bluuebunny/crossref_metadata_2025 huggingface dataset:
Erythrophagocytic tumour cells in melanoma and squamous cell carcinoma of the skin
Authors: MONTEAGUDO C. , JORDÁ E. , CARDA C. , ILLUECA C. , PEYDRÓ A. , LLOMBART‐BOSCH A.
Published: November 2003

Aims:

Erythrophagocytosis is a characteristic feature of tumour cells in malignant histiocytosis, some leukaemias, lymphomas, and also reactive histiocytes in the haemophagocytic syndrome associated with a variety of infections and neoplasms. It has also been found exceptionally in metastatic malignant epithelial cells in bone marrow and lymph nodes. We present two cases, a cutaneous malignant melanoma and an acantholytic squamous cell carcinoma, in which erythrophagocytosis by tumour cells was demonstrable by both light and electron microscopy.

Methods and results:

The melanocytic and squamous nature of these cells was supported by the immunohistochemical detection of HMB45, S100, and NKI‐C3 in the former, and cytokeratin and EMA in the latter, and at ultrastructural level by the presence of melanosomes and tonofilaments, respectively.

Conclusions:

This is, to our knowledge, the first documented report of erythrophagocytic tumour cells in human melanomas and primary carcinomas. Biological considerations apart, this unusual feature can prove to be of value to avoid a misdiagnosis of a variety of haematopoietic malignancies.
Primary alveolar soft‐part sarcoma of the mediastinum: a clinicopathological and immunohistochemical study of two cases
Authors: FLIEDER D.B. , MORAN C.A. , SUSTER S.
Published: November 2003

Aims:

Primary alveolar soft part sarcomas originating within the thoracic cavity are rare. The cases herein described highlight the ubiquitous distribution of this neoplasm and the importance of considering this tumour in the differential diagnosis of mediastinal tumours.

Methods and results:

Two cases of alveolar soft‐part sarcoma of the mediastinum are presented. The patients are two men of 22 and 23 years of age. Clinically, the patients presented with symptoms of chest pain. One tumour was in the anterior mediastinum while the second tumour was in the posterior mediastinum. Even though the bulk of the tumours were in mediastinal locations, both patients had pulmonary metastases at the time of diagnosis. Histologically, both tumours showed the classic morphology of alveolar soft part sarcoma, i.e. a proliferation of large polygonal cells with round to oval nuclei, prominent nucleoli and moderate amounts of eosinophilic cytoplasm arranged in a prominent alveolar pattern. Periodic acid–Schiff stains showed the characteristic diastase‐resistant intracytoplasmic crystals. Immunohistochemical studies showed focal myoglobin reactivity in one case, while cytokeratin, vimentin, S100 protein, chromogranin, synaptophysin, neurofilaments, leu‐enkephalin, desmin, smooth muscle actin and muscle‐specific actin were negative in both cases. The patient with the anterior mediastinal tumour died of disease 14 months after diagnosis, and the patient with the posterior mediastinal mass remained well for at least 15 years and was later lost to follow‐up.

Conclusions:

As has been observed in other anatomic areas, namely soft tissues, alveolar soft part sarcomas may follow an uncertain natural history. Interestingly, in our cases, the tumour in the anterior mediastinum followed a fatal course raising the possibility that the anatomic location of the tumour may have play a role in the behaviour of the tumour.
Multinucleated stromal giant cells of testis
Authors: COYNE J.D. , DERVAN P.A.
Published: November 2003

Aims:

This study documents the frequency of multinucleated stromal giant cells within the interstitium of the testis and looks for possible aetiological reasons for this occurrence.

Materials and methods:

We examined sections of testes from 150 unselected autopsy cases finding stromal giant cells in 43%. An aetiological association between the occurrence of multinucleated stromal giant cells in this site and hormonal or other pathogenetic influences could not be established.

Conclusions:

In many instances, this occurrence appears to be an age related phenomenon.
Hepatic stem‐like cells in hepatoblastoma: expression of cytokeratin 7, albumin and oval cell associated antigens detected by OV‐1 and OV‐6
Authors: RUCK P. , XIAO J.‐C. , PIETSCH T. , VON SCHWEINITZ D. , KAISERLING E.
Published: November 2003

Aims:

In a recent study we described a population of small epithelial cells (SEC) in human hepatoblastoma that exhibit ultrastructural features of the oval cells of rodents. Both SEC and oval cells are immunoreactive for cytokeratin 7, a marker of biliary differentiation, and it was postulated that SEC, like oval cells, are closely related to hepatic stem cells. This study was undertaken to investigate whether SEC also exhibit immunolabelling for albumin, a marker of hepatocytic differentiation, and to determine whether other antigens typical of oval cells are detectable in hepatoblastoma.

Methods and results:

Hepatoblastomas of various subtypes were investigated by electron microscopy, and by immunohistochemistry with the monoclonal antibodies OV‐1 and OV‐6, which recognize antigens associated with oval cells. Double‐labelling for cytokeratin 7 and albumin was carried out by immuno‐electron microscopy. OV‐1 stained scattered cells in seven of 12 tumours investigated and OV‐6 in nine. On immunoelectron‐microscopic investigation, SEC exhibited labelling for both cytokeratin 7 and albumin.

Conclusions:

The results demonstrate that antigens associated with oval cells are found in certain cells in hepatoblastoma. SEC, like oval cells, co‐express markers for hepatocytic and biliary differentiation. The findings further support the hypothesis that SEC are closely related to the putative bipotent hepatic stem cell, which, by definition, gives rise to both hepatocytes and biliary epithelial cells.
CD44 expression is up‐regulated in the deep zone of osteoarthritic cartilage from human femoral heads
Authors: OSTERGAARD K. , SALTER D.M. , ANDERSEN C.B. , PETERSEN J. , BENDTZEN K.
Published: November 2003

Aims:

The objective of this study was to detail the topographical and zonal distribution of the cell adhesion molecule CD44 in normal and osteoarthritic cartilage.

Methods and results:

Immunohistochemistry utilizing well characterized anti‐CD44 antibodies (clones A3D8, Bric 235, 2C5) was performed on cryostat and paraffin sections of human articular cartilage from macroscopically normal (n = 18) and osteoarthritic (n = 11) femoral heads. Samples for cryostat sections were obtained from 12 topographically different sites. Sections were divided into zones (superficial, middle, deep) and the CD44 staining scored. Chondrocytes in normal articular cartilage and cartilage from osteoarthritic femoral heads stained positive for CD44 in both cryostat and paraffin sections. Normal cartilage showed a significant decrease in CD44 staining in the deep zone as compared to the superficial zone (P < 0.05). However, cryostat sections of residual cartilage from osteoarthritic femoral heads showed increased CD44 staining in the deep zone as compared to normal articular cartilage. The CD44 staining showed no topographical variation in either the normal cartilage or the osteoarthritic residual cartilage.

Conclusions:

CD44 expression displays a distinct zonal variation in normal articular cartilage which is lost in osteoarthritic cartilage due to an up‐regulated expression in the deep zone. CD44 expression does not exhibit topographical variation.
Reproducible and highly sensitive detection of the broad spectrum epithelial marker keratin 19 in routine cancer diagnosis
Authors: KWASPEN F.H.L. , SMEDTS F.M.M. , BROOS A. , BULTEN H. , DEBIE W.M.H. , RAMAEKERS F.C.S.
Published: November 2003

Aims:

In this study the recently developed keratin 19 antibody RCK108 is biochemically and immunohistochemically characterized. Its applicability as a keratin marker in routinely processed histological tissue specimens is assessed.

Methods and results:

The keratin 19 antibody RCK108 antibody was tested on normal and malignant routinely formalin‐fixed, paraffin‐embedded tissue specimens. It stains most, although not all, glandular epithelia and showed (focal) reactivity in the basal cell compartment of stratified epithelia. It was found to react with most epithelial tumours, including adenocarcinomas, squamous cell carcinomas and endocrine tumours of various origins.

Conclusions:

Its reproducible and highly sensitive staining characteristics make RCK108 a useful antibody to be applied as a broad epithelial marker for carcinoma detection in routinely processed paraffin sections. As such, RCK108 is a specific reagent for practically all epithelial tumours. A few types of epithelial malignancies, known not to contain keratin 19, were negative for RCK108. Therefore the antibody is also useful in some narrow differential diagnostic considerations such as cholangiocellular carcinoma (RCK108 positive) vs. hepatocellular carcinoma (RCK108 negative). Another important feature of this antibody is that it shows very little reactivity in mesenchymal tissues, or mesenchymally derived tumours, as is frequently described for other keratin antibodies. A few leiomyosarcomas showed sporadic reactivity.
bcl‐2 and p53 immunophenotypes in pre‐invasive, early and advanced oesophageal squamous cancer
Authors: PARENTI A.R. , RUGGE M. , HORNG SHIAO Y. , RUOL A. , ANCONA E. , BOZZOLA L. , NINFO V.
Published: November 2003

Aims:

An inverse correlation between bcl‐2 and p53 expression has been reported in several types of epithelial tumour. The role of bcl‐2 and p53 in the development of oesophageal squamous carcinoma has yet to be established. The expression of bcl‐2 and p53 proteins has been evaluated in the multistage oesophageal tumorigenesis, which progresses from normal mucosa to dysplasia (squamous intraepithelial lesion, SIL), to invasive early and advanced oesophageal squamous cancer.

Methods and results:

Sixty‐four cases of squamous oesophageal cancer, coexisting with SIL in 18 cases, were immunohistochemically analysed for any overexpression of bcl‐2 and p53 proteins. Any association of bcl‐2 and p53 protein expression with patient survival was also analysed. We observed bcl‐2 expression that decreased significantly during the progression of oesophageal carcinogenesis. A decreasing frequency in the expression of bcl‐2 in advanced oesophageal squamous cancer coincided with frequent p53 overexpression. bcl‐2 expression was correlated with patient survival by univariate analysis. The association disappeared after adjusting for tumour stage. p53 overexpression showed no association with patient survival by either univariate or multivariate analysis.

Conclusions:

The down‐regulation of bcl‐2 and up‐regulation of p53 in advanced oesophageal squamous cancer suggest that bcl‐2 and p53 proteins may interact in the progression of oesophageal squamous cancer.
Immunohistochemical localization of cathepsin D, proliferating cell nuclear antigen and epidermal growth factor receptor in human breast carcinoma analysed by computer image analyser: correlation with histological grade and metastatic behaviour
Authors: OKAMURA K. , KOBAYASHI I. , MATSUO K. , KIYOSHIMA T. , YAMAMOTO K. , MIYOSHI A. , SAKAI H.
Published: November 2003

Aims:

The purpose of this study is to examine the relationship between immunohistochemical localization of cathepsin D (CD), proliferating cell nuclear antigen (PCNA) and epidermal growth factor receptor (EGF‐R) in 65 cases of breast carcinoma in Japanese women and traditional prognostic factors such as histological grade, lymph node status, mitotic rate and clinical stage, in order to possibly identify some indicator(s) that may be specifically associated with prognosis.

Methods and results:

Serial sections of 5‐μm thick were cut from the archival formalin‐fixed, paraffin‐embedded tissue blocks, and processed for CD, PCNA and EGF‐R immunostaining. The results were analysed by computer‐based image analysis system. All samples showed a positive immunoreaction for cathepsin D in both the parenchyma and stroma. However, the staining area and intensity varied from cell to cell in the parenchyma and stroma as well as among samples. Subsequently, the evaluation of immunostaining for CD was separately performed in both the parenchyma and stroma (CDpar and CDstr, respectively) and the combination of both components (CDtotal). PCNA and EGF‐R showed positive immunostaining almost exclusively in the parenchymal component of the carcinoma tissue specimens. CDtotal significantly correlated with the histological grade, PCNA index (PI), mitotic rate (MR), EGF‐R and lymph node metastasis. Significant correlation was also demonstrated between CDpar and the histological grade, EGF‐R and lymph node metastasis, or between CDstr and MR, EGF‐R and lymph node metastasis. EGF‐R correlated highly with the histological grade, MR score, lymph node metastases and recurrence‐free survival.

Conclusions:

Both the CD parameters and EGF‐R are valuable indicators for predicting the biological behaviour of human breast carcinoma.
Value of thrombomodulin immunostaining in the diagnosis of transitional cell carcinoma: a comparative study with carcinoembryonic antigen
Authors: ORDÓÑEZ N.G.
Published: November 2003

Aims: Thrombomodulin (TM) is a surface glycoprotein involved in the regulation of intravascular coagulation that has been reported to be expressed in a variety of tumours. We investigated TM expression in transitional cell carcinoma (TCC) and compared the value of TM immunostaining with that of carcinoembryonic antigen (CEA) for differentiating TCC from other tumours with which it may be confused.

Methods and results:

Immunostaining was performed on formalin‐fixed, paraffin‐embedded tissue sections using the avidin–biotin–peroxidase complex method. TM immunoreactivity was observed in 80 of 91 primary (51/58 urinary bladder, 10/12 renal pelvis, 3/3 ureter, 15/15 prostate, 1/3 ovary), and 18 of 20 metastatic TCCs expressed this marker. Only 37 of the 91 primary (23/58 urinary bladder, 4/12 renal pelvis, 1/3 ureter, 9/15 prostate, 0/3 ovary) and six of the 20 metastatic TCCs reacted for CEA. In order to evaluate the practical utility of TM immunostaining in surgical pathology, 30 adenocarcinomas of the prostate, 18 of the bladder, 12 of the colon, and 22 renal cell carcinomas were also stained for these markers. CEA reactivity was obtained in 12 of 30 adenocarcinomas of the prostate, 12 of 18 of the bladder, and 12 of 12 of the colon, but in none of the 22 renal cell carcinomas. Only three of the 18 adenocarcinomas of the bladder showed focal TM reactivity, but no staining for this marker was observed in any of the other types of tumours.

Conclusions:

TM is a more sensitive marker than CEA for TCC and, because it has a more restricted reactivity with other tumours, TM has more practical value in separating TCCs from adenocarcinomas of the prostate, colon and bladder, and renal cell carcinomas than CEA.
Immunophenotypic heterogeneity of hyalinizing trabecular tumours of the thyroid
Authors: PAPOTTI M. , RIELLA P. , MONTEMURRO F. , PIETRIBIASI F. , BUSSOLATI G.
Published: November 2003

Aims:

We studied 12 cases of hyalinizing trabecular tumour of the thyroid gland (HTT) with the aim of reviewing the cytological, histological and immunophenotypic features and of investigating the relationships of HTT with other thyroid neoplasms.

Methods and results:

Eleven patients were female and one male, aged 8–74 years (median 58). Ten cases had a benign behaviour, while two cases were locally aggressive. Of the latter, one developed distant metastases and the other is a recent case. All patients are alive 6–311 months after diagnosis. Cytologically, HTT was characterized by hypercellular smears with aggregates of roundish cells having features of papillary carcinoma (nuclear grooves, vacuoles) and fragments of fibrous tissue. Histologically, prominent nesting, trabecular growth patterns and a hyaline stroma (partly positive for laminin and collagen type IV) were found. One case was associated with a papillary microcarcinoma. Two additional cases had extensive areas of papillary carcinoma. In one of these, hyalinized papillary stalks were observed. All tumours contained thyroglobulin but not calcitonin. High molecular weight cytokeratin (a marker of papillary carcinoma) was focally positive in 4/12 cases only and thyroperoxidase (a marker of follicular adenomas, but not of papillary carcinoma) was found in 3/12 cases.

Conclusions:

The immunophenotypic profile and the morphological features suggest that HTTs are an heterogeneous group of tumours, some of them probably representing variants of papillary carcinoma with hyalinized stroma.
Apoptosis occurs more frequently in intraductal carcinoma than in infiltrating duct carcinoma of human breast cancer and correlates with altered p53 expression: detected by terminal‐deoxynucleotidyl‐transferase‐mediated dUTP‐FITC nick end labelling (TUNEL)
Authors: HARN H.‐J. , SHEN K.L. , YUEH K.C. , HO L.I. , YU J.C. , CHIU S.C. , LEE W.H.
Published: November 2003

Aims:

We examined the relationship between apoptosis and three different major stages of human breast carcinoma: intraductal carcinoma (DCIS), infiltrating duct carcinoma (IDC) and metastatic carcinoma in lymph nodes. We also determined the correlation between apoptosis and oestrogen receptor (ER), progesterone receptor (PR) and p53.

Methods and results:

The study investigates the extent of apoptosis in 63 breast carcinomas by in‐situ end‐labelling, in formalin‐fixed, paraffin‐processed tissue sections. The 63 breast carcinomas, included 22 DCISs, 26 IDCs, three infiltrating lobular carcinomas (ILC) and 12 metastatic lymph nodes. The apoptotic labelling index was higher in DCIS than IDC and metastatic carcinoma (P < 0.001, P < 0.007, respectively). By immunohistochemistry, we also analysed p53, ER and PR. Apoptosis correlated significantly with p53 (r = 0.748, P = 0.0004) in IDC. Also, ER correlated significantly with PR (r = 0.629, P = 0.00001). No apparent correlation was found between the apoptosis and ER or PR.

Conclusion:

Our data suggest that not only does apoptosis differ between intraductal carcinoma and infiltrating carcinoma but also it might be regulated by altered p53 expression.
Morphological and immunohistochemical characterization of granular cells in non‐hypophyseal tumours of the central nervous system
Authors: RICKERT C.H. , KUCHELMEISTER K. , GULLOTTA F.
Published: November 2003

We report 14 biopsy cases of granular cell tumours (GCT) of the central nervous system (CNS) outside the pituitary gland. In six cases the granular cells determined the morphology (actual GCT), the other eight consisted of different CNS tumours with a varying granular cell component. Pronounced immunoreactivity for ubiquitin and alpha‐1‐antichymotrypsin could be found in all investigated tumours, while GFAP, neuron specific enolase, von Willebrand factor, vimentin, S‐100 protein, alpha‐1‐antitrypsin, actin, and the neurofilaments 68 kDa and 160 kDa showed mostly weak positivity in some cases. Four out of eight GCT showed no immunoreactivity for MIB1; the other four cases had a proliferation index between 0.5% and 15%. Six out of nine cases were positive for p53. We consider granular cells to originate from different cell types. Thus, although morphologically identical, GCT are actually biologically heterogeneous. GCT of the CNS may represent gliomas of mostly astrocytic origin with a metabolically induced transformation of some tumour cells into granular cells.
Pathology of malignant mesothelioma
Authors: ATTANOOS R.L. , GIBBS A.R.
Published: November 2003

The diagnosis of malignant mesothelioma can pose several problems to the surgical pathologist. First, the morphological appearances of the tumour are known to be diverse with mimicry of a range of both reactive and neoplastic conditions. Second, due to the relative inaccessibility of the serosa, biopsy material is often scanty and fragmentary, producing a plethora of interpretive ambiguities. Third, adjunct techniques such as mucin histochemistry and immunohistochemistry, whilst useful in excluding malignant mesothelioma have little role in confirming the diagnosis. The accurate diagnosis of diffuse malignant mesothelioma is important for two reasons: (1) In relation to prognosis as it has an almost invariable fatal outcome, which contrasts with the other mesothelial neoplasms such as the benign adenomatoid tumour and the borderline malignant tumours, namely the well‐differentiated papillary mesothelioma and multicystic mesothelioma; (2) In relation to occupational‐related compensation claims following asbestos exposure. This review summarizes the aetiology of asbestos‐induced neoplasia, possible mechanisms of tumour development and highlights potential diagnostic pitfalls.
Diagnostic value of inhibin immunoreactivity in ovarian gonadal stromal tumours and their histological mimics
Authors: STEWART C.J.R. , JEFFERS M.D. , KENNEDY A.
Published: November 2003

Aims: Inhibin is a heterodimeric protein hormone which appears to be a sensitive serological and immunohistochemical marker of ovarian granulosa cell tumours. The purposes of this study were to examine inhibin immunoreactivity in a wide range of gonadal stromal neoplasms and to assess its value in the differential diagnosis of problematic ovarian tumours. Methods and results: Inhibin immunostaining was identified in eight cases of stromal hyperthecosis, 24 adult‐type granulosa cell tumours, two juvenile granulosa cell tumours, nine Sertoli cell or Sertoli–Leydig cell tumours, one gynandroblastoma, three gonadoblastomas, two cases of sex cord tumour with annular tubules, two steroid cell tumours and two sclerosing stromal tumours. Inhibin was also present in 4/6 fibrothecomas and 2/3 unclassified gonadal stromal tumours. There was no staining of neoplastic cells in any of the problematic ovarian tumours, in many of which a diagnosis of gonadal stromal tumour had been initially considered. However, inhibin was detected in reactive stromal cells in many cases. Conclusions: Inhibin is a sensitive immunohistochemical marker of a wide range of gonadal stromal tumours and is of value in the differential diagnosis of ovarian neoplasia.
Reliability of rectal biopsy in distinguishing between chronic inflammatory bowel disease and acute self‐limiting colitis
Authors: DUNDAS S.A.C. , DUTTON J. , SKIPWORTH P.
Published: November 2003

Aims: In order to assess the validity of previously proposed criteria for the differentiation of chronic inflammatory bowel disease (CIBD) from acute self‐limiting colitis (ASLC) all rectal biopsies were reported by a single histopathologist with a long‐term gastrointestinal interest over a 4.5‐year period. Methods and results: The presence or absence of distorted crypt architecture, increased lymphocytes and plasma cells, villous mucosal architecture, granulomata, basal lymphoid aggregates, basal giant cells and Paneth cell metaplasia was noted for each biopsy. The definite presence of any of the above features, with the exception of intramucosal granulomata, was regarded as indicative of CIBD. Eighteen months later all available case notes were examined and the presenting clinical symptoms and working clinical diagnosis extracted. The final diagnosis, histopathological diagnosis and the presence or absence of any of the above histopathological features were correlated and the positive predictive value of each histopathological feature was calculated. A correct diagnosis of either CIBD or ASLC was made in 80 of 84 and 29 of 31 cases, respectively. Conclusions: Villous mucosal architecture and Paneth cell metaplasia were found to be specific features of CIBD. Distorted crypt architecture, basal lymphoid aggregates and plasma cell infiltration of the lamina propria were also useful features but strict definition of these features is required and discussed. Intramucosal epithelioid granulomas were identified in eight cases of CIBD and four cases of ASLC. In association with ruptured crypts intramucosal granulomas are not specific features of Crohn’s colitis.
Atypical dermal nodules in benign melanocytic naevi
Authors: COLLINA G. , DEEN S. , CLIFF S. , JACKSON P. , COOK M.G.
Published: November 2003

Aims: The prognosis of deeply invasive melanoma can be poor and to a large extent it is unresponsive to treatment once metastases have occurred. It is therefore important that any dermal melanocytic lesions that have some features suggestive of melanoma but are nevertheless benign, should be identified. Methods and results: A series of 40 benign melanocytic naevi is described in which the clinical presenting feature was a central focus of increased pigmentation. This was found histologically to correspond to dermal nodules of large melanocytes showing some, usually mild, nuclear atypia but low indices of cellular proliferation. The nodules are found within otherwise typical melanocytic naevi. The clinical and histological differential diagnosis included invasive melanoma but in follow‐up, which is admittedly short (mean 24 months), none have recurred or metastasized. Conclusions: It is suggested that the nodules represent terminal differentiation of melanocytes rather than proliferative changes. They should be distinguished from melanoma and regarded as a variant of benign melanocytic naevi.
Value of thrombomodulin immunostaining in the diagnosis of mesothelioma
Authors: ORDÓÑEZ N.G.
Published: November 2003

Aims: Even with the benefit of immunohistochemistry and electron microscopy, the differential diagnosis between epithelial mesothelioma and pulmonary adenocarcinoma is often difficult. In most instances, the diagnosis of mesothelioma must be reached by the use of immunohistochemical markers that react with adenocarcinomas, but not with mesotheliomas. The purpose of this study is to determine the value of thrombo‐modulin (TM) as a positive marker for mesothelioma when distinguishing epithelial pleural mesothelioma from pulmonary adenocarcinoma. Methods and results: TM was expressed in 28 (80%) of 35 epithelial pleural mesotheliomas, but only five (10.9%) of 46 pulmonary adenocarcinomas had appreciable reactivity for this marker. Conclusion: It is concluded that TM can be useful in separating pulmonary adenocarcinoma from epithelial mesothelioma, but it should be used only in conjunction with other immunohistochemical markers that are currently employed in distinguishing between these two types of malignancies.
Tumoral calcinosis: a clinicopathological study of 111 cases with emphasis on the earliest changes
Authors: PAKASA N.M. , KALENGAYI R.M.
Published: November 2003

Aims: To study the pathogenesis of tumoral calcinosis (TC), we investigated 111 cases registered in Zaire over 30 years. Methods and results: The patients were 108 black Africans and three Caucasians between 3 and 74 years of age (mean, 37.7; median, 39). The gender was known in 33 males and 46 females; in 79 the gender was unknown. All but three were healthy and one had tuberculosis. The majority presented with a painless swelling in single or multiple periarticular regions. The hip was the most commonly affected (57%). Seven recurrences after surgical removal of the mass were reported. On microscopic examination, lesions were classified as follows: 24% stage I, 16% stage II and 60% stage III depending on the cellular activity at the border of the cysts. In five stage I cases only, and in no advanced stage II/III lesions, were exuberant cellular proliferative changes seen adjacent to the classical cystic form. These consisted of either ill‐defined reactive‐like perivascular solid cell nests admixed with mononuclear and iron‐loaded macrophages, or well‐organized variably sized fibrohistiocytic nodules embedded in a dense collagenous stroma. These immature changes indicated newly appearing lesions and were assumed to represent the earliest discernible stages in the evolution of TC. The unique well‐defined fibrohistiocytic nodules have not been described previously. Conclusions: These findings have thus described the full spectrum of lesions occurring in TC. We believe that the adjacent findings are potentially important either in recognizing early stages of the disease or in understanding its pathogenesis.
Melanosis coli is associated with an increase in colonic epithelial apoptosis and not with laxative use
Authors: BYERS R.J. , MARSH P. , PARKINSON D. , HABOUBI N.Y.
Published: November 2003

We have investigated the clinical presentation, laxative use and histopathology of 38 patients with a histological diagnosis of melanosis coli and measured the colonic epithelial apoptosis in these cases. The presence of lipofuscin was confirmed in all cases. Fifteen of the cases had constipation, whilst eight had diarrhoea. Neither constipation nor diarrhoea was present in 13 cases and both were present, at different times, in two. Laxatives had been used in all those with constipation, in only one with diarrhoea and in none of the others. The mean apoptotic count was significantly increased in those with melanosis coli compared with the controls. In the majority of cases with constipation there was no other abnormality, whilst an additional diagnosis was present in the majority of the remainder. Colonic epithelial apoptosis was increased in melanosis coli and the majority of cases were not associated with laxative use. These results support the proposed role of apoptosis in melanosis coli, but indicate that melanosis coli is a non‐specific marker of increased apoptosis with many possible causes, of which the use of laxatives is only one.
Nodular granulomatous phlebitis of the skin: a fourth type of tuberculid
Authors: HARA K. , TSUZUKI T. , TAKAGI N. , SHIMOKATA K.
Published: November 2003

We present five cases of granulomatous phlebitis of the skin and compare them with a case of miliary tuber‐culosis with granulomatous phlebitis. All five patients were hypersensitive to purified protein derivative, but without active tuberculosis. Although anti‐tuberculous drugs were effective, no tubercle bacilli were isolated from the skin. Clinically, subcutaneous nodules were felt along the course of the leg vein. Histologically, epithelioid cell granulomas with Langhans’ giant cells were observed within the walls of the cutaneous veins. In a later stage, granulomatous panniculitis was often associated. Using the polymerase chain reaction method, Mycobacterium tuberculosis DNA was detected in four of the five cases of granulomatous phlebitis of the skin. Granulomatous phlebitis of the skin seems to represent a relatively early phase of delayed‐type hypersensitivity reactions to Mycobacterium tuberculosis and may represent a distinct entity different from other types of tuberculid—a new tuberculid. Nevertheless, before making the diagnosis, the possibility of true tuberculosis must always be excluded. Nodular granulomatous phlebitis of the skin would be an appropriate name for the newly described condition.
Heterogeneity of gonadoblastoma germ cells: similarities with immature germ cells, spermatogonia and testicular carcinoma in situ cells
Authors: JØRGENSEN N. , MU¨LLER J. , JAUBERT F. , CLAUSEN O.P. , SKAKKEBÆK N.E.
Published: November 2003

Gonadoblastoma is defined as a neoplasm containing nests of germ cells and cells resembling Sertoli cells or granulosa cells. Gonadoblastomas arise almost exclusively in dysgenetic gonads. They are associated with an increased risk of developing germ cell tumours. Testicular germ cell tumours in adults are preceded by carcinoma in situ cells, which are characterized by their morphology, by their immunohistochemical expression of placental‐like alkaline phosphatase, the proto oncogene c‐kit and/or epitopes for the monoclonal antibodies M2A, 43–9F and TRA‐1–60, and by their aneuploid DNA content. In order to elucidate if gonadoblastomas are in situ neoplasms from the beginning, showing similarities with carcinoma in situ cells in otherwise normal testes, we investigated the germ cells in gonadoblastomas for their expression of the immunohistochemical markers of carcinoma in situ cells from six patients aged 812 months to 20 years and 4 months. In addition, the DNA content of the germ cells from five of the six patients was also determined by densitometric measurement on Feulgen stained specimens. The germ cell populations were heterogeneous both within the same patient and between the patients. Expression of the testicular carcinoma in situ markers was detected in specimens from all the patients and germ cells with an aneuploid DNA distribution pattern in accordance with testicular carcinoma in situ cells were detected. However, apparently normal immature germ cells were also present in four of the patients of whom two also had germ cells with a morphology similar to normal spermatogonia. Thus, gonadoblastoma is most likely an in situ germ cell neoplasia from the beginning. It seems probable that the germ cell tumours associated with gonadoblastomas originate from the carcinoma in situ cells inside the gonadoblastoma. Our findings of carcinoma in situ cells in gonadoblastomas from children support the theory that the cells arose prenatally.
Ovarian atypical endometriosis: its close association with malignant epithelial tumours
Authors: FUKUNAGA M. , NOMURA K. , ISHIKAWA E. , USHIGOME S.
Published: November 2003

The incidence of ovarian atypical endometriosis and its association with malignant epithelial tumours in a consecutive series of cases during the period 1987 to 1995 were studied. Atypical glandular changes were observed in four (1.7%) of 255 ovarian endometriosis cases and one patient with ovarian atypical endometriosis developed subsequent endometrioid carcinoma in the abdominal wall. Fifty‐four (24.1%) of the 224 ovarian cancers were associated with ovarian endometriosis; 21 with typical and 33 with atypical endometriosis. Clear cell carcinomas and endometrioid carcinomas were most frequently associated with endometriosis, with 54% (27 of 50 cases) and 41.9% (13 of 31), respectively. Atypical endometriosis was found in 18 clear cell carcinomas, in seven endometrioid carcinomas, in four serous carcinomas, in three mucinous borderline tumours, and in one serous borderline tumour. In 13 cases, the atypical endometriosis was in contiguity with malignant epithelial tumours. We consider that atypical endometriosis possesses a precancerous potential or is most frequently associated with clear cell and endometrioid carcinomas. Close screening of cellular atypia or hyperplasia in ovarian endometriosis and careful long‐term follow‐up of patients with atypical endometriosis is required.
Pathology of R4 spiculated lesions in the breast screening programme
Authors: DOUGLAS‐JONES A.G. , PACE D.P.
Published: November 2003

Small spiculated carcinomas are indistinguishable from benign radial scar/complex sclerosing lesions on mammography, leading to a radiological assessment of R4 (suspicious, probably malignant). The cytological and pathological features of 80 screen detected R4 spiculated lesions were reviewed. The analysis showed that there were 46 radial scars, of which 38 were benign and 8 (17%) contained foci of ductal carcinoma in situ (DCIS), and 34 spiculated carcinomas. The majority of radial scars showed some degree of epithelial hyperplasia (assessed semi‐quantitively) but the cellularity of the lesion as a whole was not related to the presence of DCIS. In 20 cases no aspiration was attempted for cytology but 40% were inadequate and only one lesion containing DCIS had cytology C4 or C5. Diagnosis of radial scar was made in all cases by localization biopsy. The carcinomas ranged in size between 4 and 15 mm (mean 8.9 mm) and were of grade 1 (21 = 63%) or grade 2 (12 = 37%). There were 16 infiltrating ductal carcinomas of no special type, 12 tubular carcinomas, three lobular carcinomas, two ductal and lobular mixed, and one mucinous carcinoma. Only one patient with carcinoma was node‐positive. For the carcinomas, 12 (35%) yielded C5 (malignant) cytology allowing pre‐operative diagnosis.
Ostensible oncocytoma of accessory lacrimal glands
Authors: PECORELLA I. , GARNER A.
Published: November 2003

Benign oncocytomas of the accessory lacrimal glands can be found in the lacrimal caruncle, plica semilunaris or conjunctival fornices, but are extremely rare. A series of 15 supposed oncocytomas of the ocular adnexa was reviewed retrospectively, and histological differences were noted with respect to the parotid gland counterpart. Lesions could be divided into three histological groups: (1) tumours composed of tubules lined by tall columnar epithelium with finely granular cytoplasm; the tubules often had dilated lumens containing mucinous secretion; (2) cystic tumours with prominent epithelial tufts projecting from much of the cyst wall; (3) tumours with solid areas composed of variably cuboidal or polygonal cells, largely in trabecular arrangement, and co‐existing with the previously described tubular and cystic elements. A striking resemblance to Warthin’s tumour without a lymphocytic component, such as may affect the parotid salivary gland, was noted in several tumours.
Melanosis of the appendix: prevalence, distribution and review of the pathogenesis of 47 cases
Authors: RUTTY G.N. , SHAW P.A.V.
Published: November 2003

The appendix is reported to be a common site for melanosis, especially at autopsy although to date there have been few studies expanding or qualifying this statement. Based on 47 cases identified from a series of 636 consecutive surgical specimens the prevalence, pattern of distribution, nature of the pigment and current knowledge of the aetiology and pathogenesis of melanosis of the appendix is reviewed and compared with melanosis coli.
Effects of radiation on the normal prostate gland
Authors: SHEAFF M.T. , BAITHUN S.I.
Published: November 2003

Prostate cancer is one of the commonest tumours of adult males. It shows a range of biological behaviour: many tumours are discovered incidentally; others will kill by producing widespread metastatic disease. Despite the fact that radiation is frequently used in the treatment of a range of pelvic lesions, including adenocarcinoma of the prostate itself, studies on the morphological changes in the normal prostate gland after irradiation are limited. This seems particularly surprising following the increasing use of needle biopsy specimens to assess the prostate. Patients who receive pelvic irradiation often suffer from lower urinary tract symptoms such as frequency and dysuria and it is possible that these may be related to prostatic and/or periprostatic injury. We therefore investigated the prostate glands removed at cystoprostatectomy for transitional cell carcinomas of the bladder which had received radiotherapy pre‐operatively. The changes were compared to control prostatic tissue from transurethral resection specimens for benign myoadenomatous hyperplasia. We found a range of inflammatory, fibrotic and reactive cytological features, including many of the changes seen in benign hyperplasia, but these were significantly more exaggerated in the post‐radiation group. In addition intraprostatic vascular and neural changes were prominent. This study documents radiation‐induced changes throughout the normal prostate gland and neighbouring soft tissue and has particular importance in current pathological practice with the increasing and widespread use of needle biopsies in the diagnosis and follow‐up of prostate cancer.
Middle‐ear adenoma (MEA): a report of two cases, one with predominant ‘plasmacytoid’ features
Authors: RIBÉ A. , FERNÁNDEZ P.L. , OSTERTARG H. , CLARÓS P. , BOMBÍ J.A. , PALACÍN A. , CARDESA A.
Published: November 2003

Middle‐ear adenomas (MEAs) are rare neoplasms which can display several histological patterns and represent a diagnostic challenge. We present two cases of MEA which share some histopathological features such as medium to small cells forming solid infiltrating tumour nests as well as scattered glandular structures with Alcian blue and PAS positive material within. The second case also displayed a distinct and predominant ‘plasmacytoid’ appearance which, in a small biopsy, might have been misleading. Both cases expressed an admixture of epithelial and neuroendocrine immunohistochemical markers, whereas ultrastructural study demonstrated electron dense granules. Taken together, these observations support a mixed epithelial and neuroendocrine nature for these neoplasms, the differential diagnosis of which includes paragangliomas and other tumours or tumour‐like lesions involving less frequently the middle ear, such as meningiomas, plasmacytomas and inflammatory polyps. The existence of MEAs with plasmacytoid features should be remembered to avoid confusion with plasmacytomas, plasmacytoid myoepithelioma and plasma cell inflammatory infiltrates.
CD40 antibodies defining distinct epitopes display qualitative differences in their induction of B‐cell differentiation
Authors: BJÖRCK P. , PAULIE S.
Published: November 2003

IgE production can be obtained in vitro by stimulating B lymphocytes with CD40 antibodies and interleukin‐4 (IL‐4). This stimulation also results in homotypic aggregation and cell proliferation. We have shown previously that IgE synthesis may be dependent on additional signals provided by the close cellular contact. Thus inhibition of the aggregation by lymphocyte function‐associated antigen‐1 (LFA‐1) antibodies leads to a decrease in IgE production. In the present study we show that the inhibitory effect of LFA‐1 antibodies is critically dependent on the CD40 antibody used for stimulation. Thus, while previously using the monoclonal antibody (mAb) S2C6, IgE production induced by the CD40 antibody mAb89 was generally higher and could be enhanced more than fivefold in the presence of LFA‐1 antibodies. Similarly, the addition of the CD23 mAb MHM6, which blocked aggregation to a similar degree as the LFA‐1 antibodies, inhibited S2C6‐induced IgE production but enhanced that induced by mAb89. In contrast to these opposing effects on IgE synthesis, proliferation induced by the two CD40 antibodies was affected similarly by the blocking antibodies. As the interaction between CD23 and CD21 has been suggested to involve recognition of carbohydrate structures on CD21 by the lectin‐like domain on CD23, we also tested the effect of some different sugars on IgE synthesis and proliferation. Addition of fucose‐1‐phosphate to anti‐CD40 and IL‐4‐stimulated B cells completely inhibited IgE synthesis and proliferation. Inhibtion was also seen with mannose‐6‐phosphate but not with glucose‐1‐phosphate. In contrast to the MHM6 antibody, the effect of the sugars was similar irrespective of the CD40 antibody used for stimulation. The study shows that different antibodies to CD40 may give rise to qualitatively distinct signals depending on the epitope recognized.
Flow cytometric analysis of cytokine receptors on human Langerhans' cells. Changes observed after short‐term culture
Authors: LARREGINA A. , MORELLI A. , KOLKOWSKI E. , FAINBOIM L.
Published: November 2003

It is well established that granulocyte–macrophage colony‐stimulating factor (GM‐CSF), interleukin (IL)‐1 and tumour necrosis factor‐α (TNF‐α) are involved in Langerhans' cell (LC) development and dendritic cell traffic. However, little is known about the pattern of cytokine receptors on human LC and their modulation during different stages of maturation. The expression of cytokine receptors was studied by flow cytometry on both freshly isolated LC (fLC) and 72‐hr cultured LC (cLC). Epidermal cell suspensions enriched in LC were obtained after skin trypsinization and Ficoll–Hypaque gradient. LC were identified by their CD1a positivity. Although the majority of fLC were positive for the α chain of GM‐CSF receptor (GM‐CSFR), the β chain of GM‐CSFR was detected only on 15% of CD1a+ cells. fLC were also positive for IL‐1 receptor (IL‐1R) type 1, IL‐1R type 2, 75 000 molecular weight TNF receptor (TNFR) and interferon‐γ receptor (IFN‐γR). IL‐6R and its transducing signal gp130 were present in a subset of fLC. Granulocyte colony‐stimulating factor receptor (G‐CSFR), macrophage colony‐stimulating factor receptor (M‐CSFR), the α and β chain of IL‐2R, IL‐4R, IL‐7R, IL‐8R and 55 000 molecular weight TNFR were not detected on fLC. After culture, LC up‐regulated the expression of both the α and β chains of GM‐CSFR, IL‐1R type 2, α and β chains of IL‐2R, IL‐6R and gp130. In contrast, IL‐1R type 1 and 75 000 molecular weight TNFR were down‐modulated and the expression of IFN‐γR was not affected by culture. These results suggest that LC undergo changes in the cytokine receptor repertory during in vitro maturation.
Dynamic changes in circulating and antigen‐responsive T‐cell subpopulations post‐Mycobacterium bovis infection in cattle
Authors: POLLOCK J. M. , POLLOCK D. A. , CAMPBELL D. G. , GIRVIN R. M. , CROCKARD A. D. , NEILL S. D. , MACKIE D. P.
Published: November 2003

Bovine tuberculosis is a threat to animal and human health in several countries. Greater understanding of the immunology of the disease is required to develop improved tests and vaccines. This study has used a model of bovine tuberculosis, established in the natural host, to investigate the dynamic changes that occur in the circulating T‐cell subpopulations after infection. When the phenotypic composition of the peripheral blood lymphocytes was determined pre‐ and post‐experimental infection, the response to disease comprised three phases. Firstly, the WC1/γδ T cells decreased and then increased, suggesting localization to developing lesions and clonal expansion. Secondly, the CD4 : CD8 ratio increased. Thirdly, the CD4 : CD8 ratio decreased to less than pre‐infection measurements. The latter changes suggested sequential involvement of CD4 and then CD8 T cells. The proportion of cells expressing interleukin‐2 receptor (IL‐2R) also increased. Panels of T‐cell clones were established at various stages post‐infection and all clones that exhibited antigen responsiveness were phenotyped. T‐cell clones from early infection were WC1/γδ and CD4 in phenotype, while CD8 clones appeared later in infection, eventually becoming dominant. Therefore, from in vivo and in vitro evidence, it was suggested that there is a dynamic progression in the T‐cell subpopulations involved dominantly in responses to mycobacteria.
Expression of both B7‐1 and CD28 contributes to the IL‐2 responsiveness of CTLL‐2 cells
Authors: BELANI R. , WEINER G. J.
Published: November 2003

The CTLL‐2 bioassay is used frequently to determine interleukin‐2 (IL‐2) concentrations in experimental samples, including samples that contain reagents which affect the CD28–B7 interaction. We therefore evaluated whether the CD28–B7 pathway plays a role in the growth of CTLL‐2 cells. Flow cytometry demonstrated that CTLL‐2 cells express both CD28 and B7‐1. CTLA4–immunoglobulin (CTLA4‐Ig) inhibited the growth of CTLL‐2 cells over a range of IL‐2 concentrations, suggesting that the CD28–B7 interaction plays an important role in the growth of CTLL‐2 cells. Anti‐B7‐1 antibody also inhibited CTLL‐2 proliferation at all concentrations of IL‐2. These results indicate that the CTLL‐2 bioassay may not be a reliable means of determining IL‐2 levels in experimental samples containing reagents that affect the CD28–B7 interaction. They also suggest that co‐expression of CD28 and B7 may contribute to the growth of malignant T cells.