bluuebunny/crossref_metadata_2025 huggingface dataset:
Expression of CD 30 and nerve growth factor‐receptor in neoplastic and reactive vascular lesions: an immunohistochemical study
Authors: RUDOLPH P. , LAPPE T. , SCHMIDT D.
Published: April 2007

A total of 118 biopsies from 20 different types of benign, malignant and reactive vascular proliferations were examined for the expression of the CD30 antigen using the monoclonal antibodies BerH2 and HRS4 on paraffin‐embedded sections. The results were compared with those obtained using an antibody directed against the partially homologous nerve growth factor‐receptor. The vascular character of the lesions was assessed by means of endothelial markers and the expression of intermediate filaments was verified immunohistochemically. CD30 was expressed in the endothelial component of more than the half of all tumours, with the exceptions of Kaposi's sarcoma and teleangiectatic granuloma. There was a slightly higher rate of Ki‐1 positivity in malignant lesions. Nerve growth factor‐receptor could be demonstrated in a similar percentage in both endothelium and pericytes, but no correlation with CD30 could be established. We conclude, therefore, that these antigens are not adequate for the differential diagnosis of vascular lesions, nor do they help distinguish between benign and malignant lesions. Their expression seems to reflect different states of cellular function or activation. It does not necessarily occur simultaneously or in the same cell type.
Proliferating cell nuclear antigen in gallbladder carcinoma
Authors: ROA I. , ARAYA J. , SHIRAISHI T. , YATANI R. , VILLASECA M. , WISTUBA I. , DE‐ARETXABALA X.
Published: April 2007

Proliferating cell nuclear antigen (PCNA) expression was studied in 103 gallbladder carcinomas and 23 metastatic lesions as well as in 25 control non‐neoplastic gallbladder specimens. Positive nuclear staining was observed in 88% of controls, in 92% of carcinomas and in 70% of metastases. The mean number of positive cells was 21.2% in controls, 44.1% in primary carcinomas and 32% in metastatic cancer cells. Differences which were significant were control v. primary tumour, P<0.000001; control v. metastasis, P<0.01 and primary tumour v. metastasis, P<0.006. In 57 (60%) of the primary tumours there was positive staining in over 40% of tumour cells. We were not able to demonstrate any relationship between macroscopic or microscopic features and PCNA expression. However, tumours confined to the mucosa expressed PCNA more frequently than did more advanced tumours.
The cytological spectrum of the monocytoid B‐cell reaction: recognition of its large cell type
Authors: PLANK L. , HANSMANN M.‐L. , FISCHER R.
Published: April 2007

To analyse the cytological features of benign monocytoid B‐cells, we investigated, histologically and immunohisto‐chemically, 78 reactive lymphadenopathies expressing monocytoid B‐cell reactions. Within a broad cytological spectrum of reactive monocytoid B‐cells, two cytological types can be recognized: 1 the common type composed of medium‐sized cells with irregular or bean‐shaped nuclei and inconspicuous nucleoli, and 2 the large cell type composed of cells considered to represent large transformed monocytoid B‐cells, with less pleomorphic round nuclei with vesicular chromatin and moderately basophilic, prominent nucleoli. In between these variants transitional forms showing evolution to large transformed monocytoid B‐cells occurred. While monocytoid B‐cell reactions in 70.5% of all cases were composed predominantly of the common type of monocytoid B‐cells, in 29.5% of cases the large transformed cells prevailed. The two distinctive cytological types of reactive monocytoid B‐cells, seem to have their neoplastic counterparts in monocytoid B‐cell lymphoma, including its large cell variant.
Recurrent hepatitis B in liver allografts: a distinctive form of rapidly developing cirrhosis
Authors: HARRISON R.F. , DAVIES M.H. , GOLDIN R.D. , HUBSCHER S.G.
Published: April 2007

Recurrent hepatitis B virus (HBV) infection in the liver allograft is a significant cause of morbidity and mortality in those transplanted for chronic HBV disease. A detailed histological and immunohistochemical study of recurrent HBV disease in liver allografts was carried out using archival paraffin‐embedded tissue. A total of 34 follow‐up liver biopsies from 14 patients transplanted for HBV were available for study. In addition to routine stains, sections were stained with antibodies to a range of HBV antigens. Two patients transplanted for acute HBV remained free of re‐infection. Five of seven patients transplanted for chronic HBV disease who were followed‐up, developed HBV‐associated cirrhosis 12–23 months later. Hepatocyte ballooning, high nucleocapsid antigen load, ductular proliferation and immature fibrous tissue characterized this unusual cirrhosis, which developed rapidly from fibrosing cholestatic hepatitis in at least three cases. Death from liver failure supervened quickly in three of the five patients. These findings support the concept that HBV infection in the liver allograft can be a different disease from that occurring in the non‐transplant setting, and may be related to high antigen load.
Expression of epidermal and nerve growth factor receptors in human thymus and thymomas
Authors: PESCARMONA E. , PISACANE A. , PIGNATELLI E. , BARONI C.D.
Published: April 2007

The expression of epidermal growth factor (EGF) and nerve growth factor (NGF) receptors has been investigated by immunohistochemical analysis in eight normal human thymuses and in 15 thymomas. Thymomas were classified into five different histological types—medullary, mixed, predominantly cortical, cortical thymoma and well‐differentiated thymic carcinoma. In fetal and paediatric normal thymus, EGF‐receptor was expressed by subcapsular, cortical and medullary epithelial cells, whereas immunoreactivity for NGF‐receptor was detected on only subcapsular and Jullary epithelial cells. In thymomas, independent of their histological type, EGF‐receptor was expressed by a large majority of epithelial cells. In contrast, the pattern of expression of NGF‐receptor in thymomas was different for the various histological types. These findings indicate that the expression of both EGF and NGF receptors in human thymomas substantially reflects their expression in normal thymus, and suggest that EGF and NGF may play a role in the ontogenesis of the human thymus as well as in the histogenesis of thymomas.
Immunocytochemical characterization of neuroendocrine tumours of the larynx
Authors: SALIM S.A. , MILROY C. , RODE J. , CORRIN B. , HAMID Q.
Published: April 2007

Twenty‐two neuroendocrine tumours of the larynx were investigated using a panel of immunocytochemical markers. Three were small cell carcinomas, eight were large cell neuroendocrine carcinomas and 11 were paragangliomas. Twenty were positive for protein gene product 9.5, 19 for neuron‐specific enolase, 15 for chromogranin A, nine for bombesin, eight for substance P, eight for neuropeptide Y, eight for metenkephalin, seven for somatostatin, five for calcitonin, eight for calcitonin gene‐related peptide and one for vasoactive intestinal polypeptide. Bombesin immunoreactivity was largely restricted to the small cell carcinomas and large cell neuroendocrine carcinomas and neuropeptide Y, metenkephalin and substance P to the parangangliomas. This comprehensive immunocytochemical analysis of neuroendocrine tumours of the larynx demonstrates that these tumours represent special entities but have similar patterns of immunostaining to those of neuroendocrine tumours in other sites.
Salivary‐type myxoid myoepithelioma of the sinonasal tract: a potential diagnostic pitfall
Authors: BÉGIN L.R. , BLACK M.J.
Published: April 2007

A 38‐year‐old woman presented with otalgia and facial pain. She was found to have a tumour involving the right maxillary sinus and pterygopalatine fossa. Exclusively composed of a myxoid population of spindle and stellate cells within a mucosubstance‐rich matrix, it was originally interpreted as a mesenchymal neoplasm. However, immunophenotypic characterization revealed a pure population of salivary‐type myoepithelial cells with cytoplasmic co‐expression of cytokeratin, vimentin, muscle‐specific actin, S‐100 protein and glial fibrillary acidic protein. Sinonasal myxoid myoepithelial neoplasia is exceedingly rare and represents a potential diagnostic pitfall.
Histopathological features and grading in rhabdomyosarcomas of childhood
Authors: WIJNAENDTS L.C.D. , LINDEN J.C. VAN DER , UNNIK A.J.M. VAN , DELEMARRE J.F.M. , VOUTE P.A. , MEIJER C.J.L.M.
Published: April 2007

Rhabdomyosarcoma represents a large group of soft tissue sarcomas displaying heterogeneous histopathological features. In addition to their histopathological classification, the variable expression of a number of histopathological features may contribute to the heterogeneity and may be related to prognosis. Tissue sections of 113 well‐documented, protocol‐treated patients with long term follow‐up (mean 6 years) were analysed by a panel of four paediatric pathologists. The following features were assessed: presence of rhabdomyoblasts, degree of maturation of rhabdomyoblasts, heterogeneous maturation patterns, mitotic activity, tumour necrosis, myxoid component, and septa. A scoring system was allocated to each index. High degree of maturation (amount of cytoplasm greater than surface area of the nucleus), absence of tumour necrosis (< 10% of tumour surface), and absence of septa (< 10% of tumour surface) significantly correlated with a favourable clinical course. Reproducibility in the assessment of these three features was good: mean κ varying from 0.53 to 0.64. A rhabdomyosarcoma score function for survival was defined by: (‐0.27 x degree of maturation score) + (0.007 x percentage septated area) + (0.031 x percentage tumour necrosis). Based on the score a two‐grade system was elaborated, i.e. grade I (score < ‐0.20) v. grade II (score < ‐0.20). Rhabdomyosarcoma grade appeared to be the best factor in predicting patients survival: 69% long‐term survival in patients with grade I v. 33% in patients with grade II (P= 0.0001). Moreover, this grading system was shown to have discriminative power within the group of patients with embryonal rhabdomyosarcoma: patients with a grade I tumour fared significantly better than those with a grade II tumour (63%v. 41% long‐term survival, P= 0.03). This study, therefore, demonstrated the prognostic value of this grading system and its useful application within the group of patients with embryonal rhabdomyosarcomas.
Distribution of the cdc2 gene product in normal tissues: an immunocytochemical study using four new monoclonal antibodies
Authors: DOUSSIS‐ANAGNOSTOPOULOU I.A. , TENNANT R.C. , GANNON J. , GATTER K.C.
Published: April 2007

The reproductive cycle in eukaryotic cells is partly controlled by the p34 protein kinase, the product of the cdc2 gene. We report here the tissue reactivity of four new anti‐cdc2 monoclonal antibodies in relation to the known proliferation markers Ki‐67 and JC1. In tissues where proliferation occurs, germinal centres in the tonsil, basal layers of tonsular epithelium and skin, cortex of the thymus, seminiferous tubules of the testis and epithelium of the colon, the anti‐cdc2 antibodies gave positive nuclear staining as did the proliferation markers. The percentage of positive cells was, however, lower with the cdc2 antibodies. Given the role of the cdc2 gene at specific points of the cell cycle, these antibodies are potentially useful as markers of different phases of the cell cycle and may help to detect abnormalities in cell cycle control in disease.
Florid basal cell hyperplasia of the prostate
Authors: VOORDE W. VAN DE , BALDEWIJNS M. , LAUWERYNS J.
Published: April 2007

Florid basal cell hyperplasia of the prostate is an uncommon proliferative condition, most often associated with adenomatous hyperplasia. It is considered a benign lesion although confusion with prostatic cancer is possible when one is not familiar with the histopathological appearance. We report another two cases of the glandular type of basal cell hyperplasia with immunohistochemical findings. Both lesions were composed of crowded and rather small glands with piling up of basaloid cells. They showed immunohistochemical positivity for high molecular weight cytokeratin 34βE12, confirming their relationship with basal cells. We detected focal positivity of these basal cells for α‐smooth muscle actin, suggesting myoepithelial differentiation. Paucity of actin‐positive smooth muscle cells in the stroma was noticed. One of the lesions showed some mild cytological atypia with prominent nucleoli and increased mitotic activity.
Atypical carcinoid tumour of the lung: a study of 33 cases with prognostic features
Authors: VALLI M. , FABRIS G.A. , DEWAR A. , HORNALL D. , SHEPPARD M.N.
Published: April 2007

Atypical carcinoids of the lung (well‐differentiated neuroendocrine carcinomas) are rare tumours of uncertain prognosis. We have studied 33 cases—male to female ratio 2:1, age range 22–75 years, mean 55 years, 80% smokers, 15 peripheral and 18 central, tumour size 1.2–9.5 cm. Microscopically they had a nesting/insular, trabecular or lobular pattern. Nuclear morphology was variable, round cells, large cells and spindle cells being identified with small cell areas in five tumours. Mitotic activity varied from 4 to 80 per 1.52 mm2. Areas of necrosis were seen in all tumours. All 33 tumours were cytokeratin positive (AE1/AE3 and CAM 5.2), 32 were positive for neuron‐specific enolase, synaptophysin and chromogranin A. Electronmicroscopy showed dense core granules in 29 available cases. Nineteen cases were stage I, nine stage II, four stage III and one stage IV. Follow‐up information was available for 22 cases. Size, location, stage and large cell/small cell morphology were important prognostic indicators. Large tumour size, large cell or mixed large cell/small cell morphology, peripheral localization and advanced stage were adverse prognostic indicators. Mitotic activity and the presence of necrosis did not appear to influence stage or behaviour.
Castleman's disease. Differences in follicular dendritic network in the hyaline vascular and plasma cell variants
Authors: NGUYEN D.T. , DIAMOND L.W. , HANSMANN M.L. , ALAVAIKKO M.J. , SCHRÖDER H. , FELLBAUM C. , FISCHER R.
Published: April 2007

Twenty‐seven cases of the hyaline vascular variant and 10 cases of the plasma cell variant of Castleman's disease were studied with the paraffin resistant monoclonal antibodies Ki‐FDC1p and/or Ki‐M4p against follicular dendritic cells. Studies with the monoclonal antibody Ki‐M9, for the detection of sinus lining cells, were also performed on the available frozen tissue in four cases of the hyaline vascular variant. In nine of the 10 plasma cell variant cases, the predominant type of follicular dendritic cell network was similar to that seen in normal or reactive germinal centres. In contrast, the hyaline vascular variant demonstrated either an expanded, disrupted, follicular dendritic cell network (10 cases) or multiple tight collections of follicular dendritic cells (16 cases). Sinus lining cells were not detected in the four cases studied. The difference in the predominant type of dendritic meshwork is an additional distinguishing feature to separate the plasma cell and hyaline vascular variants of Castleman's disease. The patterns of dendritic network seen in the hyaline vascular type, together with the absence of sinus lining cells, appear to favour the hamartoma theory proposed for this variant.
Primary splenic large cell anaplastic lymphoma associated with HIV infection
Authors: BELLAMY C.O.C. , KRAJEWSKI A.S.
Published: April 2007

We report a case of primary splenic B‐cell CD30 positive large cell anaplastic lymphoma developing in an HIV positive patient. The tumour cells expressed Epstein–Barr virus‐associated antigens.
Polymorphous sweat gland carcinoma
Authors: SUSTER S. , WONG T.‐Y.
Published: April 2007

We describe nine cases of a distinctive cutaneous neoplasm showing features of eccrine adnexal differentiation that were characterized by their variegated histological appearance and low‐grade malignant behaviour. The term polymorphous sweat gland carcinoma is proposed to designate these lesions. The tumours presented as large, longstanding, slow growing, dermal nodules showing a marked predilection for the extremities. Six patients were women. The patients were aged 42–70 years (mean, 59.8 years). Histologically, the lesions were characterized by a highly cellular proliferation displaying a variety of growth patterns, including solid, trabecular, tubular, pseudopapillary and cylindromatous, with prominent stromal changes including haemorrhage, hyalinization and cystic change, and displaying moderate cytological atypia and mitoses. Focal areas showing features associated with eccrine differentiation (i.e. tubular structures, small glandular lumina) could be identified in all cases. Clinical follow‐up in six cases showed that two of the lesions recurred locally over a period of 3–6 years, and one tumour metastasized to regional lymph nodes 3 years after excision. Polymorphous sweat gland carcinoma should be considered in the differential diagnosis of neoplastic epithelial dermal proliferations; complete but conservative surgical excision appears to be the treatment of choice for these lesions.
Cytokeratin expression and distribution in adamantinoma of the long bones and osteofibrous dysplasia of tibia and fibula. An immunohistochemical study correlated to histogenesis
Authors: BENASSI M.S. , CAMPANACCI L. , GAMBERI G. , FERRARI C. , PICCI P. , SANGIORGI L. , CAMPANACCI M.
Published: April 2007

Twenty‐four cases of adamantinoma and 24 cases of osteofibrous dysplasia of the long bones were studied to evaluate the expression and distribution of cytokeratin (CK) subtypes in relation to histogenesis and differentation. The immunohistochemical study was performed on tissue fixed in buffered formalin and embedded in paraffin wax utilizing antibodies to vimentin, factor VIII, epithelial membrane antigen and cytokeratins of different molecular weights. In all cases the vimentin antibody marked positively in stroma, endothelium and osteoblasts, while factor VIII expression was confined to endothelial cells. In 71% of adamantinomas, vimentin showed strong immunoreactivity in the tumour cells of nests and tubules. CKAE1/AE3 and CK19 were strongly expressed in all morphological patterns of adamantinoma emphasizing their epithelial origin, while the antibodies to CK8 and CK18 showed a high percentage of negative responses. In osteofibrous dysplasia the epithelial‐like component was much smaller than in adamantinoma and was present in scattered islands composed of a few cells positive for CKAE1/AE3 and CK19 and negative for other keratins. These results suggest that these two lesions are of a similar histogenesis.
bcl‐2 proto‐oncogene and Epstein–Barr virus latent membrane protein‐1 expression in AIDS‐related lymphoma
Authors: SCHLAIFER D. , BROUSSET P. , ATTAL M. , MASSIP P. , PAYEN C. , MARCHOU B. , HUGUET F. , MULLER C. , LAURENT G. , PRIS J. , DELSOL G.
Published: April 2007

The expression of bcl‐2 protein and Epstein–Barr virus (EBV) latent membrane protein 1 (LMP‐1) was investigated in 18 cases of lymphoma occurring in the acquired immunodeficiency syndrome (AIDS). EBV small RNAs were detectable in tumour cells in all cases by in situ hybridization with EBER oligonucleotides. LMP‐1 expression was detected in 61% of the cases, and 55% were positive for bcl‐2. Dual expression of LMP‐1 and bcl‐2 was found in 8/18 (44%) cases, while five cases (28%) expressed either LMP‐1 or bcl‐2 and five expressed neither. Thus, there was an inconsistent relationship between the presence of EBV and the expression of bcl‐2. One LMP‐1 negative case was found to express bcl‐2 in reactive lymphocytes but not in lymphoma cells. No clinical features were found to correlate statistically with LMP‐1 or bcl‐2 expression in the tumour cells. However, CD4 counts at diagnosis were significantly lower in bcl‐2 positive cases (P < 0.05). The respective roles of EBV LMP‐1 and the expression of bcl‐2 in lymphogenesis in AIDS patients remains complex and is not yet fully understood.
The distribution of adhesion molecules in chronic periaortitis
Authors: RAMSHAW A.L. , PARUMS D.V.
Published: April 2007

Chronic periaortitis is a local complication of human atherosclerosis. It is defined as the triad of advanced atherosclerosis, medical thinning and aortic adventitial chronic inflammation. It is present to a variable degree in association with atherosclerotic abdominal aortic aneurysms. These aortic adventitial infiltrates differ from those described solely within the atheroma itself, in that they consist predominantly of B lymphocytes. Many of the lymphocytes are activated and proliferating, and germinal centres are common. In this study, an immunohistochemical analysis was carried out on fresh surgical aortic aneurysm tissue in order to investigate the presence and distribution of activation‐inducible adhesion molecules, and to correlate this with the degree of inflammation. A consistent finding was the presence of E‐selectin on endothelial cells in up to 50% of the vessels throughout the aortic wall and at the base of the atheroma, independent of the severity of inflammation. ICAM‐1 expression was abundant on many cell types and increased with the severity of chronic inflammation, being strongest in the germinal centres. VCAM‐1 expression was predominant on follicular dendritic cells and also increased with severity of inflammation. VCAM‐1 expression was also detected on vessels within lymphoid follicles. The pattern of expression of the adhesion molecules suggests a role in the initiation and progression of chronic inflammation associated with advanced atherosclerosis.
Pathological prognostic factors in breast cancer. III. Vascular invasion: relationship with recurrence and survival in a large study with long‐term follow‐up
Authors: PINDER S.E. , ELLIS I.O. , GALEA M. , O'ROUKE S. , BLAMEY R.W. , ELSTON C.W.
Published: April 2007

The invasion of vascular spaces (lymphatic and/or blood vessel) by tumour, as assessed on routine haematoxylin and eosin sections, was investigated in a consecutive series of 1704 women with primary operable invasive breast carcinoma. Strict morphological criteria were used. Patients were under 70 years of age and received definitive surgery with no adjuvant systemic therapies. Information from regular follow‐up (range 3–17 years) was recorded on to a computer database. Definite vascular invasion was seen in 22.8% of cases and concurrence between pathologists was high. In univariate analyses, vascular invasion was strongly associated with lymph node stage (P≤ 0.0001), tumour size (P≤ 0.0001), histological grade (P≤ 0.0001) and type of tumour (P≤ 0.0001). In multivariate analyses vascular invasion was of independent prognostic significance for both survival and for local recurrence of tumour; patients with tumours showing no vascular invasion had a significant survival advantage and a reduced risk of local recurrence. No association with oestrogen receptor status or menopause status was seen. The results confirm that histological assessment of vascular invasion provides independent prognostic information in primary operable breast carcinoma which may be helpful in making clinical decisions.
Solid cell nests of the thyroid in medullary thyroid carcinoma
Authors: OZAKI O. , ITO K. , FUJISAWA T. , KAWANO M. , IWABUCHI H. , KITAMURA Y. , SUGINO K. , MIMURA T.
Published: April 2007

Solid cell nests of the thyroid gland were studied in 44 patients with medullary thyroid carcinoma. In 10 (22.7%) patients, solid cell nests were revealed in the vicinity of tumour foci (five cases) or in the contralateral thyroid lobe and isthmus (four cases); in one case the location was indeterminate. In all seven cases in which immunohistochemical studies were carried out, solid cell nests showed negative staining for thyroglobulin, calcitonin and chromogranin A, findings which were distinct from those in medullary thyroid carcinoma. It is therefore suggested that solid cell nests of the thyroid are not precursors of this tumour.
T (Thomsen–Friedenreich) antigen and other simple mucin‐type carbohydrate antigens in precursor lesions of gastric carcinoma
Authors: CARNEIRO F. , SANTOS L. , DAVID L. , DABELSTEEN E. , CLAUSEN H. , SOBRINHO‐SIMõES M.
Published: April 2007

In a previous report we suggested that T antigen appeared to be associated with gastric carcinoma. To verify this hypothesis and characterize the pattern of expression of simple‐mucin type carbohydrate antigens (Tn. sialyl‐Tn and T before and after neuraminidase) in normal gastric mucosa and precursor lesions of gastric carcinoma, we studied the mucosa adjacent to 100 cases of gastric carcinoma, gastric biopsies of 60 dyspeptic patients, eight adenomatous polyps and eight hyperplastic polyps. The expression of the antigens was more related to the cell type and underlying lesions than to the coexistence of carcinoma. The most distinctive findings concerned intestinal metaplasia, dysplasia and hyperplastic lesions. In intestinal metaplasia, Tn was found mostly in columnar cells and sialyl‐Tn in goblet cells. T was more prevalent in incomplete intestinal metaplasia than in complete. A high prevalence of sialyl‐Tn expression and cell membrane immunoreactivity for T antigen, similar to those previously found in gastric carcinomas, were observed in three adenomatous polyps, one hyperplastic polyp, five cases of adenomatous dysplasia in the neighbourhood of intestinal carcinomas and four cases of marked foveolar hyperplasia, three of which were from the mucosa adjacent to diffuse carcinomas. We conclude that adenomatous and hyperplastic lesions share with gastric carcinomas features of aberrant glycosylation, namely the cell membrane expression of T antigen.
Gastric epithelial atypia complicating hepatic arterial infusion chemotherapy
Authors: KWEE W.S. , WILS J.A. , SCHLANGEN J. , NUYENS C.M. , ARENDS J. W.
Published: April 2007

Severe gastric lesions developed in five patients during hepatic arterial infusion chemotherapy employing 5‐fluorouracil plus either leucovorin or mitomycin C. Ulceration with marked epithelial atypia was observed with striking structural distortion and cellular pleomorphism of the affected gastric mucosa. These features should be considered to be a complication of such treatment and should not be misinterpreted as malignancy.
Hepatic granulomas in Northern Ireland: a thirteen year review
Authors: McCLUGGAGE W.G. , SLOAN J.M.
Published: April 2007

The finding of epithelioid cell granulomas within liver biopsies is a not uncommon occurrence. We undertook this study to investigate the underlying conditions responsible for a diagnosis of granulomatous hepatitis in Northern Ireland during the thirteen year period 1980–1992. One hundred and sixty‐three patients with hepatic granulomas were identified, accounting for 4% of all liver biopsies undertaken during the period of the study. In 145 cases (89%) a definite clinical diagnosis was established. The most common clinical diagnoses were primary biliary cirrhosis which accounted for 90 cases (55%) and sarcoidosis which accounted for 30 cases (18%). Other less common conditions associated with hepatic granulomas included tuberculosis (3 cases), Crohn's disease (3 cases), chronic active hepatitis (2 cases), drug hypersensitivity (2 cases) and extra‐hepatic biliary obstruction (2 cases). Six patients were identified with a clinical diagnosis of psoriasis. Other miscellaneous conditions accounting for single examples of granulomatous inflammation were schistosomiasis, gout, Hodgkin's disease, secondary adenocarcinoma, collapse and necrosis of tumour following radiotherapy and chemotherapy, granulomatous inflammation within the wall of an abscess cavity and idiopathic cirrhosis. Only eighteen cases (11%) remained idiopathic with no definite diagnosis established after detailed investigation. The findings confirm the wide range of clinical conditions which can result in hepatic epithelioid cell granulomas. This has been emphasised in several previous major studies which are reviewed in this paper.
Monoclonal antibody HML‐1 reactivity with adult T‐cell leukaemia/lymphoma and other lymphomas
Authors: KITAJIMA S. , TOKUNAGA M. , GOTO M. , SATO E. , UTSUNOMIYA A. , OHTSUKA M. , HANADA S. , ARIMA T.
Published: April 2007

Human T‐cell leukaemia/lymphoma virus type 1 (HTLV‐1), a causative virus of adult T‐cell leukaemia/lymphoma (ATLL), is known to be transmitted by breast‐feeding. Using a monoclonal antibody HML‐1 which labels human intestinal intra‐epithelial T lymphocytes, we have immunohistochemically examined ATLL tissues in order to evaluate the possibility that HTLV‐1 infected intestinal T cells are the origin of ATLL cells. Previously this antibody was reported to react with intestinal T‐cell malignant lymphomas but not with peripheral tumours, or any B‐cell lymphomas. We investigated 181 patients with malignant lymphomas and found that 19 out of 113 ATLLs were positive for HML‐1. T‐cell malignant lymphomas excluding ATLL also reacted with HML‐1 (7/24), but all the B‐cell lymphomas 0/33) and non‐neoplastic lymph node and skin lesions (0/10) were negative for HML‐1. In patients with ATLL and other T‐cell malignant lymphomas, the positivity level of HML‐1 was relatively higher in stomach (3/7) and tonsil (2/6) than that in lymph nodes (15/100) and skin (8/47). We observed one HML‐1 positive ATLL patient with tumour formation in the skin and lymphadenopathy and marked infiltration of the large intestine but minimal involvement of other organs. Although HML‐1 was frequently expressed in gastric infiltration of ATLL, the level of positivity was too low in lymph nodes to support the hypothesis that HTLV‐1 infected intestinal T cells are the origin of ATLL cells. Some of the HML‐1 positive ATLL cases co‐expressed CD30. Furthermore, three of six cases of Ki‐1 lymphoma (large anaplastic cell lymphoma) were positive for HML‐1. We conclude that expression of HML‐1 in ATLL reflects an activated state of the lymphoma cells, but not the intestinal origin of ATLL cells.
Integrated decision support system/image archive for histological typing of breast cancer using a relation oriented inference system
Authors: DIEST P.J. VAN , BELIËN J.A.M. , ZANSTRA P.E. , WILHELM W.W. , BAAK J.P.A.
Published: April 2007

Histological typing of invasive breast cancer according to the World Health Organisation criteria is prognostically relevant, because some histological subtypes have a markedly better prognosis. However, reproducibility of histological typing is not high because of the absence of strict typing criteria, variations in the application of the typing criteria and the usually limited illustration of the relevant criteria. The aim of this study was to develop an expert system based on highly structured histological typing criteria, integrated with high‐quality microscope images to illustrate the typing criteria. This system should be useful as a decision support system in the diagnosis of breast cancers and should increase the reproducibility of histological typing. Criteria for typing were extracted from textbooks and, based on experience, these criteria were structured and implemented in the Relation Oriented Inference System (ROIS), in which information can be structured by defining relations. Illustrative black and white images were digitized and integrated into the shell. The performance of the resulting decision support system was evaluated by a group of six pathologists using a set of slides covering the spectrum of the most frequently occurring histological types of invasive breast cancer. The pathologists first assessed histological type according to standard morphological procedures. The cases were then reassessed with the decision support system available for consultation. The use of the decision support system appeared to influence the previously assessed histological type in about half of the cases. Using the decision support system, histological typing was more uniform and more in accord with a ‘gold standard’ set by two experts. The integrated decision support system/image archive for histological typing of breast cancer seems to be a useful instrument in daily diagnostic breast histopathology as well as being a potential teaching tool. It may contribute to a more reproducible and prognostically relevant histological typing of breast cancer.
Nodular hyperplasia surrounding fibrolamellar carcinoma
Authors: SAXENA R. , HUMPHREYS S. , WILLIAMS R. , PORTMANN B.
Published: April 2007

We report a case of acetaminophen‐induced liver necrosis in a 14‐year‐old girl. At autopsy, a 9 cm subcapsular nodule was present in the right lobe of the liver which showed distinct zonation: a central greyish white area of fibrolamellar carcinoma with a peripheral fleshy, tan‐coloured rim ranging from 1 to 2 cm in thickness. This peripheral zone consisted of nodular, hyperplastic parenchyma resembling the changes seen in focal nodular hyperplasia, and stood out from the adjacent necrotic parenchyma. The sparing of this zone from the deleterious effects of acetaminophen provides indirect evidence of a predominantly arterial rather than portal blood supply to this region. The arterial supply was most probably derived from the tumour vasculature and may explain the parenchymal hyperplasia sometimes reported adjacent to a fibrolamellar carcinoma. Awareness of this phenomenon is essential when evaluating a needle biopsy, as sampling of this region may lead to a false negative diagnosis.
Stereological analysis of the synovial membrane in rheumatic disorders: diagnostic value of volume‐weighted mean nuclear volume estimation
Authors: ARTACHO‐PÉRULA E. , ROLDÉAN‐VILLALOBOS R. , COLLANTES‐ESTÉVEZ E. , LÓPEZ‐BELTRÉAN A.
Published: April 2007

Quantitative evaluation of nuclear size of synoviocytes was performed on 48 synovial biopsies in various rheumatic disorders: osteoarthritis (n = 10), rheumatoid arthritis (11), and chronic non‐specific synovitis (14). Thirteen tissue specimens from non‐inflammatory synovial membrane were included as a control group. Using the point‐sampled intercepts method, unbiased stereological estimates of volume‐weighted mean nuclear volume (nuclear νv) were obtained. A slight increase in nuclear volume was observed in osteoarthritis in comparision with the control group with an overlap in 90% of cases. However, in rheumatoid arthritis there was a significant increase of nuclear νv. Significant differences were found between rheumatoid arthritis and the control and osteoarthritis groups (P0.001). In biopsies from patients diagnosed as chronic non‐specific synovitis the averaged nuclear νv values were between those in osteoarthritis and rheumatoid arthritis with a wide range of data. Similar, but less significant differences were demonstrated between rheumatic disorders when using mean nuclear area. Further analysis of chronic non‐specific synovitis patients in combination with nuclear νv estimates as a simple, unbiased, complementary tool are required to better establish the diagnostic value of nuclear stereology in the diagnosis of rheumatic disorders.
Detection of Epstein–Barr virus small RNAs in routine paraffin sections using non‐isotopic RNA/RNA in situ hybridization
Authors: HAMILTON‐DUTOIT S.J. , PALLESEN G.
Published: April 2007

The Epstein–Barr virus (EBV) is associated with an increasing range of reactive and neoplastic lesions. There is a need for a sensitive and specific method for detecting latent EBV in routine histological sections. We report the use of a highly sensitive paraffin section RNA/RNA in situ hybridization (ISH) technique using digoxigenin‐labelled antisense riboprobes for demonstrating EBV encoded‐small RNAs (EBERs), EBV gene products that are transcribed in abundance during latent EBV infection. We applied EBER‐ISH to 846 paraffin embedded specimens, including cases of reactive lymphoid hyperplasia (n= 28), infectious mononucleosis (16), Burkitt's lymphoma (44), immunodeficiency‐associated lymphomas in transplant recipients (9) and AIDS patients (128), Hodgkin's disease (130), CD30 antigen positive lymphomas (106), peripheral T‐cell lymphomas (104), sporadic B‐cell non‐Hodgkin's lymphomas (162), undifferentiated nasopharyngeal carcinoma (86), salivary gland lymphoepithelioma (11), and oral hairy leukoplakia (5). Strong, reproducible EBER staining was seen in EBV latently infected cells in archival surgical biopsy and autopsy specimens. EBER‐ISH is specific, has a sensitivity comparable to that of the polymerase chain reaction, and is now the method of choice for the in situ detection of latent EBV infection.
Primary non‐Hodgkin's lymphoma of the intestine: a morphological, immunohistochemical and clinical study of 31 Chinese cases
Authors: LI C. , OUYANG Q. , LIU K. , WANG Y. , YANG X.
Published: April 2007

Thirty‐one cases of primary non‐Hodgkin's lymphoma of the intestine were investigated. Twenty‐one were of B‐cell and 10 of T‐cell origin. The B‐cell lymphomas comprised two cases of low‐grade B‐cell lymphoma of mucosaassociated lymphoid tissue (MALT), one of centroblastic/centrocytic type, three of high‐grade B‐cell lymphoma coexisting with a low‐grade B‐cell lymphoma of MALT, nine of centroblastic, three of immunoblastic and three of Burkitt type. Of the T‐cell lymphomas, eight were of pleomorphic medium‐to large‐sized cell type and two of large cell anaplastic type. All the B‐cell lymphomas expressed CD20 (L26) and/or Ki‐B5; in six there was monotypic immunoglobulin light chain restriction. Membrane positivity for CD45RO (UCHL1) was observed in the 10 cases of T‐cell lymphoma, but the tumour cells did not express monocyte‐macrophage markers. Clinically, the patients with T‐cell lymphomas were usually young males with constitutional symptoms and their prognosis was significantly worse than those of patients with intestinal B‐cell lymphoma.
Apoptosis of bile duct epithelial cells in hepatic allograft rejection
Authors: NAWAZ S. , FENNELL R.H.
Published: April 2007

Liver biopsy remains the ‘gold standard’ for monitoring rejection in liver transplant patients. Portal inflammation, bile duct damage and endothelialitis are recognized features of hepatic allograft rejection. The pathogenesis of the bile duct injury during rejection, however, remains unclear. To define the mechanism of bile duct damage, we studied the light‐ and electronmicroscopic appearance of hepatic tissue from selected patients in whom allograft failure was solely due to rejection. Of the 25 orthotopic liver transplant rejection cases examined, 17 were mild, seven were moderate and one was severe rejection. Light microscopy examination of the damaged bile duct epithelium revealed evidence of apoptosis which was confirmed by electronmicroscopy. Furthermore, there appeared to be a positive correlation between the grade of rejection and the number of apoptotic cells. Also included in the study were 13 cases of chronic active hepatitis and 10 normal livers which showed the least apoptotic cells. We conclude that the identification of apoptotic cells in damaged bile ducts in allograft biopsies might be helpful in the diagnosis of rejection and in assessment of the severity of rejection.
Amputation neuroma of the hepatic hilum after orthotopic liver transplantation
Authors: COLINA F. , GARCÍA‐PRATS M.D. , MORENO E. , GARCÍA‐MUÑOZ H. , BALLESTÍN C. , MAYORDOMO J.I. , GÓMEZ‐SANZ R. , GONZÁLEZ‐PINTO I.
Published: April 2007

Amputation neuromas following biliary surgery have been previously reported. There are no descriptions, however, of amputation neuroma following liver transplantation. Serial hilum sections taken from 93 hepatectomy specimens obtained during the clinical course of 262 consecutive orthotopic liver transplantations revealed 26 amputation neuromas (27.9% of the specimens examined). The finding was confirmed by immunohistochemistry with numerous S‐100 protein positive cells intermingled with neurofilaments interrupting the perineurial layer of cells testing positive for epithelial membrane antigen. Neuromas were found in liver specimens obtained between 89 and 775 days post‐transplant (mean time, 211 days). The incidence of neuroma was higher in specimens resected more than 3 months post‐transplant. There was only one symptomatic patient, who died from extrahepatic cholestasis demonstrated at autopsy to be caused by a hilar neuroma obstructing the main bile duct.
Abnormal integrin receptor expression in two cases of familial nephronophthisis
Authors: RAHILLY M.A. , FLEMING S.
Published: April 2007

Familial nephronophthisis is one of the inherited human cystic kidney diseases and is characterized by progressive renal failure. We have investigated abnormalities of cell‐matrix interactions using immunocytochemistry and electron microscopy in three renal biopsies from two patients with familial nephronophthisis and compared our findings to those seen in thirty other renal biopsies. We found expression of the α5 integrin fibronectin receptor in all three samples of nephronophthisis but in no other renal diseases. There was also enhanced expression of the α2 integrin in nephronophthisis but this appeared to be a common response to tubular injury. Electron microscopy showed thickening of the tubular basement membrane and a loss of organization of the basal pole of tubular epithelium. We conclude that altered cell‐substratum adhesion contributes to the pathogenesis of nephronophthisis.
Secretoneurin in bronchopulmonary carcinoids—immunohistochemical comparison with chromogranins A and B and secretogranin II
Authors: TÖTSCH M. , PADBERG B‐C. , SCHRÖDER S. , ÖFNER D. , BÖCKER W. , FISCHER‐COLBRIE R. , SCHMID K.W.
Published: April 2007

Ninety‐nine classical and 11 atypical bronchopulmonary carcinoids were investigated immunohistochemically with an antibody against secretoneurin, a peptide proteolytically processed from secretogranin II (chromogranin C), as well as antibodies against chromogranin A and B and secretogranin II. Secretoneurin was immunolocalized in 86 tumours (78 classical and eight atypical carcinoids); secretogranin II was found in the same tumours in a similar distribution, whereas chromogranin A was present in all 100 and chromogranin B in 106 tumours investigated. Bronchopulmonary carcinoids are usually not associated with clinically or biochemically distinct syndromes. Although we found bronchial carcinoids with different immunohistochemical chromogranins/secretogranin patterns, no correlation with the biological behaviour of these tumours could be demonstrated.
Phyllodes tumours of the breast: a clinicopathological review of thirty‐two cases
Authors: MOFFAT C.J.C. , PINDER S.E. , DIXON A.R. , ELSTON C.W. , BLAMEY R.W. , ELLIS I.O.
Published: April 2007

We have reviewed the histological features and clinical outcome in 32 women with phyllodes tumours of the breast diagnosed in Nottingham between 1975 and 1990. We assessed 23 tumours as histologically benign, four as borderline and five as malignant. After clinical follow up for periods ranging from 36 months to 221 months (median 135 months), six of 23 benign tumours have recurred locally; in all these cases the original tumours had been incompletely excised. There were no recurrences amongst 10 benign tumours in which excision had been complete. Benign tumours which recurred showed a tendency to greater stromal cellularity and more pronounced stromal overgrowth than incompletely excised lesions which did not recur, but these differences were not statistically significant. The recurrent tumours resembled the respective original lesions histologically, except in one case in which two local recurrences were histologically malignant. The recurrent tumours were controlled by further excision or mastectomy in all cases and none have metastasized. All four borderline tumours were completely excised at initial surgery and none have recurred or metastasized. One of the five malignant tumours recurred within two months of incomplete excision, with widespread infiltration of the chest wall, although the patient died of unrelated causes. The other four malignant tumours have not recurred. We conclude that presence of tumour at the margins of the excised specimen is the major determinant of local recurrence in phyllodes tumours and that the histological features are of secondary importance. These findings are discussed in relation to other published series in the literature.
Hypertrophic cardiomyopathy — pathology and pathogenesis
Authors: DAVIES M.J. , McKENNA W.J.
Published: April 2007

Genes on five loci on separate chromosomes are responsible for a familial disease in which all or part of the ventricular muscle undergoes thickening with a histological picture of irregular hypertrophy and disorganized arrangement of myocytes (disarray). The three genes identified so far encode for β heavy chain myosin (chromosome 14), troponin T (chromosome 1) and α tropomyosin (chromosome 15). It is postulated that the phenotype within the heart is produced by abnormal myofibril formation and alignment leading to an abnormal cell shape and, thus, disarray. While all the myocytes carry the gene, the regional selectivity of the hypertrophy is unexplained. The phenotypic expression of the disease within affected members of one family, all of whom are heterozygous for the same gene abnormality, is very varied. Asymptomatic carriers are common, and new mutations do not account for most apparently isolated cases. The phenotypic expression of the disease was studied in 75 hearts. The increase in total heart weight ranged from near normal to over 800 g. Ventricular involvement was diffuse and symmetric in 42%. The commonest asymmetric form involved the anteroseptal region (31%) but sporadic cases involved only the posterior or lateral wall. A minority of cases (9.5%) did not show macroscopic wall thickening. Fibrosis is often associated with dysplastic changes in the media of small intramyocardial arteries and may lead to the ventricular wall simulating a dilated cardiomyopathy. A subaortic patch of endocardial thickening on the ventricular septum due to contact with the anterior cusp of the mitral valve was found in a third of cases. The variation in the macroscopic appearances of the disease is so great that extensive histological examination is required in cases of sudden death to confirm or exclude the diagnosis. Exaggerated responses to hypertension or prolonged physical training may produce left ventricular hypertrophy closely mimicking hypertrophic cardiomyopathy but disarray is absent. Such cases may die suddenly. High circulating levels of angiotensin are thought to be responsible, either because of renal disease or due to polymorphisms in the angiotensin converting enzyme gene.