bluuebunny/crossref_metadata_2025_split huggingface dataset:
Histological changes in the hypofunctional pituitary gland following conventional radiotherapy for adenoma
Authors: Nishioka H , Ito H , Haraoka J , Hirano A 
Published: March 2003

Histological changes in the hypofunctional pituitary gland following conventional radiotherapy for adenoma Aims: Although delayed hypopituitarism is a common complication of conventional radiotherapy of sellar tumours, histological changes that may account for it have been rarely reported. To elucidate the changes, hypofunctional pituitary glands following irradiation were studied. Methods and results: Two pituitary glands obtained at autopsy from patients who had been irradiated for adenoma and exhibited hypopituitarism were examined. In both cases diffuse fibrosis was observed in the adenohypophysis, whereas the neurohypophysis remained unchanged. Immunohistochemistry showed that stellate‐shaped S100 protein‐positive cells were increased in number and distributed among the endocrine cells. Some irradiated endocrine cells showed dense granular immunoreactivity for mitochondrial protein, cytochrome oxidase and manganese‐superoxide dismutase. In addition to faint reactivity with anti‐cytokeratin 8, 18 antibody, many cells were densely positive with anti‐cytokeratin 1, 5, 10, 14 antibody. Conclusions: These results indicate that radiation‐ induced fibrosis is associated with an increased number of folliculo‐stellate cells and the presence of metabolic dysfunctional mitochondria resembling mitochondria in oncocytes. Squamous metaplasia in the irradiated endocrine cells was also noted. Various intracellular changes may participate in delayed pituitary hypofunction following radiotherapy.
Histomorphometric assessment of bone turnover in uraemic patients: comparison between activation frequency and bone formation rate
Authors: Ballanti P , Coen G , Mazzaferro S , Taggi F , Giustini M , Calabria S , Ferrannini M , Bonucci E 
Published: March 2003

Histomorphometric assessment of bone turnover in uraemic patients: comparison between activation frequency and bone formation rate Aims: The histomorphometric assessment of bone formation rate (BFR/BS) in bone biopsies from uraemic patients is of crucial importance in differentiating low from high turnover types of renal osteodystrophy. However, since BFR/BS relies on osteoblasts, activation frequency (Ac.f), encompassing all remodelling phases, has recently been preferred to BFR/BS. This study was carried out to consider whether estimation of Ac.f is superior, in practical terms, to that of BFR/BS in distinguishing between different rates of bone turnover in uraemic patients. Methods and results: Bone biopsies from 27 patients in predialysis (20 men and seven women; mean age 53 ± 12 years) and 37 in haemodialysis (22 men and 15 women; mean age 53 ± 12 years) were examined. The types of renal osteodystrophy were classified on the basis of morphology. Bone formation rate and Ac.f were evaluated according to standardized procedures. The Ac.f was calculated both as a ratio between BFR/BS and wall thickness (W.Th) and as a reciprocal of erosion, formation and quiescent periods (EP, FP and QP). Patients were affected by renal osteodystrophy with predominant hyperparathyroidism (two predialysis and 16 dialysis), predominant osteomalacia (three predialysis and seven dialysis) or that of advanced (nine predialysis and five dialysis) or mild (seven predialysis and four dialysis) mixed type or adynamic type (six predialysis and five dialysis). Activation frequency, which with either formula requires the measurement of W.Th, i.e. the thickness of bone structural units (BSUs), was not calculated in three dialysis patients with severe hyperparathyroidism and in one predialysis and four dialysis patients with severe osteomalacia, because only incomplete BSUs were found. In dialysis, EP was higher in the adynamic than in the other types of osteodystrophy. During both predialysis and dialysis, FP was higher in osteomalacia than in the other forms of osteodystrophy, and in adynamic osteopathy than in hyperparathyroidism or in advanced and mild mixed osteodystrophy. During predialysis and dialysis, QP was higher in the adynamic than in the other forms of osteodystrophy. Correlations were found between BFR/BS and Ac.f, during predialysis (r=0.97) and dialysis (r=0.95). Conclusions: The superiority of Ac.f in assessing bone turnover, in comparison to BFR/BS, is conceptual rather than practical. The highest values for FP in osteomalacia and for QP in adynamic bone allow a clearer characterization of these low turnover conditions.
Follicular adenoma with papillary architecture: a lesion mimicking papillary thyroid carcinoma
Authors: Mai K T , Landry D C , Thomas J , Burns B F , Commons A S , Yazdi H M , Odell P F 
Published: March 2003

Follicular adenoma with papillary architecture: a lesion mimicking papillary thyroid carcinoma Aims: The purpose of this study was to investigate the significance of ‘benign’ encapsulated follicular thyroid nodules with papillary structures. Methods and results: Twenty‐one cases of encapsulated neoplastic thyroid nodules with papillary structures and nuclear features not diagnostic of papillary thyroid carcinoma (PTC) were obtained. All cases were reviewed with particular attention to nuclear features (fine chromatin pattern, optical clearing, grooves and inclusions). Representative sections were submitted for measurement of the maximum diameter of 200 round or nearly round nuclei and for immunostaining for MIB1, CK19, HBME and Ret oncogene protein. Nine cases displayed scattered optically clear nuclei or nuclear grooves in less than 30% of total neoplastic cells. They were grouped in the category of thyroid nodules with limited nuclear features of papillary thyroid carcinoma (PTC), but not diagnostic of PTC. The other 12 cases had fine or coarse chromatin, but lacked other features of nuclei in PTC. The diameter of the nuclei ranged from 5.6 to 7.2 μm and were smaller than those of PTC (6.3–10.0 μm). Immunostaining revealed positive reactivity for MIB1 in the papillary structures. Immunostaining for CK19 and HBME varied from negative or focally weak to diffusely moderate reactivity. Ret oncogene protein immunostaining showed focal and weak reactivity in one case and was negative in other cases of the study. Clinical follow‐up from 6 months to 15 years revealed no evidence of metastasis. Conclusions: The papillary structures in the study cases are unlikely to represent degenerative changes due to their proliferative activity. In view of (i) the encapsulation and the uniformity of the constituent cells, (ii) the varying degrees of immunoreactivity for CK19 and HBME and negative immunoreactivity for Ret oncogene protein, and (iii) the absence or insufficiency of nuclear criteria for the diagnosis of PTC and the absence of lymph node metastasis in all study cases, we believe that these lesions represent the papillary variant of follicular adenoma. Recognition of this pathological entity is important to avoid an over‐diagnosis of PTC.
Different patterns of β‐catenin expression in gastric carcinomas: relationship with clinicopathological parameters and prognostic outcome
Authors: Grabsch H , Takeno S , Noguchi T , Hommel G , Gabbert H E , Mueller W 
Published: March 2003

Different patterns of β‐catenin expression in gastric carcinomas: relationship with clinicopathological parameters and prognostic outcome Aims: The cadherin–catenin complex is known to play a critical role in maintenance of cell adhesion. Additionally β‐catenin (β‐ct) can also take part in signal transduction and nuclear β‐ct expression could be correlated with poor prognosis in several malignancies. Since, in gastric cancer, this role of β‐ct is still uncertain, we investigated the expression pattern of β‐ct as well as the possible prognostic role. Methods and results: β‐catenin expression was immunohistochemically investigated in a retrospective series of 401 R0‐resected gastric carcinomas. Out of these cases, 54 tumours (13.5%) revealed a preserved membranous β‐ct expression similar to that in normal gastric mucosa. In 80 tumours β‐ct expression was moderately reduced and in 117 tumours highly reduced. In 150 tumours (37.4%), no or only a weak membranous β‐ct expression was found. Additionally, in 53 tumours, a strong β‐ct expression could be observed in the cytoplasm with a simultaneous nuclear β‐ct immunoreactivity in 17 of these 53 tumours, while nine tumours only showed nuclear immunoreactivity without cytoplasmic staining. There were no significant correlations between the degree of membranous β‐ct expression or the different staining pattern (membranous vs. cytoplasmic/nuclear) and the grade of tumour differentiation, the histological tumour type according to Lauren, as well as with the prognostic parameters pT, pN category and vascular invasion. No associations could be found with tumour cell proliferation and the expression of E‐cadherin, irrespectively of the different β‐ct staining pattern. Univariate analysis revealed no influence on survival, either for membranous or for cytoplasmic/nuclear β‐ct expression. Conclusion: Our data on 401 tumours suggest that activation of the Wnt/β‐catenin signalling does also occur in a subset of gastric carcinomas. However, in gastric cancer, neither the presence of cytoplasmic/nuclear β‐ct expression nor the reduction or loss of membranous β‐ct expression is correlated with a specific histological tumour type, tumour progression or prognosis.
MLH1 and MSH2 protein immunohistochemistry is useful for detection of hereditary non‐polyposis colorectal cancer in young patients
Authors: Paraf F , Gilquin M , Longy M , Gilbert B , Gorry P , Petit B , Labrousse F 
Published: March 2003

MLH1 and MSH2 protein immunohistochemistry is useful for detection of hereditary non‐polyposis colorectal cancer in young patients Aims: Hereditary non‐polyposis colorectal cancer is related to germline mutations of DNA mismatch repair genes MLH1 and MSH2, which result in microsatellite instability and loss of protein expression of the corresponding mutated gene in the tumour tissue. Methods and results: MLH1 and MSH2 protein expression was studied by immunohistochemistry in paraffin‐embedded surgical samples of 100 colorectal adenocarcinomas occurring before 50 years of age. Absence of tumour cell nuclear staining with positive internal control (normal mucosa, lymphoid follicles) was considered negative. Loss of MLH1 or MSH2 expression was found in 20 cases with microsatellite instability in 15 cases. Twelve of these patients had a family history of colorectal cancer. Compared with MLH1‐ and MSH2‐positive cases, MLH1‐ or MSH2‐deficient colorectal adenocarcinomas were significantly associated on multivariate analysis with a younger age (38 vs. 43 years, P;0.0224), a larger tumour size (60 ± 6 vs. 46 ± 2 mm, P=0.0291), an expanding margin (85% vs. 51%, P=0.0159), a higher number of tumour‐infiltrating lymphocytes assessed by CD3 immunostaining (202 ± 48 vs. 33 ± 4 CD3+ lymphocytes/10 high‐power fields, P=0.0039), and a grade 2 Crohn's like lymphoid reaction (70% vs. 9%, P=0.0037). The two groups were not different for tumour site, differentiation, pTNM stage, vascular and perineural invasion, peripheral adenomatous residue, and 5‐year survival rates. Conclusions: MLH1‐ or MSH2‐deficient colorectal carcinomas of young patients exhibit pathological and molecular features similar to hereditary non‐polyposis colorectal cancer. This suggests that MLH1 and MSH2 immunohistochemistry is valuable for detecting hereditary non‐polyposis colorectal cancer in young patients.
Ber‐EP4 immunoreactivity depends on the germ layer origin and maturity of the squamous epithelium
Authors: Rossen K , Thomsen H K 
Published: March 2003

Ber‐EP4 immunoreactivity depends on the germ layer origin and maturity of the squamous epithelium Aim: To map the expression of Ber‐EP4 in well‐differentiated squamous epithelia, metaplastic squamous epithelia and dysplastic squamous epithelia of different origins. Methods and results: Squamous epithelium of different origin was stained using a standard immunohistochemistry method applied to paraffin sections. We found that normal squamous epithelium of the oral cavity, oesophagus, uterine cervix, vagina, anal canal, and branchial cysts are Ber‐Ep4‐negative, as are the mature squamous metaplasia of bronchial mucosa, urinary bladder mucosa and uterine cervical mucosa. In contrast, immature squamous metaplasia of bronchial mucosa, or uterine cervical mucosa, and squamous dysplasia of oral mucosa of endodermal origin, or uterine cervical mucosa in most cases expressed Ber‐EP4. Conclusion: Squamous epithelia of ectodermal origin never express Ber‐EP4, whether normal, hyperplastic, dysplastic or neoplastic. In contrast, squamous epithelium of endodermal origin sometimes contains the target glycoproteins of Ber‐EP4 when immature, metaplastic, dysplastic or neoplastic. The results indicate that the differences in expression of Ber‐EP4 in squamous epithelium depend primarily on germ layer origin, and on the maturity of the epithelium.
Expression of cell cycle regulatory proteins in the multistep process of oesophageal carcinogenesis: stepwise over‐expression of cyclin E and p53, reduction of p21WAF1/CIP1 and dysregulation of cyclin D1 and p27KIP1
Authors: Ohbu M , Kobayashi N , Okayasu I 
Published: March 2003

Expression of cell cycle regulatory proteins in the multistep process of oesophageal carcinogenesis: stepwise over‐expression of cyclin E and p53, reduction of p21WAF1/CIP1 and dysregulation of cyclin D1 and p27KIP1 Aims: Cell cycle regulatory proteins were analysed by immunohistochemistry in order to clarify how their expression changes with the degree of atypia as oesophageal surface squamous epithelium progresses from normal mucosa, through reactive change, low‐grade dysplasia, and high‐grade dysplasia to mucosal invasive carcinoma. Methods and results: Immunostaining for cyclin D1, cyclin E, p21, p27, p53 and Ki67 proteins was performed using 22 normal mucosa, 17 reactive change, 22 low‐grade dysplasia, 15 high‐grade dysplasia and 22 mucosal invasive carcinoma specimens. Normal mucosa, low‐grade dysplasia and high‐grade dysplasia samples were taken from patients without any oesophageal invasive carcinoma by endoscopic biopsy or endoscopic mucosal resection, and reactive change and mucosal invasive carcinoma were obtained from oesophagectomy material. Stepwise over‐expression of cyclin E (P < 0.0001) and p53 (P < 0.0001), reduction of p21 (P=0.0189) and dysregulation of cyclin D1 and p27 were observed in the multistep process of oesophageal carcinogenesis. Significant differences in expression of p27 (P < 0.0001), p53 (P=0.0299) and Ki67 (P=0.0101) were observed between reactive change and low‐grade dysplasia. Furthermore, expression of cyclin D1, cyclin E, p27 and p53 in mucosal invasive carcinoma were significantly different from those in high‐grade dysplasia (P=0.0079, P=0.0237, P=0.0042 and P= 0.0299, respectively). Conclusions: Cell cycle regulatory proteins, cyclin E, p53 and p21 show stepwise over‐expression or reduction with progression of oesophageal carcinogenesis, correlating with the increased cell proliferation observed with Ki67 labelling. We conclude that immunohistochemical analysis for p27, p53 and Ki67 is practically useful for the discrimination between low‐grade dysplasia and reactive change. Cyclin D1, cyclin E, p27 and p53 help to distinguish high‐grade dysplasia from mucosal invasive carcinoma.
Fatty acid synthase is highly expressed in carcinoma, adenoma and in regenerative epithelium and intestinal metaplasia of the stomach
Authors: Kusakabe T , Nashimoto A , Honma K , Suzuki T 
Published: March 2003

Fatty acid synthase is highly expressed in carcinoma, adenoma and in regenerative epithelium and intestinal metaplasia of the stomach Aims: To investigate the relation of fatty acid synthase (FAS) expression to the clinicopathological characteristics of gastric cancers and gastric tumorigenesis. Methods and results: FAS expression was examined immunohistochemically in 626 gastric cancers, 51 gastric adenomas, and non‐neoplastic epithelium contiguous with cancer tissue including normal foveolae, intestinal metaplasia, regenerative epithelium, and gastric glands. FAS expression was found in more than 70% of gastric cancers. Interestingly, it occurred preferentially in differentiated carcinomas, male cases, and in patients over 51 years old. Although previous reports showed that FAS expression is closely related to cancer progression, in gastric cancers FAS expression had no relationship with prognosis, cancer progression as indicated by depth of invasion, venous and lymphatic permeation, and distant metastasis. Gastric tubular adenoma and intestinal metaplasia, which are thought to be associated with well‐differentiated gastric carcinomas, showed a frequency of FAS expression similar to that of differentiated carcinomas; however, normal foveolae and gastric glands showed no or less FAS expression. Conclusions: FAS expression occurs at the early stage of tumorigenesis and plays important roles in the formation of precancerous foci rather than in the progression of carcinoma of the stomach.
Splenic small B‐cell lymphoma with predominant red pulp involvement: a diffuse variant of splenic marginal zone lymphoma?
Authors: Mollejo M , Algara P , Mateo M S , Sánchez‐Beato M , Lloret E , Medina M T , Piris M A 
Published: March 2003

Splenic small B‐cell lymphoma with predominant red pulp involvement: a diffuse variant of splenic marginal zone lymphoma? Aims: Splenic marginal zone lymphoma (SMZL) has been characterized by a micronodular pattern of infiltration, biphasic cytology, follicular replacement and the presence of marginal zone differentiation. Here we describe four cases with some distinctive features, such as diffuse splenic infiltration, lack of micronodules, marginal zone cytology, p53 inactivation and cutaneous involvement. Methods and results: In the course of a review of cases of SMZL, we recognized the existence of a subset of four cases of splenic B‐cell lymphoma, with predominantly red pulp involvement, absence of follicular replacement, and a monomorphous population of tumoral cells resembling marginal zone B‐cells, with scattered nucleolated blast cells. The immunophenotype (bcl2+, CD5−, CD10−, CD43−, CD23−, cyclin D1−, IgD− (3/4)) was consistent with SMZL. Bone marrow infiltration (4/4) and peripheral blood involvement (2/4) showed similar findings to those described for SMZL in these locations. However, unlike classical SMZL, 2/4 had cutaneous involvement, and 4/4 cases showed either p53 mutation or anomalous p53 staining (p53+, p21−). Conclusions: In spite of a diffuse pattern of splenic infiltration, cutaneous involvement and p53 alterations, these cases have findings that overlap with those corresponding to classic SMZL (symptomatology, morphology of bone marrow, lymph nodes, peripheral blood involvement, and immunophenotype). We suggest that these cases be considered a putative variant of SMZL.
Ki67 protein: the immaculate deception?
Authors: Brown D C , Gatter K C 
Published: March 2003

Ki67 protein: the immaculate deception? This article updates our previous review of Ki67 published in Histopathology 10 years ago. In this period the numbers of papers published featuring this antibody has increased 10‐fold from 338 to 3489 indicating the considerable enthusiasm with which this antibody has been studied. This review attempts to provide an update on the characterization of the Ki67 protein, its function and its use as a prognostic or diagnostic tool.
Marginal zone cell lymphoma—an update on recent advances
Authors: Maes B , De Wolf‐Peeters C 
Published: March 2003

Marginal zone cell lymphoma—an update on recent advances The marginal zone represents one of the distinct compartments of the B‐cell area in lymphoid tissues. It is especially well developed in the spleen and in Peyer's patches of the gut, but not in lymph nodes, with the exception of the ones in the mesenterium. However, the pronounced proliferation of so‐called `monocytoid B‐cells' that may be seen in some inflammatory conditions of the lymph node may be regarded as a nodal reactive marginal zone cell expansion. The cellular compositions of the marginal zone and the monocytoid B‐cell proliferation are similar and both show a heterogeneous population of B‐cells, of which the functions are being slowly unravelled. Neoplasms originating in the marginal zone have been recognized in the past and are listed in the REAL classification as marginal zone B‐cell lymphomas including extranodal MALT‐type lymphomas, splenic marginal zone lymphomas and nodal (monocytoid) marginal zone lymphomas. Marginal zone cell lymphomas display a broad morphological spectrum, which is reflected by the heterogeneity of the cellular composition and the variation in the growth pattern of the lymphoma, but is independent of the anatomical site. All three marginal zone cell lymphomas share immunophenotypic, genetic and chromosomal similarities which will be discussed. The morphologic features are dealt with only briefly as they have been extensively discussed elsewhere.
Cytokeratin 19 and galectin‐3 immunohistochemistry in the differential diagnosis of solitary thyroid nodules
Authors: Beesley M F , McLaren K M 
Published: March 2003

Aims : The immunohistochemical expression of cytokeratin 19 (CK19) and galectin‐3 was evaluated in 69 thyroid lesions to assess their potential asmarkers in the diagnosis and classification of thyroid malignancy. The following were studied: 26 cases of papillary carcinoma, 12 of follicular carcinoma, 20 follicular adenomas, two medullary carcinomas, one anaplastic carcinoma and eight multinodular goitres.Methods and results : Formalin‐fixed paraffin‐embedded thyroid tissues were stained immunohistochemically for both CK19 and galectin‐3. CK19 expression was found in all 26 papillary carcinomas, five of 12 follicular carcinomas, two of two medullary carcinomas and one case of anaplastic carcinoma. Only five of 20 follicular adenomas were positive for CK19, and this was in a focal distribution. Two of eight multinodular goitres stained focally positive. Galectin‐3 expression was found in 22 of 26 papillary carcinomas, 12 of 12 follicular carcinomas and one of two cases of medullary carcinoma. Only two of 20 follicular adenomas were positive. Three of eight multinodular goitres showed focal galectin‐3 expression.Conclusions : Our findings suggest that the immunohistochemical localization of CK19 and of galectin‐3 is a useful adjunct to the histopathological diagnosis of a solitary thyroid lesion. The expression of CK19 favours a diagnosis of papillary carcinoma in all its variant patterns. Galectin‐3 may serve as a marker for the recognition of follicular carcinoma, particularly the minimally invasive form.