bluuebunny/crossref_metadata_2025 huggingface dataset:
Inconsistent association of Epstein‐Barr virus with CD56 (NCAM)‐positive angiocentric lymphoma occuring in sites other than the upper and lower respiratory tract
Authors: KOBASHI Y. , NAKAMURA S. , SASAJIMA Y. , KOSHIKAWA T. , YATABE Y. , KITOH K. , MORI S. , UEDA R. , YAMABE H. , SUCHI T.
Published: November 2003

We previously described nine cases of angiocentric lymphoma of a possible natural killer (NK)‐cell lineage with a surface CD3− CD56+ phenotype occurring in sites other than the upper and lower respiratory tract. This study was performed to investigate the association of Epstein‐Barr virus (EBV) with these lymphomas, using the polymerase chain reaction (PCR) for the presence of EBV‐DNA, in situ hybridization (ISH) for EBV‐encoded small RNAs (EBERs) and immunohistology for EBV‐determined nuclear antigen‐2 (EBNA‐2) and latent membrane protein‐1 (LMP‐1) in paraffin sections. PCR and ISH produced almost identical results, and EBERs were identified in the nuclei of the lymphoma cells of three cases, two of which exhibited LMP‐1 in the cytoplasm of tumour cells without EBNA‐2 expression. Molecular genetic analysis revealed EBV to be incorporated into these three EBER‐positive cases either clonally or biclonally. It was revealed by re‐evaluation of their morphology with the established EBV status on each case that, in contrast to the rather variable and irregular cellular composition of the EBV‐ positive tumours, the EBV‐negative tumours stood out because of their remarkably uniform ‘blastoid’ appearance, and could be grouped as blastic NK‐cell lymphoma. The relationship of the EBV‐positive cases with nasal NK‐cell tumours has yet to be clarified.
bcl‐2 is preferentially expressed in tumours of muscle origin but is not related to p53 expression
Authors: SOINI Y. , PÄÄKKÖ P
Published: November 2003

bcl‐2 is a proto‐oncogene which inhibits apoptosis. In contrast, p53 tumour suppressor gene is known to induce apoptosis. In this study we analysed immunohistochemically 63 mesenchymal tumours for the expression of bcl‐2 and p53 proteins with a special emphasis on muscle‐derived tumours. bcl‐2 was expressed in all seven rhabdomyosarcomas and in five out of seven leiomyosarcomas. In benign muscle tumours, bcl‐2 expression was found in all four epithelioid leiomyomas and in six out of 14 leiomyomas. In non‐neoplastic muscle cells, occasional weak bcl‐2 positivity was found in muscle cells of vascular walls and myometrium. In mesenchymal tumours of other lineages, bcl‐2 positivity was only found in four out of 12 malignant fibrous histiocytomas and in one out of three liposarcomas. p53 positivity was found in 14 tumours, 13 of which were sarcomas. No association was found between p53 and bcl‐2 positivity. Our results suggest that bcl‐2 expression is activated significantly more often in muscle derived tumours than in mesenchymal tumours of other lineages. Our results also suggest that p53 status does not directly affect the expression of bcl‐2 in sarcomas.
Low grade gastric B‐cell lymphoma of mucosa associated lymphoid tissue in immunocompromised patients
Authors: WOTHERSPOON A.C. , DISS T.C. , PAN L , SINGH N , WHELAN J , ISAACSON P.G
Published: November 2003

An increased incidence of non‐Hodgkin‘s lymphoma is seen in patients with immunodeficiency from any cause. The majority of these are high grade B‐cell lymphoma and most are associated with the Epstein‐Barr virus (EBV). In post‐transplant lymphoma/lymphoproliferative disorders the tumour may regress following reduction of immunosuppression but in AIDS the lymphomas show a characteristic aggressive course and poor prognosis. We describe low grade B‐cell gastric lymphoma of mucosa associated lymphoid tissue (MALT) in three immunocompromised patients (two post‐transplant, one HIV positive). In each case, the tumour showed classical morphological features of gastric MALT lymphoma and was not associated with EBV. Helicobacter pylori was identified in each case. Clinical follow‐up suggests that the behaviour in these tumours is similar to that seen in MALT lymphomas in immunocompetent patients and not typical of the lymphomas usually associated with immunosuppression. Although the finding of MALT lymphoma in immunosuppressed patients might be coincidental, the association of some MALT lymphomas with autoimmune disease suggests that dysregulation of the immune system might play a role in the pathogenesis of these tumours.
Mixed tumour of the vagina
Authors: FUKUNAGA M. , ENDO Y. , ISHIKAWA E. , USHIGOME S.
Published: November 2003

A 33‐year‐old Japanese woman presented with a polypoid 2.5 × 2.5 × 1.9 cm mass located in the posterior wall of the lower vagina. Microscopically, the tumour was composed of benign epithelial and stromal‐type elements. Predominant epithelial elements were mucinous glands with squamous metaplasia and islands of mature squamous epithelium. The stromal‐type cells showed reticular or short fascicular patterns with a transition to the epithelial elements. There was no dual epithelial‐myoepithelial combination in the glands as seen in so‐called mixed tumours (pleomorphic adenomas) of the salivary gland. Immunohistochemically, the epithelial elements were strongly positive for cytokeratin, PKK1 and epithelial membrane antigen, while the stromal‐type cells co‐expressed PKK1 and vimentin. Staining for S‐100 protein, muscle actin, alpha‐smooth muscle actin, desmin, and CD34 was uniformly negative in the tumour cells. The DNA pattern was diploid. The patient is alive and well without recurrence for 50 months after excision. These results indicate that an epithelial cell proliferation, probably of the remnant vestibular gland, plays a major role in the development of mixed tumours of the vagina.
Immunohistochemical evaluation of nm23‐H1 gene product in transitional cell carcinoma of the bladder
Authors: NAKOPOULOU L.L. , CONSTANDINIDES C.A. , TZONOU A. , LAZARIS A.CH. , ZERVAS A. , DIMOPOULOS C.A.
Published: November 2003

The expression of the nm23‐H1 gene has been suggested to have an inverse association with metastases in certain tumours. The aim of this study was to investigate the relationship of nm23‐H1 immunohistochemical expression with pathological tumour variables and survival in a series of transitional cell carcinomas (TCCs) of the bladder. Formalin‐fixed, paraffin‐embedded archival tissue from 87 carcinomas (Ta‐T1 45 cases) and T2‐T4 (42 cases) was immunostained (Strept ABC/ HRP) with the NDPK‐A monoclonal antibody (NDPK‐A) against nm23‐H1 protein. The tumours had already been evaluated for immuno‐expression of p53 protein. In addition, DNA analysis was performed by flow cytometry. Results were analysed using the linear trend in proportions test, the Fisher’s exact test and multivariate analysis. Paradoxically, advanced tumour stage showed significant correlation with nm23‐H1 immunopositivity in muscle invasive TCCs (Pt = 0.01). Patients with nm23‐H1 positive, muscle invasive TCCs had a worse prognosis at a level of suggestive statistical significance (PF = 0.08). In multivariate analysis, using a Cox’s proportional hazards survival model with six variables, tumour grade, disease stage and synchronous p53 and nm23‐H1 detection showed significant correlation with poor patient survival (P = 0.014, P = 0.049 and P = 0.05, respectively).
Immunohistochemical expression of p53 proteins in Wilms’ tumour: a possible association with the histological prognostic parameter of anaplasia
Authors: CHEAH P.L. , LOOI L.M. , CHAN L.L.
Published: November 2003

Wilms’ tumour (nephroblastoma) has been associated with chromosomal abnormalities at the 11p13, 11p15 and 16q regions. A study into the possibility of mutations occurring within p53, the ubiquitous adult tumour suppressor gene, in Wilms’ tumour was carried out. Thirty‐eight ca ses were studied. Of these 36 were categorised into the favourable histology group and two into the unfavourable histology group based on the National Wilms’ Tumour Study criteria. Archival formalin‐fixed, paraffin‐embedded tissue sections from each case were stained with a polyclonal (AB565:Chemicon) and a monoclonal (DO7:Dako) antibody raised against p53 protein using a peroxidase‐labelled streptavidin biotin kit (Dako). ‘Cure’ (disease‐free survival of 60 months or longer) was documente d in 39% of cases with favourable histology tumours. Eleven percent in this group succumbed to the disease. Both cases with unfavourable histology died. Four out of 36 (11%) tumours with favourable histology demonstrated weak to moderate staining with both AB565 and DO7 in more than 75% of tumour cells. In contrast, p53 protein expression in unfavourable histology tumours was significantly increased compared with the favourable histology group (P = 0.021) with both cases demons trating immunopositivity in >75% of tumour cells when stained with AB565 and DO7. The intensity of staining ranged from moderate to strong in both cases. It appears from this preliminary study that the immunohistochemical expression of p53 protein in Wilms’ tumour, presumably a result of mutation in the p53 tumour suppressor gene, correlates with histological classification, histological categorisation being one of the useful features in the prognostic assessment of Wilms’ tumours.
AN IMMUNOCYTOCHEMICAL ASSESSMENT OF 19 CASES OF CUTANEOUS ANGIOSARCOMA
Authors: ORCHARD G.E. , ZELGER B. , WILSON JONES E. , RUSSELL JONES R.
Published: November 2003

Four endothelial cell markers, two selective cytokeratin markers and a monoclonal smooth muscle antibody (SMA) were employed in the assessment of 19 cases of cutaneous angiosarcoma classified according to their degree of tumour differentiation. No labelling was seen for SMA or with cytokeratin markers MNF116 and CBL170. Expression of factor VIII‐related antigen was seen in two tumours and positivity for CD34 (QBend 10 antibody) was found in four tumours. By contrast the pan‐endothelial cell marker Ulex europeaus agglutinin 1 (UEA‐1) and the CD31 marker JC70A labelled all cases of cutaneous angiosarcoma with the exception of one poorly differentiated tumour. These data confirm the endothelial cell origin of angiosarcoma, they demonstrate that CD31 and UEA1 are reliable markers in routinely processed tissue, and they suggest a lymphatic derivation for the tumour. This finding is in marked contrast to Kaposi‘s sarcoma where CD34 is the most reliable marker.
Accessory cells in Crohn's disease of the terminal ileum
Authors: SARSFIELD P. , JONES D.B. , WRIGHT D.H.
Published: November 2003

We present a study which describes the immunophenotype and distribution of accessory cells in 13 resections of terminal ileum from patients with Crohn's disease. A panel of antibodies working in paraffin‐embedded tissue was employed and these included PGM1 (CD68), S‐100 protein, WR18 (HLA class II), factor XIIIa and acid cysteine proteinase inhibitor. This study revealed a heterogeneity of accessory cell populations which was profoundly influenced by local inflammatory and repair mechanisms. Both acid cysteine proteinase activity and S‐100 protein positive cells are identified in more actively inflamed areas. The acid cysteine proteinase activity positive dendritic cell population was particularly numerous in ulcer bases. S‐100 protein positive dendritic cells had a more limited distribution in close proximity to the epithelium in inflamed but otherwise intact mucosa adjacent to the areas of ulceration. PGM1 revealed normal distribution of macrophages within histologically uninvolved areas and, in addition, also stained granulomas and large numbers of dendritic cells in the inflamed, ulcerated and scarred areas. Factor XIIIa positive dendritic cells were especially numerous in areas of active scarring where they co‐localized with PGM1 positive cells. They were largely absent from the more superficial ulcerated areas. HLA class II was strongly expressed on mononuclear inflammatory and dendritic cells. The strength of epithelial staining for HLA class II reflected the intensity of adjacent inflammation, except on ulcer‐associated epithelium which consistently showed up‐regulation independent of the severity of the inflammatory process. This study shows that localized alterations in the accessory cell distribution in Crohn's disease correlate with different states in the evolution of the inflammatory and repair process of the disease. The more acute lesions are associated with recruitment of acid cysteine proteinase activity and S‐100 protein positive dendritic cells while factor XIIIa stained dentritic cells are especially numerous in areas of scarring.
Immunohistochemical study of c‐erbB‐2 expression in carcinoma ex‐pleomorphic adenoma
Authors: COSTA ROSA J. , FONSECA I. , FÉLIX A. , SOARES J.
Published: November 2003

A series of 19 cases of carcinoma ex‐pleomorphic adenoma was studied for the immuno‐expression of c‐erbB‐2 oncoprotein. Twelve tumours showed a malignant component with only one histological type; in the remaining seven there was co‐existence of areas of various carcinoma types, adenocarcinoma NOS being the most frequent. Membranous c‐erbB‐2 reactivity was found in 21.1% of the cases, all corresponding to high‐grade adenocarcinomatous areas. The low‐grade carcinoma types that formed the malignant mixed tumours components were negative. Benign pleomorphic adenoma areas, either adjacent or intermingled with carcinomatous areas, were also consistently negative, proving that c‐erbB‐2 accumulation is associated with the acquisition of the malignant phenotype. The finding of a preferential association between c‐erbB‐2 overexpression and high‐grade malignant mixed tumour may indicate prognostic implications for the oncogene protein and may also be indicative of its specific relationship with the putative pathway of malignant transformation in pleomorphic adenomas.
Expression of adhesion molecules and extracellular matrix proteins in glioblastomas: relation to angiogenesis and spread
Authors: VITOLO D. , PARADISO P. , UCCINI S. , RUCO L.P. , BARONI C.D.
Published: November 2003

We studied the immunohistochemical expression of inducible adhesion molecules, integrins and extracellular matrix proteins in 10 cases of glioblastoma multiforme in order to investigate their angiogenesis, local invasiveness, poor metastasizing properties and their lack of tumour infiltrating leukocytes. In glioblastomas endothelial proliferations represent the majority of vascular structures; they were positive for endothelial markers (vWF, CD31, VE‐cadherin) and negative for macrophage markers (CD68, PAM‐1). Immunohistologically, they were subtyped into: 1 solid‐glomeruloid ICAM‐1, α2β1, α3β1, α5β1 negative; 2 channelled‐branching ICAM‐1 negative and α2β1, α3β1, α5β1 positive; 3 channelled‐telangiectatic ICAM‐1, α2β1, α3β1, α5β1 positive. In channelled proliferations, the expression and distribution of tenascin and merosin in the basal membrane was similar to that of normal brain vessels. The expression of all these molecules might indicate different steps of maturation of endothelial proliferations. The majority of endothelial proliferations may be immunohistologically considered as incomplete vascular structures; this might account for the low metastasizing tendency and low recruitment of leukocytes by these tumours. Neoplastic astrocytes were GFAP‐1, ICAM‐1, VCAM‐1, α2β1, α3β1 and α5β1 immunoreactive and α6β4 negative; this allows them to interact with extracellular matrix proteins and might, in part, explain the tendency of glioblastomas to infiltrate locally.
Cytokeratin immunolocalization and lectin binding studies in oesophageal squamous dysplasia
Authors: ITAKURA Y. , SASANO H. , ABE K. , FURUKAWA Y. , MORI S. , NAGURA H.
Published: November 2003

We examined full thickness specimens of oesophageal squamous dysplasia from both cancer‐free and cancer patients using immunohistochemical labelling for cytokeratin subtypes 10/13 and 14 and for involucrin, binding studies for various lectins, and PAS/D staining before and after diastase treatment. We studied specimens from patients with oesophageal carcinoma (52 normal epithelia, and 49 with mild, 38 with moderate, and 32 with severe dysplasia), and 32 specimens from cancer‐free patients (five normal epithelia and 16 with mild and 11 with moderate dysplasia). Abnormal cytokeratin expression patterns in atypical cells, i.e. both cytokeratin 10/13 and cytokeratin 14 immunoreactivity in the same cells was detected in 41 of 99 specimens with dysplasias in cancer patients. Helix aspersaErythrina cristagalli and Robinia pseudoacacia binding was consistently negative in atypical cells in squamous dysplasia. The non‐atypical layer of squamous dysplasia, which was morphologically indistinguishable from the corresponding layer of normal oesophageal squamous epithelium, showed abnormal involucrin expression in 39/101 specimens, Helix aspersa binding in 74/106, diastase sensitive PAS staining in 52/110, Erythrina cristaglli binding in 28/107, and Robinia pseudoacacia binding in 16/100. There were no significant differences in the expression of these markers in dysplasia between cancer patients and cancer‐free individuals with the exception of increased Robinia pseudoacacia binding in the non‐atypical layer in cancer‐free patients. The results indicate that abnormal patterns of cytokeratin expression and lectin binding occur not only in atypical cells but also in non‐atypical cells in oesophageal squamous dysplasia.
The effects of chemotherapy on breast cancer tissue in locally advanced breast cancer
Authors: AKTEPE F. , KAPUCUOĞLU N. , PAK I.
Published: November 2003

It is well known that chemotherapy induces cytomorphological changes in neoplastic and non‐neoplastic tissue. Thirty‐one stage III breast‐carcinoma patients, treated with both pre‐operative chemotherapy and mastectomy, were evaluated to define the effects of systemic chemotherapeutic agents in tumours, non‐neoplastic breast tissue, and lymph nodes. Histological changes were compared with those observed in patients who had been treated by surgery alone. Cytoplasmic vacuolization was the most striking change in the tumour cells (59%). Chemotherapy was especially effective in the terminal duct lobular unit in non‐neoplastic breast tissue. Lobular atrophy was observed in 20 (65%) cases, and lobular cellular atypia was seen in 16 (52%). The rate of ductal cellular atypia (42%) was not different from the control group. The most important changes seen in the non‐neoplastic stromal component were fibrosis and hyalinization. These were found in 31 out of 727 evaluated lymph nodes. In serial sections, metastatic deposits were seen in or around these fibrotic or hyalinized areas. Chemotherapy is widely used in the treatment of early and locally advanced breast carcinomas. Familaritiy with chemotherapy induced changes in breast tissue and lymph nodes have considerable importance in the accurate interpretation of these specimens.
A critical appraisal of six modern classifications of ductal carcinoma in situ of the breast (DCIS): correlation with grade of associated invasive carcinoma
Authors: DOUGLAS‐JONES A.G. , GUPTA S.K. , ATTANOOS R.L. , MORGAN J.M. , MANSEL R.E.
Published: November 2003

The in‐situ component of 180 cases of screen detected infiltrating duct carcinoma of the breast was classified according to six published classifications for ductal carcinoma in situ based on architecture, necrosis and cytology. All cases were assessed independently by two experienced observers to assess inter‐observer variation. The differentiation of ductal carcinoma in situ as assessed by all the classification systems correlated with the grade of the associated invasive carcinoma (chi‐squared between 50 and 107: P<0.0001). Disagreements were commonest in the assessment of architecture and least common in the assessment of necrosis. For cytonuclear grade most disagreements (62.2%) involved the distinction between low and intermediate as against 33.9% disagreements for intermediate vs. high. Nuclear grade alone and necrosis alone were correlated with the grade of invasive carcinoma associated with the ductal carcinoma in situ and the Nottingham prognostic index of the patient. The Van Nuys classification of ductal carcinoma in situ is commended because it has a low inter‐observer disagreement, is significantly correlated with the grade of the infiltrating carcinoma, uses simple well‐defined criteria (with no requirement for percentage estimations), is applicable to small numbers of ducts and, most importantly, appears to correlate with disease‐free survival.
Intrasinusoidal bone marrow infiltration: a possible hallmark of splenic lymphoma
Authors: FRANCO V. , FLORENA A.M. , CAMPESI G.
Published: November 2003

A particular type of lymphomatous bone marrow infiltration defined as intrasinusoidal and occuring in seven patients with splenomegaly and mild to moderate thrombocytopenia is reported. Immunocytochemistry highlighted the intrasinusoidal pattern and showed a mature B‐cell phenotype. Four patients underwent splenectomy and a diagnosis of splenic marginal cell lymphoma was made. The disease course seems to be chronic and quite indolent. All patients are alive and well; follow‐up ranges from 2 to 42 months. The value of bone marrow biopsy as a primary diagnostic tool in splenic marginal zone lymphomas is discussed.
Fluorescence in‐situ hybridization (FISH) reveals that in chronic myelogenous leukaemia (CML) following interferon‐α therapy, normalization of megakaryocyte size is associated with the loss of bcr/abl translocation
Authors: THIELE J. , SCHMITZ B. , GROSS H. , KVASNICKA H.M. , NIEDERLE N. , LEDER L.‐D. , FISCHER R.
Published: November 2003

Aims:

In addition to predominant granulocytic proliferation, bone marrow morphology in Philadelphia chromosome positive (Ph1+) CML is characterized by atypical dwarf or microforms of megakaryocytes. However, following therapy with interferon‐α2b (IFN), these micromegakaryocytes occur less frequently. The purpose of this study was to elucidate whether the reappearance of normal megakaryocytes may be associated also with a reduction of the bcr/abl‐positive cell clone.

Methods and results:

Fluorescence in‐situ hybridization (FISH) technique in combination with immunomorphometry (CD61) was performed on trephine biopsies. A total of 311 CD61‐positive megakaryocytes, including precursors and atypical microforms, were evaluated in pre‐treatment specimens derived from 11 patients with Ph1+ CML. A specific fusion site marking the bcr/abl translocation was found in 87% of megakaryocytes which showed a size of 169 ± 35 μm2. In untreated patients, atypical microforms (size 200 μm2) were observed in 66% of the total megakaryocytic population. Following IFN therapy 369 megakaryocytes could be analysed in sequential examinations and were found to display a significant decrease (63%) in positive fusion signals. In addition there was also a significant enhancement in average size (252 ± 66 μm2) reflecting a reduction in the number of micromegakaryocytes (43%). These findings were particularly conspicuous in three patients with a major to complete cytogenetic remission.

Conclusions:

A normalization of megakaryocyte size following IFN therapy in CML is significantly associated with a loss of the bcr/abl translocation site and therefore indicates a (partial) recovery of normal haematopoiesis.
Role of microliths in the aetiology of chronic submandibular sialadenitis: a clinicopathological investigation of 154 cases
Authors: HARRISON J.D. , EPIVATIANOS A. , BHATIA S.N.
Published: November 2003

Aims:

Confusion about the aetiology and pathogenesis of chronic submandibular sialadenitis led to the present investigation of 154 cases in which many clinical and histological features were analysed.

Methods and results:

By far the greatest number of histological factors, namely liths, atrophy, fibrosis, parenchymal inflammation, lymphoid germinal centres, mucous and ciliary metaplasia, salivary extravasation and glycosaminoglycan accumulation, was related to the degree of inflammation, which appears to be of the greatest importance in the aetiology and pathogenesis. Inflammation, atrophy and fibrosis were related to duration of symptoms, which supports the concept of a chronological progression through increasingly severe histological changes.

Conclusions:

Inflammation possibly arises from ascending infection in a normal gland and exerts an obstructive and destructive effect on the parenchyma with the development of the related histological changes and a vicious circle involving further ascending infection. Normal glands contain microliths that possibly by localized obstruction cause atrophic foci that are reservoirs for ascending infection. Microliths and liths were unrelated: microliths were related to age as in normal glands whereas liths were related to duration of symptoms and appeared to be secondary to the sialadenitis. Many glands showed minimal changes, which raises the possibility of conservative treatment.
Clinicopathological characteristics of peripheral primitive neuroectodermal tumour of skin and subcutaneous tissue
Authors: BANERJEE S.S. , AGBAMU D.A. , EYDEN B.P. , HARRIS M.
Published: November 2003

Aims:

To study the clinical and pathological features of primary malignant peripheral primitive neuroectodermal tumours (PNETs) of the skin and subcutaneous tissue, to discuss the differential diagnosis, and to review the existing literature on these tumours.

Methods and results:

Eight cases of PNETs presenting in the skin and subcutaneous tissue were identified from the pathology records of the Christie Hospital, Manchester. Detailed immunohistochemical studies were performed on all cases and seven tumours were subjected to electron microscopic examination. Detailed clinical and follow‐up information was obtained on seven cases. Six tumours occurred in children and adolescents and two were seen in young adults (age range, 8–36 years). No sex or site predilection was observed. Five tumours occupied the dermis and subcutis and three were entirely located in the subcutaneous tissue. Microscopically, they were composed of small round cells and seven tumours contained glycogen. Only one tumour focally exhibited Homer–Wright rosettes and neuropil. Two tumours contained rhabdoid or plasmacytoid cells in places and all cases showed microcystic and pseudovascular spaces. Immunostains revealed MIC2 (8/8), NSE (7/8), PGP9.5 (7/8), β2 microglobulin (7/8), neurofilament protein (6/8), S100 protein (3/8), synaptophysin (2/8) and Leu‐7 (1/8) positivity. Anomalous cytokeratin (4/8), desmin (2/8), myoglobin (2/8), NKIC3 (4/8) and GFAP (1/8) staining was also noted. Ultrastructurally, neuroendocrine granules were detected in five cases and one case exhibited microtubules in processes. Adequate follow‐up information was available in four cases. One patient died of metastatic disease. One child developed axillary lymph node metastasis but is alive with no evidence of disease 96 months after treatment. Two other patients are alive with no residual or recurrent disease 44 and 52 months after excision and radio/chemotherapy.

Conclusion:

PNETs are rare malignant small round cell tumours of the skin and subcutaneous tissue which are probably underdiagnosed. A correct diagnosis can be made on light microscopic features, demonstration of neuroendocrine granules on electron microscopy and a combination of MIC2, β2 microglobulin, and more than one neural marker positivity. These neoplasms should be differentiated from other cutaneous neoplasms composed of small round cells. The number of cases of cutaneous PNETs studied so far is rather small, and no firm conclusion can be drawn about their behaviour but long‐term survival is possible in some cases.
Comparison of A and B‐type lamin expression in reactive lymph nodes and nodular sclerosing Hodgkin's disease
Authors: JANSEN M.P.H.M. , MACHIELS B.M. , HOPMAN A.H.N. , BROERS J.L.V. , BOT F.J. , ARENDS J.W. , RAMAEKERS F.C.S. , SCHOUTEN H.C.
Published: November 2003

Aims:

In order to clarify the differentiation and proliferation status of the Reed–Sternberg and Hodgkin cells we studied A and B‐type lamin expression with specific monoclonal antibodies in nodular sclerosing Hodgkin's disease. Its normal counterpart, the reactive lymph node, was also examined for lamin subtype expression.

Methods and results:

The CD20 positive centrocytes and centroblasts of the follicle centre in the reactive lymph nodes expressed lamin B1, but were not or only very weakly positive for lamin B2 or A‐type lamin antibodies. Mantle zone lymphocytes displayed lamins B1 and B2, but were negative for A‐type lamins. Furthermore, CD3‐ and CD20‐positive lymphocytes in the medulla and paracortex lacked A‐type lamins, but were positive for both B‐type lamins. Finally, the proliferation marker Ki67 was mainly detected in the centroblasts, but also in a fraction of the A‐type lamin negative cells in the paracortex and medulla. In Hodgkin's disease, all cells expressed lamins B1 and B2, whereas A‐type lamins were primarily observed in CD30‐positive Reed–Sternberg and Hodgkin cells. About 20% of the Reed–Sternberg and Hodgkin cells expressed Ki67, with co‐expression of lamin A in most of these cells.

Conclusions:

Ki67 and A‐type lamin staining were in general mutually exclusive in lymph nodes, indicating that A‐type lamin positive cells are not proliferative. This suggests also that the A‐type lamin expression in Reed–Sternberg and Hodgkin cells is correlated with a relatively mature phenotype of these malignant cells. However, some of these differentiated malignant cells still have a capacity to proliferate as indicated by Ki67 positivity. Our observation that lamin B2 expression in the follicle centre cells of the reactive lymph node is low or absent indicates that this lamin subtype is not always expressed in nucleated cells, which is in clear contrast to the results obtained in previous studies in other diseases and in normal tissues. Absence of lamin B2 expression may be associated with the follicle centre stage of B‐cells.
Identification of oncocytic lesions of salivary glands by anti‐mitochondrial immunohistochemistry
Authors: SHINTAKU M. , HONDA T.
Published: November 2003

Aims:

To evaluate the immunohistochemistry using an anti‐mitochondria antibody in the investigation of various oncocytic lesions of the salivary glands.

Methods and results:

Ten cases of adenolymphoma (Warthin's tumour) and one case each of benign oncocytoma and oncocytic carcinoma of the salivary glands were examined. Normal salivary glands were also tested. They were investigated immunohistochemically using mouse monoclonal antibody against human mitochondria. In normal salivary glands, epithelial cells of the striated ducts showed a thick linear immunoreactivity, which corresponded well to the intracytoplasmic distribution pattern of mitochondria. In addition, a small number of swollen epithelial cells showing an intense, finely granular immunoreactivity in the cytoplasm were scattered in the ductal system and acini (‘oncocytic metaplasia’). Almost all neoplastic cells involved in adenolymphoma, benign oncocytoma, and oncocytic carcinoma showed an intense, finely granular immunoreactivity in the cytoplasm.

Conclusions:

Immunohistochemistry using the anti‐mitochondria antibody proved to be a highly sensitive and specific method for light microscopic identification of mitochondria and superior to routine H & E or PTAH stain especially in the detection of isolated oncocytic cells.
Stereological estimates of the nuclear/cytoplasmic ratio and star volume on fibreoptic biopsies are of prognostic value for survival in a preliminary study of advanced squamous cell carcinoma of the lung
Authors: CARVALHO H.A. , SALDIVA P.H.N. , TAKAGAKI T.Y. , CAPELOZZI V.L.
Published: November 2003

Aims:

This study evaluated the role of morphometric and clinical parameters in establishing the prognosis of patients submitted to radiotherapy for advanced squamous cell carcinoma of the lung.

Methods and results:

Morphometric studies were performed by point counting techniques. Forty patients were included in this study. Group 1 patients (n = 22) were those with survival equal to or less than 6 months; group 2 (n = 10) patients had a survival of 7 to 12 months; and group 3 (n = 8) included patients with survival greater than 12 months. To characterize these three groups of patients, models combining categorical and continuous variables were constructed by means of discriminant analysis. Weight loss, histological grade, nuclear/cytoplasmic ratio and star volume of the nuclei were selected during the backward procedure as relevant variables to characterize the three groups of patients. The overall sensitivity of the model was 90%.

Conclusions:

Our results indicate that histopathological data may help to predict prognosis in patients with advanced squamous cell lung carcinoma, and encourage the use of morphometric procedures in histopathological analysis of this type of lung tumour.
Rheumatic Aschoff nodules revisited. II: Cytokine expression corroborates recently proposed sequential stages
Authors: FRASER W.J. , HAFFEJEE Z. , JANKELOW D. , WADEE A. , COOPER K.
Published: November 2003

Aims:

A recent immunohistochemical analysis of the Aschoff lesions in rheumatic fever, combining immunohistochemical analysis with comparative morphology, permitted the division of the Aschoff nodules into three stages: (1) Aschoff nodule without admixed lymphocytes, (2) Aschoff nodules with a few T lymphocytes, and (3) Aschoff nodules containing many admixed lymphocytes of both B‐ and T‐cell phenotype. It was postulated that the order of progression was from stage 1 with macrophages only, to accumulation of first T lymphocytes (stage 2) and then B lymphocytes (stage 3). This study was undertaken to determine the role and distribution of interleukin 1 (IL‐1), interleukin 2 (IL‐2) and tumour necrosis factor alpha (TNFα) in the various stages of the rheumatic Aschoff nodule to investigate our hypothesis on the progression of these nodules.

Methods and results:

Sixteen fresh valve specimens from patients with acute rheumatic fever undergoing valve surgery were obtained. Tissue sections from 14 specimens identified as containing Aschoff nodules were subjected to immunohistochemistry for (1) T and B lymphocytes, to stage the lesions according to our previously proposed criteria; (2) IL‐1, IL‐2 and TNFα; and (3) CD4 and CD8 to phenotype the T lymphocytes. The stage 1 and 2 lesions expressed IL‐1 and TNFα in the macrophages. The stage 3 lesions showed more variable expression of all three cytokines including IL‐2 within T lymphocytes.

Conclusion:

TNFα and IL‐1 secretion in macrophages is required for T and B lymphocytes activation and aggregation; suggesting that macrophages arrive at the scene of rheumatic injury prior to the lymphocytes. IL‐2 is usually expressed later in the inflammatory process and was found only in the lymphoid aggregates. This study therefore produces corroborative evidence for our previously proposed developmental stages of the Aschoff nodule.
Pathogenetic role of the stromal cells in endometriosis and adenomyosis
Authors: MAI K.T. , YAZDI H.M. , PERKINS D.G. , PARKS W.
Published: November 2003

Ten cases of endometriosis of bowel, ovaries, uterine serosa and 10 cases of adenomyosis were studied. Blocks of tissue with areas of interest were submitted for serial sectioning of the entire block. Some sections were immunostained for oestrogen receptor, vimentin, Ber‐EP‐4 and cytokeratins. The common finding was the presence of type 1 nodules, consisting of isolated nodules of endometrial stromal cells without endometrial glands, along blood or lymphatic vessels. The stromal cells showed positive immunoreactivities for oestrogen receptor and vimentin, and negative reactivities for cytokeratins. Due to the absence of connection with adjacent endometriosis or adenomyosis, it is likely that these endometrial stromal nodules arise from the multipotential pericytes. In addition, in serosa of all cases of endometriosis, type 2 nodules, having adjacent mesothelium (Ber‐EP4 −) changing into epithelium (Ber‐EP4 +) and type 3 nodules, with non‐endometrial epithelium (oestrogen receptor −) changing into endometrial gland (oestrogen receptor +) were identified. We believe that the formation of type 1 nodules from the pericytes and the transformation of the mesothelium into endometrial glands in type 2 and 3 nodules are accomplished through the process of induction by the endometrial stroma, and the proliferation is controlled by genetic, hormonal and immunological factors. Type 1, 2 and 3 nodules are likely to represent a histological continuum in the development of early endometriosis. Subsequent to the formation of endometriosis in the serosa, the pathway of development of endometriosis and adenomyosis is similar. Through the processes of induction and proliferation there is an increase in size of the stroma of type 1 nodules and that of endometrial tissue with subsequent fusion of the stroma of type 1 nodules and that of foci of adenomyosis or endometriosis. Consequently, there is enlargement of the stroma of the foci of adenomyosis or endometriosis. The ‘newly enlarged stroma’ serves as ‘new soil’ for further growth of the endometrial glands in the endometrial tissue.
Pseudomesotheliomatous angiosarcoma: a pleuropulmonary lesion simulating malignant pleural mesothelioma
Authors: FALCONIERI G. , BUSSANI R. , MIRRA M. , ZANELLA M.
Published: November 2003

We report two cases of autopsy confirmed angiosarcoma in adult males, presenting as diffuse pleuropulmonary tumours and simulating malignant mesothelioma. Both the lesions grew along the serosal surfaces and were characterized by variably thick rinds of tissue encasing the lung. The pulmonary parenchyma showed diffuse, dark red, subpleural consolidations and multiple cavitations. Histologically, the lesions were composed by atypical spindle and polygonal, epithelioid cells showing rudimentary vascular differentiation and exhibiting strong positivity for factor VIII, CD31, CD34 and vimentin. We conclude that angiosarcoma may present with preponderant or exclusive involvement of pleura and peripheral lung and that it should be added to the list of tumours capable of simulating malignant mesothelioma.
Genetic evidence for a clonal link between low and high‐grade components in gastric MALT B‐cell lymphoma
Authors: PENG H. , DU M. , DISS T.C. , ISAACSON P.G. , PAN L.
Published: November 2003

High‐grade MALT lymphomas often contain low‐grade tumour components; both cell populations have been shown to express the same immunoglobulin light chain previously. However, the clonal link between the low and high‐grade components has not been established at the genetic level. To investigate this link, we have examined low‐ and high‐grade components microdissected from tissue sections of four high‐grade gastric MALT lymphomas. PCR and sequence analyses were performed to identify clone‐specific rearranged immunoglobulin heavy chain gene sequences. In each of these cases, the PCR products from the two components were identical in size by electrophoresis. Direct sequencing revealed common clone‐specific immunoglobulin heavy chain gene rearrangements in both lesions of each case, providing genetic evidence for a clonal link. These results support the proposal that high‐grade MALT lymphomas generally evolve from low‐grade clones.
Early adenocarcinoma of the oesophagus and oesophageal cyst
Authors: SANTACROCE C.M. , FLÉJOU J.‐F.
Published: November 2003

Aims: An increased risk of adenocarcinoma of the oesophagus has been demonstrated in patients with long segments of Barrett’s mucosa. The risk of cancer associated with short segments of metaplasia of the oesophagogastric junction is not known. Methods and results: We report a case of early adenocarcinoma of the oesophagus arising on short tongues of Barrett's mucosa associated with an oesophageal cyst. The patient was a 68‐year‐old man with no previous clinical history of gastro‐oesophageal reflux disease. The fortuitous discovery of an oesophageal cyst lead to the diagnosis of short tongues of Barrett's mucosa with high‐grade dysplasia. On pathological examination of the resected specimen, an early adenocarcinoma had developed in Barrett’s mucosa, localized just above the oesophageal cyst. Conclusions: As oesophageal cysts can cause symptoms suggestive of reflux, we hypothesize that this association may not be fortuitous.
p53 expression in CMV‐infected cells: association with the alternative expression of the p53 transactivated genes p21/WAF1 and MDM2
Authors: GARCÍA J.F. , PIRIS M.A. , LLORET E. , ORRADRE J.L. , MURILLO P.G. , MARTÍNEZ J.C.
Published: November 2003

The p53 tumour suppressor gene is a cell cycle regulator, able to induce cell cycle arrest to allow DNA repair or apoptosis. The molecular mechanisms underlying p53 action imply transactivation of p53 dependent genes such as WAF1 (for wild type p53 associated fragment 1) and the murine double minute (MDM2) gene. In some cases, inactivation of the p53 gene results from p53 gene mutations leading to p53 protein accumulation, but in others it may results from mechanisms other than mutation, such as interaction with viral or cellular proteins. The expression of p53 protein and p53 transactivated gene proteins p21/WAF1 and MDM2, combined with in situ detection of apoptosis, was studied in specimens of CMV‐infected patients as an in vivo model of p53 alteration not due to point mutation. p53 positivity was found in CMV + cells in different tissues, in cells with typical inclusion bodies, and in in situ hybridization and immunohistochemistry CMV + cells without inclusions (hidden infection). Although this p53 reactivity was accompanied by the expression of MDM2 and p21/WAF1 proteins, the patterns of MDM2 and p21/WAF1 protein expression were mutually exclusive, and were associated with the presence or absence of inclusion bodies. Nuclei bearing inclusion bodies were usually MDM2 +, p21/WAF1−, while hidden infected cells were usually MDM2−, p21/WAF1 +. Apoptosis was not detected in any tissue section from CMV‐infected patients. Two alternative patterns were found in CMV‐infected tissues: p53 +, p21/WAF1 +, MDM2−, or p53 +, p21/WAF1−, MDM2 + protein expression. These may represent examples of p53 dependent alternative effects in the course of CMV infection. Early stages are represented by CMV + cells without inclusion bodies, which display p53 and p21/WAF1 expression, suggesting that p53 could be acting as a growth suppressor protein. Late CMV infection is represented by cells harbouring inclusion bodies. These cells showed a p53 +, p21/WAF1−, MDM2 + profile, consistent with MDM2 mediated p53 inactivation. The absence of p21/WAF1 expression and lack of apoptosis suggest that the p53 protein expressed by MDM2 + cells could be functionally inactivated in CMV‐infected cells with inclusion bodies. Previous studies have suggested that p53 inactivation by MDM2 over‐expression occurs in sarcomas and lymphomas. Our observations seem to indicate that this mechanism of MDM2 mediated p53 inactivation may play a role in the late phase of CMV infection.
Hybrid central giant cell granuloma and central odontogenic fibroma‐like lesions of the jaws
Authors: ODELL E.W. , LOMBARDI T. , BARRETT A.W. , MORGAN P.R. , SPEIGHT P.M.
Published: November 2003

Ten lesions from eight cases are presented of a rare intra‐osseous jaw lesion with the combined histological features of giant cell granuloma and central odontogenic fibroma. Lesions arose over a wide age range and presented as monolocular or multilocular radiolucencies with cortical expansion and, in one case, perforation. Two lesions recurred after curettage, one being eradicated by a second curettage and one by conservative excision. Histologically, zones of typical giant cell granuloma lay in a fibrous stroma containing islands, strands and clusters of epithelial cells. Islands often contained duct‐like spaces or hyaline basement membrane globules. Trabeculae of osteoid were present in five lesions. Recurrent lesions showed features identical to the initial lesion, including recurrence of the prominent epithelial component. These features cannot be conclusively ascribed to a variant of either giant cell granuloma, central odontogenic fibroma or aneurysmal bone cyst, but the clinical features are slightly more suggestive of giant cell granuloma. Attention is drawn to the characteristic and potentially confusing histological appearances. The presence of giant cell granuloma‐like areas in central odontogenic fibroma‐like lesions is associated with an increased risk of recurrence following curettage.
Squamoid eccrine ductal carcinoma
Authors: WONG T‐Y. , SUSTER S. , MIHM M.C.
Published: November 2003

We describe three cases of a distinctive cutaneous adnexal neoplasm showing features of eccrine ductal differentiation that were characterized by a prominent squamoid component. The tumours presented as solitary dermal nodules on the head and neck areas and the extremities in elderly patients. Histologically, they were characterized by a prominent squamous proliferation with atypia, keratinous cyst formation and squamous eddies which seemed to merge with areas showing eccrine ductal differentiation, including ductular formations in continuity with eccrine ductal epithelium. Clinical follow‐up in one case showed multiple local recurrences over a period of 3 years despite complete surgical excision. Squamoid eccrine ductal carcinoma should be considered in the differential diagnosis of cutaneous adnexal neoplasms showing squamoid and ductal features of differentiation.
Epstein–Barr virus (EBV) and Hodgkin's disease in a multi‐ethnic population in Malaysia
Authors: PEH S.C. , LOOI L.M. , PALLESEN G.
Published: November 2003

The Epstein–Barr virus (EBV) has been implicated as a contributing factor in the development of Hodgkin's disease. Western cases of Hodgkin's disease have shown the presence of EBV in Hodgkin and Reed–Sternberg cells in approximately 50%. We studied a total of 100 consecutive cases of Hodgkin's disease from Malaysia, with the aim to elucidate its association with EBV in a multi‐ethnic Asian population. Of 34 patients (34%) less than 15 years of age (childhood), 25 had classical Hodgkin's disease (eight nodular sclerosis, 16 mixed cellularity, one lymphocyte depleted) and nine had lymphocyte predominance Hodgkin's disease. Of the 66 from patients aged 15 years and above, 33 had nodular sclerosis, 24 mixed cellularity, two lymphocyte depleted, one unclassifiable and six lymphocyte predominance Hodgkin's disease. The ethnic distribution of classical Hodgkin's disease was: Malay 23, Chinese 32 and Indian 30 (Malay:Chinese:Indian = 1:1.4:1.3), and the ethnic distribution in the 15 cases of lymphocyte predominance Hodgkin's disease was: Malay four, Chinese 10 and Indian one. Taking into account the ethnic distribution of the general population and of hospital admissions, there appears to be a significant predilection of classical Hodgkin's disease cases in ethnic Indian compared to non‐Indian patients (chi‐squared test, 0.025 > P > 0.01). Eighty‐one cases were tested for the presence of EBV by in situ hybridization for EBV encoded RNA, and 57 cases by immunostaining for EBV latent membrane protein 1. In the younger age group, all except one of the 15 cases (nine mixed cellularity, six nodular sclerosis) showed the presence of EBV (93%). In the older age group, EBV was detected (52%) in the following proportion: 6/27 nodular sclerosis, 19/22 mixed cellularity, 1/2 lymphocyte depleted, 1/1 unclassifiable. None of the 14 cases of lymphocyte predominance Hodgkin's disease showed the presence of EBV in the Hodgkin and Reed–Sternberg cells. The findings suggest a strong association of EBV with Hodgkin's disease in Malaysians (41/67, 61%), in particular childhood cases (93%). In adults, the association with EBV is significantly higher in the mixed cellularity subtype (86%) compared with the nodular sclerosis subtype (22%).