bluuebunny/crossref_metadata_2025 huggingface dataset:
Endometrioid adenocarcinoma of the uterus with a minimal deviation invasive pattern
Authors: Landry D , Mai K T , Senterman M K , Perkins D G , Yazdi H M , Veinot J P , Thomas J
Published: December 2004

Aims:  Minimal deviation adenocarcinoma of endometrioid type is a rare pathological entity. We describe a variant of typical endometrioid adenocarcinoma associated with minimal deviation adenocarcinoma of endometrioid type.

Methods and results:  One ‘pilot’ case of minimal deviation adenocarcinoma of endometrioid type associated with typical endometrioid adenocarcinoma was encountered at our institution in 2001. A second case of same type was received in consultation. We reviewed 168 consecutive hysterectomy specimens diagnosed with ‘endometrioid adenocarcinoma’ specifically to identify areas of minimal deviation adenocarcinoma of endometrioid type. Immunohistochemistry was done with the following antibodies: MIB1, p53, oestrogen receptor (ER), progesterone receptor (PR), cytokeratin 7 (CK7), cytokeratin 20 (CK20), carcinoembryonic antigen (CEA), and vimentin (VIM). Four additional cases of minimal deviation adenocarcinoma of endometrioid type were identified. All six cases of minimal deviation adenocarcinoma of endometrioid type were associated with superficial endometrioid adenocarcinoma. In two cases with a large amount of minimal deviation adenocarcinoma of endometrioid type, the cervix was involved. The immunoprofile of two representative cases was ER+, PR+, CK7+, CK20–, CEA–, VIM+. MIB1 immunostaining of four cases revealed little proliferative activity of the minimal deviation adenocarcinoma of endometrioid type glandular cells (0–1%) compared with the associated ‘typical’ endometrioid adenocarcinoma (20–30%). The same four cases showed no p53 immunostaining in minimal deviation adenocarcinoma of endometrioid type compared with a range of positive staining in the associated endometrioid adenocarcinoma.

Conclusions:  Minimal deviation adenocarcinoma of endometrioid type more often develops as a result of differentiation from typical endometrioid adenocarcinoma than de novo. Due to its deceptively benign microscopic appearance, minimal deviation adenocarcinoma of endometrioid type may be overlooked and may lead to incorrect assessment of tumour depth and pathological stage. There was a tendency for tumour with a large amount of minimal deviation adenocarcinoma of endometrioid type to invade the cervix.
Paget's disease of the oesophagus associated with mucous gland carcinoma of the lower oesophagus
Authors: Haleem A , Kfoury H , Al Juboury M , Al Husseini H
Published: December 2004

Aim:  To report a rare case of oesophageal Paget's disease and its rarer combination with submucosal gland carcinoma of the lower oesophagus.

Methods and results:  A 74‐year‐old Saudi female was admitted with the complaint of dysphagia. Endoscopic examination showed an ulcerated tumour at the gastro–oesophageal junction. Initial biopsy showed an undifferentiated carcinoma with pagetoid spread in the oesophageal stratified squamous epithelium. Oesophago‐gastrectomy specimen showed a lobulated, poorly differentiated mucous gland carcinoma at the gastro–oesophageal junction. The tumour showed focal acinar differentiation and obvious cancerization of the submucosal glands, somewhat similar to the breast lobular carcinoma in situ. One of the isolated and cancerized submucosal glands also showed carcinoma in situ of its duct. Oesophageal surface epithelium showed extensive pagetoid spread, both over and away from the main tumour. The pagetoid tumour cells showed selective positivity for cytokeratin 7, cytokeratin Cam 5.2, BerEP4 and to a lesser extent for CEA.

Conclusions:  As far as we know, this is the fifth case report of oesophageal Paget's disease and the first report of its association with the underlying mucous gland carcinoma.
Philadelphia chromosome and/or bcr‐abl mRNA‐positive primary thrombocytosis: morphometric evidence for the transition from essential thrombocythaemia to chronic myeloid leukaemia type of myeloproliferation
Authors: Pajor L , Kereskai L , Zsdrál K , Nagy Z , Vass J A , Jáksó P , Radványi G
Published: December 2004

Aims:  The incidence, bone marrow morphology and genetic features of bcr+ essential thrombocythaemia were investigated.

Methods and results:  Sixty‐four consecutive patients meeting the criteria of essential thrombocythaemia have been investigated for bcr‐abl rearrangement and chimera mRNA expression. Reverse transcriptase‐polymerase chain reaction indicated bcr‐abl expression in six patients, in two of whom large fraction of the blood and bone marrow cells proved to be positive for Philadelphia chromosome (Ph) by fluorescent in‐situ hybridization (FISH) and conventional cytogenetic analysis. In the remaining four patients FISH analysis could not detect Ph+ cells among the blood cells, but in one of these four patients conventional cytogenetic analysis indicated a very small fraction (2%) of Ph+ mitoses in the bone marrow (bcr+ essential thrombocythaemia patients). In three of these four patients, X‐chromosome‐linked clonality assay showed that the disease is of uncommitted stem cell origin. During an average of 57 month long follow‐up no transformation to chronic myeloid leukaemia type of disease or acceleration/blastic crisis could be observed in the four bcr+ essential thrombocythaemia patients. They did not differ significantly from typical essential thrombocythaemia patients in quantitative indices of bone marrow cellularity or the size of megakaryocytes. In these two parameters as well as in the total nucleolus organizer region area per nucleus, however, significant differences could be detected between these four as well as typical chronic myeloid leukaemia patients. Statistical analysis of the morphometric data obtained from all six Ph+ and bcr+ essential thrombocythaemia patients combined indicated a shift of the bone marrow morphology towards the chronic myeloid leukaemia type of myeloproliferation.

Conclusions:  These investigations indicate that bcr+ essential thrombocythaemia is infrequent among essential thrombocythaemia patients, and this condition resembles essential thrombocythaemia more than chronic myeloid leukaemia. Various expansions of the Ph+ clone appear to lead to either essential thrombocythaemia or, rather, chronic myeloid leukaemia type of myeloproliferation; however, data in the present study do not indicate that bcr+ essential thrombocythaemia would be a form fruste variant of chronic myeloid leukaemia.
Cyclin E immunoexpression in gastric cancer does not correlate with clinicopathological parameters
Authors: Chetty R , Sitti C W
Published: December 2004

Aims:  To ascertain whether cyclin E immunoexpression relates to clinicopathological characteristics of gastric cancer and is of possible routine use.

Methods and results:  One hundred and twenty‐four gastrectomy specimens were assessed for age, gender, histological subtype, lymph node status and Helicobacter pylori infection. Immunohistochemistry using a commercially available antibody to cyclin E was then applied to the cases. The immunohistochemical staining was correlated with clinicopathological features. Fifty‐three of 124 cases were cyclin E‐positive, with 28 of these cases showing >50% of the tumour cells staining. However, no statistical significance was obtained between cyclin E immunostaining and any clinicopathological parameter, especially lymph node spread.

Conclusions:  We have not demonstrated any significant relationship between cyclin E immunopositivity and any of the usual clinicopathological parameters (especially lymph node involvement) and therefore cyclin E immunohistochemistry alone does not appear to have a role in the assessment of gastric cancer currently.
H‐caldesmon expression in myofibroblastoma of the breast: evidence supporting the distinction from leiomyoma
Authors: Magro G , Gurrera A , Bisceglia M
Published: December 2004

Aims:  The ultrastructural detection of leiomyomatous rather than myofibroblastic features in some cases of myofibroblastoma of the breast led some electron microscopically orientated pathologists to doubt the commonly accepted myofibroblastic nature of such a tumour, so the alternative terms ‘myogenic stromal tumour’ or ‘variant of leiomyoma’ have been proposed. The aim of this study was to analyse the immunohistochemical expression of h‐caldesmon, a reliable marker in distinguishing smooth muscle versus myofibroblastic cellular differentiation, in a large series of myofibroblastomas of the breast to clarify whether these tumours are basically leiomyomatous. Moreover, cases from primary myofibroblastic lesions of the breast, such as fibromatosis and inflammatory myofibroblastic tumour, were analysed to assess whether h‐caldesmon expression parallels that observed in their soft tissue counterparts.

Methods and results:  Paraffin‐embedded sections from 12 cases of myofibroblastoma, seven cases of fibromatosis, and one case of inflammatory myofibroblastic tumour were evaluated immunocytochemically for the expression of h‐caldesmon. As expected, all myofibroblastic lesions failed to express h‐caldesmon. Conversely, focal staining, ranging from 2% to 10% of neoplastic cells, was detected in myofibroblastomas, even though it was restricted to 50% of analysed cases.

Conclusions:  Our results, indicating that smooth muscle differentiation occurs in a minority of the myofibroblastoma cells exclusively in half of the analysed cases, support the separation of myofibroblastoma from leiomyoma. The detection of smooth muscle cells in breast myofibroblastoma is easily explained if we postulate its histogenesis from the CD34+ fibroblasts of mammary stroma capable of multidirectional mesenchymal differentiation, including smooth muscle. We recommend retention of the term myofibroblastoma for all the desmin‐positive and/or α‐smooth muscle actin‐positive spindle cell tumours of the breast consistent with the previously well‐established morphological criteria for such neoplasms, unless one is dealing with a typical leiomyoma easily recognizable at light microscopy.
Fibrinogen storage disease without hypofibrinogenaemia associated with acute infection
Authors: Marucci G , Morandi L , Macchia S , Betts C M , Tardio M L , Dal Monte P R , Pession A , Foschini M P
Published: December 2004

Aims:  The presence of ground glass hepatocytes in a liver biopsy may be related to different conditions, including fibrinogen storage disease. Three types of fibrinogen storage disease have been described, namely types I, II and III. Type I is an hereditary hypofibrinogenaemia genetically characterized by a mutant variant of the fibrinogen molecule designated as fibrinogen Brescia, consistent with a γ284 Gly→Arg mutation. Only rare cases of types II and III fibrinogen storage disease have been described. The purpose of the present paper is to describe two cases of fibrinogen storage disease without associated hypofibrinogenaemia, which appeared during acute infectious diseases.

Methods and results:  Both patients were female, aged 77 and 73 years, who developed high transaminases during an infectious disease. In each case blood coagulation tests were within the normal range, and despite clinical and laboratory investigations no possible cause for liver disease could be found. Liver biopsies were performed; in both cases weakly eosinophilic cytoplasmic inclusions were observed. Using immunohistochemistry the inclusions were found to be due to fibrinogen accumulation. At ultrastructural level features corresponding to type II inclusions were observed. Molecular studies, performed in case 2, excluded the mutation typical of type I fibrinogen storage disease. Both patients also presented features of chronic hepatitis. In case 1, giant cell granulomas were additionally present. No close relatives of the patients presented any clinical or laboratory features of liver disease. In both patients altered liver function test values gradually, spontaneously, returned to within normal ranges after infectious disease was resolved.

Conclusions:  These cases suggest that, on rare occasions, hepatocytes may accumulate fibrinogen during an infectious disease.
Biopsy of a biopsy: validation of immunoprofiling in gastric cancer biopsy tissue microarrays
Authors: Gulmann C , Butler D , Kay E , Grace A , Leader M
Published: December 2004

Aims:  Tissue microarrays offer an efficient way of examining a large number of tumour cases on a single glass slide. A major concern, however, is tumour heterogeneity. Also, the use of tissue microarrays in biopsy material is unexplored. The purpose of the present study was to assess the possibility and validity of arraying three 0.6‐mm cores per case in endoscopic gastric cancer biopsies for immunophenotyping.

Methods and results:  Thirty‐eight cases were studied with immunohistochemical staining for p53, CD44v6 and vascular endothelial growth factor. Full tissue sections were compared with triple core‐tissue microarrays. Thirty‐six cases contained three cores with tumour, one case contained two cores with tumour and one case contained only a single core with viable tumour and was excluded. Three further cores had been lost from three separate cases on the sections for immunohistochemistry. κ values for whole‐sections versus tissue microarrays ranged between 0.77 and 0.94. p53 immunohistochemical staining (interpretation as + or –) yielded the best result with only 1/37 mismatches, whereas CD44v6 (graded both for intensity and extent) showed 3/37 mismatches. The small depth of tissue in cores from biopsies necessitates all cores being arrayed flush with the face of the recipient wax block for maximizing the number of sections available. Compared with the first section over 30 additional 4‐µm sections were available before the first case (with one core left) had to be excluded and 80 sections before half the tissue cores were lost.

Conclusions:  It is impracticable to array more than 120–150 cores per block. Tissue microarray with three cores per case is feasible and valid for studying biopsy material.
Association of histochemical expression of Maackia amurensis leukoagglutinin‐positive glycoconjugates with behaviour of human gastric cancer
Authors: Tang W , Mafune K , Nakata M , Konishi T , Kojima N , Mizuochi T , Makuuchi M
Published: December 2004

Aims:  To investigate the relationship between sialylation of glycoconjugates and clinicopathological characteristics of gastric cancer.

Methods and results:  Sialylation of glycoconjugates was examined histochemically in 71 gastric cancers using Maackia amurensis leukoagglutinin (MAL), a lectin that recognizes the trisaccharide sequence NeuAcα2,3Galβ1,4GlcNAc/Glc. Positive staining with MAL was observed in the tumour region of all of the samples, but the populations of MAL‐positive tumour cells in the tumour region varied among the samples. In the corresponding non‐cancerous regions, however, no positive staining was observed. Calculating the percentage of MAL‐positive tumour cells as part of the total tumour cells with respect to the MAL‐staining index (MI) allowed the gastric cancer to be classified into two distinct groups: high and low levels of MI, with a cut‐off level of 40% of MI. Furthermore, statistical analyses using the MI level and clinicopathological characteristics of the tumour indicated that a high MI level in gastric tumour tissues is related to a poorer prognosis.

Conclusions:  The appearance of MAL‐positive glycoconjugates in gastric tumour cells is associated with the behaviour of gastric cancer.
How accurate are subjective judgements of a continuum?
Authors: Deolekar M , Morris J A
Published: December 2004

Aims:  To assess the accuracy of subjective judgements of a uni‐dimensional continuum.

Methods and results:  Twenty‐four observers were asked to estimate the position of a dot placed between two lines using a 100‐point scale. Each observer judged 20 different positions. Ninety‐five percent of observations were between −7 and +9 of the true value. The median and the mean value of the estimates for each position were within one or two points of the true value in most cases with a maximum deviation of five. There was perfect correlation between the ranks of the median and the mean and the true value (correlation coefficient +1, P < 0.00001). The κ values for interobserver agreement varied from 0.98 for two categories to 0.55 for 10 categories and 0.39 for 20 categories. Information transmitted increased from 0.98 bits with two categories to 2.83 bits with 20 categories.

Conclusions:  The experiment indicates that subjective judgements can be accurate but it is necessary to use a large number of categories. One hundred‐point scales allow confidence intervals to be calculated and the intervals are reduced if the results from several observers are pooled. The mean and the median of the judgements of a large number of observers are close to objective reality and this approach could be used to define a gold standard of rankings of pathological continua such as cervical dyskaryosis or tumour differentiation. There is a reciprocal relationship between κ values and information transmitted which demonstrates the fallacy of using κ statistics in studies of continua.
Association of maspin expression with the high histological grade and lymphocyte‐rich stroma in early‐stage breast cancer
Authors: Kim D H , Yoon D S , Dooley W C , Nam E S , Ryu J W , Jung K C , Park H R , Sohn J H , Shin H S , Park Y E
Published: December 2004

Aims:  Maspin is a recently described member of the serpin family or protease inhibitors that is known to be a tumour suppressor gene product. Loss of maspin expression has been found in most breast cancer cases and is correlated with cell motility and tumour invasiveness. However, its precise role in human breast cancer remains to be discovered. We aimed to evaluate the role of maspin in early‐stage breast cancer.

Methods and results:  We analysed the expression of maspin in 192 stage I and II primary breast cancers by immunohistochemistry. Of these cases, 34.4% showed maspin expression. Maspin expression was more frequently found in invasive ductal carcinoma (36.4%) than in invasive lobular carcinoma (7.1%). High maspin expression was demonstrated in breast cancers showing high histological grade or lymphocyte‐rich stroma (P < 0.05). Maspin expression was not associated with overall and disease‐free survival rate of breast cancer.

Conclusions:  The results indicate that different biological mechanisms may be responsible for maspin expression in histologically distinct types of breast cancer. Our survey suggests that maspin expression in breast cancer might have a compensatory role rather than prognostic one.
Over‐expression of tenascin‐C in malignant pleural mesothelioma
Authors: Kaarteenaho‐Wiik R , Soini Y , Pöllänen R , Pääkkö P , Kinnula V L
Published: December 2004

Aims:  Tenascin‐C is an extracellular matrix glycoprotein known to have anti‐adhesive characteristics and to be expressed in various human malignant neoplasms. We hypothesized that the expression of tenascin‐C would be increased in human malignant pleural mesothelioma, and its accumulation associated with the prognosis of the patients with this disease.

Methods and results:  Thirty‐seven cases of mesothelioma were studied by immunohistochemically using a monoclonal antibody against tenascin‐C, and with a semiquantitative scoring system for tenascin‐C in different areas of the tumours. In 10 selected cases tenascin‐C mRNA in‐situ hybridization was also analysed. Since transforming growth factor‐beta (TGF‐β) is known to induce both the synthesis of tenascin‐C and the growth of mesotheliomas, an immunohistochemical analysis of TGF‐β1, ‐β2 and ‐β3 was also performed. Normal pleura (n = 7) and metastatic pleural adenocarcinomas (n = 7) were used as controls. Tenascin‐C protein was expressed in every histological subtype of malignant mesothelioma, being most prominent in the fibrotic stroma of a tumour, around tumour cells and at the invasive border, whereas tenascin‐C mRNA was scarce in tumour cells. The patients with less immunohistochemical expression for tenascin‐C tended to live longer (P = 0.028 by Fishers' exact probability test). All mesotheliomas showed positivity for at least one isoform of TGF‐β.

Conclusions:  In conclusion, high expression of tenascin‐C protein in malignant pleural mesotheliomas may play a role in its invasive growth, and might serve as a prognostic marker of the disease.
The pathology of acute hepatic disintegration in hereditary haemorrhagic telangiectasia
Authors: Blewitt R W , Brown C M , Wyatt J I
Published: December 2004

Aims:  Hereditary haemorrhagic telangiectasia is a rare inherited disease in which telangiectases affect skin, mucous membranes and the gastrointestinal tract. Hepatic involvement is common but usually asymptomatic. We report a case of acute hepatic disintegration in hereditary haemorrhagic telangiectasia, document the histopathological findings and present a hypothesis to explain them.

Methods and results:  The patient presented at the age of 34 years with abdominal pain, leading to the surgical removal of a severely inflamed gallbladder. Signs of liver damage became increasingly apparent over the next few weeks, with disruption of the intrahepatic biliary tree and marked vascular shunting, necessitating liver transplantation. Six months after the transplant a diagnosis of hepatic hereditary haemorrhagic telangiectasia was made. The principal features of hepatic hereditary haemorrhagic telangiectasia are periportal telangiectases and sinusoidal congestion and dilatation. Acute hepatic disintegration is characterized by disruption of liver structure, hepatocyte necrosis, haemorrhage and extravasation of bile.

Conclusions:  Periportal telangiectases in a liver biopsy are highly suggestive of hereditary haemorrhagic telangiectasia. Acute hepatic disintegration is likely to be a consequence of rupture of telangiectases and ischaemic necrosis of intrahepatic bile ducts. Patients with hereditary haemorrhagic telangiectasia are at risk of acute hepatic disintegration following intra‐abdominal sepsis.
Erythropoietin as an angiogenic factor in gastric carcinoma
Authors: Ribatti D , Marzullo A , Nico B , Crivellato E , Ria R , Vacca A
Published: December 2004

Aims:  Previous studies have shown that increased vascularity is associated with haematogenous metastasis and poor prognosis in gastric cancer. The role of erythropoietin (Epo) in angiogenesis has not been completely clarified, although its involvement has been reported. In this study we correlated microvascular density and Epo receptor (Epo‐R) expression in endothelial and tumour cells with histopathological type in gastric cancer.

Methods and results:  Specimens of primary gastric adenocarcinomas obtained from 40 patients who had undergone curative gastrectomy were investigated immunohistochemically by using anti‐CD31 and anti‐Epo‐R antibodies. Stage IV gastric carcinoma had a higher degree of vascularization than other stages, and Epo‐R expression in both endothelial and tumour cells increased in parallel with malignancy grade and was highly correlated with the extent of angiogenesis.

Conclusions:  Epo‐R level correlates with angiogenesis and progression of patients with gastric carcinoma and we suggest that Epo might have a trophic effect on the vasculature of the gastrointestinal tract. Understanding mechanisms of gastric cancer angiogenesis provides a basis for a rational approach to the development of an anti‐angiogenic therapy in patients with gastric cancer.
Differential diagnosis of skin lesions after allogeneic haematopoietic stem cell transplantation
Authors: Canninga‐van Dijk M R , Sanders C J , Verdonck L F , Fijnheer R , Van Den Tweel J G
Published: December 2004

Allogeneic haematopoietic stem cell transplantation (i.e. bone marrow or peripheral blood stem cell transplantation) is a common procedure in the treatment of various haematological disorders such as aplastic anaemia, (pre)leukaemias, some malignant lymphomas, multiple myeloma and immunodeficiency states. Many of these patients develop erythematous skin lesions following transplantation. Although graft‐ versus‐host disease is the major differential diagnosis in these situations, many other causes of erythema are encountered. The large number of transplant patients means that more and more pathologists are confronted with the challenging problem of making a correct diagnosis in these situations. In this review article we therefore describe the different causes of erythema and their differential diagnoses. In most cases the clinical presentation is related to the microscopical features. Besides acute and chronic graft‐versus‐host disease, we discuss the (common) drug reactions and non‐specific features such as Sweet's syndrome, erythema nodosum and eosinophilic folliculitis. In addition, we deal with the recurrence of original diseases and infections. With this knowledge every pathologist should feel comfortable when looking at skin biopsies of patients after haematological stem cell transplantation.
Expression of HER‐2/neu gene and protein in salivary duct carcinomas of parotid gland as revealed by fluorescence in‐situ hybridization and immunohistochemistry
Authors: Skálová A , Stárek I , Vanecek T , Kucerová V , Plank L , Szépe P , Di Palma S , Leivo I
Published: December 2004

Aims:  Salivary duct carcinoma is a highly malignant salivary gland tumour with aggressive clinical behaviour, characterized by histological resemblance to invasive ductal carcinoma of the breast. Amplification of HER‐2/neu oncogene and over‐expression of its gene product have both prognostic and therapeutic implications in breast cancer. Recent report on salivary duct carcinomas for HER‐2/neu using immunohistochemistry (IHC) has shown over‐expression in most cases. However, correlation between IHC and molecular genetic analysis of HER‐2/neu in salivary duct carcinoma has not yet been performed.

Methods and results:  We have now evaluated 11 cases of salivary duct carcinomas for HER‐2/neu status using IHC and fluorescent in‐situ hybridization (FISH). To our knowledge, this is the first molecular genetic analysis of HER‐2/neu in salivary duct carcinoma.

Conclusions:  In immunohistochemistry, over‐expression of HER‐2/neu protein was identified as distinct membrane staining in most carcinoma cells in all our salivary duct carcinoma cases, while only four cases revealed an amplification of HER‐2/neu gene by means of FISH analysis. Both amplified and non‐amplified salivary duct carcinomas with strong immunohistochemical staining for HER‐2/neu protein were associated with poor clinical outcome for the patients. Apparently, HER‐2/neu protein over‐expression could also be controlled by mechanisms other than gene amplification. In the group of salivary gland tumours other than salivary duct carcinoma, strong over‐expression was detected only in three cases of carcinoma ex pleomorphic adenoma. Thus, over‐expression of HER‐2/neu protein is also a useful marker of malignant transformation in pleomorphic adenomas.
Smooth muscle cell differentiation in mammary stromo‐epithelial lesions with evidence of a dual origin: stromal myofibroblasts and myoepithelial cells
Authors: Di Tommaso L , Pasquinelli G , Damiani S
Published: December 2004

Aims:  We investigated the origin of myoid cells in benign stromo‐epithelial lesions of the breast in order to ascertain their myoepithelial or myofibroblastic origin.

Methods and results:  We selected 22 stromo‐epithelial lesions of the breast and reviewed their morphological features at haematoxylin–eosin (H&E) level. The lesions were classified as fibrous stromo‐epithelial lesions (without evidence of myoid differentiation at H&E level) (13 cases), type 1 myoid stromo‐epithelial lesions (myoid cells directly merging with the myoepithelial layer) (three cases), type 2 myoid stromo‐epithelial lesions (bundles of myoid cells unrelated to the glands) (six cases). All cases were studied immunohistochemically and myoid stromo‐epithelial lesions were also studied with electron microscopy. The myoid component in two out of three cases of type 1 myoid lesions showed immunohistochemically co‐expression of smooth muscle and myoepithelial markers. In contrast, the remainder showed immunohistochemical results identical to those found in type 2 myoid lesions (positivity with SMA, desmin, calponin, CD34 and bcl2 and negativity with cytokeratin 14 and p63). Ultrastructural study confirmed the presence of cells with myoepithelial features in type 1 myoid lesions and of cells with myofibroblastic features in type 2 myoid lesions.

Conclusions:  Myoid cell differentiation is common in stromo‐epithelial lesions of the breast, and is evident in H&E sections in up to 40% of cases. In addition, the origin of myoid cells is myofibroblastic in most cases, but in some cases, cells present immunohistochemical and ultrastructural evidence of myoepithelial origin.
Microvessel densities and microvascular architecture in colorectal carcinomas and their liver metastases: significant correlation of high microvessel densities with better survival
Authors: Prall F , Gringmuth U , Nizze H , Barten M
Published: December 2004

Aims:  Microvessel densities in cancers have been shown to be a prognostic factor for some types of cancer. For colorectal cancer, however, the situation is far from clear.

Methods:  A consecutive series of 173 colorectal carcinomas was investigated, and to these were added 55 liver metastases originating from colorectal cancer. Microvessels were counted in hotspots (factor VIII immunostaining, 0.74 mm2). The capillary architecture was scored according to the degree of order and envelopment of the neoplastic glands. Endothelial proliferation was determined by factor VIII/Ki67 double labelling.

Results:  Mean microvessel densities were 51.8 for colorectal carcinomas (range 8–140) and 31.9 for liver metastases (range 3–101). Stratification according to stage, depth of infiltration and nodal involvement showed a significant inverse relation with increase. Mean microvessel densities in primaries were significantly higher than in metastases. Kaplan–Meier analysis showed a significantly higher cancer‐specific survival for high microvessel densities (median as cut‐off) and for a more ordered microvascular architecture. Endothelial proliferation in carcinomas was significantly higher than in normal mucosa.

Conclusions:  Contrary to other types of cancer, for colorectal cancer high microvessel densities confer good rather than poor prognosis. We hypothesize that neoangiogenesis, though extant in colorectal cancer, is not rate‐limiting in the metastatic cascade.
Colorectal carcinomas with high MIB‐1 labelling indices but low pKi67 mRNA levels correlate with better prognostic outcome
Authors: Duchrow M , Ziemann T , Windhövel U , Bruch H‐P , Broll R
Published: December 2004

Aims:  Antibodies specific to the proliferation‐associated protein pKi67 (e.g. Ki67, MIB‐1) are routinely used in oncology to assess the proliferation index of tumour cells. In untransformed cells the amount of pKi67 present at any time of the cell cycle is strictly regulated. To achieve a better understanding of expression and regulation of this protein in tumour cells, we investigated both pKi67 mRNA and protein expression in routinely fixed and embedded tissue of colorectal carcinoma.

Methods and results:  We determined a median pKi67 specific in‐situ hybridization labelling index of 42% (9–79%) and a median Ki67 index (MIB‐1 labelling index) of 59% (26–94%) in 47 resected colorectal adenocarcinomas of different stages and grades. In 32 cases expression of pKi67 mRNA and protein correlated well but we observed a significant difference between both values in 15 tumours. In these cases more than 30% of the cells expressed the protein but not the mRNA of pKi67, possibly due to cell cycle arrest. Patients belonging to this group had a significantly (P < 0.012) better prognosis.

Conclusions:  Tumours with a high pKi67 protein level but low mRNA expression are likely to proliferate more slowly than calculated on the basis of their Ki67 staining index, which possibly explains the patients' improved outcome.
Expression of HMGI(Y) associated with malignant phenotype of human gastric tissue
Authors: Nam E S , Kim D H , Cho S J , Chae S W , Kim H Y , Kim S M , Han J J , Shin H S , Park Y E
Published: December 2004

Aims:  We evaluated the association between HMGI(Y) expression and the detection of malignant cells by simple reverse transcriptase‐polymerase chain reaction (RT‐PCR) and correlated the level of HMGI(Y) expression and the clinicopathological data in gastric cancer.

Methods and results:  We analysed HMGI(Y) expression in 62 gastric cancer tissues and 28 normal gastric tissues by RT‐PCR and immunohistochemical study. HMGI(Y) expression evidenced by RT‐PCR was observed in 42 (67.7%) of 62 gastric cancer samples, whereas eight (28.6%) of 28 normal gastric tissues were positive (P = 0.001). In immunohistochemical staining for HMGI(Y), 48 (77.4%) of 62 gastric cancers were positive for HMGI(Y), whereas four (6.5%) of 62 normal gastric mucosae around the tumour were weakly positive, particularly in cells of some hyperplastic glands (P < 0.001). There was no significant correlation between the levels of HMGI(Y) expression and stage, tumour size, histological grade, invasion depth, or lymph node metastasis.

Conclusions:  Our results suggest that HMGI(Y) expression could be associated with malignant phenotype in human gastric tissue, and that HMGI(Y) may contribute to gastric tumorigenesis.
Ossifying fibromyxoid tumour of soft parts, with focus on unusual clinicopathological features
Authors: Holck S , Pedersen J G , Ackermann T , Daugaard S
Published: December 2004

Aims:  Ossifying fibromyxoid tumour is a rare lesion that generally occurs in the soft tissues of proximal limbs/girdle, or head and neck. Histologically, it usually consists of bland, mitotically inactive, S100+ cells in a fibromyxoid matrix with a characteristic peripheral ossification. However, we present two cases that deviated from this pattern.

Material and methods:  One tumour, which was removed from the axilla of a 55‐year‐old female, was unusual in its large size (120 mm in diameter) and in its restriction of bone formation to its central zones. The other tumour, which occurred in a 62‐year‐old female, was remarkable in its acral location on the hand and high mitotic activity (four mitoses per high‐power field). These features caused concern and follow‐up of the patients was recommended. So far there have been no recurrences (25 and 18 months after surgery, respectively). An additional previously undescribed feature was the presence of fibronexus‐like structures by electron microscopy in the second case. However, a myofibroblastic phenotype was not supported by the immunohistochemical findings.

Conclusion:  Though a distinct entity, ossifying fibromyxoid tumour may exhibit a wider clinicopathological spectrum than generally recognized.
Reporting needle core biopsies of breast carcinomas
Authors: Hoda S A , Harigopal M , Harris G C , Pinder S E , Lee A H S , Ellis I O
Published: December 2004

Many breast carcinomas are now diagnosed in needle core biopsies, after either mammographic detection or symptomatic presentation. There is dispute, however, about the range of information that should be included in the diagnostic report of these small and possibly unrepresentative samples. Is it sufficient to simply report the presence of carcinoma, in situ or invasive? Or should the histopathologist give a more detailed report including features of prognostic and predictive significance? If so, what is the evidence that the further information is, first, of clinical benefit and, second, not unreliable because of sampling variability? To address the question ‘What should be included in reports of needle core biopsies of breast carcinomas?’ contributions were invited from authors in the USA and the UK.
Haemorrhagic dermatomyofibroma (plaque‐like dermal fibromatosis): clinicopathological and immunohistochemical analysis of three cases resembling plaque‐stage Kaposi's sarcoma
Authors: Mentzel T , Kutzner H
Published: December 2004

Aims:  Dermatomyofibroma (plaque‐like dermal fibromatosis) represents a distinct clinicopathological entity in the spectrum of cutaneous mesenchymal neoplasms showing a myofibroblastic line of differentiation. These benign neoplasms occur frequently, but not exclusively, in young women, and the shoulder girdle as well as the upper trunk are common locations. Histologically, dermatomyofibroma is characterized by a plaque‐like proliferation of cytologically bland spindle‐shaped tumour cells containing an ill‐defined, pale eosinophilic cytoplasm and elongated, neuroid nuclei. Neoplastic cells are arranged in bundles and fascicles orientated parallel to the skin surface, adnexal structures are spared and elastic fibres are increased and fragmented. Immunohistochemically, tumour cells express vimentin and variably muscle actin and α‐smooth muscle actin, but are negative for desmin, CD34, S100, and epithelial markers. The main differential diagnosis includes hypertrophic scar, dermatofibroma (fibrous histiocytoma), pilar leiomyoma, neurofibroma, adult myofibromatosis, extra‐abdominal fibromatosis and plaque‐stage dermatofibrosarcoma protuberans.

Methods and results:  We report three cases of dermatofibroma arising in male patients aged 31, 36, and 47 years on the thigh, chest wall and back, respectively. All lesions were completely excised and no local recurrence has been reported. Histologically, the neoplasms showed classical features of dermatomyofibroma; however, in addition abundant extravasated erythrocytes, scattered inflammatory cells, numerous capillaries, and sieve‐ and slit‐like spaces, features resembling plaque‐stage Kaposi's sarcoma, were noted. In none of the cases did spindled tumour cells stain positively for CD34, and HHV8 was not detected by polymerase chain reaction.

Conclusions:  The reported cases widen the clinicopathological spectrum of dermatomyofibroma and emphasize plaque‐stage Kaposi's sarcoma as an additional differential diagnosis.
E‐cadherin loss rather than β‐catenin alterations is a common feature of poorly differentiated thyroid carcinomas
Authors: Rocha A S , Soares P , Fonseca E , Cameselle‐Teijeiro J , Oliveira M C , Sobrinho‐Simões M
Published: December 2004

Aims: To investigate the immunohistochemical and molecular genetic features of the cadherins/catenins complex in thyroid carcinoma based on the hypothesis that poorly differentiated carcinoma of the thyroid represents an intermediate step between well‐differentiated and undifferentiated carcinomas.

Methods and results: Immunohistochemistry for E‐, P‐ and N‐cadherins and α‐, β‐ and γ‐catenins was performed in a series of 17 cases of poorly differentiated carcinoma of the thyroid. All cases showed absence of membranous expression of E‐cadherin with no aberrant expression of P‐ or N‐cadherins; regarding catenins there was heterogeneous loss of expression with membranous immunolocalization of the three catenins in most cases. Molecular analysis of the E‐cadherin gene and exon 3 of the β‐catenin gene was also performed by polymerase chain reaction/single‐strand conformation polymorphism and sequencing. No mutations in either gene were detected in any case.

Conclusions:  In contrast to previous reports, our results suggest that loss of E‐cadherin rather than β‐catenin mutation is the crucial event in determining the differentiation ‘level’ of thyroid carcinomas.
Lack of histologically suspicious features, proliferative activity, and p53 expression suggests benign diagnosis in phaeochromocytomas
Authors: Salmenkivi K , Heikkilä P , Haglund C , Louhimo J , Arola J
Published: December 2004

Aims:  The malignancy of phaeochromocytomas is difficult to predict. Traditionally, only a metastasized tumour is considered malignant. The aim of this study was to assess the histopathological and clinical features, as well as the proliferative activity, and to analyse p53 and p21 expression in 105 phaeochromocytomas.

Methods and results:  All malignant phaeochromocytomas (n = 8) showed at least one of the histologically suspicious features, i.e. over five mitoses/10 high‐power fields, necrosis, capsular or vascular invasion. Malignant tumours were larger, but the age and gender of the patients were not significantly different. All benign (n = 33) and most of the borderline (18/21) adrenal phaeochromocytomas had less than 6% Ki67+ tumour cells, while most malignant tumours (6/7) expressed Ki67 in >6% of the cells. p53+ immunohistochemistry was found in two malignant tumours, while p21 expression did not correlate with malignancy.

Conclusions:  These data suggest that the lack of histologically suspicious features, low proliferative activity, smaller size, and negative p53 immunostaining point to a benign diagnosis in phaeochromocytomas.
HER2 oncogene amplification in extramammary Paget's disease
Authors: Tanskanen M , Jahkola T , Asko‐Seljavaara S , Jalkanen J , Isola J
Published: December 2004

Aims:  To study HER2 oncogene amplification and over‐expression in skin samples of 23 patients with extramammary Paget's disease (EMP). EMP is a rare intra‐epidermal adenocarcinoma, which has been reported to over‐express the HER2 oncoprotein.

Methods and results:  HER2 gene amplification, detected by chromogenic in‐situ hybridization, was found in 43% (10/23) of the lesions. HER2 protein over‐expression (3+ immunostaining intensity) was found in 12 tumours (52%), including all 10 tumours with gene amplification. Two tumours showed low‐level (2+) HER2 immunostaining. Mammary Paget's lesions, which were used as controls, showed HER2 amplification and over‐expression in all 10 cases studied.

Conclusions:  These results indicate that HER‐2 protein over‐expression in EMP is common and due exclusively to gene amplification. They open up the possibility of HER2‐targetted immunotherapy for patients with HER2+ disease.
Calponin and h‐caldesmon expression in synovial sarcoma; the use of calponin in diagnosis
Authors: Fisher C , Montgomery E , Healy V
Published: December 2004

Aims:  To assess the frequency of expression and potential diagnostic utility of calponin and caldesmon in synovial sarcomas.

Methods and results: Immunohistochemistry with antibodies to calponin and h‐caldesmon was undertaken in paraffin sections from 50 synovial sarcomas (19 biphasic and 31 monophasic, of which one biphasic and eight monophasic tumours had poorly differentiated areas), 10 each of malignant peripheral nerve sheath tumour (MPNST), solitary fibrous tumour (SFT), dermatofibrosarcoma (DFSP), Ewing's sarcoma (ES/PNET), and neuroblastoma, eight alveolar rhabdomyosarcomas, five adult fibrosarcomas and five carcinosarcomas. Nine of 19 biphasic synovial sarcomas were positive for calponin in spindle and glandular areas, nine in spindle cells only, and one in glands only. All monophasic synovial sarcomas and poorly differentiated areas expressed calponin; in monophasic tumours this was focally (29% of cases), moderately (39%), or diffusely (32%) positive and the poorly differentiated areas were usually moderately or diffusely positive. Four synovial sarcomas showed focal reactivity for h‐caldesmon. Calponin was found in 4/10 MPNST, 7/10 SFT, 4/10 DFSP, 3/5 fibrosarcomas and the spindle component of the carcinosarcomas. H‐caldesmon was weakly positive in 1/10 MPNST, 4/10 SFT, 0/10 DFSP, 0/5 fibrosarcomas and 1/5 carcinosarcomas (glands only). Both markers were negative in the other small round cell tumours.

Conclusions: Calponin can be used as an additional marker for synovial sarcoma. Its absence argues against the diagnosis. The presence of calponin might be useful in distinguishing poorly differentiated synovial sarcoma from other small round cell tumours. H‐caldesmon is not helpful in diagnosis of synovial sarcoma.
Expression of differentiation and proliferation related proteins in epithelium of prophylactically removed ovaries from women with a hereditary female adnexal cancer predisposition
Authors: Piek J M J , Verheijen R H M , Menko F H , Jongsma A P M , Weegenaar J , Gille J J P , Pals G , Kenemans P , Van Diest P J
Published: December 2004

Aims:  To investigate the occurrence of preinvasive neoplastic lesions in ovarian surface epithelium and ovarian inclusion cyst epithelium of women with a hereditary predisposition to the development of female adnexal (ovarian and fallopian tube) carcinoma and to assess the expression of differentiation and proliferation related proteins within putative sites of origin of serous ovarian carcinoma, the ovarian surface epithelium and ovarian inclusion cyst epithelium.

Methods:  Twenty‐one ovaries, prophylactically removed from 11 women predisposed to the development of female adnexal cancer (cases) were compared with 22 ovaries from 11 women without such predisposition (controls). Archival histological specimens were screened for hyperplastic and dysplastic epithelial lesions. In both the ovarian surface and inclusion cyst epithelia, the percentage of cells was determined that stained positively for Ki67, p21, p27, p53, cyclin A, cyclin D1, bcl‐2 and the presence of HER‐2/neu, oestrogen (ER‐α) and progesterone receptors (PR).

Results:  No preinvasive neoplastic lesions were detected. However, hyperplastic areas were found in three cases and in four controls (NS). ER‐α (P = 0.013), PR (P < 0.001), bcl‐2 (P = 0.008), p21 (P = 0.046) and p27 (P = 0.008) were expressed in a significantly higher percentage of cells in inclusion cyst epithelium than in ovarian surface epithelium (both groups). The latter showed higher bcl‐2 expression in cases (P = 0.05) compared with controls. The inclusion cyst epithelium of cases showed higher expression of bcl‐2 (P = 0.006) and PR (P = 0.039) compared with controls. Proliferation was low in both cases and controls as reflected by low Ki67 expression. Over‐expression of p53, cyclin D1 and HER‐2/neu was not detected.

Conclusions:  Premalignant changes are not a common feature of ovaries removed prophylactically from women predisposed to the development of female adnexal carcinoma. Increased expression of p21, p27, and ER‐α is seen in inclusion cyst compared with ovarian surface epithelium of women with and without an inherited risk of adnexal carcinoma. This is most probably caused by the different intraovarian hormonal milieu of inclusion cyst epithelium. However, the increased expression of bcl‐2 and PR in the inclusion cyst epithelium of patients with a hereditary predisposition may reflect early disruption of hormonal balance and growth control.