bluuebunny/crossref_metadata_2025 huggingface dataset:
C‐cell hyperplasia in secondary hyperparathyroidism
Authors: TOMITA T. , MILLARD D.M.
Published: April 2007

Calcitonin is a hypocalcaemia producing hormone and is secreted by C‐cells of the thyroid. The current study was undertaken on a hypothesis that C‐cell hyperplasia may develop in the secondary hyperparathyroidism of chronic renal failure in response to sustained hypercalcaemia. With an immunoperoxidase staining method for calcitonin, C‐cell hyperplasia was noted in four of six cases of autosomal dominant polycystic kidney disease and in three of six cases of acquired renal cystic disease, an overall incidence of 58% compared with an incidence of 36% (five of 14) in cases of primary hyperparathyroidism with parathyroid adenoma. Thus, both primary and secondary hyperparathyroidism may trigger C‐cell hyperplasia in an attempt to produce a hypocalcaemic effect.
Modes of Helicobacter colonization and gastric epithelial damage
Authors: CHAN W.Y. , HUI P.K. , LEUNG K.M. , THOMAS T.M.M.
Published: April 2007

A total of 144 gastric biopsies colonized by Helicobacter‐like organisms were studied under light and differential interference contrast microscopy for the modes of bacterial colonization. Biopsies were also graded for the degree of epithelial damage (epithelial‐damage‐grade: 0 to 6, in ascending order of severity) and density of Helicobacter‐like organism (Helicobacter‐grade: 0 to 6, in ascending order of bacterial density). Three modes of colonization were identified: free‐in‐mucus, surface‐adhesion and intercellular colonization. Because light miscroscopy cannot definitely prove the presence of intracellular colonization, bacteria located between cells and below the apical cell border were counted together as intercellular colonization. Bacteria free‐in‐mucus were seen in all biopsies. Surface adhesion was seen in 50–87.9% of biopsies, without obvious correlation with the epithelial‐damage‐ and Helicobacter‐grades. The incidences of intercellular and intracellular colonization were directly proportional to the epithelial‐damage‐ and Helicobacter‐grades. Free‐in‐mucus as the predominant mode of colonization was mainly seen in biopsies with lower (1–3) epithelial‐damage‐ and Helicobacter‐grades. Conversely, biopsies with intercellular colonization as the predominant mode of colonization were mainly cases with higher (4–6) epithelial‐damage‐ and Helicobacter‐grades. In cases showing predominantly bacteria between cells, 69.2% had a gastric ulcer whereas only 38.8% of cases showing predominantly bacteria free‐in‐mucus showed ulceration (P<0.01). These results indicate that Helicobacter‐like organisms can invade and penetrate between epithelial cells. When free‐in‐mucus, Helicobacter‐like organisms are less likely to induce epithelial damage. However, the more invasive modes of colonization (intercellular) were associated with severe epithelial damage and high Helicobacter density. The major factor associated with invasive modes of colonization was the quantity of bacteria. It is proposed that reduction or eradication of Helicobacter‐like organisms in the colonized stomach can decrease bacterial invasion, minimize Helicobacter‐induced epithelial damage and reduce the risk of gastric ulcer.
Intestinal pseudo‐obstruction with deficient smooth muscle α‐actin
Authors: SMITH V.V. , LAKE B.D. , KAMM M.A. , NICHOLLS R.J.
Published: April 2007

We describe a 48‐year‐old woman with chronic constipation since early childhood who has an intestinal myopathy associated with a hitherto undescribed absence by immunostaining of smooth muscle α‐actin confined to the intestinal circular muscle. There were no abnormalities in other contractile proteins (myosin, tropomyosin, filamin, caldesmon or desmin) and despite the abnormality of a contractile protein isoform in the circular muscle, no significant morphological changes were identified by light microscopy or ultrastructural examination. A possible developmental mechanism for the observed change is proposed. The use of specific antibodies to isoforms of contractile proteins may have potential value in the study of intestinal myopathies.
From slow virus to prion: a review of transmissible spongiform encephalopathies
Authors: LANTOS P.L.
Published: April 2007

Spongiform encephalopathies include seven neurodegenerative diseases: three in man (Creutzfeldt‐Jakob disease, Gerstmann‐Sträussler‐Scheinker disease and kuru) and four in animals (scrapie, mink encephalopathy, bovine spongiform encephalopathy and chronic wasting disease in deer and elks). They are all transmissible to a variety of species, and man‐to‐man propagation of the diseases in the form of iatrogenic transmission has been well‐documented. The infectious agent is highly unusual and the pathogenesis of infection remains controversial. The term prion was introduced to describe the proteinaceous infectious agent. Purification of this agent yielded a unique sialoglycoprotein, associated with the neuronal cell membrane, which is all or part of the infectious agent. Molecular genetics revealed variations in the prion protein; these are linked to or associated with the inherited forms of spongiform encephalopathies: familial Creutzfeldt‐Jakob disease and Gerstmann‐Sträussler‐Scheinker disease. The histological triad of spongiform change, neuronal loss and astrocytosis dominate the histological picture of spongiform encephalopathies. A recent case which did not develop any of the histological hallmarks of disease, but did have genetic abnormalities typical of the disease, indicates that the true incidence of Creutzfeldt‐Jakob disease may be considerably higher than previously accepted, and a combination of molecular screening and immunohistochemistry for prion protein should complement traditional neuropathology to establish the diagnosis. The descriptive term of spongiform encephalopathy may now have to be abandoned in favour of prion disease.
Low‐grade gastric B‐cell lymphoma of mucosa‐associated lymphoid tissue (MALT): a multifocal disease
Authors: WOTHERSPOON A.C. , DOGLIONI C. , ISAACSON P.G.
Published: April 2007

Gastrectomy specimens from five patients following gastroscopic biopsies which showed low‐grade B‐cell lymphoma of mucosa‐associated lymphoid tissue (MALT) were examined by serially sectioning and paraffin wax embedding using a ‘swiss roll’ technique. This procedure allowed the construction of a map of the specimen on which the distribution of the lymphoma could be plotted. In each case confluent lymphoma was identified. In addition small foci of lymphoma consisting of 1–4 lymphoid follicles surrounded by neoplastic centrocyte‐like cells were seen. The positions of these ‘micro‐lymphomas’ were plotted on the gastrectomy maps, showing multiple foci distributed throughout the gastric mucosa. The identification of these microscopic lesions may explain the development of local relapse, often after a long disease‐free interval, in patients with gastric MALT lymphoma treated by partial gastrectomy where excision appears to have been complete. Patients treated in this way should, therefore, be followed‐up indefinitely, with regular endoscopy and gastric biopsy, in order to identify early local disease relapse.
Frequent expression of haemopoietic and non‐haemopoietic antigens by neoplastic plasma cells: an immunohistochemical study using formalin‐fixed, paraffin‐embedded tissue
Authors: PETRUCH U.R. , HORNY H.‐P. , KAISERLING E.
Published: April 2007

There is increasing evidence that neoplastic plasma cells express various haemopoietic and non‐haemopoietic antigens. Since this issue could raise problems in diagnostic histopathology, we have investigated 51 cases of multiple myeloma (plasmacytoma) systematically with a broad panel of antibodies applicable on paraffin‐embedded and mildly decalcified tissue.

In approximately 90% of the cases the neoplastic plasma cells reacted with at least one antibody detecting haemopoietic antigens: MB2 (75%), DF‐T1/CD 43 (59%), UCHL1/CD 45RO (47%), Ki‐B3 (41%), anti‐LCA/CD 45 (40%), L26/CD 20 (26%), 4KB5/CD 45RA (18%), Ber H2/CD 30 (10%), anti‐neutrophil elastase (4%), anti‐Leu‐7/CD 57 (8%), Dako‐M1/CD 15 (2%), KP1/CD 68 (2%) and anti‐glycoprotein IIIa (2%). In approximately 70% of the cases the cells reacted with antibodies against non‐haemopoietic antigens: anti‐epithelial membrane antigen (65%), BMA120 (53%), anti‐vimentin (44%), anti‐pan‐cytokeratin/KL1 (8%), anti‐carcino‐embryonic antigen (6%) and HMB45 (6%).

Lack of awareness of the frequent expression of both haemopoietic and non‐haemopoietic antigens by neoplastic plasma cells could lead to mis‐diagnosis of plasmacytomas as malignant lymphomas or even as carcinomas or sarcomas.
Mammary hamartoma—a review of 35 cases
Authors: FISHER C.J. , HANBY A.M. , ROBINSON L. , MILLIS R.R.
Published: April 2007

Mammary hamartomas are macroscopically well‐delineated tumours composed of a variable mixture of epithelial elements, fat and fibrous tissue. Such lesions are an under‐recognized entity and, as they can be visualized by mammography, may be seen more frequently with the advent of the UK National Breast Screening Programme. The clinical and pathological features of 35 cases of mammary hamartoma seen at the Imperial Cancer Research Fund Clinical Oncology Unit at Guy's Hospital between 1979 and 1990 have been reviewed. Hormone receptor analysis on nine cases gave high progesterone with low oestrogen levels, probably reflecting their premenopausal status. Immunohistochemistry showed that the positive receptor staining was confined to the epithelial elements. In 25 cases pseudo‐angiomatous hyperplasia was evident in the stroma of the lesion. The importance of distinguishing the interanastomosing stromal spaces seen in the latter condition from low‐grade angiosarcoma is emphasized; the relationship between pseudo‐angiomatous hyperplasia and mammary hamartoma is discussed; and the possibility that the former represents a permanently dilated form of the lymphatic labyrinth suggested.
The desmoplastic melanocytic naevus: a distinct histological entity
Authors: MACKIE R.M. , DOHERTY V.R.
Published: April 2007

Fifteen cases of desmoplastic melanocytic naevi are described in 12 female and three male patients, ranging in age from 8 to 83 years. The commonest site for the lesions was the upper limb. The lesions were characterized by a dense sclerotic or desmoplastic appearance of the dermal collagen surrounding a population of predominantly epithelioid naevus cells, some of which had a bizarre but non‐malignant cytology. The cause of the stromal change is not established. We suggest that these lesions constitute a discrete entity which should be described in standard textbooks of dermatopathology.
AgNOR counts and histological grade in stage pTa bladder tumours: reproducibility and relation to recurrence pattern
Authors: HANSEN A.B. , BJERREGAARD B. , OVESEN H. , HORN T.
Published: April 2007

Silver‐stained nucleolar organizer regions (AgNORs) were studied in 90 patients with a single, primary, non‐invasive papillary bladder tumour (stage pTa). All tumours were locally resected and patients were followed for 5 years (n= 68) or until the development of an invasive recurrence (n= 22).

AgNOR counts showed wide overlaps between the different tumour grades. Furthermore, AgNOR counts were unable to predict the non‐invasive recurrence pattern (none, single, multiple). Almost equivalent invasive recurrence rates were found among the following AgNOR counts and Bergkvist grades: AgNOR ≤ 5 (0%) and grade I (5%); AgNOR > 5, but ≤ 8 (20%) and grade II (20%); and AgNOR > 8 (77%) and grade III (67%). Combining the two parameters showed that an AgNOR count > 8 resulted in a 75 and 80% invasive recurrence rate in grade III and II tumours respectively. The reproducibility for AgNOR counting was moderate (K= 0.52) and no better than Bergkvist grading (K= 0.50).
Transforming growth factor α expression in normal gastric mucosa, intestinal metaplasia, dysplasia and gastric carcinoma—an immunohistochemical study
Authors: NASIM M.M. , THOMAS D.M. , ALISON M.R. , FILIPE M.I.
Published: April 2007

Using a monoclonal antibody (GF10) and a standard immunohistochemical technique, immuno‐expression of transforming growth factor α (TGF‐α) was found consistently within the differentiated compartment of normal adult human gastric mucosa. In 70% of mucosal samples exhibiting intestinal metaplasia there was more or less uniform TGF‐α immunoreactivity throughout the intestinalized mucosa. Similarly, 60% of cases of dysplasia and 60% of gastric carcinomas showed strong immunoreactivity in most of the cells. However, whereas 93% of intestinal‐type cancers showed strong immunoreactivity only 30% of the diffuse type were stained and then only weakly. Transforming growth factor α expression is thus a fairly regular feature of several types of differentiated gastric epithelia (normal, metaplastic, dysplastic and intestinal‐type carcinoma), while its relative absence may be a factor in the histogenesis of the diffuse type of gastric carcinoma.
Epstein‐Barr virus latent and replicative gene expression in oral hairy leukoplakia
Authors: .SANDVEJ K. , KRENÁCS L.K. , HAMILTON‐DUTOIT S.J. , RINDUM J.L. , PINDBORG J.J. , PALLESEN G.
Published: April 2007

Oral hairy leukoplakia is an epithelial lesion of the tongue associated with productive infection by Epstein‐Barr virus (EBV). However, no data concerning the pattern of EBV latent gene expression have been reported, and it remains unresolved whether true latent infection occurs in basal cell layers of oral hairy leukoplakia. We have studied six cases of oral hairy leukoplakia using monoclonal antibody immunohistology for EBV latent–EB nuclear antigen (EBNA) 1, EBNA 2 and latent membrane protein 1 (LMP 1); immediate‐early (BZLF1); and replicative (EA, VCA, MA) proteins, and for the EBV‐receptor (CD21 antigen). EBV DNA was demonstrated by nucleic acid in situ hybridization. Mid‐ to upper‐zone keratinocytes contained EBV DNA and co‐expressed EBNA 1, EBNA 2 (5 of 6 cases), LMP 1, BZLF1 protein, EA, VCA and MA. No EBV genome or gene expression could be demonstrated in basal or parabasal cells. Spinous keratinocytes were labelled by anti‐CD21 antibodies HB5 and B2, but did not express the EBV‐receptor as defined by reactivity with OKB7. The co‐expression of latent and replicative infection‐associated antigens is striking, indicating possible functional roles for latent proteins during the productive cycle. Our results suggest that oral hairy leukoplakia is caused by repeated direct infection of upper epithelial cells with virus from saliva or adjacent replicatively infected cells, rather than by a latent EBV infection of basal epithelial cells with a differentiation‐dependent switch to productive infection as previously proposed.
Pagetoid infiltration in primary cutaneous melanoma
Authors: FALLOWFIELD M.E. , COOK M.G.
Published: April 2007

Pagetoid infiltration of the epidermis by melanocytes, also termed ‘buckshot spread’, is regarded by some as being essential for the confident histopathological diagnosis of primary cutaneous melanoma. We have reviewed 340 melanomas received over a 23 year period to assess the frequency of pagetoid infiltration and whether its presence bears any relationship with other histopathological features. Conspicuous pagetoid infiltration was present in 32.1% of the lesions and occasional melanocytes were observed within the stratum spinosum in a further 23.5% of cases. However, no melanocytes could be seen above the basal layer in 44.4% of the melanomas. The presence of pagetoid infiltration showed inverse correlation with tumour thickness, level of invasion, growth phase and mitotic count, and positive correlation with the presence and severity of regression. No association was found with the site of the primary lesion, melanocytic dysplasia or lentigo maligna in the adjacent epidermis, or with the presence of residual benign naevus cells in the epidermis. Thus, pagetoid infiltration of the epidermis was commonest in in situ or thin horizontal growth phase melanomas, and was conspicuous in only one‐third of cases. While its presence is useful in the diagnosis of melanoma, its absence should not preclude it.
Distribution of the cytoskeletal protein β‐tubulin in normal lung, cryptogenic fibrosing alveolitis and lung tumours
Authors: SHEPPARD M.N. , THURLOW N.P.
Published: April 2007

Tubulin is the major protein of microtubules. The immunocytochemical distribution of tubulin within the human respiratory tract has not been investigated in detail and no analysis of diseased lung or lung tumours has been undertaken. We therefore studied the distribution of β‐tubulin in formalin‐fixed normal lung (n= 6), cryptogenic fibrosing alveolitis (n= 10) and lung tumours (n= 66), using a monoclonal antibody to β‐tubulin. In normal lung positive immunostaining was observed in all ciliated epithelium from the trachea down to bronchiolar level; blood vessel endothelium, vascular smooth muscle and nerve bundles were also strongly positive; pneumocytes, cartilage and airway smooth muscle gave weak staining. A similar distribution of β‐tubulin was seen in cryptogenic fibrosing alveolitis, but with strong tubulin immunostaining of fibroblasts in the interstitium and of the cytoplasm of ciliated respiratory epithelial cells. In lung tumours, six of 17 (35%) adenocarcinomas, one of two adenosquamous and one of 17 (5%) squamous cell carcinomas gave strong immunostaining. All six large cell carcinomas gave strong immunostaining for tubulin. In neuroendocrine tumours, two of seven (28%) carcinoids, two of seven (28%) atypical carcinoids and seven of 10 (70%) small cell carcinomas were strongly positive for tubulin. β‐Tubulin is widely distributed in the normal and diseased respiratory tract and is found in many lung tumours, particularly in large cell and small cell carcinomas which are highly aggressive in behaviour.
Teratoid Wilms' tumour: a report of two cases
Authors: MAGEE J.F. , ANSARI S. , McFADDEN D.E. , DIMMICK J.
Published: April 2007

We report two cases of Wilms' tumour in which the degree of heterologous differentiation was sufficient to warrant the diagnosis of teratoid Wilms' tumour. The first description of neural elements in this Wilms' variant and the first cytogenetic analysis of teratoid Wilms' tumour are presented.
Stereological estimate of nuclear volume in endometrial adenocarcinoma of endometrioid type: reproducibility and intra‐tumour variation
Authors: NIELSEN A.L. , NYHOLM H.C.J.
Published: April 2007

Stereological volume weighted mean nuclear volume estimate (Vv) is reported to be highly reproducible and to provide excellent prognostic information for some tumours. The aim of the present study was to investigate the reproducibility and the intra‐tumour variation of nuclear Vv and compare it with a morphometric nuclear estimate, i.e. the mean shortest nuclear axis, and with conventional histopathological parameters used in the grading of endometrial adenocarcinomas. Sixty‐three endometrioid adenocarcinomas were included in the study. Both Vv and mean shortest nuclear axis showed an acceptable reproducibility and the correlation between them was moderate (Sperman test; rs = 0.8). One‐third of the tumours showed a marked intra‐tumour variation. A considerable discrepancy between Vv and/or mean shortest nuclear axis and nuclear and architectural grade was found.
Epstein‐Barr virus in angioimmunoblastic T‐cell lymphomas
Authors: KHAN G. , NORTON A.J. , SLAVIN G.
Published: April 2007

Epstein‐Barr virus (EBV) has been proposed as a possible infective agent involved in the pathogenesis of angioimmunoblastic lymphadenopathy (AIL), a progressive and often fatal lymphoproliferative disorder. We have studied 19 cases of AIL‐like lymphomas for the presence of EBV using a sensitive in situ hybridization technique based on the detection of Epstein‐Barr encoded RNAs with digoxigenin‐labelled oligonucleotide probes. EBV was found in 11 cases; in seven of these EBV was detected in occasional cells. Immunocytochemical studies to investigate viral gene expression, revealed the presence of EBV‐encoded latent membrane protein only in those cases which had appreciable numbers of positive cells by in situ hybridization. The intensity of staining varied from case to case and the overall proportion of cells staining for latent membrane protein in a given case was considerably less than that by in situ hybridization. In situ hybridization for cytomegalovirus and human herpes virus type‐6 was negative in all cases. We discuss these findings in the light of the proposed role of EBV in the pathogenesis of AIL and conclude that the presence of EBV is a consequence of the disease rather than the cause.
Idiopathic portal hypertension: a histopathological study of 26 Japanese cases
Authors: LUDWIG J. , HASHIMOTO E. , OBATA H. , BALDUS W.P.
Published: April 2007

Analysis of 25 liver biopsy specimens and one autopsy specimen from 26 Japanese patients (23 women and three men) with idiopathic portal hypertension revealed findings that collectively appeared diagnostic for the condition. Changes in the portal tract included capillary dilatation, phlebosclerosis, and fibro‐elastosis of the stroma. Many portal veins were dilated and had herniated into the surrounding hepatic parenchyma. Portal vein obliteration and loss of bile ducts were a rare complication. The acinar architecture was disturbed by: 1 capillary and necro‐infiammatory bridging, mostly between portal tracts and terminal hepatic veins; 2 the formation of isolated megasinusoids in a random distribution; 3 displaced and abnormally large hepatic vein branches with or without phlebosclerosis and 4 slender, curved fibrous septa (hairline septa). Early nodular regeneration was found in 25% of the cases. Our review supports the contention that incomplete septal cirrhosis may be a late manifestation of idiopathic portal hypertension. It is not clear whether the biopsy findings in Japanese patients differ only in severity from those in western patients, or whether the conditions differ pathogenetically. Some histopathological findings in the Japanese cases, in particular the necroinflammatory changes, are difficult to reconcile with portal hypertension as a primary haemodynamic abn rmality.
Primary malignant melanoma of the rectum
Authors: NICHOLSON A.G. , COX P.M. , MARKS C.G. , COOK M.G.
Published: April 2007

The diagnosis of a primary rectal malignant melanoma has been the subject of considerable argument for many years, principally on the grounds that extension from a primary anal lesion was often impossible to exclude. This paper provides evidence that certain melanomas can be recognized as primary rectal tumours, not only from careful anatomical assessment of the site of the tumour, but also by showing that they arise on a background of benign melanocytic proliferation in the rectal mucosa. The clinical presentation of these lesions, their possible mechanism of origin and their treatment is discussed.
Signet ring cell differentiation in adenocarcinoma of the prostate: a study of five cases
Authors: GUERIN D. , HASAN N. , KEEN C. E.
Published: April 2007

Signet ring cell differentiation in adenocarcinoma of the prostate is uncommon. In a review of 200 cases of prostatic carcinoma, we identified five cases with this change, all in moderately to poorly differentiated prostatic carcinomas. The signet ring cells in prostatic carcinoma contain an intracytoplasmic lumen, shown on electronmicroscopy to be lined by microvilli. Transition stages were seen from solid to acinar to signet ring cells to mucinous variants. We believe that this change is part of the spectrum of appearances of prostatic carcinoma and should not be regarded as a subtype of specific significance.
The distribution of adhesion molecules in human atherosclerosis
Authors: WOOD K.M. , CADOGAN M.D. , RAMSHAW A.L. , PARUMS D.V.
Published: April 2007

Chronic inflammatory cells are a recognized component of atherosclerotic plaques at all stages of development. As adhesion molecules play a fundamental role in inflammatory processes, we have carried out an immunohistochemical investigation of the distribution of endothelial leucocyte adhesion molecule‐1 (ELAM‐1)*, intercellular adhesion molecule‐1 (ICAM‐1) and vascular cell adhesion molecule‐1 (VCAM‐1) in human atherosclerotic lesions. Autopsy specimens from abdominal aorta and coronary arteries were obtained from 21 cases within 24 h of death. ELAM‐1 and ICAM‐1 were consistently expressed by the entire intimal endothelium of normal coronary arteries and also by the intimal endothelium overlying aortic fatty streaks. Both coronary artery and aortic lesions showed strong staining for ICAM‐1 on and around macrophages. VCAM‐1 was not detected on intimal endothelial cells, but strong staining of adventitial lymphoid aggregates for this molecule was seen. This work suggests a role for ELAM‐1 and ICAM‐1 in mononuclear cell recruitment during atherogenesis.
Metal deposition in post‐surgical granulomas of the urinary tract
Authors: HENRY L. , WAGNER B. , FAULKNER M.K. , SLATER D.N. , ANSELL I.D.
Published: April 2007

Fourteen cases of post‐surgical granulomatous inflammation of the urinary tract were studied to investigate the possible deposition in the tissues of metals derived from the diathermy instruments used. The granulomas showed central necrosis, palisaded histiocytes and giant cells. On electronmicroscopy both amorphous material and electrondense particles were seen in the granulomas. The former appeared to be necrotic tissue. The particles were metallic in nature. Energy dispersive analysis of X‐rays showed the presence of tungsten, iron, copper, nickel, chromium, zinc and vanadium. Tungsten particles were always pure. Other single particles contained two or more of the remaining elements, indicating the presence of alloy metals. Analysis of the diathermy instruments showed the cutting loops to be pure tungsten and the ‘rollerballs’ to be of nickel silver containing copper, zinc, nickel, manganese and iron. Both the loops and balls are supported on stainless steel wires containing iron, chromium, nickel, manganese, molybdenum, copper and vanadium. It is proposed that metallic fragments from the instruments were deposited in the tissues during the surgical procedures and elicited an immunological reaction with granuloma formation. Tungsten is probably inert but nickel, chromium, copper and zinc are immunogenic. Under certain circumstances both nickel and chromium may also be carcinogenic.
Immunohistochemical characteristics of Hodgkin and Reed‐Sternberg cells in relation to age and clinical outcome
Authors: ENBLAD G. , SUNDSTROM C. , GLIMELIUS B.
Published: April 2007

One hundred and fifty‐four cases of Hodgkin's disease diagnosed between 1985 and 1988 from an unselected population were stained with a panel of six monoclonal antibodies; LN1, MB2, L26 (CD20), all B‐cell antibodies, UCHL1 (CD45 RO), mainly T‐cell antibody, Leu M1 (CD15J, Ber H2 (CD30) and the polyclonal CD3, T‐cell antibody. The results were related to age, histopathological subgroup and prognosis. There was no significant difference in staining patterns in the 90 patients below the age of 60 compared with the 54 patients above that age. In the entire group, significantly fewer mixed cellularity cases were positive with Ber H2 and Leu M1 compared to nodular sclerosis. Disease‐free survival tended to be better for cases stained with T‐cell related antibodies. This study thus indicated differences in behaviour between T‐cell positive and negative Hodgkin's disease and that there are antigenic differences between nodular sclerosis and mixed cellularity subgroups. We could not, however, show any phenotypic differences between the tumour cells in young and old patients.
The relevance of antibody concentration to the immunohistological quantification of cell proliferation‐associated antigens
Authors: McCORMICK D. , YU C. , HOBBS C. , HALL P.A.
Published: April 2007

A number of different factors can profoundly influence the quantification of immunostained cells. Given the characteristics of immunohistological detection systems with non‐linearity of signal and antigen concentration, we investigated the relationship of signal (number of stained cells) to the dilution of antibody employed. Three antibodies were studied which have been advocated as being effective in fixed material as markers of cell proliferation: PC10 (anti‐proliferating cell nuclear antigen (PCNA)), Ki‐Sl and MIB1 (a novel anti‐Ki‐67). Serial sections of tonsil were immunostained with a range of antibody dilutions using a fixed detection system and the number of stained cells quantified. Similar experiments were performed on tumour xenografts with known growth fraction and, in vitro, on 1 human diploid fibroblasts in logarithmic growth phase. With both PC10 and Ki‐Sl the number of stained cells increased with decreasing antibody dilution with no plateau being identified. In contrast, MIB1 showed a clear plateau. Immunocytological data indicate that PCNA and Ki‐Sl antigen are present at low (but detectable) levels in at least: some non‐cycling cells and thus an artificial ‘cut‐off’ has to be employed in'assessing the number of proliferating cells with these antibodies. The superiority of MIB1 probably reflects the rapidity of catabolism of the Ki‐67 antigen at the end of M phase. Taken together, these data point to the importance of carefully considering fundamental immunochemical properties such as antibody concentration (as well as antibody affinity and sensitivity of detection system) when employing immunological markers of cell proliferation in quantitative procedures.
Pigmented ganglioneuroblastoma: a tumour cell ‘storage disease’?
Authors: O'DOWD G.M. , GAFFNEY E.F.
Published: April 2007

We report a composite nodular ganglioneuroblastoma, distinctive for the presence of coarsely granular black intracellular pigment, which was histochemically indistinguishable from.melanin. Ultrastructurally, the pig‐ment was resolved as numerous heterogeneous lyso‐somes, containing material compatible with oxidized lipid residues, the accumulation of which may reflect. acquired lysosomal dysfunction in individual tumour cells‐a tumour cell ‘storage disease’.
Granulomatous hidradenitis suppurativa and cutaneous Crohn's disease
Authors: ATTANOOS R.L. , APPLETON M.A.C. , HUGHES L.E. , ANSELL I.D. , DOUGLAS‐JONES A.G. , WILLIAMS G.T.
Published: April 2007

Three patients with concurrent hidradenitis suppurativa and Crohn's disease are presented. The notable histological feature in each hidradenitis resection was the presence of numerous discrete epithelioid granulomas in areas of non‐inflamed dermis. The purpose of the study was to determine the incidence of epithelioid granulomas in 101 hidradenitis patients and their significance in relation to systemic granulomatous disease. Discrete epithelioid granulomas were identified in 8% of the resections (10 patients). One patient had Crohn's disease and one other pulmonary sarcoidosis. Seven patients with granulomatous hidradenitis neither had nor developed any other disease during the 3‐year follow‐up period. Clinical review identified a further two patients with Crohn's disease but associated with non‐granulomatous changes in the skin resections. Foreign body type granulomas were identified in 25% of the resections adjacent to ruptured hair follicles, sinus tracts or nearby degenerate sweat glands. The study shows that, although foreign body type granulomas are a common finding in hidradenitis, the presence of discrete epithelioid granulomas in the dermis away from the site of active inflammation is unusual and should alert the pathologist to the possibility of systemic granulomatous disease such as Crohn's disease or sarcoidosis.
The nature of atypical multinucleated stromal cells: a study of 37 cases from different sites
Authors: PITT M.A. , ROBERTS I.S.D. , AGBAMU D.A. , EYDEN B.P.
Published: April 2007

The morphology, immunophenotype and ultrastructure of atypical multinucleated stromal cells in 37 specimens from different anatomical sites were compared. Overall, cellular morphology was similar between sites but nuclear features, immunophenotype and ultrastructure varied and reflected that of adjacent normal mononuclear stromal cells. It is concluded that the atypical multinucleated stromal cells represent a reactive change in the indigenous stromal cells. In all the cases mast cells were seen as a prominent component of the inflammatory infiltrate and many of them were intimately related to the atypical stromal cells. It is suggested that reactive stromal cell changes may relate to an interaction with mast cells.
An immunophenotypic survey of malignant melanomas
Authors: BISHOP P.W. , MENASCE L.P. , YATES A.J. , WIN N.A. , BANERJEE S.S.
Published: April 2007

An immunohistochemical study of 106 malignant melanoma specimens from 59 patients, using formalin‐fixed, paraffin‐embedded material, is reported. Negativity for HMB‐45 was seen in 11% of specimens. The rate of positivity with CAM 5.2 was 7%. One specimen showed α‐smooth muscle actin (αSMA) positivity. For 11 of the 12 cases in which anomalous immunophenotypes were seen, multiple specimens were available; nine of these showed evidence of an alteration in the immunophenotype between specimens. Comparing the primary tumours with local recurrences and metastases, there was, variously, loss of HMB‐45, S‐100 protein and NKI/C3 positivity, and acquisition of CAM 5.2 and αSMA positivity. In some cases, the change of immunophenotype appeared to occur in a single step. However, one case with six consecutive specimens showed evidence of progressive loss of HMB‐45, S‐100 protein and NKI/C3 with concomitant gain of CAM 5.2 staining. The implications for the use of immunophenotyping in diagnostic practice are discussed.
Alveolar soft‐part sarcoma: evidence for its myogenic origin and for the involvement of 17q25
Authors: SCIOT R. , CIN P. DAL , VOS R. DE , DAMME B. VAN , WEVER I. DE , BERGHE H. VAN DEN , DESMET V. J.
Published: April 2007

A typical case of alveolar soft‐part sarcoma was examined using ultrastructural, immunohistochemical and cytogenetic methods. Immunohistochemical stains were performed on frozen sections and showed strong desmin expression with the three anti‐desmin antibodies used. In addition, the tumour cells were weakly positive for vimentin and myosin. Neural markers were negative. Chromosomal analysis showed consistent involvement of 17q25—an abnormality which has been reported in another alveolar soft‐part sarcoma. The histogenesis of alveolar soft‐part sarcoma is still debatable but our findings support a myogenic origin. The finding of an apparently identical chromosomal abnormality in two of three thus far examined cases of alveolar soft‐part sarcoma is of interest and must await further confirmation, but it may result in the identification of a chromosomal marker for this enigmatic tumour and thus pave the way for further molecular elucidation.
Melanocytic lesions in lymph nodes associated with congenital naevus
Authors: HARA K.
Published: April 2007

Two cases of melanocytic lesions in lymph node associated with congenital naevus are presented. The first was a 30‐year‐old man with a nodular melanoma arising in a small congenital naevus. The second was a 2‐year‐old male infant with a giant congenital naevus. In both cases, naevus cell aggregates were observed in the capsule, trabeculae, perisinusoidal areas and lymphatic vessels surrounding the nodes. In the first case, clusters of large atypical melanocytes were present amongst naevus cell aggregates in the perisinusoidal areas as well as in the lymphoid parenchyma. Between the naevus cells and large atypical melanocytes, transitional forms were observed which supports the idea that the presence of large atypical melanocytes is indicative of benign naevus cells. In the second case, marginal sinuses were packed with clusters of large melanin‐rich cells. Immunohistochemically, these cells were S‐100 protein negative, but ultrastructural studies proved them to be melanocytes. They were considered indicative of spread of benign naevus cells via lymphatic vessels. Arrested migration of naevus cells during embryogenesis and benign spread of naevus cells are possible explanations for the histogenesis of naevus cell aggregates in lymph nodes associated with congenital naevus.
DNA content in gallbladder carcinoma: a flow cytometric study of 96 cases
Authors: ROA I. , ARAYA J. C. , SHIRAISHI T. , YATANI R. , WISTUBA I. , VILLASECA M. , ARETXABALA X. DE
Published: April 2007

The DNA content in gallbladder carcinoma and its relation to histological and cytological features was studied in 79 primary gallbladder carcinomas and 16 metastases. Abnormal DNA content was observed in 48 (51%) of 95 cases. In primary carcinomas, 44 (55.6%)showed a diploid DNA content, and 35 (44.4%) were aneuploid. The majority of the metastatic lesions were aneuploid DNA (81.3%; P=0.006). Marked differences in the coefficient of variation estimated by manual, Kosugi and Dean methods were detected (P=0.005). Seventy‐one per cent of early gallbladder carcinomas had a normal DNA content. In contrast 54% of the cases with subserosal or serosal infiltration had normal DNA content. In primary tumours the degree of architectural atypia had a close relationship with the degree of cellular atypia (P=0.00001). Only two (15%) of 13 cases with mild architectural atypia, and 34 (51.5%) of 66 cases with marked architectural atypia were aneuploid. Only one (10%) of 10 cases with mild cellular atypia and 35 (51%) of 69 with high cellular atypia had abnormal DNA content (P=0.01) The importance of DNA content as a marker in gallbladder carcinoma remains uncertain and its clinical importance requires further clinicopathological studies.
Enzyme‐linked immunosorbent assay for p53 in gastrointestinal malignancy: comparison with immunohistochemistry
Authors: JOYPAUL B. V. , VOJTESEK B. , NEWMAN E. L. , HOPWOOD D. , GRANT A. , LANE D. P. , CUSCHIERI A.
Published: April 2007

Mutations in the p53 nuclear oncogene occur frequently in a wide spectrum of human malignancies and the mutant protein may prove to be a useful diagnostic or prognostic marker. It can be detected in fixed tissues by immunohistochemistry, but the type of fixative and conditions of fixation used can introduce variability. For routine clinical use, a method of analysis which is more easily standardized would, therefore, be of benefit. A two‐site enzyme‐linked immunosorbent assay (ELISA) was used to measure the level of p53 protein in soluble extracts from 20 gastrointestinal cancers (11 colonic, nine gastric). Immunohistochemistry was also performed on the paraffin‐embedded sections of these tumours and the results of the two assays were compared. ELISA detected p53 at various levels in 10 cases, all of which were also positive by immunohistochemistry. Of the other 10, eight were immunohistochemically negative but two were positive. When the immunohistochemically positive specimens were ranked by scoring the degree of staining, there was a highly significant correlation with the quantitative ELISA results. Our study shows that the ELISA is sensitive and highly specific. It offers an alternative and simple method of assessing the p53 status in human tissues.
Aberrant p53 protein expression in cervical intra‐epithelial neoplasia
Authors: PöLLÄNEN R. , SOINI Y. , VÄHÄKANGAS K. , PÄÄKKö P. , LEHTO V.‐P.
Published: April 2007

We investigated aberrant p53 expression in 81 cases of cervical intra‐epithelial neoplasias (CIN) using a polyclonal antibody CM‐1. The presence of human papillomavirus (HPV) DNA was evaluated by in situ and dot blot hybridization. Significant (more than 1% of cells positive) p53 positivity was found in three cases (4%) of which only one contained HPV DNA. In an additional nine cases, occasional p53 staining was found in basal epithelial cells, frequently associated with epithelial hyperplasia and increased subepithelial inflammation. The results show that aberrant p53 expression is an infrequent finding in CIN lesions. It can be seen in lesions both with and without HPV infection. Most importantly, there was no p53 expression in most cases of HPV‐negative CIN, suggesting that p53 inactivation is not an obligatory step in the development of cervical dysplasia. However, our findings do not exclude the possibility that p53 mutations can occur later in the course of cervical carcinogenesis.
Granulomatous gastritis: a morphological and diagnostic approach
Authors: ECTORS N.L. , DIXON M.F. , GEBOES K.J. , RUTGEERTS P.J. , DESMET V.J. , VANTRAPPEN G.R.
Published: April 2007

The final diagnosis of granulomatous gastritis is based on morphological findings and clinical and laboratory data. Detailed analysis of the morphological features of the granulomas together with associated mucosal changes could generate more information on aetiology and pathogenesis. Biopsies from 71 patients diagnosed as having granulomatous gastritis were reviewed. Thirty‐seven of these patients (52%) had Crohn's disease. In 18 patients (25%) an isolated granulomatous gastritis was diagnosed. In seven patients (10%) the final diagnosis was a foreign body reaction. Of the remaining cases, four (7%) corresponded to tumour‐associated granulomas and one case each of sarcoidosis (1%), Whipple's disease (1%) and vasculitis‐associated disease (1%). Two cases (3%) were unclassifiable. The granulomas were mainly found in the antrum (64% antrum only, 11% antrum and corpus, 6% transitional mucosa corpus‐antrum). Granulomas were usually small. This was particularly true for those found in patients with Crohn's disease. Multiple granulomas were observed in the sarcoidosis, the Whipple's disease and vasculitis‐associated cases. A pattern of chronic gastritis with atrophy was present in 95% of the biopsies (68/71 patients). Helicobacter pylori was detected in 92% of the biopsies (64/71 patients).
Prolapse‐induced inflammatory polyps of the colorectum and anal transitional zone
Authors: CHETTY R. , BHATHAL P.S. , SLAVIN J.L.
Published: April 2007

A clinicopathological study of polypoid lesions of the lower gastrointestinal tract from 12 patients was undertaken. Clinically, the majority had signs and symptoms of rectal prolapse despite having a variety of other primary diagnoses (e.g. carcinoma of the bowel or diverticular disease). Three patients were asymptomatic. The polyps were more common in females and were usually solitary. Histologically, fibrin ‘caps’, fibromuscular hypertrophy and obliteration of the lamina propria, goblet cell hypertrophy and serrated tubules were consistently noted. The fibromuscular tissue often extended into the lamina propria in a radial fashion. This study shows that mucosal prolapse underpins a variety of lesions that are part of a histological spectrum of changes. Inflammatory cloacogenic polyps, inflammatory ‘cap’ polyps, polypoid prolapsing mucosal folds of diverticular disease and inflammatory myoglandular polyps are all due to mucosal prolapse.
Proliferating cell nuclear antigen immunostaining and survival in cerebral astrocytoma
Authors: THEUNISSEN P.H.M.H. , BLAAUW G.
Published: April 2007

In order to test the prognostic value of a proliferation index in cerebral astrocytoma, proliferating cell nuclear antigen immunostaining was performed on formalin‐fixed and paraffin‐embedded biopsies of 42 astrocytomas (21 serial stereotactic and 21 open surgical biopsies). Tumours were categorized as having a low (< 50%) or high (> 50%) labelling index. Tumour grading was also carried out. Several clinicotherapeutic factors were recorded. At least 40 months follow‐up was available on all surviving patients. Survival estimated by the Kaplan and Meier method was significantly longer in tumours with a low proliferation index than in those with a high one (mean 20.4 months v. 10 months). According to Cox multiple regression analysis, the age of the patient and grading were significantly related to survival, whereas the proliferation index lost its significance.
Methodology of immunohistological detection of oestrogen receptor in human breast carcinoma in formalin‐fixed, paraffin‐embedded tissue: a comparison with frozen section methodology
Authors: SNEAD D.R.J. , BELL J.A. , DIXON A.R. , NICHOLSON R.I. , ELSTON C.W. , BLAMEY R.W. , ELLIS I.O.
Published: April 2007

We describe a method of immunohistochemically assessing oestrogen receptor status on routinely processed formalinfixed tissue, using a commercially available monoclonal antibody (Abbott H222). with pronase predigestion of tissue sections and overnight antibody incubation. The staining was assessed using the H score system. A series of 94 cases of breast cancer were analysed and the results were compared with assessment by oestrogen receptor immunocytochemical assay performed on frozen section. Direct comparison of the paired sets of H scores obtained with frozen tissue and formalin‐fixed tissue showed a highly significant correlation of 0.8 (P < 0.001) between the two methods of oestrogen receptor assessment. Chi‐squared analysis using H score cut off points of 50 and 100 also showed a similar significant association (P < 0.001). We conclude that this oestrogen receptor method, applicable to formalin‐fixed, paraffin‐embedded tissue, gives accurate results on routinely fixed tissue and could be used as an alternative to other methods.
Juxtacortical malignant schwannoma with heterologous elements
Authors: ANDREW S.M. , FREEMONT A.J.
Published: April 2007

A case of malignant schwannoma with heterologous elements occurring in the periosteum of a long bone is reported. We believe that this is the first time such a tumour has been reported at this site.
The histological diagnosis of clinically documented cases of cryptogenic organizing pneumonia: diagnostic features in transbronchial biopsies
Authors: DINA R. , SHEPPARD M.N.
Published: April 2007

Eleven cases of clinically diagnosed cryptogenic organizing pneumonia were examined in order to establish the histological features found at transbronchial biopsy and to correlate this with open lung biopsy which followed in six cases. The essential pathological feature was the presence of buds of granulation tissue (Masson bodies) indicating organization of a persistent exudate by fibroblasts and capillaries within alveoli, with preservation of the alveolar architecture. In addition, both acute and chronic inflammatory cells were present in the interstitium. These features, combined with the clinical history, were sufficient for a diagnosis in seven of the 11 cases on transbronchial biopsies. Four biopsies lacked these features. Patients proceeded to open lung biopsy in addition to the two with histological features of cryptogenic organizing pneumonia on transbronchial biopsy, but where the clinician wanted to eliminate other pathology because of rapid clinical deterioration. Five of the six cases coming to open lung biopsy confirmed cryptogenic organizing pneumonia with Masson bodies within alveoli, but changes were focal in three with very few Masson bodies in one. One case which had the features on transbronchial biopsy lacked them in the open lung biopsy. Transbronchial biopsy, therefore, can yield diagnostic material in the majority of patients with cryptogenic organizing pneumonia while open lung biopsy, which is considered the gold standard for interstitial lung disease, may yield negative results because of sampling error and the rapid evolution and changing pattern of the disease.