bluuebunny/crossref_metadata_2025 huggingface dataset:
Histiocytic necrotizing lymphadenitis (Kikuchi–Fujimoto disease): continuing diagnostic difficulties
Authors: Menasce L P , Banerjee S S , Edmondson D , Harris M
Published: March 2003

Aims: To describe the clinicopathological and immunophenotypic features of 25 cases of Kikuchi–Fujimoto disease (K–F), which remains a poorly recognized entity and is still frequently confused with malignant lymphoma, and to discuss the main diagnostic problems experienced by the referring pathologist.

Methods and results

Haematoxylin and eosin sections of 27 lymph node biopsies were re‐examined. Immunostains for B‐lymphocytes, T‐lymphocytes and macrophages were performed. Clinical and follow‐up data were obtained through a questionnaire to the referring pathologist or from the patients' notes where available. The suggested initial diagnoses are discussed. The lymph nodes showed a necrotizing process characterized by patchy or confluent areas of necrosis associated with karyorrhexis and absence or paucity of granulocytes. This was associated with a proliferation of large blastic cells consisting of a mixture of T‐lymphocytes and histiocytes. Fragmentation of the biopsy was a frequent feature. The diagnosis of K–F was suggested by the referring pathologist in three cases only. The most common suggested diagnosis was that of a non‐Hodgkin's lymphoma.

Conclusion

This series documents continuing difficulties in the diagnosis of Kikuchi–Fujimoto disease in the UK and emphasizes that cases are still being mistakenly diagnosed as malignant lymphomas. The diagnosis of Kikuchi–Fujimoto disease merits active consideration in any nodal biopsy showing fragmentation, necrosis and karyorrhexis, especially in young women presenting with cervical lymphadenopathy.
Prognostic relevance of apoptotic cell death in non‐Hodgkin's lymphomas: a multivariate survival analysis including Ki67 and p53 oncoprotein expression
Authors: Korkolopoulou P , Angelopoulou M K , Kontopidou F , Tsenga A , Patsouris E , Thomas‐Tsagli E , Kittas C , Pangalis G A
Published: March 2003

Aims: To evaluate the independent prognostic value of apoptotic versus proliferative fractions in a series of 92 patients with non‐Hodgkin's lymphomas (NHL).

Methods and results

Apoptotic fractions were quantified by use of the TdT (terminal deoxynucleotidyl‐transferase)‐mediated in‐situ end‐labelling technique (TUNEL), the percentage of positive cells constituting the apoptotic index (AI). Proliferative rate was expressed as percentage of Ki67 positive cells (Ki67 LI). Tissues were also stained for p53 protein with the DO‐1 antibody. Patients were followed up until death (n = 33) or for an average of 63 months (n = 56). AI increased with malignancy grade and proliferative activity but was not related to location, cell of origin, clinical stage, bone marrow involvement and p53 expression. In multivariate analysis, overall survival was independently influenced by grade, stage, p53 LI and chemotherapy. The independent predictors of disease‐free survival were Ki67 LI location and chemotherapy. AI turned out to be the only independent (negative) predictor of post‐relapse survival. On the other hand, a low Ki67 LI increased the risk of relapse (logistic regression analysis) whereas a low p53 LI increased the probability of complete response.

Conclusions

Our results suggest that the combined assessment of apoptotic fraction, proliferative rate and p53 expression may provide important prognostic information independent of other clinicopathological parameters in NHL.
Diagnostic lessons of mucosal melanoma with osteocartilaginous differentiation
Authors: Banerjee S S , Coyne J D , Menasce L P , Lobo C J , Hirsch P J
Published: March 2003

Aims: To document the clinical, morphological and immunohistochemical features of two cases of primary mucosal melanoma with osteocartilaginous differentiation.

Materials and methods

Two cases of mucosal melanoma with cartilage and bone formation are reported, one arising in the vagina of a 79‐year‐old woman and one in the oral cavity of a 67‐year‐old man. The vaginal melanoma exhibited only cartilaginous differentiation. The oral cavity mucosal melanoma exhibited both bone and cartilage formation and was remarkable for its multifocality, long history not associated with metastases and its lengthy manifestation of dual morphologies: some of the tumours were typical in situ/invasive melanotic melanomas whilst the others were composed of amelanotic spindle and epithelioid cells with osteocartilaginous tissue. One of the lesions exhibited in situ and invasive melanoma with transition to an osteogenic tumour in places. The patient also developed non‐osteogenic malignant melanomas in the nasal cavity and nasopharynx.

Conclusions

Malignant melanomas showing foci of osteocartilaginous differentiation are extremely rare with only 18 cases reported. Primary mucosal malignant melanomas of vagina and oral cavity showing osteocartilaginous differentiation have not previously been documented. Primary vaginal melanoma with cartilaginous differentiation must be distinguished from primary malignant mixed Müllerian tumour whilst malignant change in a pleomorphic adenoma, sarcomatoid carcinoma, osteogenic sarcoma and mesenchymal chondrosarcoma are included in the differential diagnosis of primary oral mucosal melanomas with osteocartilaginous differentiation. In this context, immunohistochemistry using antibodies to cytokeratin, S100 protein and MIC2 is of value.
Utility of cytokeratin subsets for distinguishing poorly differentiated synovial sarcoma from peripheral primitive neuroectodermal tumour
Authors: Machen  , Fisher  , Gautam  , Tubbs  , Goldblum
Published: March 2003

Aims: Poorly differentiated synovial sarcoma (PDSS) is a round cell sarcoma that may be difficult to distinguish from other round cell sarcomas, such as peripheral primitive neuroectodermal tumour (pPNET), on histological examination alone. Furthermore, these two tumours may show overlapping immunophenotypes, as some cases of PDSS express CD99, and, on the other hand, pPNET may express epithelial markers. The goal of this study was to determine the utility of cytokeratin (CK) subsets in distinguishing between these two lesions.

Methods and results

We evaluated 13 cases of pPNET with RT‐PCR detected EWS/FLI‐1 fusion transcript and 21 cases of PDSS for the immunohistochemical expression of CK7 and CK19. All cases of PDSS had areas of recognizable monophasic or biphasic synovial sarcoma that expressed at least one epithelial marker. Thirteen of 21 (62%) PDSS stained with AE1/AE3. CK7 and 19 were expressed in 11 (52%) and nine (43%) cases, respectively. Although six of 19 (32%) PDSS demonstrated cytoplasmic staining for CD99, none showed a membranous pattern of immunoreactivity. In contrast, 12 of 13 (92%) pPNET showed strong membranous immunoreactivity for CD99. Four tumours (31%) showed focal staining with AE1/AE3, two of which (15%) stained for CK19. CK7 was not detected in any of the pPNETs.

Conclusions

Although AE1/AE3 may be found in up to 31% of cases of pPNET, the expression of CK7 makes this diagnosis less likely.
Clear cell chondrosarcoma: a pathological and immunohistochemical study
Authors: Masui,  , Ushigome  , Fujii
Published: March 2003

Aim

Clear cell chondrosarcoma (CCC) is a rare malignant cartilaginous neoplasm of bone. CCC is characterized by clear cells (CCC cells), osteoclasts and osteoblasts. Many important questions concerning the varied histological features of CCC, and the interactions between CCC cells and coexisting osteoclasts and osteoblasts have not been fully investigated and remain controversial. The aim of this study is to clarify and explain the varied histological features and the possible interaction between tumour cells (CCC cells) and stromal cells such as osteoclasts and osteoblasts.

Methods and results

Four cases of CCC were histologically and immunohistochemically studied in order to elucidate the biological nature and histological characteristics. A comparative study with chondroblastoma and grade I conventional chondrosarcoma (CC) was also performed. S100 protein and type II collagen were expressed in CCC cells, chondroblastoma cells and CC cells. CD68 and matrix metalloproteinase‐9 were expressed in coexisting histiocytes and osteoclasts. Parathyroid hormone‐like protein (PTH‐LP) was expressed in histiocytes, osteoclasts, osteoblasts, chondroblastoma cells and CCC cells. Platelet‐derived growth factor (PDGF) and its receptor (PDGF‐R) were observed in osteoblasts, chondroblastoma cells and CCC cells. However, PTH‐LP, PDGF and PDGF‐R were not expressed in CC cells. PCNA (proliferating‐cell nuclear antigen) was expressed more intensely in CCC than in chondroblastoma.

Conclusion

These observations suggest that CCC cells trigger the varied histological changes in association with several cytokines. The difference of PCNA expression between CCC and chondroblastoma seemed to be related to the biological difference between the two tumours.
Histogenesis of gastric foveolar metaplasia following duodenal ulcer: a definite reparative lineage of Brunner's gland
Authors: Kushima R , Manabe R , Hattori T , Borchard F
Published: March 2003

Aims

We aimed to clarify the histogenesis of gastric metaplasia in the duodenal mucosa, particularly in association with a reparative lineage of Brunner's glands.

Methods and results

Using immunohistochemical methods with recently developed antimucin monoclonal antibodies (mAbs) that distinguish foveolar and deep mucins of the gastric type, as well as mAb MIB‐1, the histogenesis of gastric metaplasia was investigated in the duodenal wall of 20 surgically resected specimens. In duodenal ulcers extending into Brunner's glands with destruction of the muscularis mucosae, proliferating cells positive for MIB‐1 were scattered in Brunner's glands. Interestingly, a group of proliferating cells was often seen next to the ulcerated surface. These cells were also positive for M1 (gastric‐foveolar type mucin) but negative for M2 (deep gastric and Brunner glands' mucin). In regenerating ducts through granulation tissue, the proliferating cell zone was elongated, above which foveolar‐type cells positive for M1 but negative for M2 were detected, indicating that the G‐zone is newly established in Brunner's glands at the floor of an ulcer to produce gastric‐foveolar cells. Subsequently, an organoid growth of the normal stomach mucosa is completed in the duodenum.

Conclusions

This study indicates a possible histogenetic pathway of gastric metaplasia in close association with a reparative lineage of Brunner's glands, suggesting that the occurrence of the gastric‐foveolar type epi‐thelium is not a simple expansion of Brunner's duct but a true metaplasia.
Down‐regulation of p27Kip1 expression is correlated with increased cell proliferation but not expression of p21waf1 and p53, and human papillomavirus infection in benign and malignant tumours of sinonasal regions
Authors: Saegusa M , Nitta H , Hashimura M , Okayasu I
Published: March 2003

Aims

Although p27Kip1(p27) is a cyclin‐dependent kinase inhibitor and a contribution to tumorigenesis has been hypothesized, the possible role in tumours arising in the nasal and paranasal sinus regions is still unknown.

Methods and results

Seventy‐six sinonasal tumours, including 28 inverted papillomas (IPs) and 48 squamous cell carcinomas (SCCs), were immunohistochemically investigated, along with 46 exophytic papillomas (EPs) of upper respiratory tract and 34 samples of normal paranasal sinus epithelium. The results were also compared with expression of p21WAF1 (p21) and p53, cell proliferation assessed in terms of Ki67 labelling indices (LIs), and human papillomavirus (HPV) infection. The average p27 scores decreased from normal through to malignant lesions, while Ki67 LI scores showed a stepwise increase, the inverse correlation between scores for all categories being significant (r = − 0.639, P < 0.0001). In the SCCs, p27 expression was significantly higher in keratinizing than nonkeratinizing type tumours (P < 0.05), while there was no association with p21 and p53 expression. Although HPV DNAs for type 16 and 18 were detected in two (7.4%) of 27 EPs, six (35.8%) of 28 IPs, and nine (28.1%) of 32 SCCs, no relation with p27 scores was evident.

Conclusion

Loss of p27 expression correlates with increased cell proliferation in sinonasal tumours. Moreover, the expression appears to be associated with keratinization in SCCs of the paranasal sinus. These findings indicate that p27 expression may be a useful marker for the dysregulation of cell kinetics in these tumours.
Development of dysplastic mucinous epithelium from endometriosis of the appendix
Authors: Mai  , Burns
Published: March 2003

Aim

We report an unusual case of mucinous metaplasia and epithelial dysplasia occurring in endometriotic epithelium in the appendix.

Methods and results

A 39‐year‐old woman developed an appendiceal endometriosis in which the endometrial glands displayed extensive areas consisting of mucinous epithelium and Paneth cells. Focally the mucinous epithelium showed low‐grade epithelial dysplasia. These changes occurred in portions of the endometriotic tissue closest to the appendiceal lumen. Both the intestinal and endometrial epithelial components were surrounded by typical endometrial‐type stroma showing positive reactivity for oestrogen receptor.

Conclusions

Formation of the mucinous epithelium most likely represents a metaplastic process of the endometrial epithelium rather than a result of a simple ‘collision’ of the appendiceal and endometrial epithelium. Further support for this being a metaplastic process was the presence of glandular structures containing a mixture of mucinous cells, goblet cells, Paneth cells, ciliated and nonciliated endometrial cells, and ciliated and nonciliated mucinous cells, all showing the same positive reactivity for oestrogen receptor. The disposition of mucinous epithelium in the foci of endometriosis in this case suggests that the appendiceal mucosa or extracellular mucin may play a role as an inducer of mucinous cell metaplasia in endometriotic epithelium.
Small epithelial cells in extrahepatic biliary atresia: electron microscopic and immunoelectron microscopic findings suggest a close relationship to liver progenitor cells
Authors: Xiao  , Ruck  , Kaiserling
Published: March 2003

Aims: It is still unclear whether hepatic stem cells that give rise to both biliary epithelial cells and hepatocytes exist in the human liver. The aim of this study was to investigate whether cells with ultrastructural and immunophenotypical features similar to those of the oval cells of rodents or the small epithelial cells (SEC) described recently in hepatoblastoma, i.e. putative hepatic progenitor cells, are found in the liver of patients with extrahepatic biliary atresia.

Methods and results

Liver biopsies from 10 infants with extrahepatic biliary atresia were investigated by transmission electron microscopy. Single and double immunolabelling for cytokeratin 7, a marker of biliary differentiation, and albumin, a marker of hepatocytic differentiation, was investigated by immunoelectron microscopy. Electron microscopy revealed SEC that were ultrastructurally similar to the oval cells and coexpressed albumin and cytokeratin 7. The SEC exhibited a spectrum of differentiation that, in addition to relatively undifferentiated cells, included cells that exhibited morphological and immunophenotypical signs of differentiation towards biliary epithelial cells and hepatocytes.

Conclusions

The findings demonstrate that SEC with morphological and immunophenotypical features of the oval cells of rodents and the SEC described in hepatoblastoma are found in the liver of patients with extrahepatic biliary atresia. The data further support the hypothesis that the SEC represent possible candidates for hepatic progenitor cells.
Electron microscopy in tumour diagnosis: continuing to complement other diagnostic techniques
Authors: Eyden B
Published: March 2003

The histopathological diagnosis of tumours has been transformed by immunohistochemistry. Used with experience and judgement, a panel of antibodies or antisera, combined when necessary with antigen retrieval, will enable the accurate typing of most problematic tumours. This has led many histopathologists to question whether the electron microscope has any residual utility for tumour diagnosis; the machines are large, costly to purchase and maintain, and will accept only minute samples of tissue. The following articles by Mierau and by Eyden, both strong advocates, comment on the current and future role of electron microscopy in tumour diagnosis.
Loss of expression of transforming growth factor beta type II receptor correlates with high tumour grade in human breast in‐situ and invasive carcinomas
Authors: Gobbi  , Arteaga  , Jensen  , Simpson  , Dupont  , Olson  , Schuyler  , Plummer  , Page
Published: March 2003

Aims

Loss of transforming growth factor beta type II receptor (TGFβ‐RII) expression has been associated with resistance to TGFβ‐mediated inhibition of cell proliferation and tumour progression. We investigated whether the expression of TGFβ‐RII is related to the progression of human breast cancer and whether there is a correlation between TGFβ‐RII expression and phenotypic markers of biological aggressiveness.

Methods and results

Immunohistochemical methods were used to detect TGFβ‐RII in archival breast samples including benign proliferative lesions, ductal carcinoma in situ (DCIS) and invasive mammary carcinomas (IMC). Neoplastic cells showed reduced expression of TGFβ‐RII in comparison to the normal breast tissue and benign lesions. There was a significant inverse correlation between loss of TGFβ‐RII expression and tumour grade within both DCIS (P = 0.004) and IMC (P = 0.001) groups. There was an inverse correlation between TGFβ‐RII expression and both mitotic count (P = 0.001) and clinical stage (P = 0.004). Oestrogen receptor (P = 0.07) and lymph node status (P = 0.10) were not significantly associated with TGFβ‐RII expression.

Conclusions

These data indicate that decreased expression of TGFβ‐RII may contribute to breast cancer progression and is related to a more aggressive phenotype in both in‐situ and invasive carcinomas.
The cytokeratin profile of medullary carcinoma of the breast
Authors: Tot T
Published: March 2003

Aims

: The cytokeratin (CK) phenotype and vimentin expression of 31 medullary carcinomas was studied using commercially available antibodies on archived material. Comparing the phenotype of typical and atypical tumours and the phenotype of metastases, the biological significance of cytokeratin and vimentin expression in medullary carcinomas of the breast was determined.

Methods and results

: Antibodies to CK4, CK5 and 6, CK7, CK14, CK8 and 18, CK19, CK20 and to vimentin were used. All the typical and atypical medullary carcinomas and the metastases (10 cases) stained negatively for CK4 and positively for CK8–18 (CAM5.2). Almost all the tumours were CK7 and CK19 positive and CK20 negative. Twelve per cent of the tumours contained CK14. Twenty‐five per cent of the typical, 43% of the atypical and 20% of the metastatic medullary carcinomas showed CK5–6 positivity. No association between the cytokeratin–vimentin profile of the tumours and axillary node metastases, tumour size or oestrogen receptor status was found but instability of CK expression was demonstrated by comparing the primary tumours with their metastases.

Conclusions

: Medullary carcinomas of the breast express all the glandular type CKs including CK19 and additionally a proportion of the tumours expresses some of the CKs typical for myoepithelial cells. There was no correlation with prognostic factors.
γδ T‐cell lymphomas: a homogeneous entity?
Authors: De Wolf‐Peeters  , Achten
Published: March 2003

γδ T‐cells comprise an immunologically distinct lymphoid population, characterized by specific morphological, phenotypical and functional properties. Therefore it seems reasonable to speculate that neoplasms derived from this particular T‐cell subset display distinct features. Indeed, the prototype γδ T‐cell lymphoma, hepatosplenic T‐cell lymphoma constitutes a unique clinicopathological entitity which is intimately associated with a γδ T‐cell phenotype. However, γδ T‐cell lymphomas have also been described in other extranodal sites where, unlike reactive γδ T‐cells and hepatosplenic γδ T‐cell lymphomas, they display an important morphological heterogeneity. Moreover, these nonhepatosplenic γδ T‐cell lymphomas are essentially not that different from their αβ T‐cell receptor for antigen (TCR)‐expressing counterparts and thus may be incorporated in the established T‐cell lymphoma subclasses. However, subtle differences regarding their histopathological appearance as well as their biological behaviour indicate that further studies to determine the exact significance of TCR expression are required. Such inquiries may contribute to the general understanding of T‐cell lymphomagenesis in general, which is still obscure.
Immunohistochemical assessment of Ki67 and p53 expression assists the diagnosis and grading of ulcerative colitis‐related dysplasia
Authors: Wong N A C S , Mayer N J , MacKell S , Gilmour H M , Harrison D J
Published: March 2003

Aims

: To assess whether Ki67 and p53 immunostaining may assist the diagnosis and grading of ulcerative colitis‐related dysplasia.

Methods and results

: Location of Ki67 staining and location and intensity of p53 staining were assessed in ulcerative colitis (UC) cases showing the features of high‐grade dysplasia (HGD, n = 14), low‐grade dysplasia (LGD, n = 22), ‘indefinite for dysplasia’ (n = 12), or regenerative atypia (RA, n = 22). Good intra‐ and inter‐observer reproducibilities were demonstrated in the performance of these assessments. All the dysplasia cases showed extension of Ki67 staining above the basal third of the crypt. Moderate intensity p53 staining was seen in 10/22 RA cases, but strong intensity p53 staining was seen only in cases of dysplasia. All the cases of HGD showed extension of Ki67 and p53 staining above the basal two thirds of the crypt.

Conclusions

: Restriction of Ki67 staining to the basal third of the crypt appears to exclude a diagnosis of dysplasia whereas strong intensity p53 staining suggests a diagnosis of dysplasia. Restriction of Ki67 or p53 staining to the basal two‐thirds of the crypt appears to exclude a diagnosis of HGD.
Calretinin expression in ameloblastomas
Authors: Altini M , Coleman H , Doglioni C , Favia G , Maiorano E
Published: March 2003

Aims

Calretinin is a 29‐kDa calcium‐binding protein which is expressed in the central and peripheral nervous systems as well as in many other normal and pathological human tissues. The objective of this study was to determine whether calretinin was expressed in the epithelium of ameloblastomas.

Methods and results

Twenty‐seven cases of unicystic ameloblastoma and 31 cases of solid and multicystic ameloblastoma were studied. Five‐micron sections were immunohistochemically stained using either antiserum 7696 from Swant, or antiserum 18–0211 from Zymed with a standard ABC method. The results were identical with the two antisera. Positive staining was seen in 22 cases (81.5%) of unicystic ameloblastomas. This generally consisted of diffuse, intense nuclear and cytoplasmic staining of several cell layers of the more superficial cells both in the characteristic and nondescript areas of the cyst linings. In the solid and multicystic ameloblastomas, staining occurred in 29 (93.5%) of the cases. The staining was almost always restricted to the stellate reticulum‐like epithelium, was generally intense and diffuse in distribution. Areas of squamous metaplasia stained particularly intensely as did the cells surrounding micro‐ and macro‐cysts. In both groups of lesions, most of the cases that did not stain were intensely inflamed.

Conclusions

The biological significance of calretinin expression in ameloblastomas is not known and its use as a distinctive, specific immunohistochemical marker for ameloblastic tissues remains to be confirmed. However, the results of this study raise the possibility that calretinin may be an important diagnostic aid in the differential diagnosis of cystic and solid ameloblastic tumours.
Systematic review and meta‐analysis in anatomic pathology
Authors: Heatley M K
Published: March 2003

Systematic reviews and meta‐analyses are techniques of data retrieval and analysis which complement traditional narrative reviews. They are widely used in clinical medicine and are finding an increasing role in anatomical pathology. Performing high quality systematic review and meta‐analysis requires the accumulation of large numbers of cases from well planned and executed studies and is facilitated if data is presented in a standardized manner. Techniques which allow data from individual patients included in a variety of different studies are now being developed indicating that in future research papers may require a more detailed description of results than in the past. This need may be met by posting anonymised data on the Internet. Systematic reviews and meta‐analyses are never complete since data are continually contributed and analyses constantly updated. As with any research paper, the results of these techniques require careful evaluation and the role of the expert reviewer is enlarged by these methodologies.
Cytogenetic evidence of clonality in cutaneous benign fibrous histiocytomas: a report of the CHAMP Study Group
Authors: Vanni R , Fletcher C D M , Sciot R , Dal Cin P , De Wever I , Mandahl N , Mertens F , Mitelman F , Rosai J , Rydholm A , Tallini G , Van Den Berghe H , Willén H
Published: March 2003

Aims

: Cutaneous benign fibrohistiocytic tumours are among the most common soft tissue lesions. Their biological nature, in particular whether they are neoplastic or reactive, has long been disputed. Some morphological subtypes can be confused with sarcoma. Since available karyotypic data in these lesions are scarce, this study was undertaken to determine whether their cytogenetic analysis might demonstrate clonality and might help in differential diagnosis.

Methods and results

: Thirteen karyotyped benign cutaneous fibrous histiocytomas (BFH) were morphologically reassessed and classified as ordinary BFH (eight cases), cellular BFH (four cases), and one ankle‐type lesion. Five cases (38%) showed clonal cytogenetic changes, although the aberrations varied and did not correlate with histological subtypes. Karyotypic aberrations were more common in cellular BFH (3/4) than in the ordinary BFH (2/8).

Conclusions

: The demonstration of clonal chromosome abnormalities, in at least some cases, supports the neoplastic nature of cutaneous BFH. The karyotypic changes identified are different from those in dermatofibrosarcoma, with which cellular BFH is often confused histologically.
The diagnosis of dysplasia and malignancy in Barrett's oesophagus
Authors: Geboes K , Van Eyken P
Published: March 2003

Barrett's metaplasia is associated with an increased risk for adenocarcinoma. Adenocarcinoma develops through a multistep process characterized by defects in genes and morphological abnormalities. The early morphological changes of the process are called ‘dysplasia’. Dysplasia is defined as an unequivocal neoplastic (premalignant) transformation confined within the basement membrane. For most Western pathologists malignancy is defined as invasion and characterized by a breach through the basement membrane. Japanese pathologists rely on cytological atypia and complex branching of crypts. Cytological and architectural abnormalities allow identification of dysplasia on routinely stained sections. A distinction is made between low‐ and high‐grade dysplasia. The differential diagnosis between low‐grade dysplasia and reactive changes can be difficult. Therefore a second opinion is strongly recommended, not only for high‐grade dysplasia but also for low‐grade. Immunohistochemistry for p53 and flow cytometry for detection of aneuploidy can support the diagnosis. Identification of dysplasia and malignancy depends on the number of biopsy samples examined. The minimum number of biopsies required has not yet been determined and depends partly on the length of the metaplastic segment. It has been proposed to sample with four quadrant biopsies at 20‐mm intervals. New endoscopic techniques can increase the diagnostic yield. Endoscopically visible lesions increase the risk of finding malignancy. The time sequence for the progression of dysplasia is not known but progression from low‐ to high‐grade and cancer has been shown to occur over a period of years although it may not be inevitable.
Inducible nitric oxide synthase expression is increased in the brain in fatal cerebral malaria
Authors: Maneerat Y , Viriyavejakul P , Punpoowong B , Jones M , Wilairatana P , Pongponratn E , Turner G D H , Udomsangpetch R
Published: March 2003

Aims

: Nitric oxide (NO) has been hypothesized to play a major role in the pathogenesis of cerebral malaria caused by P. falciparum infection. NO may act as a local neuroactive mediator contributing to the coma of cerebral malaria (CM). We hypothesized that increased expression of inducible nitric oxide synthase (iNOS) may cause increased release of NO, and examined the expression and distribution of iNOS in the brain during CM.

Material and results

: Brain tissues from fatal cases of cerebral malaria in Thai adults were examined using immunohistochemical staining to detect iNOS. The distribution and strength of staining was compared between 14 patients with CM, three of whom were recovering from coma, and controls. iNOS expression was found in endothelial cells, neurones, astrocytes and microglial cells in CM cases. There was also strong staining in macrophages surrounding ring haemorrhages. iNOS staining was decreased in recovering malaria cases compared to acute CM, and was low in controls. Quantification showed a significant association between the intensity and number of iNOS positive vessels with the severity of malaria related histopathological changes, although the total number of cells staining was not increased compared to recovering CM cases.

Conclusions

: This study indicates that an acute induction of iNOS expression occurs in the brain during CM. This occurs in a number of different cells types, and is increased in the acute phase of CM compared to cases recovering from coma. As NO may activate a number of secondary neuropathological mechanisms in the brain, including modulators of synaptic function, induction of iNOS expression in cerebral malaria may contribute to coma, seizures and death.
Interleukin‐13 and interleukin‐13 receptor in Hodgkin's disease: possible autocrine mechanism and involvement in fibrosis
Authors: Ohshima K , Akaiwa M , Umeshita R , Suzumiya J , Izuhara K , Kikuchi M
Published: March 2003

Aims: Hodgkin's disease (HD) is characterized by the presence of Hodgkin and Reed–Sternberg (H–RS) cells against a hyperplastic background of reactive cells such as lymphocytes, histiocytes, plasma cells, eosinophils, neutrophils, and stromal cells. There is ample evidence to suggest that proliferation and survival of HD‐derived cells is due to cytokine signalling. Recently, high expression of interleukin (IL)‐13 was described in HD‐derived cell lines. Here we investigated the possible involvement of IL‐13 in the pathophysiology, especially autocrine pathways of H–RS cells.

Methods and results: The expression of IL‐13 and IL‐13 receptor (IL‐13R) was determined by immunostaining and reverse transcriptase‐polymerase chain reaction in 39 cases of HD, including 17 cases with nodular sclerosis (NS) type, 19 cases with mixed cellularity (MC), and three cases with lymphocyte predominance (LP) type. Expression of IL‐13 was confined to H–RS cells and a few lymphocytes. IL‐13R was expressed in H–RS cells, lymphocytes, histiocytes, fibroblasts, and endothelial cells. H–RS cells of MC and NS types frequently expressed both IL‐13 and IL‐13R. However, the number of IL‐13‐positive H–RS cells was statistically higher in NS‐type than in MC‐type, but the number of IL‐13R was similar. IL‐13R‐positive fibroblasts were frequently encountered in NS‐type. H–RS cells of LP type rarely expressed IL‐13.

Conclusions: Our results suggest that IL‐13 might be involved in autocrine pathways of H–RS cells and fibrosis at least in NS‐type. Our results also indicated that in addition to the morphological and phenotypic differences, the neoplastic cells of LP type might be functionally different from H–RS cells of MC‐ and NS‐types.
Myocardial fibrosis assessment by semiquantitative, point‐counting and computer‐based methods in patients with heart muscle disease: a comparative study
Authors: Vasiljević J D , Popović Z B , Otašević P , Popović Z V , Vidaković R , Mirić M , Nešković A N
Published: March 2003

Aims: No study has directly compared different histomorphometric methods of quantification of myocardial fibrosis. Therefore we compared the results of semiquantitative, point‐counting and computer‐based methods in the assessement of myocardial fibrosis in a consecutive series of endomyocardial biopsy samples from patients with heart muscle disease.

Methods and results: Histological samples (at least three per patient) were obtained by endomyocardial biopsy from 11 patients with focal myocarditis and from 24 ambulatory patients with idiopathic dilated cardiomyopathy, or during surgery in 10 patients who underwent partial left ventriculectomy. Samples were cut and stained with Masson‐trichrome for better contrast. From each sample, a representative field was digitized, and the amount of fibrosis was assessed by semiquantitative scoring, by point‐counting, and by computer‐based software. Semiquantitative scoring correlated with both point‐counting (Spearman's r = 0.69, P < 0.0001) and computer‐based (Spearman's r = 0.83, P < 0.0001) methods. There was also a good correlation between point‐counting and computer‐based methods (r = 0.71, P < 0.0001). However, when compared with the point‐counting method, the computer‐based method overestimated percent fibrosis by 3.0 ± 6.7% (P = 0.004). This overestimation correlated with the mean percent fibrosis (r = 0.38, P = 0.014).

Conclusions: Our data show good correlations between the three methods of myocardial fibrosis assessment. However, systematic differences between them emphasize that this should be taken into consideration when comparing results of the studies using different methods of fibrosis assessment.
Intra‐abdominal spindle cell lesions: a review and practical aids to diagnosis
Authors: Al‐Nafussi A , Wong N A C S
Published: March 2003

Intra‐abdominal spindle cell lesions: a review and practical aids to diagnosis

Intra‐abdominal spindle cell lesions are uncommon and often present a diagnostic challenge. An important group of such lesions are the gastrointestinal stromal tumours. Other intra‐abdominal spindle cell lesions include fibromatosis, various sarcomas—in particular, leiomyosarcoma, liposarcoma, and malignant peripheral nerve sheath tumour—and, in women, endometrial stromal sarcoma. Less common lesions are inflammatory myofibroblastic tumours, the mesenteric spindle cell reactive lesions, retroperitoneal fibrosis, and solitary fibrous tumour. A variety of intra‐abdominal tumours of nonmesenchymal origin may have a spindle cell/sarcomatoid morphology; these include sarcomatoid carcinoma, malignant melanoma and, in women, sarcomatoid granulosa cell tumour. Finally, metastatic sarcomas from pelvic or extra‐abdominal organs need also be considered. A set of practical aids to the diagnosis of intra‐abdominal spindle cell lesions is presented to assist pathologists dealing with such lesions, particularly with regards to the consideration of differential diagnoses.
Development of follicular dendritic cell sarcoma in hyaline‐vascular Castleman’s disease of the nasopharynx: tracing its evolution by sequential biopsies
Authors: Chan A C L , Chan K W , Chan J K C , Au W Y , Ho W K , Ng W M
Published: March 2003

Development of follicular dendritic cell sarcoma in hyaline‐vascular Castleman’s disease of the nasopharynx: tracing its evolution by sequential biopsies

Aims: Hyaline‐vascular Castleman’s disease (HVCD) and follicular dendritic cell (FDC) sarcoma occurring in the nasopharynx are both extremely rare. We report the first case of transformation of the former into the latter as documented by sequential biopsies. The steps involved in the transformation were described in detail and the possible role of p53 studied.

Methods and results: The patient presented at the age of 23 years with nasopharyngeal HVCD. Hyaline‐ vascular Castleman’s disease with FDC overgrowth was diagnosed in a recurrence 8 years later, and a frank FDC sarcoma developed at the same site 11 years after initial presentation. The patient remained disease‐free 3 years after excision and adjuvant chemotherapy. The FDC sarcoma comprised swirling fascicles of spindly cells with indistinct cell borders. The tumour cells expressed the FDC markers CD21, CD35 and CNA.42 and in‐situ hybridization for Epstein–Barr virus‐encoded RNAs was negative. Over‐expression of p53 protein was observed in the FDC sarcoma and an increased number of weakly p53‐positive spindly cells could also be demonstrated in the HVCD specimen. This finding suggested a possible role of p53 in the evolution from HVCD to FDC sarcoma. Critical analysis of the literature shows that, among the 13 reported cases of FDC sarcoma associated with Castleman’s disease, possible progression from the latter to the former is documented in only two cases.

Conclusions: The sequential changes observed in the current case provide further evidence to strengthen the role of HVCD as a possible precursor of FDC sarcoma. There is a possible role of p53 in the transformation process but confirmation by future studies is needed.
CD10 and Bcl10 expression in diffuse large B‐cell lymphoma: CD10 is a marker of improved prognosis
Authors: Ohshima K , Kawasaki C , Muta H , Muta K , Deyev V , Haraoka S , Suzumiya J , Podack E R , Kikuchi M
Published: March 2003

CD10 and Bcl10 expression in diffuse large B‐cell lymphoma: CD10 is a marker of improved prognosis

Aims: Diffuse large B‐cell lymphoma (DLBCL), the most common subtype of non‐Hodgkin’s lymphoma, is clinically and pathologically heterogeneous. The Bcl10 gene was recently isolated from the breakpoint region of t(1;14)(p22;q32) in mucosa‐associated lymphoid tissue (MALT) lymphomas, and is considered to be an apoptosis‐associated gene. CD10 is considered to be a marker of follicular centre B‐cell differentiation. To assess the clinical significance and roles of CD10 and Bcl10 in DLBCL, we analysed 138 cases, using immunohistochemical methods.

Methods and results: CD10 expression was limited to the cytoplasm, whereas Bcl10 expression was detected in the cytoplasm and/or nuclei. CD10 expression was detected in 39 of 138 cases (28.2%), cytoplasmic Bcl10 in 68 cases (49.2%), and nuclear Bcl10 in 34 cases (24.6%). Nuclear Bcl10 was detected in 14 of 28 cases (50%) of extranodal DLBCL, but only 20 of 110 cases (18.2%) of nodal DLBCL. Cytoplasmic Bcl10 was detected in 19 of 28 cases (67.8%) of extranodal DLBCL and 49 of 110 cases (44.5%) of nodal DLBCL. CD10 expression closely correlated with improved survival (68% overall survival (OS) vs. 48% OS), but not with site of disease. A high International Prognostic Index (IPI) was considered to be a poor prognostic factor associated with a shorter OS. CD10 expression was detected in 27 of 84 cases (32.1%) with low‐risk IPIs, and in 12 of 54 cases (22.2%) with high‐risk IPIs. In the low‐risk group, cases expressing CD10 carried a better prognosis than CD10− cases (93% OS vs. 71% OS), whereas this was not the case in the high‐risk group (25% vs. 20%).

Conclusions: Bcl10 expression was associated with extranodal DLBCL, but not with prognosis. CD10 expression was closely associated with improved survival, but not with risk as predicted by IPI. Overall, our results suggest that CD10 expression may be useful, in combination with clinical parameters, for determining the prognosis of DLBCL.
Intratumoral hypoxia resulting in the presence of a fibrotic focus is an independent predictor of early distant relapse in lymph node‐negative breast cancer patients
Authors: Colpaert C , Vermeulen P , Van Beest P , Goovaerts G , Weyler J , Van Dam P , Dirix L , Van Marck E
Published: March 2003

Intratumoral hypoxia resulting in the presence of a fibrotic focus is an independent predictor of early distant relapse in lymph node‐negative breast cancer patients

Aims: To examine the importance of a fibrotic focus—a scar‐like area in a carcinoma—as a marker of intratumoral hypoxia that correlates with angiogenesis and with clinical outcome in node‐negative breast cancer.

Methods and results: One hundred and four T1–2N0M0 breast carcinoma patients were divided into two groups: group 1 (n=46) showing early distant relapse (median disease‐free survival 25 months) and group 2 (n=58) showing no evidence of disease (median follow‐up 91.5 months). All tumours were evaluated for medial/lateral location, size, histological grade, mitotic activity, necrosis, fibrotic focus, angiogenesis, vascular permeation and growth pattern. Multiple regression analysis showed that only histological grade and the presence of a fibrotic focus were independent predictors of early distant relapse. A fibrotic focus was present in 53% of the tumours. The relative size (fibrotic focus/tumour ratio) was significantly correlated with an unfavourable outcome. The presence of necrosis inside the fibrotic focus and the absolute and relative size of the fibrotic focus were significantly correlated with angiogenesis. A fibrotic focus was significantly associated with large, expansively growing tumours with high histological grade and numerous mitoses.

Conclusion: A fibrotic focus can be used as a surrogate for quantifying angiogenesis and is an independent predictor of early metastasis in lymph node‐negative breast cancer.
A unique basal pattern of p53 expression in ulcerative colitis is associated with mutation in the p53 gene
Authors: Noffsinger A E , Belli J M , Miller M A , Fenoglio‐Preiser C M
Published: March 2003

A unique basal pattern of p53 expression in ulcerative colitis is associated with mutation in the

p53

gene

Aims: The p53 protein is implicated in the control of cell proliferation, differentiation, and death. As part of a study characterizing p53 alterations in colonic mucosa of patients with ulcerative colitis, we identified a unique pattern of basal p53 immunoreactivity.

Methods and results: Tissue samples (n=180) from 42 ulcerative colitis patients were evaluated for p53 alterations by immunohistochemistry, loss of heterozygosity analysis, polymerase chain reaction‐single‐strand conformation polymorphism and direct sequencing. In addition, the expression of the p53‐ associated proteins p21waf1/cip1 and MDM2 was evaluated immunohistochemically. Three basic patterns of p53 immunoreactivity were observed: (i) isolated immunoreactive cells in the crypt bases; (ii) strongly positive cells confined to the basal half of the glands; and (iii) diffusely staining cells. The basal staining pattern was observed in both non‐neoplastic tissues and in some areas of dysplasia, and was associated with normal expression of p21waf1/cip1 in all cases, and with p53 mutation in seven of 11 cases.

Conclusions: The basal pattern of p53 expression is associated with mutation in the p53 gene, and appears to be an early change in a subgroup of ulcerative colitis patients. The significance of this pattern of immunoreactivity and the mechanism by which it develops are discussed.
Combined examination of p27Kip1, p21Waf1/Cip1 and p53 expression allows precise estimation of prognosis in patients with gastric carcinoma
Authors: Liu X P , Kawauchi S , Oga A , Suehiro Y , Tsushimi K , Tsushimi M , Sasaki K
Published: March 2003

Combined examination of p27Kip1, p21Waf1/Cip1 and p53 expression allows precise estimation of prognosis in patients with gastric carcinoma

Aims: In order to estimate the prognostic values of p27Kip1, p21Waf1/Cip1, and p53, alone and in combination, we investigated immunohistochemically the expression of p27Kip1, p21Waf1/Cip1, and p53 proteins in gastric carcinomas.

Methods and results: The expression of p27Kip1, p21Waf1/Cip1, and p53 was immunohistochemically examined in 140 gastric carcinomas. Positive expression of p27Kip1 and p21Waf1/Cip1 correlated significantly with a favourable prognosis (P < 0.05), whereas, positive expression of p53 tended to correlate with poor prognosis. Multivariate survival analysis revealed that TNM stage of tumour (P < 0.001), lymph node state (P=0.005), and p27Kip1 expression (P=0.006) were independent prognostic factors. A striking stratification of mortality rate was found when patients were divided into four groups according to the expression of p21Waf1/Cip1 and p27Kip1. The mortality rate was higher in patients with both p21Waf1/Cip1‐ and p27Kip1‐negative gastric carcinoma than in patients with one or both positive carcinomas (P < 0.01). In addition, if the four p21Waf1/Cip1/p27Kip1 groups were compared based on p53 status, p53+ cases tended to have a higher mortality rate than p53‐ cases.

Conclusion: Our results suggest that low expression of both p27Kip1 and p21Waf1/Cip1 could be useful as markers of poorer prognosis, and the combined examination of p27Kip1, p21Waf1/Cip1 and p53 expression allows reliable estimation of prognosis for patients with gastric carcinoma.
Expression of angiogenic factors and hypoxia inducible factors HIF 1, HIF 2 and CA IX in non‐Hodgkin's lymphoma
Authors: Stewart M , Talks K , Leek R , Turley H , Pezzella F , Harris A , Gatter K
Published: March 2003

Expression of angiogenic factors and hypoxia inducible factors HIF 1, HIF 2 and CA IX in non‐Hodgkin's lymphoma

Aims: Angiogenesis in solid tumour pathology is well established but less is known about its role in haematological malignancies. Our study investigated the immunohistochemical expression of a variety of angiogenic and hypoxic factors and microvessel densities on 110 cases of high‐ and low‐grade non‐Hodgkin's lymphomas and reactive lymphoid tissues.

Methods and results: Expression of vascular endothelial growth factor (VEGF) was present in 82 (96%) of the non‐Hodgkin's cases and 35 (100%) of the reactive lymphoid tissue cases. Both hypoxia inducible factors 1α and 2α (HIF 1α, 2α) were weakly expressed in the majority of high‐ and low‐grade lymphomas. Carbonic anhydrase IX (CA IX), a HIF‐inducible membrane‐bound enzyme, expression was not abundant with membranous staining being present in seven (8%) of the lymphoma cases and none of the reactive cases. Thymidine phosphorylase (TP) was distributed amongst macrophages and follicular dendritic cells but was not present in the neoplastic population. The vasculature was stained using CD34 which gave rise to a distinct vascular, predominantly paracortical network present in low‐grade lymphomas and reactive lymphoid tissue but which was lost in high‐grade lymphomas.

Conclusion: Our results suggest that non‐Hodgkin's lymphomas may be less angiogenic and hypoxically driven than most solid tumours, which has implications for possible future therapies.