97 malignant breast tumours using the monoclonal antibody RTJ1. Twenty‐eight cases (28.8%) showed c‐erbB‐3 overexpression, 31 cases (32%) showed normal levels of c‐erbB‐3 and 38 cases (39.2%) were c‐erbB‐3 negative. c‐erbB‐3 overexpression was positively but not significantly related to negative lymph node status and survival over a 10‐year follow‐up period.
Observer variation in the assessment of chronic gastritis according to the Sydney system
Authors: ANDREW A. , WYATT J.I. , DIXON M.F.
Published: April 2007

The main aims of the Sydney system for the classification of gastritis are to improve uniformity in histopathological reporting and to provide a flexible matrix of rules for grading the histological features. We sought to determine the level of interobserver agreement between pathologists in the application of the Sydney system. Three histopathologists independently examined H & E, alcian blue/PAS and modified Giemsa stained sections of two antral and two corpus gastric biopsies from 69 consecutive dyspeptic patients. After elimination of five unsuitable cases, each observer graded chronic inflammation, polymorph activity, atrophy, intestinal metaplasia and Helicobacter pylori density in the antrum and corpus on a 0–3 scale according to the Sydney system criteria. The pairwise agreement on final diagnosis and the overall and conditional agreement on histological grades were examined by kappa statistics. Agreement on the final diagnosis ranged from 83–94% with kappa values of 0.699 (‘good’) to 0.887 (‘excellent’). Conditional probability of agreement on a diagnosis of H. pylori positive gastritis was 99%, but wider disagreements were apparent in the recognition of H. pylori negative gastritis, reactive gastritis and even normal biopsies. Overall agreement for grade ranged from 70% for antral atrophy to 94% for intestinal metaplasia in the corpus with ‘moderate’ or ‘good’ kappa values. We conclude that the diagnostic and grading criteria described in the Sydney system can be applied consistently by histopathologists. The findings underline its potential usefulness in routine practice.
Monoclonal Epstein‐Barr virus genomes but lack of EBV‐related protein expression in different types of gastric carcinoma
Authors: OTT G. , KIRCHNER TH. , MÜLLER‐HERMELINK H.K.
Published: April 2007

Thirty‐nine resection specimens of gastric carcinomas have been investigated for the presence of EBV RNA sequences using a highly sensitive non‐radioactive in situ hybridization technique. Transcribed EBER sequences were found in seven (18%), including four cases of undifferentiated carcinoma with prominent lymphoid infiltration and three gastric adenocarcinomas. In the positive tumours all, or nearly all, tumour nuclei were distinctly labelled. No positive signals could be detected in the non‐dysplastic epithelial cells or the reactive inflammatory infiltrate. Clonality analysis using specific probes to the variable tandem repeat region of the EBV yielded single episomal bands in all four cases tested, two of which were undifferentiated carcinomas and two adenocarcinomas. By means of immunohistology, no expression of the EBV‐related proteins LMP or EBNA‐2 was present in tumour cells of positive cases in in situ or blotting attempts. Our results suggest that infection of gastric carcinomas by the EB virus occurs early in tumourigenesis but, in contrast to nasopharyngeal carcinomas, does not result in the expression of EBV‐specific proteins.
Foam cell replication and smooth muscle cell apoptosis in human saphenous vein grafts
Authors: KOCKX M.M. , CAMBIER B.A. , BORTIER H.E. , MEYER G.R. DE , DECLERCQ S.C. , CAUWELAERT P.A. VAN , BULTINCK J.
Published: April 2007

Occlusion of saphenous vein grafts is a major problem after coronary artery bypass grafting. Segments of occluded and suboccluded implanted aortocoronary grafts were obtained during re‐intervention bypass grafting in 47 patients yielding a total of 80 vein grafts. The grafts were studied by immunohistochemistry for smooth muscle cells (ÉL‐SMC actin), macrophages (HAM56), cell replication (PCNA, Ki‐67) and transmission and scanning electronmicroscopy (TEM, SEM). In 81% of the examined grafts the (sub)occlusion was due to a myo‐intimal thickening and an associated luminal accumulation of foam cells and mural thrombi. The foam cells were constantly found at the luminal site of the myo‐intimal thickening and within the luminal part of adherent thrombi. Transmission electronmicroscopy demonstrated phagocytosis of platelets and platelet fragments by the foam cells. A significant fraction of the foam cells demonstrated nuclear immunoreactivity for Ki‐67 and PCNA. The myo‐intimal thickening of the vein grafts was composed of smooth muscle cells lying in a fibrous tissue matrix. The smooth muscle cells were surrounded by prominent basal lamina and showed ultrastructural features of apoptosis. Our results support the hypothesis that phagocytosis of lipid rich platelets by monocytes set up a mechanism for foam cell formation and replication in human saphenous vein grafts. The transformation of a smooth muscle cell rich myo‐intimal thickening towards a fibrous, cell poor intimal thickening could be induced by progressive smooth muscle cell loss through apoptosis.
Expression of tenascin, type IV collagen and laminin during human intrahepatic bile duct development and in intrahepatic cholangiocarcinoma
Authors: TERADA T. , NAKANUMA Y.
Published: April 2007

Expression of tenascin, type IV collagen and laminin during human intrahepatic bile duct development and in cholangiocarcinoma was examined by immunohistochemistry. In the developing hilar bile ducts, tenascin was expressed in the mesenchyme around the epithelial cells migrating from the ductal plate into the mesenchyme at 10–14 weeks of gestation. Tenascin was also expressed in the mesenchyme around newly formed hilar bile ducts at 15‐20 weeks of gestation, but its expression disappeared after 21 weeks of gestation. Type IV collagen and laminin were expressed around the ductal plate, around epithelial cells migrating from the ductal plate into the mesenchyme, and around newly formed hilar bile ducts, and their expression was present throughout fetal life. By contrast, in the development of peripheral bile ducts, tenascin expression was not found. Type IV collagen and laminin were identified around the ductal plate, migrating epithelial cells and peripheral bile ducts. In cholangiocarcinoma, tenascin and type IV collagen were expressed in the stroma, but laminin was not identified. These findings suggest that tenascin may play a role in hilar bile duct development and that type IV collagen and laminin may play a role in both hilar and peripheral bile duct development. Expression of tenascin and type IV collagen in the stroma of cholangiocarcinoma may be the result of malignant transformation of intrahepatic biliary epithelium; tenascin in peritumoral stroma may stimulate carcinoma cell proliferation and growth in cholangiocarcinoma.
Nasal T‐cell lymphoma: a clinicopathological and immunophenotypic analysis of 13 cases
Authors: GORP J.VAN , BRUIN P.C.DE , SIE‐GO D.M.D.S. , HEERDE P. VAN , OSSENKOPPELE G.J. , RADEMAKERS L.H.P.M. , MEIJER C.J.L.M. , TWEEL J.G.VAN DEN
Published: April 2007

Thirteen cases of nasal lymphomas with T‐cell or natural killer (NK)‐cell phenotype were studied, with attention to clinical presentation and follow‐up, the presence of Epstein‐Barr virus (EBV) using in situ hybridization (EBER), the immunophenotype, and the presence of cytotoxic granules. All but two patients presented with stage I disease. In three cases local progression resulted in involvement of the central nervous system. When dissemination occurred, this was predominantly to extranodal localizations, in two cases to the skin. Response to therapy was highly variable, but patients treated with radiotherapy with or without additional chemotherapy had a better prognosis than patients treated with initial chemotherapy alone. All lymphomas were associated with EBV, and most cases howed cytotoxic features, ten of which were CD56 positive. In eight cases a T‐cell origin was proven, but in five ases a possible NK‐cell origin could not be excluded, No clinical differences were seen between true T‐cell lymphomas and possible NK‐cell neoplasms. Nasal T‐cell lymphomas should be considered as a distinct clinicopathological entity, strongly associated with EBV, and with cytotoxic features in most cases. No prognostic parameters were detected to predict dissemination and response to therapy.
Pathology of hepatitis C virus infection
Authors: DHILLON A.P. , DUSHEIKO G.M.
Published: April 2007

This paper reviews our current knowledge of hepatitis C virus, its structure, epidemiology and pathological effects in man. The histopathological features of acute and chronic hepatitis due to hepatitis C virus are detailed and illustrated. The possible pathogenetic mechanisms involved in the liver injury are outlined and the significance of genotypic subtypes of the virus and of host genetic predisposition in relation to the liver injury and the response to therapy are summarized.
Reproducibility of a histogenetic classification of thymic epithelial tumours
Authors: CLOSE P.M. , KIRCHNER T. , UYS C.J. , MÜLLER‐HERMELINK H.K.
Published: April 2007

A histogenetic classification of thymic epithelial neoplasms proposed by Müller‐Hermelink and co‐workers has been shown by a number of recent studies to be of clinical and prognostic value. Reproducibility is an important criterion for the acceptance of any new classification for general diagnostic use. The reproducibility of this classification was tested on 51 cases of thymic epithelial neoplasia, by comparing results obtained by pathologists working from published criteria only with those results obtained by the pathologists who developed the classification. In 78% of cases there was complete concordance of results. Analysis of the 22% discordant cases showed that this discordance was due to a degree of subjectivity in determining cut‐off points between categories adjacent to each other in the morphological spectrum of thymic epithelial neoplasia (medullary v. mixed, cortical v. well‐differentiated thymic carcinoma). In terms of the important clinical distinction between benign (medullary and mixed) thymomas and those with more aggressive biological behaviour (cortical types and well‐differentiated thymic carcinoma), the degree of reproducibility was 96%. The high degree of reproducibility of this histogenetic classification of thymic epithelial neoplasms should facilitate its acceptance and use in routine diagnostic pathology.
Frequent expression of FAS/APO‐1 in Hodgkin's disease and anaplastic large cell lymphomas FAS/APO‐1 in Hodgkin's disease and anaplastic large cell lymphomas
Authors: XERRI L. , CARBUCCIA N. , PARC P. , HASSOUN J. , BIRG F.
Published: April 2007

FAS/APO‐1 (CD95) is a membrane glycoprotein belonging to the tumour necrosis factor/nerve growth factor receptor family, and which can trigger apoptosis in some lymphoid cell lines. Immunohistochemistry combined with Northern blotting allowed determination of the pattern of FAS/APO‐1 expression in a series of Ki‐1 [CD30] positive lymphoid malignancies, including 27 Hodgkin's disease and eight anaplastic large cell lymphomas. CD30 negative tumours used as controls included 27 B‐cell non‐Hodgkin's lymphomas, 14 T‐cell non‐Hodgkin's lymphomas, four reactive lymphadenitis, and non‐lymphoid tissues. Immunohistochemistry, performed on frozen sections, revealed a strong FAS/APO‐1 expression in 25 out of 27 (92%) Hodgkin's disease cases, predominantly in Reed Sternberg cells; 50 to 100% of the neoplastic cells in eight out of (100%) anaplastic large cell lymphoma cases were positive. In contrast, positive FAS/APO‐1 immunostaining was observed only in 22 out of 41 (53%) CD30 negative non‐Hodgkin's lymphomas. Northern blot analysis detected variable amounts of the FAS/APO‐1 transcript in the immunohistochemistry‐positive samples. These results suggest possible hyper‐expression of FAS/APO‐1 (CD95) in Hodgkin's disease and anaplastic large cell lymphomas.
Endovascular papillary angioendothelioma‐like tumour associated with lymphoedema
Authors: FUKUNAGA M. , USHIGOME S. , SHISHIKURA Y. , YOKOI K. , ISHIKAWA E.
Published: April 2007

A case of endovascular papillary angioendothelioma‐like tumour associated with lymphoedema is described. Microscopically, the tumour was composed of anastomosing vascular channels, some of which contained papillary projections, producing tuft‐like or glomeruloid appearances. The dermis also showed moderate lymphoedema and lymphocyic infiltrate. The tumour resembled endovascular papillary angioendothelioma but also had several features that differed from typical examples: occurrence in an old patient and less prominent endothelial hobnail features and lymphocytic infiltrate. Three types of proliferating cells were observed: 1 mature flattened endothelial cells, which were strongly positive for endothelial markers (factor VIII‐related antigen, CD31, CD34) and bound ulex europaeus agglutinin 1; 2 immature endothelial cells with round nuclei and vacuolated or pale cytoplasm, which were strongly positive for CD31 and muscle‐specific actin (HHF35) and focally positive for other endothelial markers; and 3 stromal spindle cells in papillary or glomeruloid areas, which were positive for vimentin, HHF35, and alpha‐smooth muscle actin but negative for desmin. The tumour was diploid by flow cytometry. The patient was well without disease twelve months after the excision. We postulate that this tumour was caused by circulatory disturbance, namely lymphoedema associated with syringomyelia and a Charcot's joint.
Granular cell tumours of the lower respiratory tract
Authors: MONTPRÉVILLE V. THOMAS DE , DULMET E.M.
Published: April 2007

Granular cell tumours rarely involve the lower respiratory tract. We report eight cases surgically resected at our institution. There were four females and four males, aged between 18 to 56 years (mean 40). One tumour associated with a peripheral lung adenocarcinoma was asymptomatic. The other lesions presented with obstructive pneumonitis (3 cases), haemoptysis (2), dyspnea (1) or cough (1). These tumours were tracheal (1) or bronchial (6) and one case was located in the lung parenchyma. Four cases were multicentric with associated lesions located in a bronchus (2), the oesophagus (1) or a mediastinal lymph node (1). All tumours, with the largest diameter ranging from 0.5–4.5 cm, were histologically invasive. The tumours were positive for S‐100 protein, neuron specific enolase, KP1 (CD68) and vimentin. No tumour expressed desmin, keratin or p53 oncoprotein. Our study demonstrates that, in spite of marked anatomical and clinical polymorphism, the rare granular cell tumours of the lower respiratory tract have a constant histological appearance. Our observations confirm that large tumours (> 8–10 mm) usually extend beyond the tracheo‐bronchial cartilages and, therefore, only surgical treatment may avoid recurrence.
Colorectal adenomas in surgical specimens from subjects with hereditary non‐polyposis colorectal cancer
Authors: JASS J.R.
Published: April 2007

An understanding of the early morphogenesis of hereditary non‐polyposis colorectal cancer is relevant to screening strategies. If most of these cancers were to evolve through the classical adenoma‐carcinoma sequence, screening and removal of adenomas at relatively long intervals might be a safe and cost‐effective approach. We have reviewed 131 cancers from 117 affected members of 34 such families. One hundred and four cancers were initial symptomatic lesions, eight were cancers detected in asymptomatic screened individuals, one was a synchronous cancer and 18 were metachronous cancers. None of the 131 cancers was a small, superficial type. Residual adenoma (contiguous with cancer) was present in three out of three (100%) in situ cancers, eight out of nine (89%) cancers involving only submucosa, four out of 14 (29%) cancers limited to the muscle coat and 13 of 105 (12%) cancers extending beyond the muscle coat. Twenty‐one out of 28 (75%) residual adenomas had a villous component. Only one was flat. Of the eight asymptomatic cancers, seven arose within tubular (two) or tubulovillous adenomas (five). The eighth was not associated with an adenoma but was 35 mm in diameter and extended through the bowel wall. Discrete adenomas (contiguous excluded) were present in 22% of surgical specimens and 31% of specimens from subjects older than 50 years. A relatively high proportion (30%) had a villous component and 43% were at least 10 mm in diameter. Patients with one or more discrete adenomas in their first surgical specimen were more likely to develop multiple cancers. The findings are consistent with the view that adenomas do not occur with increased frequency in hereditary non‐polyposis colorectal cancer but are more likely to be large and adopt a villous configuration. There is little evidence for morphogenetic pathways involving flat adenoma or de novo carcinoma in these cases.
Hepatobiliary cystadenoma with mesenchymal stroma: expression of oestrogen receptors in formalin‐fixed tissue
Authors: SCOTT F.R. , MORE L. , DHILLON A.P.
Published: April 2007

We report three cases of hepatobiliary cystadenoma with mesenchymal stroma in which oestrogen receptor immunostaining was carried out, after using a microwave method of antigen retrieval. In one of the tumours immunoreactivity for oestrogen receptors was demonstrated within the mesenchymal stromal cells. The presence of oestrogen receptors supports the theory that oestrogens act as tumour promoters and may explain the female predilection.
The prognostic significance of vascular invasion in stage T1 bladder cancer
Authors: LOPEZ J.I. , ANGULO J.C.
Published: April 2007

Transurethral resection specimens from 170 T1 bladder carcinomas were reviewed for the presence of vascular (blood vessel and/or lymphatic) invasion by tumour cells. Such a finding was noted in 17 cases (10%), and occurred most frequently in high grade tumours. Tumour recurrence was documented in 11 of these cases (65%), including seven patients who showed progression to more invasive disease (T2–T4) and six patients (55%) who died of disease. Five‐year survival for cases without vascular invasion was 81% versus 44% for those with. This was a statistically significant difference (log‐rank, P= 0.004). Neoplasms of high grade (grades 2 to 3), without a papillary configuration, and exceeding 5 cm were associated with vascular invasion (chi‐squared: P < 0.001, P= 0.043, and P= 0.061 respectively). In multivariate analysis vascular invasion proved to be an independent prognostic factor (Cox's regression, P= 0.015). We therefore stress the clinical relevance of a thorough evaluation of the state of vascular invasion in stage T1 bladder cancer.
Plasminogen activator inhibitor‐2 expression in inflamed appendix
Authors: WHAWELL S.A. , THOMPSON E.M. , FLEMING K.A. , THOMPSON J.N.
Published: April 2007

Plasminogen activator inhibitors are thought to be responsible for the abolition of fibrinolytic activity in inflamed peritoneum. This reduction in the fibrin clearing capacity of the peritoneum promotes the formation of intraabdominal adhesions. High concentrations of plasminogen activator inhibitor‐2 (PAI‐2) have been previously found in inflamed peritoneal tissue using immunoassays, but it is undetectable in normal peritoneum. The aim of this study was to localize plasminogen activator inhibitor‐2 production in tissue by in situ mRNA hybridisation. Sections of normal and inflamed human appendix were hybridised with a digoxigenin labelled cDNA probe. In normal appendix staining was confined to macrophages in the mucosa. Macrophage staining was also seen in inflamed tissue but with a wider distribution throughout the appendix wall. PAI‐2 was also localized to mesothelial cells of inflamed but not normal appendix. Cell identities were confirmed using immunohistochemistry directed against cell specific markers. Staining was absent from control slides incubated with plasmid DNA or PAI‐2 probe following ribonuclease digestion. The identification of the cells expressing the PAI‐2 gene in peritoneum increases our understanding of the pathophysiological process leading to fibrin deposition within the abdomen during peritonitis.
Arterial lesions associated with medial disorganization and fibrosis in endomyocardial biopsies from human cardiac allografts
Authors: BOYLE J.J. , LAWRIE G. , McPHADEN A.R. , RICHENS D. , LINDOP G.B.M.
Published: April 2007

We describe distinctive arterial lesions in endomyocardial biopsies from patients with human cardiac allografts. The lesions affected principally the media of small arteries and consisted of misorientation of smooth muscle cells and fibrosis. This remodelling was most prevalent in the subadventitial zone, but sometimes extended to involve the full thickness of the media. In the most extreme cases medial smooth muscle cells ran parallel to the long axis of the vessel and were segregated into small bundles and single cells separated by collagen which merged with the adventitial fibrosis. The intima was always normal. Abnormal arteries were present in 16% of 603 consecutive biopsies from 44 patients, and 39% of lesions occurred in 16% of patients. No lesions were found in endomyocardial biopsies from 25 non‐transplanted patients, nor in mucosal biopsies from both transplanted and non‐transplanted patients, confirming that the appearances were not due to biopsy artefact. There was early arterial remodelling in biopsies within two weeks of transplantation and none of the stages resembled vascular rejection. Fifty per cent of biopsies from some patients contained arterial lesions, suggesting that in susceptible patients they are common.
Dermal spindle cell lipoma: plexiform and nodular variants
Authors: ZELGER B.W.H. , ZELGER B.G. , PLÖRER A. , STEINER H. , FRITSCH P.O.
Published: April 2007

We report on eleven cases of a distinctive dermal spindle cell lipoma characterized by a mixture of mature adipocytes and spindle‐shaped cells in a fibromucinous background. Six lesions showed a moderately well circumscribed plexiform pattern, five a well demarcated nodular pattern with compression of surrounding connective tissue and prominent stromal fibrosis. Clinically, the plexiform type mostly occurred in the thigh‐groin‐buttock area and the nodular type in the head‐neck or acral location. While plexiform lesions were predominantly seen in middle‐aged females, nodular types occurred in young adults of either sex. No recurrence was seen in five patients with follow‐up. The tumour cells were vimentin positive and a thin cytomplasmic rim of S‐100 protein positivity was seen in mature adipocytes. Ultrastructural studies revealed lipoblastic differentiation of spindle‐shaped cells with lipid droplets and basal lamina formation. Dermal spindle cell lipomas seem to be the dermal counterpart of the most subcutaneously located spindle cell lipoma.
The pathology of hysterectomy specimens following trans‐cervical resection of the endometrium
Authors: McCULLOCH T.A. , WAGNER B. , DUFFY S. , BARIK S. , SMITH J.H.F.
Published: April 2007

The pathological findings in 29 hysterectomy specimens from a series of 175 patients undergoing trans‐cervical resection of the endometrium are presented. In all but one case endometrium was present. Although all phases of the normal menstrual cycle were represented, in nine (28%) cases the endometrium appeared inactive, sometimes showing appearances similar to those in Asherman's syndrome. Adenomyosis was present in five (17%) cases and simple hyperplasia in one case. Haematocolpos was present in two cases. Inflammation was uncommon, usually mild in degree and present in the superficial myometrium. Four (14%) cases contained epithelioid or foreign body granulomas in the superficial myometrium. Deposits of haemosiderin and amorphous brown and/or particulate black pigment were seen in a total of 20 (69%) cases. A combination of transmission electronmicroscopy and energy dispersive analysis of X‐rays showed these pigments to be a combination of charred organic material and metals, the latter corresponding to the composition of the diathermy cutting loop and electrocautery rollerball used in the ablative surgery.
Acral‐lentiginous naevus of plantar skin
Authors: CLEMENTE C. , ZURRIDA S. , BARTOLI C. , BONO A. , COLLINI P. , RILKE F.
Published: April 2007

In a consecutive series of 165 plantar naevi, a group of 36 benign naevi with sufficiently distinctive histopathological features to justify their classification as a special entity, here designated acral‐lentiginous naevus, was identified. The main morphological features distinguishing the acral‐lentiginous naevi from other acral non‐lentiginous naevi are: elongation of rete ridges, continuous proliferation of melanocytes at the dermo‐epidermal junction, presence of single scattered melanocytes, or less commonly small clusters, within the upper epidermis, poor or absent lateral circumscription, melanocytes with abundant pale cytoplasm and round to oval, sometimes hyperchromatic, nuclei and prominent nucleoli present at the dermo‐epidermal junction. Some histological features of acral‐lentiginous naevi are similar to those of dysplastic naevi; however, anastomosing rete ridges, cytological atypia and well‐formed lamellar fibroplasia are absent. The histopathological criteria to distinguish these naevi from melanoma are: the lack of pagetoid lateral spread, the absence of mitotic activity in the deep dermal component and the evidence of dermal naevocytic differentiation. The identification of this benign acral naevus, that we have identified as the benign counterpart of acral lentiginous melanoma, is important in order to avoid misdiagnoses and consequent under‐ or over‐treatment of doubtful pigmented lesions of acral skin.