bluuebunny/crossref_metadata_2025 huggingface dataset:
Problem‐based learning and libraries: a survey of the literature
Authors: RANKIN JOCELYN A.
Published: March 2003

Problem‐based learning is seen as an effective response to calls for reform in medical education. A literature review showed that librarians studying the effects of problem‐based learning on library and learning resources have found that the new curriculum results in increased library resource use. Also, librarians typically provided more educational programmes and assumed greater faculty responsibilities in their own institutions. While significant research on problem‐based learning libraries has been completed, there are still many topics to be explored.
Mentoring in professional associations: continuing professional development for librarians
Authors: Ritchie Ann , Genoni Paul
Published: March 2003

This article argues for the inclusion of mentoring as a form of continuing professional development to be offered by professional associations to their members. It discusses the comparatively recent emergence of formal and facilitated mentoring programmes, which differ from the traditional model. These developments have increased its suitability to being offered as part of structured programmes of continuing professional development. The article also considers that mentoring within a profession has some advantages as a form of continuing professional development that make it particularly suited to meeting the needs of mentors, mentorees and the professional associations that sponsor mentoring programmes.
Delivery of health informatics education and training
Authors: Brittain J. Michael , Norris A. C.
Published: March 2003

An overview is provided of education and training in health information management in the context of national information strategies. Although the article focuses upon British programmes, there are examples from North America, Australasia and other countries. Reference is made to international activities in the development of generic courses for education and training, the need for education and training, the content of courses, and methods of delivery, including Internet‐based training and education. Governments and health authorities in many countries have recognized the urgent need for a highly educated and trained workforce in information management, but universities have been slow to respond, until the last few years. However, there is now a plethora of education and training programmes in North America, most European countries, and Australasia.
Apoptosis in thyroid neoplasms: relationship with p53 and bcl‐2 expression
Authors: Moore  , Ohene‐Fianko  , Garcia  , Chakrabarti
Published: March 2003

Aim:

Cell gain and loss occurs concurrently in tumours. Apoptosis may play a major role in determining the growth and aggressiveness of the tumours. The aim of this study was to investigate whether apoptosis is related to the degree of differentiation and expression of mutated p53 and bcl‐2 in thyroid neoplasms.

Methods and results:

Fifty‐three thyroid tumours of various histological types and 10 multinodular goitres were investigated semiquantitatively for the presence of apoptosis using a DNA end ligase method. Simultaneously, quantitative immunostaining was performed for bcl‐2 and p53, two known regulators of apoptosis. No apoptosis was detected in normal thyroid tissues, multinodular goitres and in four follicular adenomas, all of which were positive for bcl‐2. On the other hand, two anaplastic and one insular carcinomas showed marked increase in apoptosis along with intense p53 positivity and bcl‐2 negativity. The majority of the follicular carcinomas showed results similar to that of follicular adenomas. No apoptosis was detected in 41% of papillary carcinomas, the majority of these being p53 negative and bcl‐2 positive. Forty‐four per cent of the papillary carcinomas demonstrated low apoptosis rate, with variable bcl‐2 positivity and mostly negative for p53. Fifteen per cent of papillary carcinomas showed a high apoptosis rate. They were p53 negative and mostly negative for bcl‐2. The differences of staining in various tumours with respect to p53, bcl‐2 and apoptosis were statistically significant. Correlation analysis demonstrated a significant relationship between apoptosis and bcl‐2 expression in thyroid tumours (P < 0.001), whereas no relationship was seen with p53.

Conclusion:

These data suggest that bcl‐2 expression in thyroid neoplasms is related to apoptosis. p53 expression is associated with high grade thyroid tumours, but may not be important in the apoptotic pathways in all thyroid tumours.
Spontaneous regression of hepatocellular carcinoma
Authors: Kaczynski  , Hansson  , Remotti  , Wallerstedt
Published: March 2003

Aims:

To determine the clinical and histopathological features of a case of a spontaneous regression of hepatocellular carcinoma (HCC).

Case details:

HCC was found incidentally in a 73‐year‐old man during a laparotomy for evaluation of gastric retention. Despite no treatment being given, he improved gradually with no sign of tumour as evidenced by coeliac angiography 15 months later, as well as by explorative laparotomy after another 2 years. The patient died 15 years after the primary diagnosis of HCC, without known evidence of tumour recurrence. The patient's clinical records were reviewed, and paraffin‐embedded liver tissue was re‐evaluated. Both histological and immunohistochemical features were compatible with the diagnosis of a well differentiated HCC. Conceivable causes of the spontaneous regression of this and other reported cases are discussed, but the phenomenon remains enigmatic.

Conclusions:

This case with a histologically proven HCC and a very long follow‐up time confirms that spontaneous regression does occur. Since the case was found incidentally our report also implies that this may not be as rare as reported.
Metallothionein and apoptosis in primary human hepatocellular carcinoma and metastatic adenocarcinoma
Authors: Deng  , Chakrabarti  , Waalkes  , Cherian
Published: March 2003

Aims:

Differences in expression of metallothionein (MT) have been reported in various human tumours. MT is mainly expressed in proliferating epithelial tumour cells but in human hepatocellular carcinoma (HCC) there is only a minimal expression of MT. Since MT is a zinc binding protein and certain inducers of MT including zinc play a role in apoptosis, studies were undertaken to compare the expression of MT and the presence of apoptotic cells (APPC) in both primary HCC and metastatic adenocarcinoma.

Methods and results:

Histological sections of 13 cases of primary HCC and eight cases of metastatic adenocarcinoma were obtained from archival samples. They were stained for MT using a polyclonal antibody which cross‐reacts readily with human MT and for APPC by the TUNEL technique. Normal human liver had consistent MT staining with no detectable APPC. The primary HCC showed moderate MT staining with a small number of APPC while metastatic adenocarcinoma showed no MT staining with a large number of APPC.

Conclusions:

These results suggest a relationship between absence of MT and appearance of APPC in human liver tumours, especially in metastatic adenocarcinomas.
De‐differentiated chondrosarcoma is not a ‘de‐differentiated’ chondrosarcoma
Authors: Aigner T , Dertinger S , Neureiter D , Kirchner T
Published: March 2003

Aims: De‐differentiated chondrosarcoma is characterized by the presence of two distinct chondroid and nonchondroid tumour portions. The aim of our study was to investigate the distribution of extracellular matrix components in this tumour entity and thus to shed light on its histogenetic origin.

Methods and results

Histochemical and immunohistochemical analyses were performed for collagen subtypes I, II, III and VI and cartilage proteoglycans in three samples of de‐differentiated as well as conventional chondrosarcomas (various grades). In the chondroid tumour areas of de‐differentiated chondrosarcoma, typical cartilage matrix components could be detected similar to chondroid areas of grade 1 and 2 conventional chondrosarcomas. In contrast, the tumour matrix of the nonchondroid portions of de‐differentiated chondrosarcomas contained matrix molecules which are typical for fibroblastic tissue. This matrix composition was not identical with less differentiated (nonchondroid) areas of grade 2 and 3 conventional chondrosarcomas.

Conclusions

Our results confirm the chondroid nature of the differentiated portion of de‐differentiated chondrosarcoma and indicate a nonchondrocytic nature of the nonchondroid portion. De‐differentiated chondrosarcoma should not be considered as a ‘de’‐differentiated chondrosarcoma (grade 4 neoplasm), but as a tumour entity showing two types of mesenchymal differentiation.
Male adnexal tumour of probable Wolffian origin occurring in a seminal vesicle
Authors: Middleton L P , Merino M J , Popok S M , Ordonez N G , Ayala A G , Ro J Y
Published: March 2003

Aims: Adnexal tumours of probable Wolffian origin are rare low‐grade malignant neoplasms that have been previously described in the broad ligament, ovaries and retroperitoneum of females. All are characterized by small, bland epithelial cells growing in a diffuse, trabecular, or tubular pattern. The majority of the cases reported have pursued a benign clinical course. However, recurrences and distant metastases have been described. We present a case of a male adnexal tumour of probable Wolffian origin occurring in the left seminal vesicle of a 29‐year‐old man with 23 years of follow‐up.

Results

The diagnosis is supported by immunohistochemical and electron microscopic findings: The tumour cells were immunoreactive for cytokeratin and vimentin while smooth muscle antigen and S100 protein were uniformly negative. By electron microscopy cells were arranged in an acinar pattern and surrounded flocculent, electron‐dense material. Individual cells contained numerous dense bodies and free ribrosomes. The patient had recurrences at 14 and 23 years after initial diagnosis.

Conclusion

This is the first report of this entity in a male. The literature on this unusual tumour is reviewed and the clinicopathological, immunohistochemical and ultrastructural features are described. The differential diagnosis of this seemingly indolent tumour is discussed with genitourinary tumours having a more aggressive clinical course.
Primary primitive neuroectodermal tumour of the parotid gland
Authors: Deb R A , Desai S B , Amonkar P P , Aiyer P M , Borges A M
Published: March 2003

Aims

Primitive neuroectodermal tumour (PNET) is a malignant small round cell tumour that exhibits neuroepithelial differentiation. Isolated cases of PNET have been reported in visceral sites such as the kidney, uterus, ovary, testis, urinary bladder and pancreas. We present two cases of PNET of the parotid gland.

Methods and results

The first case was a 60‐year‐old woman, who presented with a parotid swelling of 10 months duration. The second case was a 45‐year‐old man, who presented with a recurrent temporofacial swelling of 6 months duration. Histological evaluation, in conjunction with immunohistochemistry, confirmed the diagnosis of PNET.

Conclusions

This is the first documentation of PNET of the salivary gland. The probable origin is from the facial nerve.
Reduced number of Langerhans cells in oesophageal mucosa from AIDS patients
Authors: Charton‐Bain  , Terris  , Dauge  , Marche  , Walker  , Bouchaud  , Xerri  , Potet
Published: March 2003

Aims

The oesophageal mucosa is a frequent target of opportunistic infections in human immunodeficiency virus (HIV) infection. Langerhans cells (LC) are known as a target and reservoir of HIV in the skin. The aim of this study was to characterize oesophageal LC in HIV‐infected patients.

Methods and results

Thirty oesophageal biopsies were obtained from 29 patients (median age 35.5), all in stage IV of the HIV Center of Disease Control Classification. We performed histological assessment of the oesophageal mucosa and immunohistochemical detection of oesophageal LC using an anti‐CD1a antibody, followed by morphometric analysis. Biopsies from 17 noninfected patients were studied using the same procedure. LC in oesophageal mucosa of the HIV positive patients showed a significantly and dramatically decreased number (LC(N) median = 5.85/mm2) and surface/epithelial surface (LC (S) ratio = 0.09) when compared with HIV‐negative controls (LC(N) median = 29.7/mm2, LC(S) ratio = 1.83) with P = 0.003 for LC(N) and P < 0.0001 for LC(S).

Conclusion

These data suggest that oesophageal LC are, like their epidermal counterparts, a preferential target for HIV infection. Their alterations may provide a clue to the pathogenesis of the decreased local oesophageal immunity and to the occurrence of opportunistic infections.
Benign atypical naevi: diagnostic difficulties and continued controversy
Authors: Blessing
Published: March 2003

Benign melanocytic naevi exhibit a wide spectrum of histological appearances. Some share significant clinical and histological features and are recognized as entities. Included among these are pagetoid/junctional Spitz naevus, pigmented spindle cell naevus, halo naevus, recurrent and traumatized naevus, ultraviolet (UV) irradiated naevus, naevus in infants, acral naevus, genital naevus and naevi from other specific anatomic locations. However, there still remains a diagnostic grey area of acquired predominantly junctional naevi with architectural and cytological atypia. Only a small percentage of these will fulfil the criteria for dysplastic naevus if criteria are strictly applied. Therefore, there exists a group of otherwise ordinary acquired naevi with atypical junctional activity, mostly mild, whose biological significance is unclear. In older individuals, although junctional activity in otherwise benign naevi does occur, extra care should be exercised in order to prevent the diagnosis of melanoma in situ being overlooked.
Metaplastic (infarcted) Warthin's tumour of the parotid gland: a possible consequence of fine needle aspiration biopsy
Authors: Di Palma  , Simpson  , Skálová  , Michal
Published: March 2003

Aims

The metaplastic (or infarcted) variant of Warthin's tumour is characterized by replacement of much of the original oncocytic epithelium by metaplastic squamous cells, along with areas of extensive necrosis, fibrosis and inflammatory change. The pathogenesis is unknown, but it is most likely to be vascular in origin. An association with a previous fine needle aspiration (FNA) has been suggested, and this is explored further.

Methods and results

Nine metaplastic Warthin's tumours were collected from several centres: all arose in the parotid gland, and all showed the characteristic histological features. Eight had previously undergone FNA some 1–4 months before surgery; the other case had had an incisional biopsy.

Conclusions

It is important to recognize metaplastic Warthin's tumour, because the differential diagnoses of this benign neoplasm include mucoepidermoid and squamous carcinoma, both primary and metastatic. The tumours in this study followed FNA or biopsy, and we believe this association is unlikely to be coincidental. Although many metaplastic Warthin's tumours clearly arise spontaneously, we conclude that the balance of probabilities favours the view that FNA is capable of causing metaplastic change in a Warthin's tumour, and may have done so in these cases. If so, this previously unusual subtype will become increasingly common, as FNA becomes more widely used (and its value appreciated) in the investigation of patients with a mass in the neck.
c‐met tyrosine kinase receptor expression is associated with abnormal β‐catenin expression and favourable prognostic factors in invasive breast carcinoma
Authors: Nakopoulou  , Gakiopoulou  , Keramopoulos  , Giannopoulou  , Athanassiadou  , Mavrommatis  , Davaris
Published: March 2003

Aims

Receptor‐type tyrosine kinases are important in cell signal transduction and proliferation. Abnormal expression of tyrosine kinases often leads to malignant transformation. c‐met is a tyrosine kinase receptor and its ligand is hepatocyte growth factor (HGF). In this study, we have evaluated c‐met expression in 69 invasive breast carcinomas and statistically analysed this expression with known clinicopathological prognostic parameters and patients' survival. We also studied for the first time c‐met expression in association with E‐cadherin and β‐catenin expression.

Methods and results

Immunohistochemistry (ABC‐HRP method) was peformed for the detection of c‐met, E‐cadherin and β‐catenin. c‐met immunoreactivity was observed in 58% of cases and was associated with the lobular type of breast carcinomas (P = 0.012), low histological grade ductal carcinomas (P = 0.05), favourable prognostic and predictive factors such as oestrogen and progesterone receptor immunohistochemical expression and negative c‐erbB‐2 expression (P = 0.05, P = 0.014 and P = 0.03, respectively). c‐met immunoreactivity did not correlate with lymph node status, tumour size and stage of the disease. Cox's proportional hazard regression model demonstrated that tumours with positive c‐met immunoreactivity correlated significantly with favourable patients' survival (P = 0.028). When c‐met staining was compared with E‐cadherin and β‐catenin expression, a statistical significant correlation was established between c‐met immunoreactivity and abnormal β‐catenin expression (P = 0.025) suggesting possible involvement of c‐met in the downregulation of the E‐cadherin–catenin complex, possibly through tyrosine phosphorylation of β‐catenin.

Conclusion

c‐met immunohistochemical expression seems to be associated with abnormal β‐catenin expression, good prognostic and predictive factors and favourable outcome in breast cancer patients.
Cytokeratin 5/6 immunohistochemistry assists the differential diagnosis of atypical proliferations of the breast
Authors: Otterbach F , Bànkfalvi À , Bergner S , Decker T , Krech R , Boecker W
Published: March 2003

Aims:

This study was performed to determine the diagnostic value of keratin 5/6 (CK 5/6) immunophenotyping on routinely processed breast tissues.

Methods and results:

Six hundred and ninety‐nine breast lesions, including normal tissues as well as benign and malignant lesions in 321 formalin‐fixed, paraffin‐embedded samples from 158 different patients were investigated immunohistochemically, following wet autoclave pre‐treatment for antigen retrieval. In normal breast tissues, both myoepithelial and luminal epithelial cells expressed CK 5/6 in varying amounts. While myoepithelial immunoreactivity was most pronounced in the duct system, luminal epithelial immunoreactivity was strongest in the terminal duct lobular units. In ductal hyperplasias (DH), luminal epithelial cells predominantly revealed CK 5/6 immunoreaction. In contrast, neoplastic epithelial cells in atypical ductal and lobular hyperplasias (ADH and ALH) lacked such an expression, whereas in ductal in‐situ carcinomas (DCIS) and in infiltrating ductal carcinomas 3.7% and 7.7%, of the cases respectively, showed positive immunostaining for CK 5/6.

Conclusions:

Immunophenotyping of keratin 5/6 expression can be helpful in the diagnosis of atypical hyperplasias and in‐situ carcinomas of the breast. It is particularly valuable in the differential diagnosis between benign and atypical proliferative lesions.
Cytokeratin profile relates to histological subtypes and intrahepatic location of intrahepatic cholangiocarcinoma and primary sites of metastatic adenocarcinoma of liver
Authors: Shimonishi T , Miyazaki K , Nakanuma Y
Published: March 2003

Aims

We evaluated the cytokeratin profile of intrahepatic cholangiocarcinoma with respect to its histological classification and intrahepatic location (peripheral vs. hilar), and compared its profile with that of a variety of metastatic adenocarcinomas in liver.

Methods and results

Expression of cytokeratins 7, 8, 18, 19 and 20 was immunohistochemically examined in intrahepatic cholangiocarcinoma (n = 77) and metastatic adenocarcinoma in liver (21 colorectal, 14 gastric, three gallbladder and three pancreatic cancers). Materials were autopsy or surgical specimens. Cytokeratins 7, 8, 18 and 19 were expressed in 75 (97%), 75 (97%), 59 (77%) and 71 (92%) cases of intrahepatic cholangiocarcinoma, respectively. Moderate and extensive expression of cytokeratin 18 was more frequent in the peripheral than in the hilar type. Moderate and extensive expression of cytokeratin 19 was seen in almost all cases of well‐differentiated intrahepatic cholangiocarcinomas, while expression was decreased relatively in the moderately and decreased more in the poorly differentiated cases. While cytokeratin 20 was not found in non‐neoplastic biliary epithelia or in well‐differentiated intrahepatic cholangiocarcinomas, this cytokeratin was occasionally detectable in moderately and poorly differentiated intrahepatic cholangiocarcinomas and its expression was more frequent in the hilar type. Cytokeratin 20 expression was observed in 17 (81%) of metastatic adenocarcinomas in liver from colorectal regions, to a lesser degree in those from gastric regions, and was rare in those from gallbladder and pancreatic regions; cytokeratin 7 showed a reverse expression pattern in these metastatic adenocarcinomas in liver. The profile of cytokeratins 7 and 20 of metastatic colorectal and gastric carcinomas differed from that for intrahepatic cholangiocarcinomas, while that of metastatic gallbladder and pancreatic carcinoma was similar to that for intrahepatic cholangiocarcinomas. Moreover, cytokeratin 18 and 19 expression was significantly infrequent in metastatic gastric carcinomas than in intrahepatic cholangiocarcinomas and metastatic colorectal carcinomas.

Conclusion

The combined immunostaining of cytokeratins 7, 18, 19 and 20 is useful for the characterization of intrahepatic cholangiocarcinomas with respect to histological subtypes and intrahepatic location. It helps to differentiate intrahepatic cholangiocarcinoma from metastatic adenocarcinomas in liver and from colorectal and gastric regions; it also indicates the primary focus metastatic adenocarcinomas in livers.
Hepatocellular carcinoma with lymphoid stroma: a tumour with good prognosis after liver transplantation
Authors: Emile J‐F , Adam R , Sebagh M , Marchadier E , Falissard B , Dussaix E , Bismuth H , Reynès M
Published: March 2003

Carcinomas with lymphoid stroma arising in non‐liver‐organs have a better prognosis than other carcinomas and may be associated with Epstein–Barr virus. We determined the frequency, characteristics and prognosis of hepatocellular carcinomas with lymphoid stroma.

Histology of the livers of 162 patients with hepatocellular carcinoma, who underwent an orthotopic liver transplantation, was reviewed independently by three pathologists. Hepatocellular carcinoma with lymphoid stroma was diagnosed when all tumour samples contained more lymphocytes than tumour cells. Epstein–Barr virus was detected by in‐situ hybridization and by polymerase chain reaction. Five patients (3.6%) were classified as hepatocellular carcinomas with lymphoid stroma. All patients were males. Cirrhosis was present in four/five patients. Serum alpha‐fetoprotein levels were normal. Inter‐observer histological reproducibility was good. Tumour cells did not contain Epstein–Barr virus. The five patients were alive without tumour at three years, although two of them had adverse prognostic factors at the time of transplantation (more than one tumour with a diameter ≥40 mm). Only one patient had tumour recurrence, but he survived 7.6 years post‐transplantation. The 5‐year survival of patients with hepatocellular carcinoma with lymphoid stroma was better than that of the patients with other types of hepatocellular carcinomas (P = 0.04).

: Hepatocellular carcinoma with lymphoid stroma should be considered as a distinct clinicopathological and prognostic entity.
Epstein–Barr virus in gastric carcinomas with lymphoid stroma
Authors: Chang M S , Kim W H , Kim C W , Kim Y I
Published: March 2003

Aims

To clarify the relationship between the Epstein–Barr virus (EBV) and gastric carcinoma with lymphoid stroma (GCLS) in Koreans, and to characterize the EBV‐positive GCLS.

Methods and results

EBV infection was examined using EBER in‐situ hybridization and polymerase chain reaction in 45 cases of GCLS among Koreans, and in 292 consecutive cases of gastric carcinomas without lymphoid stroma (non‐GCLS) as controls. EBV infection was found in 30 tumours (67%) of GCLS and 10 tumours (3.4%) of non‐GCLS (P < 0.05). EBV‐positive GCLS was more prevalent in males, poorly differentiated histological type and diffuse type in Lauren's classification, and tended to be located more in the middle third of the stomach than EBV‐negative GCLS (P < 0.05). p53 overexpression was observed in 22% of GCLS (17% of EBV‐positive GCLS and 33% of EBV‐negative GCLS), and 34% of non‐GCLS (EBV‐positive GCLS vs. non‐GCLS: P = 0.056). The survival of the patient with GCLS was not correlated with EBV infection or p53 immunoexpression (follow‐up period: 11–97 months).

Conclusions

GCLS in Koreans is strongly associated with EBV infection. The prognosis in GCLS is not dependent upon either the status of EBV infection or the status of p53 immunoexpression.
Peripheral T/NK‐cell lymphoma: a report of the IXth Workshop of the European Assocation for Haematopathology
Authors: Kluin P M , Feller A , Gaulard P , Jaffe E S , Meijer C J L M , Müller‐Hermelink H K , Pileri S
Published: March 2003

In April 1998, The European Association for Haematopathology organized the IXth workshop on peripheral T‐cell and NK‐cell lymphomas and leukaemias. The workshop focused on unusual subtypes of these rare malignancies, allowing evaluation of the recently published WHO classification of neoplastic diseases of the lymphoid tissues.

 One‐hundred and three cases were centrally immunophenotyped and hybridized for EBER1/2 of Epstein–Barr virus. All cases were reviewed by a panel of experienced haematopathologists and classified according to the new WHO classification for lymphoid neoplasms. Three cases were considered as precursor T‐cell and 95 cases as peripheral T/NK‐cell lymphoma/leukaemia. Although the cases represented a selected series of unusual cases, the following conclusions could be made: (i) Most lymphomas except the hepatosplenic γ/δ T‐cell lymphomas showed a rather broad morphological spectrum, with differences both between and within individual tumours. (ii) This heterogeneity was also reflected by the immunophenotype, for instance a variable expression of CD30 was found in many enteropathy type T‐cell lymphomas. (iii) Exceptions in phenotype were regularly found in almost all categories, indicating that phenotype should not be the final determining factor in classification. (iv) The great majority of T‐cell lymphomas expressed the α/β T‐cell receptor, with the exception of all but one hepatosplenic T‐cell lymphomas and a few other extranodal peripheral T cell lymphomas. (v) Malignancies of precursor cells, blastic NK‐cell lymphoma/leukaemia, adult T‐cell lymphoma/leukaemia and most AIL‐type T‐cell lymphomas did not express cytotoxic molecules such as TIA1 and granzyme‐B. In contrast, all five aggressive NK/T‐cell lymphomas/leukaemias, a single case of large granular lymphocyte leukaemia and 40 of 47 primary extranodal lymphoma/leukaemias expressed these molecules. In hepatosplenic γ/δ T‐cell lymphoma, five of six cases showed expression of TIA1 but not of granzyme‐B. (vi) Seven tumours developed after organ‐transplant, four cases being EBV‐positive. No distinct phenotype could be attributed to these cases.

Most peripheral T/NK cell lymphomas could be categorized as distinct entities as described in the recently proposed WHO classification for lymphoid neoplasms.
Interpretation of ileal biopsies: morphological features in normal and diseased mucosa
Authors: Cuvelier C , Demetter P , Mielants H , Veys E M , De Vos M
Published: March 2003

One of the advantages of flexible colonoscopy is that the terminal ileum can easily be reached and biopsied by an experienced operator. Thus, the pathologist will, with increasing frequency, receive ileal biopsies from patients who have or may not have ileal disease and it is therefore useful to have a good knowledge of the spectrum of ileal mucosal histology and pathology, of its normal function, and of the changes seen in different conditions. It is also desirable to be aware of diseases that occur less frequently.

The ileal microscopic features are related to its absorptive function on the one hand, and to non‐specific and specific defence mechanisms of the organism against potential hazardous components on the other. As a consequence the mucosa features a constant physiological and controlled inflammatory process. Part of the ileal mucosal structure is determined by the presence of the gut‐associated lymphoid tissue (GALT) which plays a key role in discriminating harmless nutrients and harmful pathogens.

It will be important to distinguish this normal situation from alterations seen in infectious or inflammatory pathology. Further, because of the therapeutic implications, it is necessary that acute and chronic (idiopathic) inflammation are recognized. This will in general be possible by evaluating the composition of the inflammatory infiltrate and the occurrence of epithelial and mucosal architectural changes.
Apocrine adenosis of the breast: clonal evidence of neoplasia
Authors: Endoh Y , Tamura G , Kato N , Motoyama T
Published: March 2003

We report here a case of apocrine adenosis of the breast in a 66‐year‐old woman. To clarify the nature of this lesion, we examined it by clonal analysis.

The lesion, 43 mm at its greatest dimension, was ill‐circumscribed, lacking a fibrous capsule, and was composed of compact glands that showed typical histological features of apocrine adenosis. Clonality analysis, using the polymerase chain reaction (PCR)‐based method for females heterozygous for a BstXI polymorphism of the X‐linked phosphoglycerokinase (PGK) gene, revealed the monoclonal nature of the lesion.

This result strongly suggests that some populations of apocrine adenosis are already neoplastic, and this could contribute to the premalignant potential of this lesion.
Spitzoid malignant melanoma in teenagers: an entity with no better prognosis than that of other forms of melanoma
Authors: Fabrizi G , Massi G
Published: March 2003

Spitzoid malignant melanoma in teenagers: an entity with no better prognosis than that of other forms of melanoma

Aims: A rare form of melanoma in teenagers closely simulates Spitz naevus and is claimed to have a good prognosis. The aim of this study is to identify the clues for a confident diagnosis of this entity and to confirm the peculiarly good prognosis.

Methods and results: Two cases of melanoma with Spitzoid features were compared with Spitz naevus and it was found that the major distinctive criteria are: mitoses and single cell necrosis in the deepest part of the lesion, cellular and particularly nuclear and nucleolar pleomorphism, and growth pattern in solid sheets of cells. More subtle clues were the asymmetric distribution of pigment and the thinning of the epidermis with parakeratosis and exudate in the cornified layer. Both of the lesions reached the mid‐dermis. There was a fatal outcome in both patients after generalized metastatic spread. The metastatic disease in one of the cases appeared 15 years after the excision of the primary lesion.

Conclusions: Spitzoid melanoma in teenagers can be distinguished from Spitz naevus if strict criteria are followed. Spitzoid melanoma does not show a better prognosis than other types of melanoma if the follow‐up is prolonged enough.
Expression of MUC1 and MUC2 and carbohydrate antigen Tn change during malignant transformation of biliary papillomatosis
Authors: Amaya S , Sasaki M , Watanabe Y , Tsui W M S , Tsuneyama K , Harada K , Nakanuma Y
Published: March 2003

Expression of MUC1 and MUC2 and carbohydrate antigen Tn change during malignant transformation of biliary papillomatosis

Aim: Biliary papillomatosis is characterized by papillary proliferations of biliary lining cells without invasion or metastasis. The neoplastic character and biological behaviour of this disease remain still speculative. These issues were examined in this study.

Methods and results: Mucin core protein MUC1, MUC2, MUC3, MUC5AC and carbohydrate antigens (T, Tn and sialosyl Tn) were immunohistochemically examined, using 11 lesions of biliary papillomatosis from seven patients, and five lesions of biliary papillomatosis with foci of carcinoma from four patients. Five cases of papillary intrahepatic cholangiocarcinoma and 12 histologically normal livers were used as a control. Patients with biliary papillomatosis alone or with carcinoma were middle‐aged or elderly (five men and six women). Microscopically, biliary papillomatosis showed a villous, papillo‐tubular, papillary, or papillo‐villous pattern with a thin fibrovascular core. Cytologically, they were classifiable into biliary epithelial or pyloric gland‐like type. The former was frequent in the cases associated with carcinoma. Expression of MUC1, Tn antigen and sialosyl Tn antigen was frequent and marked in biliary papillomatosis alone and with carcinoma and also intrahepatic papillary carcinoma. In addition, marked expression of MUC1 and Tn antigen were rather frequent in biliary papillomatosis with carcinoma and intrahepatic biliary papillary carcinoma compared with biliary papillomatosis. MUC2 was rather frequent and marked in biliary papillomatosis alone compared to other two disease groups. Focal expression of MUC5AC and MUC2 was rather frequent and infrequent irrespective of disease group, respectively. Focal expression of T antigen was frequent in papillary ICC.

Conclusion: Biliary papillomatosis could undergo overt malignant transformation along with altered phenotypic expression of MUC proteins and mucin carbohydrate antigens.
Combined use of novel epithelial (MOC‐31) and mesothelial (HBME‐1) immunohistochemical markers for optimal first line diagnostic distinction between mesothelioma and metastatic carcinoma in pleura
Authors: González‐Lois C , Ballestín C , Sotelo M T , López‐Ríos F , García‐Prats M D , Villena V
Published: March 2003

Combined use of novel epithelial (MOC‐31) and mesothelial (HBME‐1) immunohistochemical markers for optimal first line diagnostic distinction between mesothelioma and metastatic carcinoma in pleura

Aims: To determine the value of immunohistochemistry in differentiation of malignant pleural mesothelioma from carcinoma in a pleural biopsy we optimized a double panel of MOC‐31 and HBME‐1 and compared the results with others from the literature.

Methods and results: A multi‐antibody panel was applied to biopsy samples from 44 cases of malignant pleural mesothelioma and 23 cases of carcinoma metastatic to the pleura. We used monoclonal antibodies against keratins, epithelial membrane antigen (EMA), epithelial antigen Ber‐EP4, carcinoembryonic antigen (CEA), tumour‐associated glycoprotein (B72.3), LeuM1, vimentin, desmin, epithelial related antigen (MOC‐31) and mesothelial cell (HBME‐1). Positivity for MOC‐31 and Ber‐EP4 was found to have the highest nosologic sensitivity (94.1% and 84.6%, respectively) and specificity (86.3% both antibodies) for carcinoma. Positive staining for HBME‐1 and vimentin had the highest sensitivity (90.9% and 100%, respectively) and specificity (91.3% and 60%, respectively) for mesothelioma. A two‐marker antibody panel with HBME‐1 and MOC‐31 was the most efficient for the distinction between carcinoma and malignant pleural mesothelioma.

Conclusion: A combination of MOC‐31 (an anti‐ epithelial marker) and HBME‐1 (an anti‐mesothelial marker) has a diagnostic efficiency of 76.1% for the distinction between carcinoma and mesothelioma in pleura.
Reduced expression of p21WAF1 is an indicator of malignant behaviour in anal carcinomas
Authors: Holm R , Skovlund E , Skomedal H , Flørenes V A , Tanum G
Published: March 2003

Reduced expression of p21WAF1 is an indicator of malignant behaviour in anal carcinomas

Aims: p21 and p27 protein expression were examined in a comparatively large series of patients with squamous cell carcinoma of the anal canal and compared with clinical and histopathological data (tumour stage, nodal status and differentiation).

Methods and results: We analysed the expression of p21 and p27 protein in 94 anal carcinomas by immunohistochemistry. Nuclear p21 and p27 staining were detected in 71% (67/94) and 75% (71/94) of the cases, respectively. There was no significant association between p27 staining and tumour stage, nodal status or overall survival. We observed that negative p21 immunoreactivity was significantly associated with poorly differentiated anal carcinomas. Furthermore, a shorter overall survival for patients with no p21 protein expression was seen.

Conclusions: Our data indicate that p21 levels, but not p27 expression, may be a useful predictor of survival in patients with anal carcinomas.
Differential immunoreactivity of melanocytic lesions of the conjunctiva
Authors: Sharara N A , Alexander R A , Luthert P J , Hungerford J L , Cree I A
Published: March 2003

Differential immunoreactivity of melanocytic lesions of the conjunctiva

Aims: To evaluate the expression of S100NKI/C3 and HMB45 antigens in melanocytic lesions of the conjunctiva and the ability of HMB45 to aid assessment of neoplasia.

Methods and results: Stored formalin‐fixed specimens of conjunctival melanomas and primary acquired melanosis were considered as participants and conjunctival naevi and racial melanosis as controls. Ninety‐seven conjunctival melanocytic lesions were analysed using formalin‐fixed paraffin‐embedded material. These included 20 melanomas arising in the context of primary acquired melanosis (PAM), 22 melanomas arising without evidence of pre‐existing PAM, seven cases of PAM with atypia, nine cases of PAM with no atypia, 35 conjunctival naevi and four cases of racial melanosis. S100 and NKI/C3 were similarly expressed in all lesions, with at least one of these markers positive in 100% of the lesions examined. HMB45 was expressed in 72.7% of primary melanomas and 85% of melanomas in the context of PAM; 42.8% of PAM with atypia expressed HMB45 while it was expressed in 11.1% of PAM without atypia and 8.5% of naevi. Racial melanosis cases did not express HMB45. S100 and NKI/C3 were expressed to a similar extent in all groups.

Conclusions: S100 and NKI/C3 are useful markers to assess the extent of melanocytic lesions in the conjunctiva. HMB45 immunoreactivity can act as a useful aid to histopathology for the distinction of benign from malignant conjunctival lesions, particularly in the context of primary acquired melanosis.
Splenic littoral cell haemangioendothelioma: a new low‐grade variant of malignant littoral cell tumour
Authors: Ben‐Izhak O , Bejar J , Ben‐Eliezer S , Vlodavsky E
Published: March 2003

Splenic littoral cell haemangioendothelioma: a new low‐grade variant of malignant littoral cell tumour

Aims: Littoral cell angioma is a recently described splenic vascular tumour of splenic sinus lining cells. Almost all cases of splenic littoral cell tumours hitherto described were benign.

Methods and results: A splenic littoral cell tumour recurred 8 years after splenectomy, with an abdominal mass and multiple liver metastases, resulting in the patient’s death. Histologically, the original splenic tumour showed solid areas with small necrotic foci in addition to large areas of typical littoral cell angioma. The recurrent tumours showed increased solid architecture and slightly increased nuclear atypia. The tumours showed an immunohistochemical profile positive for factor VIII, CD31, CD68, cathepsin D, and CD21 and negative for CD34 and CD8, consistent with the immunophenotype of classic littoral cell angioma. Ki67 index in the recurrent tumours was higher than in the primary tumour.

Conclusions: The mildly atypical, but not frankly malignant, histological features as well as the protracted clinical course support definition of the tumour as ‘littoral cell haemangioendothelioma’. Low rate of Ki67 staining and diploid DNA histogram with low S‐phase fraction of the tumours are in accordance with a low‐grade malignancy. Literature review revealed two other cases of littoral cell tumours with disseminated disease that may be other examples of littoral cell haemangioendothelioma. Littoral cell haemangioendothelioma should be distinguished from the overtly malignant splenic angiosarcomas, of which a few may show splenic lining cell differentiation with some immunohistochemical features of littoral cells. Due to difficulties in predicting biological behaviour based on histological features of splenic littoral cell tumours, a long‐term follow‐up for these patients, especially for those with atypical histology, is recommended.
Pseudo‐partial moles: placental stem vessel hydrops and the association with Beckwith–Wiedemann syndrome and complete moles
Authors: Paradinas F J , Sebire N J , Fisher R A , Rees H C , Foskett M , Seckl M J , Newlands E S
Published: March 2003

Pseudo‐partial moles: placental stem vessel hydrops and the association with Beckwith–Wiedemann syndrome and complete moles

Aims: To describe the clinical and histological features of a series of cases of placentas originally diagnosed as partial moles in which the final diagnosis was that of placental stem villous hydrops, mesenchymal dysplasia or Beckwith–Wiedemann syndrome.

Methods and results: We searched a computerized database containing cases of suspected or proven trophoblastic disease examined at the Trophoblastic Disease Unit at Charing Cross Hospital, London, to identify cases in which stem vessel hydrops was present without other histological features of partial mole. For each case, histological sections were examined and the histological features present recorded. There were 15 cases identified. Placental weight was above the 95th centile of the normal for gestation in all cases in which this information was documented. In an additional five cases the placenta was described as ‘large’. All cases had marked stem vessel hydropic change with cyst formation and in the majority of cases some terminal villous hydrops was also present. In 13 of the 15 cases there was marked aneurysmal dilatation of stem villous vessels. Nine had focal chorioangiomatoid change and in four of these extramedullary haematopoiesis was focally present in these areas. No excessive trophoblast proliferation was noted in any case and no trophoblastic inclusions typical of partial mole were identified.

Conclusions: This study has identified cases of stem villous hydrops, mesenchymal dysplasia or Beckwith–Wiedemann spectrum in pregnancies initially diagnosed as partial hydatidiform mole in the second half of pregnancy and has highlighted the need for detailed pathological examination and clinicopathological correlation in all such cases.
Sarcomatoid/metaplastic carcinoma of the breast: a clinicopathological study of 12 cases
Authors: Kurian K M , Al‐Nafussi A
Published: March 2003

Sarcomatoid/metaplastic carcinoma of the breast: a clinicopathological study of 12 cases

Aims: To analyse the clinical and pathological features with long‐term follow‐up of a series of 12 cases of sarcomatoid carcinoma of the breast.

Methods and results: The cases were selected from the surgical files of the Department of Pathology, University of Edinburgh, between 1977 and 1988. The following clinical parameters were recorded: the age of the patients, size of tumour, presence or absence of lymph node or distant metastases, and patient survival. Pathological assessment included: the type of epithelial and mesenchymal components, the proportion of monophasic to biphasic tumours and the presence of adjacent in‐situ carcinoma/atypical epithelial proliferation. The mean age of the patients was 61 years with a median of 64 and range 46–82 years. The mean size of the tumour was 52 mm (range 22–100 mm). None of the patients had distant metastasis at presentation and only one case had local lymph node metastasis which had a carcinomatous appearance. Five women were still alive after a minimum 12‐year follow‐up period. Four patients died of their disease (three with lung metastasis only and one with lung and bone metastases), one died of carcinoma of the cervix and two patients were lost to follow‐up. Pathologically, four cases (33.3%) had no or almost undetectable epithelial structures by light microscopy, i.e. ‘monophasic sarcomatoid carcinoma’. The remaining cases revealed varying proportions of both epithelial and mesenchymal elements, i.e. ‘biphasic sarcomatoid carcinoma’. Of the epithelial component, six (50%) tumours had predominantly carcinoma of no special type, one lobular and one tubular carcinoma. The mesenchymal component was fibromatosis/nodular fasciitis‐like, malignant fibrous histiocytoma‐like (MFH), osteosarcoma‐like and fibrosarcoma‐like in five (42%), four (33%), two (17%) and one (8%) tumours, respectively. In 3/4 monophasic tumours, the mesenchymal component was of a low‐grade fibromatosis/nodular fasciitis type. In 6/12 (50%) of the cases there was associated in‐situ atypical epithelial proliferation (five ductal carcinoma in situ (DCIS) and one atypical ductal hyperplasia).

Conclusions: From this small series it appears that sarcomatoid carcinoma is an uncommon tumour, which is large in size and tends to lack local or distant metastasis at presentation. Pathologists should be alert to the presence of the bland monophasic sarcomatoid carcinoma which has a pure mesenchymal appearance on light microscopy, but epithelial components demonstrated by cytokeratin immunohistochemistry. These showed metastases on long‐term follow‐up, similar to other histological patterns of sarcomatoid carcinoma.
Accessory cell tumour: a clinicopathological study of 16 aggressive tumours containing EBV‐positive Hodgkin and Reed–Sternberg‐like giant cells
Authors: Shimazaki K , Ohshima K , Haraoka S , Suzumiya J , Nakamura N , Kikuchi M
Published: March 2003

Accessory cell tumour: a clinicopathological study of 16 aggressive tumours containing EBV‐positive Hodgkin and Reed–Sternberg‐like giant cells

Aims: Lymph nodes contain non‐lymphoid accessory cells including follicular dendritic cells and interdigitating dendritic cells. Functionally, these cells belong to the category of immune accessory cells involved in antigen presentation to B or T‐lymphocytes. Neoplastic proliferation of these cells is very uncommon. We present here the clinicopathological features of 16 cases of accessory cell tumour.

Methods and results: We performed electron microscopic and immunohistochemical examinations, and used in‐situ hybridization for EBV‐encoded RNA (ISH‐EBV) to detect the EBV genome in 11 cases, and Southern blot analysis to assess EBV clonality in two cases. Tumour cells were composed of oval‐to‐spindle cells arranged in diffuse, vague storiform, fascicular and sometimes whorled patterns in a background of small lymphocytes. In all cases, binucleated or multinucleated Hodgkin and Reed–Sternberg‐like giant cells were encountered. Staining for CD68 was positive in all cases. CD21, CD35, Ki‐M4p, Ki‐FDC1p, and S100 exhibited variable reactivity. ISH‐EBV yielded positive labelling in seven of 11 cases, of which five exhibited EBV only in Hodgkin and Reed–Sternberg‐like giant cells. Southern blot analysis showed clonality of EBV terminal repeats (EBV‐TR) in the two cases examined. Electron microscopic examination showed that many of the tumour cells had numerous interwoven long villous cell processes connected by occasional desmosomes. Many tumours were very refractory to chemotherapy and radiation, with a few exceptions, and half of the cases classified initially as stage IV. A short survival time, of 10 months or less, was observed in seven of 16 patients.

Conclusions: Our study identified more aggressive behaviour of accessory cell tumours. Our results suggest that EBV may potentially induce activation of accessory cells to form Hodgkin and Reed–Sternberg‐like giant cells, which correspond with poor prognosis.