bluuebunny/crossref_metadata_2025 huggingface dataset:
Primary sarcomas of the lung: a clinicopathological and immunohistochemical study of 14 cases
Authors: Attanoos R.L. , APPLETON M.A.C. , GIBBS A.R.
Published: November 2003

The clinicopathological features and immunohistochemical findings in 14 primary sarcomas of the lung collected over a 30‐year‐period are presented. This represents one sarcoma per 550 bronchogenic carcinomas undergoing resection in this centre. The study group comprised six leiomyosarcomas, five malignant peripheral nerve sheath tumours, two haemangiopericytomas and one epithelioid haemangioendothelioma. The majority of cases occurred in men (nine males: five females), with mean age at presentation of 54 years for men and 47 years for women. All leiomyosarcomas were seen in men, whereas malignant peripheral nerve sheath tumours showed no particular sex preponderance. Leiomyosarcomas were larger tumours than malignant peripheral nerve sheath tumours, mean tumour diameter 15 cm (range 10–25 cm) compared to 9.5 cm (7–15 cm), respectively. All leiomyosarcomas were situated intraparenchymally whereas two of the five malignant peripheral nerve sheath tumours were endobronchial in site. Extrathoracic metastates were seen at death in two of the six leiomyosarcomas but not in any of the malignant peripheral nerve sheath tumours. Overall survival was 28 months although for the leiomyosarcoma/malignant peripheral nerve sheath tumour group alone survival was 8 months. Tumour grading appeared to be a more useful prognostic factor than tumour site (endobronchial/parenchymal) or tumour size. Haemangiopericytoma and epithelioid haemangioendothelioma were associated with a more favourable prognosis.
Ductal (endometrioid) adenocarcinoma of the prostate: a clinicopathological study of 16 cases
Authors: MILLAR E.K.A. , SHARMA N.K. , LESSELLS A.M.
Published: November 2003

Sixteen cases of ductal (endometrioid) carcinoma of the prostate are presented. The tumour presents in elderly men (age range 65–87 years) with haematuria or obstructive symptoms. Serum prostate specific antigen may be normal or raised. On cytoscopy, there is often an exophytic lesion in the region of the verumontanum. Histologically, two variants are recognized: papillary and cribriform, of which there were eight cases each. Eight cases consisted of pure ductal carcinoma and seven were mixed, containing a variable proportion of micro‐acinar carcinoma.The associated micro‐acinar carcinoma had a Gleason score of at least 5. One case of carcinosarcoma with a ductal epithelial component was also included. All cases displayed positive immunohistochemical staining for prostate specific antigen and prostatic acid phosphatase and but were negative for the basal cell marker MA903. The tumour responds well to orthodox micro‐acinar carcinoma therapy and appears notably sensitive to hormonal manipulation. Follow‐up of the mixed group is restricted to a maximum of 3 years. Of the eight pure cases, five patients are still alive with survival periods of 11, 8, 7, 3 and 1 years. Three patients died of intercurrent disease of which one patient survived 12 years, having received no treatment. This tumour, therefore, can be regarded as having a good prognosis.
An immunohistochemical study of tumour vessels in metastatic liver cancers and the surrounding liver tissue
Authors: TERAYAMA N. , TERADA T. , NAKANUMA Y.
Published: November 2003

To elucidate the phenotype of the blood vessels and the expression of the growth factors involved in angiogenesis in metastatic liver cancers, we carried out an immunohistochemical study of 57 surgically resected livers with metastatic cancer. Blood vessels in the metastatic liver cancers frequently expressed von Willebrand factor (vWF), Ulex europaeus agglutinin I (UEA I)‐binding sites, α‐smooth muscle actin (α‐SMA), type IV collagen and laminin. Sinusoidal endothelial cells around the metastatic liver cancers were positive for vWF in 33.3% of the specimens examined and for UEA I in 28.1%. α‐SMA‐positive perisinusoidal cells accumulated in the vicinity of the metastatic liver cancers in 68.4% of the specimens. Type IV collagen was detected in the perisinusoidal space close to the metastatic cancers as well as distant from them (91.2%). Laminin was detected in the perisinusoidal space in only one specimen (1.8%). Tumour cells of the metastatic liver cancers were positive for vascular endothelial growth factor, basic fibroblast growth factor (bFGF), and acidic fibroblast growth factor (aFGF) in 78.9%, 38.4% and 7.0% of the specimens, respectively. Hepatocytes close to the metastatic liver cancers expressed bFGF more strongly than those distant from the metastatic liver cancers, and their expression of bFGF was more intense than that in the tumour cells. These results suggest that: (1) tumour vessels in metastatic liver cancers consist of endothelium, basement membrane and pericytes, (2) the sinusoids adjacent to tumours undergo capillarization, and (3) vascular endothelial growth factor may contribute to angiogenesis in metastatic liver cancer. Basic fibroblast growth factor may be responsible for the sinusoidal capillarization and the peritumoral fibrosis.
Expression of cytokeratins typical for ductal and squamous differentiation in the human stomach: an immunohistochemical study of normal foveolar epithelium, Helicobacter pylori gastritis and intestinal metaplasia
Authors: SCHWERER M.J. , BACZAKO K.
Published: November 2003

The expression of the cytokeratins (CK) 1, 5, 6, 7, 10, 13 and 14 was studied immunohistochemically in gastric biopsies from both the antrum and the body of 70 patients. Normal gastric foveolar epithelium (9 cases) Helicobacter pylori gastritis (23) and intestinal metaplasia (38) were examined. Positive staining results for CK 1, 5, 10 and 14 were not observed using the 34βE12 antibody. With antibodies to CK 5/6, 7 and 13 some, but not all cases, were immunoreactive. Predominantly positive staining included less than 10% of the cells and was always restricted to the tips and the juxtaluminal areas of the foveolae. No difference was seen between the antrum and the body. Comparing normal gastric mucosa with gastritis and intestinal metaplasia, cases positive for CK 5/6 were observed less frequently in intestinal metaplasia types II and III compared to the other groups. CK 7 was expressed exclusively in intestinal metaplasia. CK 13 was seen in all groups of specimens. Thus, cytokeratins typical for ductal structures (CK 7) and squamous epithelia (CK 5/6, CK 13) can be regarded as an inconstant, but not unusual observation in the gastric mucosa. Their expression may be controlled by both differentiation‐related as well as environmental factors.
The site of inhibin production in ovarian neoplasms
Authors: FLEMMING P. , GROTHE W. , MASCHEK H. , PETRY K.U. , WELLMANN A. , GEORGII A.
Published: November 2003

Inhibin, a physiological product of ovarian follicle cells, normally absent in serum of postmenopausal women, is elevated in adult granulosa cell tumours of the ovary. Recently, high serum levels of inhibin were reported in carcinomas and, surprisingly, also in Krukenberg tumours of the ovary. This study attempted to determine the site of inhibin production in primary (111 cases), metastatic (13) and secondary (10) ovarian tumours by using immunohistochemistry. Positive staining in tumour cells was encountered in all cases of sex‐cord‐ stromal cell tumours, adult (13) and juvenile (3) granulosa cell tumours, thecofibromas (10), in a lipid cell tumour (1) and a Sertoli‐Leydig cell tumour (1). Primary and secondary tumours not derived from sex‐cord stroma revealed no positivity in tumour cells, but in theca‐like cells in the surrounding non‐neoplastic ovarian stroma. A positive reaction was not observed in non‐tumour‐bearing ovaries of a control group. The ovarian inhibin of postmenopausal women is derived from activated sex‐cord stroma or sex‐cord‐stromal neoplasms. Therefore, elevated serum inhibin concentrations in women with primary or secondary ovarian neoplasms with other histogenesis seem to be due to an activation of the non‐neoplastic ovarian stroma. Inhibin will fail to be a tumour marker in these cases. By contrast, it will be useful in proving sex‐cord differentiation by immunohistochemistry and might be used in surveillance of malignant sex‐cord derived neoplasms by serum assays.
The immunophenotype of human decidua and extra‐uterine decidual reactions
Authors: HEATLEY M.K. , MAXWELL P. , TONER P.G.
Published: November 2003

Decidua associated with products of conception from intra‐uterine and extra‐uterine gestations and decidualized tissue from the appendix, cervix and Fallopian tube were studied using a panel of antibodies and antisera. Immunolocalization of vimentin and desmin intermediate filament proteins and of α‐1‐antitrypsin and α‐1‐antichymotrypsin was identified in most of the 43 cases studied. Placental alkaline phosphatase, β human chorionic gonadotrophin, cytokeratin, smooth‐muscle actin and leukocyte markers (CD3, CD20, CD68) were also expressed in some cases. Occasional cases reacted for CD45 and S‐100 protein. Similar reaction profiles were obtained at both intra‐uterine and extra‐uterine sites. The results show that extra‐uterine mesenchymal cells which have undergone a decidual reaction correspond closely to their counterparts in the endometrial stroma. Since positive immunostaining within decidual cells for cytokeratins, placental alkaline phosphatase and β human chorionic gonadotrophin indicates that trophoblastic cells are not exclusively recognized by these antibodies, their use does not permit the confident diagnosis of an intra‐uterine gestation.
Immunohistochemical demonstration of progesterone receptor in hepatobiliary cystadenoma with mesenchymal stroma
Authors: GRAYSON W. , TEARE J. , MYBURGH J.A. , PATERSON A.C.
Published: November 2003

A case of hepatobiliary cystadenoma with mesenchymal stroma is documented in which unequivocal immunostaining for progesterone receptors was observed in mesenchymal cells. These cells were negative for oestrogen receptor. This suggests that the proliferation of the stromal component may be related to the presence of endogenous progesterone.
Expression of the CD40 antigen on normal endothelial cells and in benign and malignant tumours of vascular origin
Authors: PAMMER J. , WENINGER W. , MAZAL P.R. , HORVAT R. , TSCHACHLER E.
Published: November 2003

CD40, a member of the nerve growth factor/tumour necrosis factor‐receptor family, is expressed on endothelial cells in situ and in tissue culture. It is functionally involved in the regulation of the expression of adhesion molecules in these cells. In the current study we investigated the expression of CD40 on the endothelia of normal fetal and adult human tissues, as well as in the stroma of various neoplasms and in different inflammatory tissue reactions. By immunohistochemistry, endothelia were negative or only weakly positive for CD40 in all normal adult and most fetal organs studied. In contrast, endothelial cells of fetal and embryonic lungs, kidneys and larger vessels consistently expressed the CD40 antigen. Strong expression of CD40 on endothelial cells of blood vessels but not of lymphatic vessels was found in inflammatory reactions. In 65 tumours of vascular origin we found moderate to strong expression of CD40 in all of four juvenile proliferating capillary haemangiomas and 11 lobular capillary haemangiomas of adults. Senile and cavernous haemangiomas as well as lymphangiomas were negative or exhibited only weak CD40 reactivity. Weak to moderate CD40 expression was found in five of eight malignant neoplasms of endothelial origin. Our finding that the CD40 antigen is present on only a minority of normal endothelial cells, whereas strong staining can be detected on the majority of endothelial cells in inflammatory processes, complements previous reports which suggest that this surface receptor plays an important role in tissue inflammation. The heterogeneous pattern of expression in malignant endothelial neoplasms argues against a major role for CD40 in the pathogenesis of these tumours. Its consistent presence in juvenile and lobular capillary haemangiomas suggests rather the involvement of CD40 in the development and/or progression of these benign vascular proliferations.
Carcinosarcoma of the uterus with extensive neuroectodermal differentiation
Authors: FUKUNAGA M. , NOMURA K. , ENDO Y. , USHIGOME S. , AIZAWA S.
Published: November 2003

A case of uterine carcinosarcoma with extensive neuroectodermal differentiation occurring in a 54‐year‐old woman is described. Microscopically, the endometrial tumour was predominantly composed of a sheet‐like proliferation of small‐ and medium‐sized cells. These cells were characterized by fibrillary cytoplasmic processes, rosette‐like formations, perivascular palisading patterns, and immunoreactivity for glial fibrillary acidic protein, synaptophysin, leu 7 and neuron‐specific enolase. In limited areas, features of conventional carcinosarcoma, including squamous cell carcinoma, leiomyosarcoma and islands of the above mentioned small‐to medium‐sized cells that were intermingled, were observed. The tumour was aneuploid by flow cytometry. The patient is alive with tumour for three months. It is suggested that at least some cases of uterine primitive neuroectodermal tumour may be explained by one‐sided neuroectodermal development within a carcinosarcoma.
Immunoglobulin light chain staining in paraffin‐embedded tissue using a heat mediated epitope retrieval method
Authors: ASHTON‐KEY M. , JESSUP E. , ISAACSON P.G.
Published: November 2003

We have compared light chain immunohistochemistry in reactive lymphoid tissue and a series of paraffin‐embedded B‐cell lymphomas using standard trypsin digestion with a heat mediated epitope retrieval method. Fifty‐seven B‐cell lymphomas (18 high grade, 29 low grade and 10 cases of nodular lymphocyte predominance Hodgkin's disease), two reactive lymph nodes and eight tonsils fixed for known times between 12 h and 2 years were studied. Paraffin‐embedded tissue was stained with polyclonal anti‐kappa and anti‐lambda antibodies. For each antibody staining was performed on two sections, one treated with trypsin digestion and one with microwave heating. Sections were scored from 0 to +++ with 0 representing poor staining and +++ excellent staining. A score of ++ was considered satisfactory. Light chain restriction was recorded if present. Satisfactory staining was obtained in 34/59 cases using trypsin digestion and 56/59 cases using heat retrieval. Light chain restriction was demonstrated in 32/57 (56%) B‐cell lymphomas using trypsin digestion and 52/57 (91%) using heat retrieval. Satisfactory staining was obtained in tonsils fixed for up to 48 h using trypsin digestion and up to 2 years using heat retrieval. We have shown that for light chain immunostaining a heat mediated epitope retrieval method produces more consistent and satisfactory results and is effective over a greater range of fixation times than traditional trypsin digestion.
Immunohistochemical localization of Mcl‐1 and bcl‐2 proteins in thymic epithelial tumours
Authors: CHEN F‐F. , YAN J‐J. , CHANG K‐C. , LAI W‐W. , CHEN R.M‐Y. , JIN Y‐T.
Published: November 2003

Mcl‐1 protein is a new member of the bcl‐2 protein family. It is believed to be a blocker of apoptosis but might be different from bcl‐2 in the control of apoptosis. Using immunostaining of formalin‐fixed, paraffin‐embedded sections, we investigated the expression of Mcl‐1 in 42 thymic epithelial tumours: three medullary thymomas, five mixed thymomas, seven cortical thymomas, eight well‐differentiated thymic carcinomas, 14 squamous cell carcinomas, four lymphoepithelioma‐like carcinomas and one undifferentiated carcinoma. bcl‐2 immunocytochemical localization was also performed for comparison. High‐grade thymic carcinomas, especially squamous cell carcinomas, revealed more intense Mcl‐1 immunoreactivity as compared to other subtypes (P < 0.001). In cases that co‐expressed Mcl‐1 and bcl‐2, the less differentiated cells had more intense expression of bcl‐2, while the more differentiated cells displayed stronger Mcl‐1 immunoreactivity. The differential expression of Mcl‐1 and bcl‐2 in neoplastic cells provides evidence that these proteins may play different roles in the processes of programmed cell death in thymic neoplasms. The finding that thymic carcinomas have stronger immunoreactivity for Mcl‐1 indicates that this protein could be a useful marker to differentiate aggressive thymic epithelial tumours from indolent ones.
Gastrointestinal tumour masses due to multiple myeloma: a pathological mimic of malignant lymphoma
Authors: GRIFFITHS A.P. , SHEPHERD N.A. , BEDDALL A. , WILLIAMS J.G.
Published: November 2003

Aims:

To describe and evaluate two cases of gastrointestinal involvement by multiple myeloma.

Methods and results:

Clinical details were obtained from patients records and routine histopathological sections were correlated with haematological and immunohistochemical investigations. As shown in the accompanying illustrations, myeloma manifests as large, atypical, non‐cohesive cells which may mimic high‐grade lymphoma.

Conclusions:

Extraskeletal spread of multiple myeloma occurs more frequently than is currently recognized, but clinical involvement of gut is rarely reported. Gut involvement may occur soon after initial diagnosis of myeloma and may be of serious clinical consequence. Histologically, it may mimic high‐grade lymphoma. Failure to recognize myelomatous involvement of gut may result in inappropriate surgery or oncological therapy.
p53 tumour suppressor gene protein expression in early and advanced gallbladder carcinoma
Authors: ROA I. , VILLASECA M. , ARAYA J. , ROA J. , DE ARETXABALA X. , MELO A. , IBACACHE G.
Published: November 2003

Aims:

Gallbladder carcinoma is one of the most frequent malignant tumours occurring in Chile and the mortality rate in both sexes ranks among one of the highest in the world. Mutation of p53 tumour suppressor gene has been demonstrated in many tumours. Our aim was to determine protein expression of p53 gene in early and advanced gallbladder carcinoma.

Methods and results:

Protein expression of gene p53 was studied by immunohistochemical means in 191 gallbladder carcinomas (157 primary tumours, 34 metastases) and 25 controls. In 86 out of 191 cases (45%), protein expression of gene p53 was observed. Differences related to sex, age, or race were not observed. All gallbladder controls were negative. Twenty‐five per cent of well‐differentiated tumours were p53 positive, while moderate or poorly differentiated carcinomas reached 50% (P = 0.04). p53 expression was observed in 23.5% of early carcinomas and in 48.2% of advanced carcinomas (P = 0.01). No differences between primary tumours and metastasis were demonstrated.

Conclusions:

Protein expression of p53 tumour suppressor gene is observed in 45% of gallbladder carcinomas. The absence of expression in controls and in normal mucosa adjacent to tumours suggests its utility in differentiating atypical gallbladder epithelia from neoplastic lesions.
Lesions of 13q may occur independently of deletion of 16q in spindle cell/pleomorphic lipomas
Authors: DAL CIN P. , SCIOT R. , POLITO P. , STAS M. , DE WEVER I. , CORNELIS A. , VAN DEN BERGHE H.
Published: November 2003

Aims:

Very recent multidisciplinary investigations have allowed for the definition among lipomas of a clinical and histological subtype called spindle cell and/or pleomorphic lipoma, possibly associated with partial monosomy 16 and anomalies of chromosome 13. In order to get nearer to the underlying critical molecular changes further multidisciplinary pathological and genetic research is indicated, to identify which chromosome(s) anomalies are crucial in the development of these tumours.

Methods and results:

In an ongoing multidisciplinary study of lipomatous tumours, including clinical findings, morphology, histochemistry and cytogenetics, two instances were found of spindle cell lipoma with clonal chromosome changes. In both cases chromosome 13 was involved, whereas only one showed a partial monosomy 16.

Conclusions:

Partial monosomy 16 is a characteristic lesion in spindle cell lipoma, usually associated with anomalies of chromosome 13. The present report confirming a previous single observation indicates, however, that lesions of 13 may occur independently from lesions of 16, suggesting different underlying molecular lesions in these otherwise very similar lipomas.
Rapid verification of the identity of questionable specimens using immunohistochemistry with monoclonal antibodies directed against HLA‐class I antigens
Authors: LAGAAIJ E.L. , CRAMER‐KNIJNENBURG G.F. , VAN DER PIJL J.W. , BRUIJN J.A. , DE FIJTER J.W. , VAN KRIEKEN J.H.J.M.
Published: November 2003

Aims:

A case report is presented in which an unexpected pathological diagnosis raised the possibility that biopsies of two patients were mixed‐up. Since these biopsies were obtained from kidney transplant patients, the HLA‐typings of both patients were known.

Methods and results:

We developed an immunohistochemical method using HLA‐class I specific monoclonal antibodies to recognize the donor and recipient antigens in these biopsies. Using this method we could confirm the identity of the patients of whom the biopsies had been taken.

Conclusions:

This method, which uses the highly polymorphic HLA‐system, is potentially useful for rapid and easy verification of the identity of specimens if a mix‐up is suspected.
Adenomyoepithelioma of the skin: a case report with immunohistochemical and ultrastructural observations
Authors: WALLIS N.T. , BANERJEE S.S. , EYDEN B.P. , ARMSTRONG G.R.
Published: November 2003

Aims:

The histological, immunohistochemical and electron microscopic features of a primary adenomyoepithelioma of skin, a rare sweat gland tumour, are reported.

Methods and results:

The tumour occurred on the back of a 92‐year‐old woman. It was composed of well‐formed tubules lined by epithelial cells surrounded by clear or spindled myoepithelial cells. Immunohistochemically, the epithelial cells exhibited strong cytokeratin (CAM5.2) and weak carcinoembryonic antigen positivity. The myoepithelial cells showed diffuse positivity for smooth muscle actin and focal positivity for S100 protein. Ultrastructurally, the myoepithelial cells contained myofilaments with focal densities and hemi‐desmosomes. They were limited by well‐formed basal lamina. The tumour was associated with a small eccrine spiradenoma.

Conclusion:

We predict that the tumour will behave in a benign fashion. There is no evidence of recurrence or metastasis 28 months later.
The extent of apoptosis is inversely associated with bcl‐2 expression in premalignant and malignant breast lesions
Authors: MUSTONEN M. , RAUNIO H. , PÄÄKKÖ P. , SOINI Y.
Published: November 2003

Aims:

In this study we investigated the extent of apoptosis in benign, premalignant and malignant breast lesions and its association with the immunohistochemical expression of bcl‐2 oncoprotein.

Methods and results:

In order to detect apoptotic cells and bodies in tissue sections, the 3′‐end DNA labelling method was used. Immunohistochemical staining was performed by using the avidin–biotin–peroxidase complex technique. A monoclonal antibody agains bcl‐2 oncoprotein was used and the specificity of the antibody was confirmed by immunoblot analysis. According to the results the extent of apoptosis, as determined by the apoptotic index, was lowest in benign ductal hyperplasias and sclerosing adenoses (0.15% and 0.07%, respectively). It was moderately elevated in atypical hyperplasias and in‐situ carcinomas (0.20% and 0.40%, respectively) and highest in invasive carcinomas (0.76%). In ductal invasive carcinomas, grade I lesions showed a lower apoptotic index (0.52%) than grade II (0.72%) and grade III (1.17%) carcinomas. The apoptotic index was not significantly lower in lobular (0.82%) than in ductal invasive carcinomas (0.85%). bcl‐2 immunohistochemistry was inversely related to the apoptotic index. In all cases studied the inverse association was very strong (P = 0.0004) but it was also present when only carcinomas were analysed (P = 0.01). In benign and atypical hyperplasias, bcl‐2 positivity was observed in all cases, but such cases were less frequent in in‐situ lesions and in invasive carcinomas.

Conclusions:

The results show that there is an inverse relationship between the extent of apoptosis and bcl‐2 expression in breast lesions suggesting that its expression affects the regulation of apoptosis in them.
Clinicopathological and interphase cytogenetic analysis of desmoid tumours
Authors: KOUHO H. , AOKI T. , HISAOKA M. , HASHIMOTO H.
Published: November 2003

Aims:

Recurrence of desmoid tumours is difficult to predict from only histological findings. In this study, immunohistochemistry for counting stromal blood vessels and proliferative activity, DNA flow cytometry, and interphase cytogenetic analysis of chromosome 8 by fluorescence in‐situ hybridization (FISH) were performed to assess the correlation between their parameters and the recurrence of desmoid tumours.

Methods and results:

The cases examined included 16 extra‐abdominal desmoid and eight abdominal desmoids, comprising 14 recurrent and 10 non‐recurrent cases. Eleven (69%) of the 16 extra‐abdominal desmoids and three (38%) of the eight abdominal desmoids recurred. Patients with recurrent lesions (mean age, 20 years) were younger than those with non‐recurrent tumours (34 years). Histologically, tumours with hypervascular areas frequently recurred after surgery in comparison with those with hypovascularity. There was no significant correlation between tumour size, the labelling index of the proliferating cell nuclear antigen (PCNA) and the recurrence. In flow cytometric analysis, all the cases examined showed a diploid pattern. The FISH study revealed that the incidence of trisomy 8 was significantly higher in the recurrent (72.7%) than in the non‐recurrent cases (12.5%).

Conclusions:

These results suggest that a subgroup of desmoid tumours at risk of recurrence may be hypervascular lesions associated with trisomy 8.
Nasal T/NK cell lymphomas commonly express perforin and Fas ligand: important mediators of tissue damage
Authors: OHSHIMA K. , SUZUMIYA J. , SHIMAZAKI K. , KATO A. , TANAKA T. , KANDA M. , KIKUCHI M.
Published: November 2003

Aims:

Two molecular mechanisms of T/natural killer (NK) cell‐mediated cytotoxicity, one perforin based and the other Fas based, have been demonstrated, and both systems induce cytotoxicity in the target cells. The Fas‐based mechanism involves the transducing molecule Fas and its ligand (FasL). In addition, perforin and/or FasL are also expressed in the cytotoxic T/NK cells. This study was thus designed to investigate the Fas and perforin pathways of the cytotoxic T/NK lymphoma cells in the nasal cavity.

Methods and results:

Eight patients with nasal lymphoma were analysed using immunohistochemical staining methods. Two cases were CD3+ CD56+ (T/NK cell) type, and six were CD3− CD56+ (NK cell) type. All cases showed Epstein–Barr virus genomes by in‐situ hybridization. In addition, all cases showed the expression of TIA‐1 (GMP‐17), which is a marker of cytotoxic T and NK cells. FasL was expressed in the majority of the lymphoma cells and some histiocytes, while Fas was found in lymphoma cells and many non‐neoplastic cells. In addition, the expression of perforin was detected in almost all lymphoma cells. In the double stainings, lymphoma cells expressed both FasL and perforin. Based on these findings, both the perforin‐ and Fas‐based pathway of the cytotoxic T/NK lymphoma cells are thus considered to play an important role in the clinical features.

Conclusions:

Tissue damage is a common morphological feature in nasal T/NK cell lymphoma. The above findings therefore support the theory that tissue damage is due to both the cytotoxicity of T/NK lymphoma cells as well as to angiocentricity.
Osteoid and bone formation in a nasal mucosal melanoma and its metastasis
Authors: HOORWEG J.J. , LOFTUS B.M. , HILGERS F.J.M.
Published: November 2003

Aims:

To present a literature review and a case history concerning bone and osteoid formation by a metastasizing (mucosal) melanoma.

Case details:

Osteocartilaginous differentiation and production of osteocartilaginous structures in malignant melanoma have been described only in 12 previous cases (osteoid in 11, bone in four), all of which involved dermal melanomas. Five of these melanomas were recurrent and one was associated with neurofibromatosis. The case report concerns a 75‐year‐old man with a nasal mucosal melanoma which was treated surgically. One year later, the patient developed a local recurrence and a cervical lymph node metastasis. Both the recurrent tumour and the metastasis showed clear evidence of bone and osteoid formation.

Conclusions:

This case is the first report in the literature, clearly demonstrating bone and osteoid formation by a mucosal melanoma, not only at the primary site, but even more convincingly in a cervical lymph node metastasis.
Immunohistochemical analysis of decalcified paraffin‐embedded human bone marrow biopsies with emphasis on MHC class I and CD34 expression
Authors: LOYSON S.A.J. , RADEMAKERS L.H.P.M. , JOLING P. , VROOM T.M. , VAN DEN TWEEL J.G.
Published: November 2003

Aims:

To identify the stromal structures and haematopoietic cell lineages in normal bone marrow. The optimal conditions were studied for the reactivity of a panel of antibodies, applicable to paraffin sections of decalcified trephine biopsies using antigen retrieval methods.

Methods and results:

Two methods of antigen retrieval (pepsin and acid citrate buffer) were tested. For the demonstration of most antigens and for reduction of background staining, heating in acid citrate buffer was preferred. In the case of elastase and von Willebrand Factor (factor VIIIrAg) pepsin pre‐treatment was optimal, whereas Ulex europaeus agglutinin (UEA‐1) and α‐smooth muscle actin (α‐SMA) required no pre‐treatment. Staining patterns obtained after 48 h EDTA decalcification and short electrolytic decalcification were identical. Both methods allowed recognition of HLA‐A and HLA‐B antigens, isolated CD34+ cells, mono‐histiocytic cells (CD68+), myeloid cells (elastase and myeloperoxidase), erythroid cells (glycophorin C) and of megakaryocytic cells (Factor VIIIrAg). A relative simple lymphocyte‐subset analysis was possible in decalcified paraffin sections allowing recognition of B‐cells (CD20+) and T‐cells (CD3+ and CD45RO+) in frequencies comparable to frozen sections. Suitable stromal cell staining was achieved by vimentin and desmin antibodies, whereas the bone marrow capillary network was visualized by CD34, factor VIIIrAg and UEA‐1.

Conclusions:

This immunohistochemical study indicates that all cellular components of the haematopoietic microenvironment of the bone marrow can be identified in decalcified paraffin sections using antigen retrieval methods and that the time of decalcification can be reduced to 1–1.5 h.
Expression of c‐Met correlates with grade of malignancy in human astrocytic tumours: an immunohistochemical study
Authors: NABESHIMA K. , SHIMAO Y. , SATO S. , KATAOKA H. , MORIYAMA T. , KAWANO H. , WAKISAKA S. , KOONO M.
Published: November 2003

Aims:

Recent studies suggest the involvement of hepatocyte growth factor/scatter factor (HGF/SF) in glioma cell invasion and tumour progression. We investigated the distribution and rate of tumour cells that express c‐Met protein, which is the cell‐surface receptor for HGF/SF, in astrocytic tumours. The type of cells that express c‐Met in tumour tissues was also identified.

Methods and results:

c‐Met expression was screened immunohistochemically in a total of 43 astrocytic tumours, including 14 low‐grade astrocytomas (A), 13 anaplastic astrocytomas (AA) and 16 glioblastoma multiforme (GBM). c‐Met reactivity was demonstrated predominantly in the cytoplasm of tumour cells. Bizarre large tumour cells tended to stain intensely. Higher c‐Met expression levels (≥ 2 +, more than 25% cells were positive) were noted in 21.4% of (A) vs. 53.8% in (AA) and 87.5% in (GBM) (P < 0.001), indicating a clear relationship between c‐Met protein staining and higher grade astrocytic tumours. Moreover, c‐Met immunoreactivity was also shown in tumour microvasculature, reactive astrocytes, and neurones in the cortex infiltrated by glioma cells. In 85.7% of cases containing infiltrated cortex, neurones were positive vs. no neurones in non‐neoplastic regions (P < 0.002).

Conclusions:

This evidence suggests that c‐Met expression in the brain could be associated with astrocytoma progression and also reactive process. Immunohistochemical determination of c‐Met‐expressing cell types helps to understand possible roles of c‐Met in tumour tissues.
Retrieved endogenous biotin: a novel marker and a potential pitfall in diagnostic immunohistochemistry
Authors: BUSSOLATI G. , GUGLIOTTA P. , VOLANTE M. , PACE M. , PAPOTTI M.
Published: November 2003

Aim:

Antigen retrieval (AR) procedures are based on the effect of heating (by either microwave or pressure cooking treatments) on routinely fixed and paraffin embedded tissues. We observed that AR procedures restore the reactivity of endogenous biotin (EB) and report on the distribution of EB following AR in a series of routinely fixed and embedded tissues.

Methods and results:

Following pressure cooking or microwave treatments, a simple streptavidin–peroxidase staining revealed retrieved endogenous biotin (REB) in normal tissues (such as liver, kidney and adrenal cortex), in oxyphylic cells and in some tumours, especially in carcinomas of the kidney and of the adrenal cortex. In formalin‐fixed (but not in alcohol‐fixed) tissue sections, the heating procedures caused an intense and finely granular cytoplasmic reaction, following a routine streptavidin‐conjugated peroxidase treatment. The staining was prevented by blocking of EB by a sequential avidin–biotin treatment.

Conclusions:

Retrieval of EB reactivity can cause pitfalls in diagnostic immunohistochemistry but, alternatively, it might also constitute a useful and novel diagnostic marker.
Dedifferentiated myxoid liposarcoma: a clinicopathological study suggesting a closer relationship between myxoid and well‐differentiated liposarcoma
Authors: MENTZEL T. , FLETCHER C.D.M.
Published: November 2003

Myxoid/round cell liposarcoma is arguably the commonest type of liposarcoma occurring in the extremities and may show gradual progression from low‐grade, pure myxoid liposarcoma to high‐grade round cell liposarcoma. Rarely myxoid/round cell liposarcoma is associated with areas of well‐differentiated or pleomorphic liposarcoma (mixed liposarcoma). We describe the clinicopathological features of three unusual myxoid/round cell liposarcomas which showed morphological features of de novo dedifferentiation. All patients were male and were aged 66, 70 and 76 years, respectively. One lesion each arose in the retroperitoneum, inguinal region and peritoneal cavity. Histologically, in one case the myxoid/round cell component was juxtaposed to a high‐grade non‐lipogenic component resembling non‐pleomorphic storiform ‘malignant fibrous histiocytoma’ (‘MFH’), one case showed a combination of myxoid liposarcoma and a high‐grade myxofibrosarcoma‐like component (so‐called myxoid ‘MFH’), and in the third case, a well‐differentiated myxoid liposarcoma with a discontinuous micronodular pattern of dedifferentiation was seen. Follow‐up information of 30, 28 and 26 months revealed two recurrences each in two patients. These patients died of postoperative pulmonary embolism and abdominal haemorrhage, respectively; systemic metastases were not noted. These cases demonstrate that myxoid/round cell liposarcoma can show, albeit very rarely, histological features of dedifferentiation. Cases like these, combined with the occurrence of mixed‐type liposarcoma (well‐differentiated/myxoid liposarcoma) and the vicinity of chromosomal regions involved by specific karyotypic aberrations in these tumours, suggest that myxoid/round cell liposarcoma and well‐differentiated liposarcoma (including its dedifferentiated variant) are more closely related in biological terms than is generally believed.
Solitary fibrous tumour of the renal peripelvis
Authors: FUKUNAGA M. , NIKAIDO T.
Published: November 2003

Solitary fibrous tumours (SFTs) are rare spindle cell neoplasms generally associated with the serosal surface, especially the pleura. This report describes two SFTs arising in the renal peripelvis, occurring in 33‐ and 36‐year‐old females. The lesions lacked the characteristic features of other recognized neoplasms that occur in the kidney. Immunohistochemically, the tumour cells were diffusely and strongly positive for vimentin and CD34, and some tumour cells expressed alpha‐smooth muscle actin. Both tumours were diploid by flow cytometry. Both patients have had benign clinical courses with 7.5‐ and 1‐year follow‐up. The findings suggest that the SFTs may originate from peripelvic mesenchymal cells, a new location for SFT. SFT should be included in the differential diagnosis of spindle cell tumours arising in the renal pelvis and peripelvis.
Immunohistochemical differentiation of metastases of renal carcinomas versus other carcinomas with anti‐γGT monoclonal antibody 138H11
Authors: KAUFMANN O. , DIETEL M. , SCHERBERICH J.E. , GAEDICKE G. , FISCHER P.
Published: November 2003

Aims: Adenocarcinomas account for about 60% of metastatic cancers of unknown primary (CUP) site. In such a clinical CUP situation, histopathologists are challenged to differentiate renal cell carcinomas (RCC) from other adenocarcinomas with similar immunophenotypes, especially chemotherapeutically treatable mammary and ovarian carcinomas. Methods and results: Recently, we produced a monoclonal antibody (mAb), designated 138H11, against human gamma‐glutamyltransferase (γGT), which stained over 98% primary clear cell and chromophilic RCC on frozen sections. The 138H11 epitope could not be stained using conventional techniques in most paraffin‐embedded sections of the same origin, due to destruction by formalin fixation below the detection level. Here, we demonstrate that mAb 138H11 can specifically stain γGT in paraffin‐embedded primary and metastatic RCC after enhancement with an ultrasensitive immunohistochemical method. We analysed a selected subgroup of adenocarcinomas with immunophenotypes which would not allow a differentiation from RCC in a CUP situation. We found a predominantly membranous expression of the 138H11 target antigen in 26/51 primary RCC and 15/34 metastatic RCC. In contrast, all 43/43 primary ovarian and bronchial carcinomas as well as 54/54 metastases of ovarian, mammary, bronchial and gastric carcinomas were negative for mAb 138H11. Conclusions: The data suggest that mAb 138H11 is useful for the immunohistochemical differentiation of RCC from other metastatic adenocarcinomas if the primary site of the tumour is not known.
Lymphoepithelioma‐like salivary gland carcinoma in Taiwan: a clinicopathological study of nine cases demonstrating a strong association with Epstein–Barr virus
Authors: KUO T. , HSUEH C.
Published: November 2003

Aims: Lymphoepithelioma‐like carcinoma (LELC) of the salivary glands is a rather rare tumour. Previous studies have shown its strong association with Epstein–Barr virus (EBV) among Chinese and Eskimos. We tested this observation with nine Chinese patients with salivary gland LELC in Taiwan including one with coexisting nasopharyngeal carcinoma (NPC) and studied the prognostic significance of their histopathological features. Methods and results: This series showed a predilection for female patients and parotid glands with a median age of 50 years. Three patients died 18.5–26 months after the diagnosis including the case with NPC. Six patients were alive without recurrence for 14–45 months with a median follow‐up of 34.5 months. Histopathologically, the tumours showed either lobular or diffuse growth pattern. Granulomas and/or germinal centres were observed in most cases and both B‐ and T‐cells were found in the lymphoid infiltrates, indicating that the salivary gland LELC was capable of inducing a strong host immune reaction. Microscopic growth pattern, lymph node metastasis, and presence or absence of granulomas and/or germinal centres seemed to be important prognostic factors. Both salivary gland LELC and NPC shared similar histopathological appearance and positive immunostaining for epithelial membrane antigen and cytokeratin AE1 but not AE3. Granulomas and amyloid might occur in both tumours. A nasopharyngeal examination is indicated in patients with salivary gland LELC to exclude the possibility of coexisting or metastatic NPC. All nine cases showed positive nuclear signals for EBV‐encoded RNA by in situ hybridization including the case with NPC. Conclusions: Our study and the previously published studies show that the association of salivary gland LELC and EBV is strongly related to racial and geographical factors.
Nodular erythema elevatum diutinum mimicking cutaneous neoplasms
Authors: SHANKS J.H. , BANERJEE S.S. , BISHOP P.W. , PEARSON J.M. , EYDEN B.P.
Published: November 2003

Aims: We describe the cutaneous pseudoneoplastic lesions in two patients with nodular erythema elevatum diutinum, a rare chronic disorder in which polymorph nuclear fragmentation (leukocytoclasis) is present within dermal nodules showing spindle cells and fibrosis. In both cases diagnostic difficulty was encountered clinically and pathologically and various benign and malignant neoplasms were considered in the differential diagnosis. Methods and results: Immunohistochemically the spindle cells were negative for CAM5.2, AE1/3, S100 protein and desmin (D33). They were positive for vimentin and focally positive for CD34 and α‐smooth muscle actin. Some of the spindle cells were positive for Mac 387 and KP1(CD68). By electron microscopy, the lesions were shown to consist of fibroblasts/myofibroblasts and fusiform macrophages. Conclusions: Increased awareness of the features described will help to avoid misdiagnosis as a neoplastic process.
Pigmented renal cell carcinoma: accumulation of abnormal lysosomal granules
Authors: FUKUDA T. , KAMISHIMA T. , EMURA I. , TAKASTUKA H. , SUZUKI T.
Published: November 2003

Aims: Five cases of renal cell carcinoma (RCC) with abnormal pigmentation have been examined by histochemical, immunohistochemical and ultrastructural methods. Methods and results: Compared with conventional RCCs, there was no difference in histological findings of each case, except for the presence of pigmented cells. In three cases, tumour cells possessing various sized brown granules with neuromelanin‐like features were scattered throughout the tumour. The granules observed in one of the others were angulated lysosomes and in another tumour cells in the pigmented areas possessed the granules closely resembling those of granular cell tumour. However, melanosome or neurosecretory granules could not be detected in any of the cases examined. In three cases, some of these abnormal granules showed a weak acid phosphatase activity. On immunohistochemical examination, tumour cells showed a positive immunoreaction for epithelial markers and lacked any antigens suggesting neuroectodermal or neuroendocrine differentiation. The granules in three cases were faintly positive for lysozyme and KP‐1. Conclusions: These findings indicate that abnormal pigmentation of RCCs examined in this study is attributed to accumulation of abnormal lysosomal granules in the neoplastic cells.
Proliferation and apoptosis in primary gastric B‐cell non‐Hodgkin's lymphoma
Authors: GISBERTZ I.A.M. , SCHOUTEN H.C. , BOT F.J. , ARENDS J‐W.
Published: November 2003

To elucidate the role of cell turnover in primary gastric B‐cell non‐Hodgkin's lymphomas we studied tissue samples of 72 patients—26 small cell (25 MALT lymphomas) and 46 large cell (31 MALT lymphomas). Proliferation indices and apoptotic indices were measured by Mib‐1 expression and terminal deoxynucleotidyl‐transferase (TdT)‐mediated nick end labelling, respectively. Furthermore, expression of the apoptosis related gene‐products bcl‐2 and p53 was studied. Large cell lymphomas showed significantly higher proliferation indices (59.1% vs. 15.4%) and apoptotic indices (3.2% vs. 0.7%) than small cell lymphomas. Proliferation and apoptotic indices were positively correlated (r=0.371, P=0.03). Expression of the bcl‐2 protein was significantly higher in the small cell lymphomas. Furthermore, cases with a high bcl‐2 expression showed both a significantly decreased proliferation (P<0.0001) and apoptotic index (P=0.0096) compared to bcl‐2 negative cases. Expression of the mutant p53 protein was present in 8.0% of small cell and in 18.2% of large cell lymphomas. p53 positive cases showed significantly higher proliferation indices, but showed no correlation with apoptotic index. These data suggest that impaired apoptosis by bcl‐2 may be more prominent than proliferation in the genesis of small cell lymphomas, whereas a high cell turnover characterizes large cell primary gastric lymphomas.
Immunophenotype of hairy‐cell leukaemia after cold polymerization of methyl‐methacrylate embeddings from 50 diagnostic bone marrow biopsies
Authors: KREFT A. , BU¨SCHE G. , BERNHARDS J. , GEORGII A.
Published: November 2003

Hairy‐cell leukaemia may be difficult to diagnose in bone marrow biopsies, especially in the early stages or in its residum after complete clinical remission. To consider the impact of published data on immunophenotyping hairy‐cell leukaemias, a total of 50 diagnostic biopsies were systematically analysed with a panel of eight antibodies and compared with cases of chronic lymphatic leukaemia (CLL), 20 follicular centre lymphomas, 20 lympho‐plasmacytoid immunocytomas, 10 small‐cell T‐cell non‐Hodgkin lymphomas and 20 cases of benign nodular lymphatic hyperplasia. The panel of eight antibodies comprised DBA44, CD45, CD20, CD45R, CD45R0, CD43 and the CD68 antibodies KP1 and Ki‐M1P. The hairy‐cell leukaemias were staged histologically into four categories of bone marrow infiltration. DBA44 reacted positively in 47/50 cases. CD45 and the B‐cell markers CD20 and CD45R reacted in 49/50 and 43/50 cases, respectively. One CD68 marker, KP1, was positive in 38/50 cases but the other — Ki‐M1P — only in 1/50 cases. Chronic lymphatic leukaemia cases, the other B‐cell NHLs and lymphatic hyperplasias showed strong positivity for CD20 and CD45R, but only the immunocytomas reacted with DBA44 in 7/20 cases. The T‐cell NHLs and hyperplasias showed a strong positivity for the T‐cell markers CD45R0 and CD43. The CD68‐marker Ki‐M1P revealed a high specificity, since it was negative in all NHLs and positive only in one hairy‐cell leukaemia. Methyl‐methacrylate embedding of bone marrow biopsies under cold polymerization produces a high quality of histo‐ and cytomorphology, resulting in greater diagnostic reliability and the detection of low‐stage infiltration of hairy‐cell leukaemia. DBA44 appears as a highly specific antibody to mark hairy‐cells since only immunocytomas reacted positively in a few cases. A small panel of antibodies including DBA44, CD20, CD45R and Ki‐M1P may serve to distinguish small‐cell NHL from hairy‐cell leukaemia even at an early stage or when there are minimal residual tumour cells.