bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cellular proliferation and nuclear ploidy assessments augment established prognostic factors in predicting malignancy in testicular Leydig cell tumours
Authors: McCluggage W G , Shanks J H , Arthur K , Banerjee S S 
Published: March 2003

AimsTesticular Leydig cell tumours are rare. Although most behave benignly ≈ 10% are malignant. Clinicopathological features have been described which have some value in predicting malignant behaviour, although as with other endocrine tumours uncertainties remain in many individual cases. Our aim was to determine the clinicopathological features of 20 testicular Leydig cell tumours. We wished to investigate whether, in addition to established clinicopathological features, the MIB1 index and/or flow cytometric analysis of nuclear DNA content are of value in predicting malignancy. We also wished to investigate the frequency of p53 protein accumulation in these neoplasms.Methods and resultsTwenty testicular Leydig cell tumours were studied and the clinical case notes examined. Histological sections were assessed by pathologists involved in the study. Pathological features evaluated included: tumour size, extratesticular extension, nuclear pleomorphism, mitotic activity, necrosis and vascular invasion. Immunohistochemical staining was performed with the anti‐p53 monoclonal antibody DO‐7 and the cell proliferation marker MIB1. A flow cytometric analysis of nuclear DNA content was also performed. Three tumours behaved in a malignant fashion with the development of metastases. Another had morphological features of malignancy but the patient died a short time after diagnosis from unrelated causes. These four neoplasms were larger than benign tumours, often contained areas of necrosis and sometimes exhibited vascular invasion. They generally exhibited greater nuclear pleomorphism and a higher mitotic rate than benign tumours. Three of the four malignant tumours had a high MIB1 index (20–50%) and the fourth exhibited DNA aneuploidy by flow cytometry. Two malignant tumours showed increased expression of p53 protein, with ≈ 50% of nuclei staining with DO‐7. All benign tumours had a low MIB1 index (0–2%) and a diploid DNA profile, except for one case where there was DNA aneuploidy. There was little or no staining of benign tumours with DO‐7.ConclusionsThe study confirms that large size, marked nuclear pleomorphism, high mitotic rate, necrosis and vascular invasion are important factors in predicting malignant behaviour in testicular Leydig cell tumours. Additional prognostic value may be derived from the MIB1 index and flow cytometry. Accumulation of p53 protein, through mutational or other events, may be important in malignant progression in these tumours.
c‐erbB‐2 protein is expressed in hepatolithiasis and cholangiocarcinoma
Authors: Terada T , Ashida K , Endo K , Horie S , Maeta H , Matsunaga Y , Takashima K , Ohta T , Kitamura Y 
Published: March 2003

AimsThe c‐erbB‐2 proto‐oncogene encodes a transmembrane protein which is highly homologous to epidermal growth factor receptor. Overexpression of this c‐erbB‐2 protein has been reported in many human carcinomas, including breast carcinoma. However, there have been few studies of the expression of c‐erbB‐2 in cholangiocarcinoma and hepatolithiasis, a condition occasionally associated with cholangiocarcinoma.Methods and resultsIn this study, we evaluated immunoreactivity for the c‐erbB‐2 protein in human cholangiocarcinomas (n = 47), hepatolithiasis (n = 20), fetal livers (n = 36) and normal adult livers (n = 6). In normal adult livers and fetal livers, expression of c‐erbB‐2 protein could not be detected in hepatocytes or intrahepatic biliary cells. In hepatolithiasis, there was overexpression of c‐erbB‐2 in 15/20 (75%). The expression was found with a membranous pattern on the proliferated intrahepatic bile ducts and proliferated intrahepatic peribiliary glands around the bile ducts containing stones. Hepatocytes were negative for c‐erbB‐2 protein. Moreover, the biliary cell expression of the c‐erbB‐2 protein correlated significantly with Ki67 labelling index. On the other hand, aberrant expression of c‐erbB‐2 was found in 33/47 (70%) cholangiocarcinomas. The c‐erbB‐2 expression in cholangiocarcinomas did not correlate with Ki67 labelling index or p53 expression.ConclusionsThese results indicate that aberrant expression of c‐erbB‐2 protein is found in cholangiocarcinoma and also in noncancerous biliary proliferative lesions such as hepatolithiasis. These findings also suggest that c‐erbB‐2 oncogene participates not only in cholangiocarcinogenesis but also in biliary cell proliferation in non‐neoplastic conditions.
Mucoepidermoid carcinoma arising in Warthin's tumour of the parotid gland: report of two cases with histopathological, ultrastructural and immunohistochemical studies
Authors: Nagao T , Sugano I , Ishida Y , Tajima Y , Furuya N , Kondo Y , Nagao K 
Published: March 2003

Aims: Malignant transformation of Warthin's tumour (WT) is a rare event. We present two cases of mucoepidermoid carcinoma (MEC) arising in WT in the parotid gland.Methods and resultsTwo cases of MEC arising in WT, which were found in 185 cases of WT of the parotid gland, were investigated by light and electron microscopy, and immunohistochemistry. Both cases had largely similar macroscopic and histological features with some differences. Histologically, the tumours consisted mainly of WT with multilayered hyperplastic arrangements of oncocytic cells and focal squamous and goblet cell metaplasia. In the same tumour mass, however, the features of MEC were observed with invasion to adjacent adipose tissue. A transitional zone between WT and MEC was evident. Both patients were alive and well without evidence of recurrence 30 and 34 months after surgery, respectively. Electron microscopy revealed that cyst lining epithelial cells in WTs had abundant mitochondria whereas some of the MEC cells contained numerous tonofilaments and mucinous granules. Immunohistochemically, oncocytic cells of WTs were strongly positive for mitochondria and Salyl‐Tn was extensively stained in MECs. The labelling index for Ki67 was obviously higher in the carcinoma cells than the epithelial cells of WT.ConclusionsOur cases confirmed the possibility of malignant transformation of the epithelial component in WT to MEC.
Crystal‐storing histiocytosis and immunocytoma associated with multifocal fibrosclerosis
Authors: García J F , Sánchez E , Lloret E , Martín J , Piris M A 
Published: March 2003

AimsCrystal‐storing histiocytosis is a rare disorder described in patients with lymphoproliferative diseases, mainly in cases of multiple myeloma but also in lymphoplasmacytic lymphoma (immunocytoma). Most cases involve one single organ which, in the majority, is related directly to the presence of tumour. We describe a 44‐year‐old man with a clinical picture of multifocal fibrosclerosis (with mesenteric panniculitis, peritoneal, mediastinal and orbital fibrosis) in which the autopsy showed a systemic infiltrate of crystal‐storing histiocytes and functional alteration of the organs involved, associated with IgG‐kappa type immunocytoma.Methods and resultsHistology showed a systemic infiltration, with a predilection for adipose tissue, by a diffuse cellular infiltrate composed of small lymphocytes, plasmacytoid lymphocytes and plasma cells, admixed with large number of crystal‐storing histiocytes. Intracytoplasmic crystals were not identified either in the plasma cells or plasmacytoid lymphocytes. The neoplastic cells and the crystalline inclusions displayed reactivity with antibodies for IgG and the kappa light chain. A polymerase chain reaction study for the IgH gene showed a monoclonal rearrangement. Ultrastructural studies showed needle‐shaped crystals surrounded by a single unit membrane.ConclusionThis case is, to the authors' knowledge, the first to be described in which crystal‐storing histiocytosis is associated with a clinical picture of multifocal fibrosclerosis, which suggests that lymphoproliferative processes should be considered in the differential diagnosis of the various conditions associated with multifocal fibrosclerosis.
Perforin and Fas pathways of cytotoxic T‐cells in histiocytic necrotizing lymphadenitis
Authors: Ohshima K , Shimazaki K , Kume T , Suzumiya J , Kanda M , Kikuchi M 
Published: March 2003

AimsCell death can be divided into necrosis and apoptosis. In histiocytic necrotizing lymphadenitis (HNL), apoptosis is the main form of cell death. Two molecular mechanisms of T‐cell‐mediated cytotoxicity, one perforin‐based and the other Fas‐based, have been demonstrated, and both systems induce apoptosis of the target cells. This study was designed to investigate the Fas and perforin pathways in HNL.Methods and resultsTwelve cases of HNL were analysed using immunohistochemical staining. The Fas and/or FasL‐positive cells, including lymphocytes and histiocytes, were frequently encountered in the necrotizing lesions, however, they were rare in the nonpathological regions. The perforin and/or granzyme‐positive cells were also confined in the necrotizing lesions. In double staining, CD8‐positive lymphocytes occasionally expressed Fas and/or FasL, and histiocytes also expressed FasL and/or Fas. However, CD4‐positive lymphocytes rarely expressed FasL and/or Fas. In a flow cytometric analysis, most of the cytotoxic T‐cells, which were recognized by cytolytic granules of TIA‐1 and considered to be CD8‐positive lymphocytes, expressed FasL and Fas. The perforin‐positive lymphocytes also expressed FasL and Fas.ConclusionIn our previous study, the apoptotic cells were T‐cells, especially CD8‐positive cells rather than CD4‐positive cells. Based on these findings, in Fas and perforin pathways, the CD8‐positive cells were considered to be effector and target cells, while histiocytes could possibly be enhancers. As a result, both pathways seemed to induce an abundance of apoptosis and thus induce necrotizing lesions.
Prognostic comparison of the pathological classifications of gastric cancer: a population‐based study
Authors: Roy P , Piard F , Dusserre‐Guion L , Martin L , Michiels‐Marzais D , Faivre J 
Published: March 2003

AimsThere is controversy over the value of the pathological classifications of gastric carcinomas in the prediction of patient survival. This study was designed to assess the prognostic value of four widely used pathological classifications, in addition to classical prognostic factors.Methods and resultsRecords from the population‐based registry of digestive tract tumours in the department of Côte d'Or (France) have been analysed. All available histopathological slides of gastric cancer resected between 1976 and 1985 were reviewed and classified according to World Health Organization (WHO), Laurén, Ming and Goseki pathological coding systems. A relative survival analysis was performed using a relative survival model with proportional hazard applied to net mortality by interval. WHO, Laurén or Goseki classifications were not found to be independent prognostic factors. In addition to advanced age group, depth of parietal involvement, nodal involvement, presence of metastases, tumour site and gross appearance of the tumour, the Ming's infiltrative type was associated with a lower survival.ConclusionThis study suggests an independent prognostic value of the Ming subtypes with respect to survival in patients resected for gastric carcinoma.
Liposarcoma with meningothelial‐like whorls: a study of 17 cases of a distinctive histological pattern associated with dedifferentiated liposarcoma
Authors: Fanburg‐Smith J C , Miettinen M 
Published: March 2003

AimsWe reviewed 17 cases of liposarcoma with peculiar meningothelial‐like whorls to determine the pathological and clinical significance of this distinctive morphological finding.Methods and resultsSeventeen liposarcomas with concentric whorls simulating the whorls seen in meningioma, were retrieved from the soft tissue registry of the Armed Forces Institute of Pathology. There were 10 males and seven females with a mean age of 53 years (range 24–76 years). Twelve of the 17 cases were large retroperitoneal tumours (mean 170 mm in greatest dimensions). All 17 cases had whorls. Three cases were classified as well‐differentiated liposarcoma with whorls and bone formation. Five cases showed coalescing of whorls into areas which may be interpreted as low to intermediate grade dedifferentiation. Five cases had spindled areas associated with the whorls which correlate with classical intermediate to high‐grade dedifferentiation, Finally, four cases had a predominant spindle cell component resembling malignant fibrous histiocytoma with focal residual possible sclerosing well‐differentiated liposarcoma (scattered adipocytes, adipocytic atypia and/or floret‐type giant cells). The meningothelial‐like whorls were clustered or scattered throughout the tumours and ranged from 0.09 mm to over 10 mm in diameter in cases with coalescent whorls. Metaplastic bone was present within the whorls or in their immediate vicinity in 10 of 17 cases. Immunohistochemically, the whorl‐forming spindle cells showed α‐smooth muscle actin reactivity in three of seven cases but were negative for epithelial membrane antigen, CD21, and CD35 indicating lack of relationship with meningioma and dendritic reticulum cell sarcoma, other tumours that may contain whorls. Whorls with bone formation revealed cells adjacent to the bone to be positive for osteocalcin, a marker of osteoblastic phenotype. The spindle cells of the whorls were negative for CD34 and CD31, yet these highlighted numerous capillaries inside the whorls in a concentric manner. The whorl‐forming cells showed moderate to high MIB‐1‐index and showed p53 immunoreactivity similar to the dedifferentiated areas but differed from the areas of well‐differentiated liposarcoma, which were p53‐negative and showed a low MIB‐1‐index. Follow‐up (available in 65% cases) revealed seven patients with metastases or dead of the disease and five patients with one or more recurrences.ConclusionsThe meningothelial‐like whorls represent a mesenchymal proliferation which may undergo pericytic or myofibroblastic, or occasionally osteoblastic, differentiation in liposarcoma. These whorls do not represent dendritic or perineurial/meningothelial differentiation. The significant proliferative activity, p53 reactivity and tendency to coalesce and associate with dedifferentiated liposarcoma suggest that the meningothelial whorls may represent an early sign of dedifferentiation of liposarcoma.
Malignant proliferating trichilemmal tumours: an histopathological and immunohistochemical study of three cases with DNA ploidy and morphometric evaluation
Authors: Herrero  , Monteagudo  , Ruiz  , Llombart‐Bosch  
Published: March 2003

Aims: Malignant proliferating trichilemmal tumours (MPTT) are rare neoplasms capable of tissue invasion and metastasis, the diagnosis of which is based essentially on histological features. In difficult cases, however, evaluation of additional parameters may be needed to diagnose malignancy.Methods and resultsWe report three cases of MPTT in which, in addition to the histological features, we have determined the DNA ploidy, nuclear area and proliferative fraction. CD34 immunoreactivity has also been tested. Two cases were aneuploid, and one diploid with increased proliferating index. PCNA immunostaining labelled 40% and 80% of tumour cells in aneuploid tumours and 30% of the diploid neoplasm. In all cases, nuclear area was consistent with large pleomorphic tumour cells. No CD34 immunostaining was detected.ConclusionsAneuploidy is common in MPTT, particularly in tumours with a high proliferative fraction. Loss of CD34 immunoreactivity is an additional feature of potential, though limited, value. Therefore, evaluation of the DNA content, proliferation markers and CD34 immunostaining may be helpful in the diagnosis of MPTT.
Sustentacular cells in pulmonary neuroendocrine tumours
Authors: Gosney  , Denley  , Rešl  
Published: March 2003

AimsTo determine the prevalence of sustentacular cells across the range of pulmonary neuroendocrine tumours: typical and atypical carcinoid tumours and large cell and small cell neuroendocrine carcinomas.Methods and resultsSustentacular cells were sought in 80 pulmonary neuroendocrine tumours by immunolabelling for S100 protein, nerve growth factor receptor and glial fibrillary acidic protein. Intratumoural macrophages and Langerhans cells were identified with the KP 1 (CD68) and CD1A antibodies. S100‐positive sustentacular cells were present in 25 of 30 typical carcinoids, 20 of 25 atypical tumours, six of 10 large cell carcinomas and six of 15 small cell lesions. They were most numerous in the typical carcinoids but very few in the small cell carcinomas, their prevalance being clearly related to grade of differentiation and, in particular, to the degree of architectural organization.ConclusionsSustentacular cells are often found in pulmonary neuroendocrine tumours, especially better‐differentiated lesions with a well‐developed architecture, their prevalence clearly reflecting the degree of structural organization. Whether their prevalence is a useful prognostic indicator within a particular group of such tumours, such as the atypical carcinoids or the large cell carcinomas, as appears to be the case with paragangliomas, is unclear.
Haemophilic arthropathy resembles degenerative rather than inflammatory joint disease
Authors: Roosendaal  , van Rinsum  , Vianen  , van den Berg  , Lafeber  , Bijlsma  
Published: March 2003

AimsTo investigate the pathogenetic mechanisms of haemophilic arthropathy (HA) by comparing end‐stage arthropathy with osteoarthritis (OA; a degenerative joint disorder) and rheumatoid arthritis (RA; an inflammation‐mediated joint disease).Methods and resultsCartilage and synovium from patients with HA (n = 10), RA (n = 8), OA (n = 14) and normal control subjects (n = 6) were examined morphologically, biochemically and histochemically. Cartilage in HA exhibited characteristics of degenerative joint disease (OA), as evidenced by morphological, histochemical (Safranin‐O fast green‐iron haematoxylin, Mankin grade) and biochemical (proteoglycan synthesis, glycosaminoglycan content and DNA content) changes, whereas synovium in HA showed characteristics of inflammation‐mediated joint disease (RA), as evidenced by histochemical (inflammation, haematoxylin and eosin (H&E) and iron deposition, Perls' blue) and biochemical changes (interleukin (IL)‐1, IL‐6, tumour necrosis factor (TNF)α and catabolic properties).ConclusionHaemophilic arthropathy shows characteristics of both inflammatory and degenerative joint disease. On the basis of these results and published information, it appears that degenerative cartilage changes have a dominant role in HA and are augmented by relatively mild inflammation of the synovium.
PCR‐based clonality analysis: a reliable method for the diagnosis and follow‐up monitoring of conservatively treated gastric B‐cell MALT lymphomas?
Authors: Aiello  , Giardini  , Tondini  , Balzarotti  , Diss  , Peng  , Delia  , Pilotti  
Published: March 2003

AimsWe evaluated polymerase chain reaction (PCR) amplification of specific immunoglobulin heavy chain (IgH) gene rearrangements as a means of demonstrating monoclonality during follow‐up of conservatively treated gastric MALT lymphoma, and compared the reproducibility of PCR on sequential frozen and paraffin‐embedded endoscopic biopsies. We established an association between clonality detected by PCR and the histological observations.Methods and resultsSixty‐nine pairs of sequential frozen and paraffin‐embedded endoscopic biopsies from 21 conservatively treated patients were graded according to the Wotherspoon–Isaacson histological scoring system, which provides a measure of diagnostic confidence on a scale 0–5. PCR amplification of the IgH gene was performed using FR3/JH and FR2/JH primers. 68/69 paired samples (98.5%) showed identical mono‐ or polyclonal PCR amplification patterns. Forty‐seven out of 48 pairs of samples sharing similar histological features produced identical amplification patterns in both fresh and paraffin‐embedded tissues. In comparison with the histological grading, monoclonality was detected in 64.2% and 41.6% of samples scored 5 and 4, respectively. Conversely, among 64 samples scored 0–3, a monoclonal pattern was observed only in two samples, one of which was from a patient who relapsed 9 months later.ConclusionsPCR‐based clonality analysis by demonstration of specific IgH gene rearrangement can be easily and reliably performed on both frozen and paraffin‐embedded endoscopic biopsies. In conjunction with histological observation, this method can be used as a complementary tool to monitor MALT lymphoma regression during conservative treatment.
Nuclear expression of p53, p21 and cyclin D1 is increased in bronchioloalveolar carcinoma
Authors: McDonald  , Pilgram  
Published: March 2003

AimsThe objectives of this study were: (1) to determine, using immunohistochemistry, the level of expression of the cell cycle factors p53, p21 and cyclin D1 in a group of bronchioloalveolar carcinomas (BACs), and to compare these data to relevant published data for lung carcinoma; (2) to determine if higher expression rates for these factors in BAC were associated statistically with advanced clinical stage, greater tumour size, tobacco abuse, and/or BAC subtype; (3) to seek, using Fisher's exact t‐test and paired data groups, any significant associations within the expression data for p53, p21 and cyclin D1.Methods and resultsA panel of monoclonal antibodies against p53, p21 and cyclin D1 was applied to 19 bronchioloalveolar carcinomas (17 surgical pathology cases and two autopsies) from the tissue archives of St. Louis University. These immunohistochemical stains were graded on a semiquantitative scale according to the prevalence of nuclear staining within the tumour (< 10% positive cells = 0, 10–25% = 1+, 25–50% = 2+, 50–75% = 3+ and 75–100% = 4+). Six of 19 (32%) of BACs showed 1+ or greater p53 positivity, six of 19 (32%) showed 1+ or greater nuclear cyclin D1 positivity, and nine of 19 (47%) of BACs showed 1+ or greater p21 nuclear positivity. A statistically significant correlation was found between p53 and cyclin D1 expression (P = 0.046, Fisher's exact t‐test), but not between p53 and p21, or between p21 and cyclin D1. No statistically significant association was found between the cell cycle factor expression data and subtype of BAC (mucinous vs. nonmucinous), tumour diameter, clinical stage or tobacco‐use history.ConclusionsBACs show p53 immunostain positivity at a frequency similar to that published for p53 mutations in lung adenocarcinomas in general. Cyclin D1 and p21 nuclear expression characterizes a significant proportion of BACs, with cyclin D1 and p53 expression showing a statistically significant association. Aberrations in p53, p21, and cyclin D1 expression may be important in the development of a significant proportion of BACs.