bluuebunny/crossref_metadata_2025_split huggingface dataset:
The value of histomorphometric nuclear parameters in the diagnosis of well differentiated follicular carcinomas and follicular adenomas of the thyroid gland
Authors: Eldar  , Sabo  , Cohen  , Misselevich  , Abrahamson  , Cohen  , Kelner  , Boss  
Published: March 2003

AimsTo explore the potential of histomorphometric analysis in distinction between follicular adenomas and well differentiated follicular carcinomas of the thyroid gland. Their differentiation on routine histological study may be a challenging exercise, being contingent upon the absence or presence of vascular invasion and penetration of neoplastic follicles through the capsule of the tumour.Methods and resultsComputer‐assisted image analysis was performed to gauge the nuclear area, nuclear Ferret diameter, nuclear regularity factor, nuclear elongation factor, number of nuclear vesicles and total area of all nuclear vesicles in the follicles of 37 adenomas and 36 well differentiated carcinomas. By univariate analysis, these nuclear descriptors (with the exception of the elongation factor) were found to correlate with the benign or malignant nature of the tumours. By multivariate analysis, only the nuclear area, Ferret diameter and regularity factor were ascertained to be significant predictors of malignancy. A fitted logit model correctly predicted 91% of the cancers and 87% of the adenomas.ConclusionsHistomorphometrically gauged nuclear parameters of the tumour cells may reinforce pathologists' decision‐making by adding objective and unbiased criteria to their subjective assessment of follicular neoplasms in cases in which vascular or capsular invasion are not detected.
Reliability of intraoperative frozen section and imprint cytological investigation of sentinel lymph nodes in breast cancer
Authors: Van Diest P J , Torrenga H , Borgstein P J , Pijpers R , Bleichrodt R P , Rahusen F D , Meijer S 
Published: March 2003

AimsThe sentinel lymph node procedure enables selective targeting of the first draining lymph node, where the initial metastases will form. A negative sentinel node (SN) predicts the absence of tumour metastases in the other regional lymph nodes with high accuracy. This means that in the case of a negative SN, regional lymph node dissection is no longer necessary. Besides saving costs, this will prevent many side‐effects of lymph node dissection. The aim of this study was to evaluate the reliability of intraoperative cytological and frozen section investigation of the SN to detect metastases. This would allow the axillary lymph node dissection to be performed in the same session as the SN procedure and the excision of the primary tumour in case of a positive SN.Methods and resultsSeventy‐four SNs were detected by gamma probe detection of nanocolloid and visual localization of Patent Blue accumulations in 54 women with stage T1–2N0M0 invasive breast cancer. The identified SN were immediately investigated by frozen section and imprint cytological investigation. Diagnoses were confirmed on the paraffin material, and in case of negative frozen section and paraffin haematoxylin and eosin sections, skip sections and immunohistochemistry were performed. Thirty‐one SNs (42%) contained metastases, of which 27 were detected by the frozen section procedure (sensitivity 87%). There were no false positives (specificity 100%). The sensitivity of the imprints was 62% with a specificity of 100%. When evaluating the data per patient, for the frozen section procedure the sensitivity was 91% and the specificity 100%, and for the imprints, the sensitivity was 63% and the specificity 100%. There were no SNs in which the imprints showed metastases and the frozen section did not.ConclusionsIntraoperative frozen section analysis is a reliable procedure by which a high percentage of sentinel lymph node metastases can be detected in breast cancer patients without false positive results. This allows the surgeon to perform an immediate axillary lymph node dissection in case of positive SNs. In up to 10% of cases, the final paraffin sections will reveal micrometastases that were not detected by the frozen section, and in these patients axillary lymph node dissection will have to be performed in a second session. The imprint method is significantly less sensitive than the frozen section but may be used as an alternative when frozen section is not possible.
Scarring in papillary carcinoma of the thyroid: report of two new cases with exuberant nodular fasciitis‐like stroma
Authors: Toti  , Tanganelli  , Schürfeld  , Stumpo  , Barbagli  , Vatti  , Luzi  
Published: March 2003

AimsTo describe two new cases of papillary carcinoma of the thyroid with exuberant nodular fasciitis‐like stroma, one of which was characterized by previously unreported transformation into a poorly differentiated lesion. Moreover, we explore the presence of TGF‐β to help to clarify the pathogenesis of the collagen formation.Methods and resultsThe case characterized by an aggressive behaviour exhibited areas of transformation into a poorly differentiated (insular) carcinoma of the thyroid. In both cases, as revealed by immunohistochemistry, neoplastic cells produced and secreted high amounts of TGF‐β. On the contrary, TGF‐β immunoreaction was never present in the normal thyroid or in papillary carcinomas without collagen bundles, while a weak, exclusively intracellular reaction was present in a patchy manner in cases showing intratumoral fibrous bundles.ConclusionsThe rare variant of papillary thyroid carcinoma characterized by exuberant stroma may give rise to more aggressive lesions, as do other histotypes of differentiated thyroid carcinomas. TGF‐β, the fundamental cytokine which mediates scarring and activation of myofibroblasts, most probably induces the exuberant stroma.
Absence of Epstein–Barr virus (EBV) in intrahepatic cholangiocarcinoma confirmed by lack of EBV‐coded nuclear RNA and latent membrane protein‐1
Authors: Ozaki  , Harada  , Watanabe  , Furubo  , Tsui  , Nakanuma  
Published: March 2003

AimsStudies are disclosing that Epstein–Barr virus (EBV) is involved in the aetiology of various neoplasms including undifferentiated carcinomas of the aerodigestive tract. The aetiology of intrahepatic cholangiocarcinoma (ICC), a malignant neoplasm arising from intrahepatic biliary epithelia, has yet to be fully evaluated. To date, two cases of EBV‐related ICC have been reported, and they presented foci of lymphoepitheliomatous undifferentiated carcinoma components.Methods and resultsTo determine whether EBV is commonly involved in the developments of ICC, we performed in‐situ hybridization and immunohistochemistry for EBV in 215 cases of ICC in Japan, using a probe against EBV‐coded nuclear RNA (EBER) and a specific antibody against latent membrane protein‐1 (LMP‐1), respectively. We did not detect EBV‐infected carcinoma cells in any of the ICC cases examined. No lymphoepitheliomatous undifferentiated carcinoma components were found either.ConclusionThe results suggest that EBV infection is unlikely to be involved in the pathogenesis of ICC.
Reduced expression of the cell‐cycle inhibitor p27Kip1 is associated with progression and lymph node metastasis of gastric carcinoma
Authors: Kim  , Lee  , Nam  , Shin  , Sohn  , Park  , Yoon  , Song  , Park  
Published: March 2003

Aimsp27Kip1 (p27), a cyclin‐dependent kinase inhibitor, plays an important role as inhibiting the progression of the cell cycle. Decreased expression of p27 is associated with high histological grade and aggressiveness of several human tumours. We aimed to evaluate the role of p27 in the progression and metastasis of gastric carcinoma.Methods and resultsWe analysed the expression of p27 in 67 primary gastric carcinomas and 31 lymph node metastases by immunohistochemistry. Reduced expression of p27 was found more frequently in advanced gastric cancer (40.9%) than in early gastric cancer (15.6%) (P < 0.001). Decreased p27 expression correlated with large tumour size, high histological grade, lymphatic invasion, advanced stage, deep invasion, lymph node metastasis and recurrence. The expression of p27 showed an inverse correlation with the Ki67 labelling index. There was a significant reduction of p27 expression in metastatic tumour cells in lymph nodes (mean positive cells: 3.7%) when compared to the corresponding primary gastric carcinomas (mean positive cells: 8.1%) (P = 0.008).ConclusionsAlterations of p27 expression may play an important role in the progression and metastasis to lymph node of tumour cells in human gastric carcinoma.
Smooth muscle metaplasia in ovarian endometriosis
Authors: Fukunaga  
Published: March 2003

AimsLittle is known about smooth muscle metaplasia (SMM) in ovarian endometriosis. The clinicopathological significance of SMM in ovarian endometriosis is analysed.Methods and resultsThree hundred and twenty‐seven consecutive cases of ovarian endometriosis, including 58 cases associated with malignant ovarian epithelial tumour, between 1987 and 1996 were retrieved from hospital files and clinicopathologically analysed. The ages of the patients who showed SMM in ovarian endometriosis ranged from 28 to 70 years (average, 43.8 years). SMM was observed in 58 cases (17.7%); in 51 of 269 cases without tumour (19.0%) and in seven of 58 with tumour (12.1%). The differences in the incidence of SMM in cases with and without tumour were not statistically significant. SMM was a focal, microscopic change and there was neither smooth muscle tumour nor uterus‐like mass. Sixteen cases had short fascicles or stellate foci of SMM in the endometriotic stroma, an incomplete rim of SMM surrounding the endometriotic cysts was present in 32 cases, and 10 cases showed SMM in both the endometriotic stromal and incomplete rim of the endometriotic cysts. There was no significant histological difference in SMM between cases with and without malignant ovarian epithelial tumour.ConclusionsSMM in ovarian endometriosis is not an uncommon phenomenon. SMM may be explained in two ways. First, smooth muscle originates from metaplastic endometrial stromal cells in endometriotic foci. Second, it originates from metaplastic ovarian stromal cells in the rim of endometriosis.
Hot spot microvessel density and the mitotic activity index are strong additional prognostic indicators in invasive breast cancer
Authors: De Jong  , Van Diest  , A Baak  
Published: March 2003

AimsRecent studies have drawn attention to intratumoral microvessel density (MVD) as a prognostic factor in invasive breast cancer. Various methods have been applied to assess MVD and the prognostic value of MVD in different studies varies considerably. Counting of microvessels in the most highly vascularized area (hot spot) of a tumour is the method most widely used. In this study we compared three counting methods.Methods and resultsTo assess MVD in 112 cases of invasive breast cancer with long‐term follow‐up we performed microvessel counting in the hot spot of the tumour in four and 10 fields of vision (HS‐MVD4 and HS‐MVD10) and microvessel counting in 10 fields of vision distributed systematically over the whole tumour area (global MVD). The HS‐MVD4, HS‐MVD10 and global MVD showed good correlations with each other. HS‐MVD4 provided the highest number of microvessels (median value 71) followed by HS‐MVD10 and global MVD, with median values of 58 and 39, respectively. HS‐MVD4 showed the best prognostic value for overall survival (P = 0.0001) whereas HS‐MVD10 showed less (P = 0.01) and the global MVD showed no (P = 0.75) prognostic value. In univariate analysis, the HS‐MVD4 was the second strongest prognostic factor after tumour size. In multivariate survival analysis, the HS‐MVD4, mitotic activity index (MAI), lymph node status and tumour size were found to be independent prognostic factors. When combining MVD4 and MAI in lymph node negative patients, none of the patients with low MVD (< 71/mm2) and a low MAI (< 10 per 10 HPF) died, in contrast to patients with a high MVD or high MAI who have a 10‐year survival of 57%.ConclusionsThese data suggest that the hot spot MVD in four fields of vision is a major independent prognostic factor for overall survival in invasive breast cancer. For the first time, it is shown that hot spot MVD provides additional prognostic information to well established factors like lymph node status and the MAI, and may therefore be useful for designing treatment strategies in invasive breast cancer.
Renal lesions in von Hippel–Lindau disease: immunohistochemical expression of nephron differentiation molecules, adhesion molecules and apoptosis proteins
Authors: Paraf  , Chauveau  , Chrétien  , Richard  , Grünfeld  , Droz  
Published: March 2003

AimsRenal lesions in von Hippel–Lindau disease comprise clear cell simple cysts, atypical cysts and carcinomas. Although histological and molecular studies suggest that cystic lesions may represent precursors of carcinomas, there is no detailed phenotypic evidence of their relationship.Methods and resultsTo investigate such a possible relationship between cystic lesions and solid carcinomas, we studied the pathological and immunohistochemical features of 328 lesions of 33 kidneys originating from 23 patients with von Hippel–Lindau disease, using a panel of antibodies directed against cytoskeleton proteins, cell surface proteins, integrin subunits, adhesion molecules, lectins, and apoptosis and proliferation markers. Solid carcinomas (n = 175) were all of clear cell type and mostly nuclear grade 1. Cystic lesions (n = 138) consisted of cystic clear cell carcinomas (n = 15), atypical cysts (n = 20) and simple cysts (n = 103). Clear cells of the simple cysts, atypical cysts and solid carcinomas coexpressed cytokeratins (CK8, CK19) and vimentin, and expressed a similar pattern of tubular markers (CD24, tetraglonolobus), integrin subunits (α3, α5, α6, αv, β1) and cell adhesion molecules (ICAM 1, VCAM 1). In all lesions studied, proliferation rate (MIB1 index) was low, and apoptosis marker expression (fragmented DNA, p53, bcl‐2) inconspicuous.ConclusionsPhenotypic alterations found in solid renal cell carcinomas are already present in simple and atypical renal cysts of von Hippel–Lindau disease.
Adenocarcinoma of colon differentiating as dome epithelium of gut‐associated lymphoid tissue
Authors: Jass  , Constable  , Sutherland  , Winterford  , Walsh  , Young  , Leggett  
Published: March 2003

AimsAn early adenocarcinoma of the ascending colon was confined to a mass of gut‐associated lymphoid tissue (GALT). The first description of an adenocarcinoma of colon differentiating as dome epithelium is presented.Methods and resultsA plaque‐like carcinoma was identified opposite the ileocaecal valve in an asymptomatic 56‐year‐old man with a family history of colorectal cancer. Malignant epithelium was confined to a mass of GALT filling but limited to the submucosa. Characterization of the neoplasm was undertaken by means of mucin histochemistry, immunohistochemistry, electron microscopy and assessment of DNA microsatellite instability status. The malignant epithelium comprised well differentiated columnar cells with a microvillous brush border and expressing MUC1, but no goblet cells or expression of MUC2. The demonstration of focal clusters of intraepithelial B‐lymphocytes supported the presence of functioning M‐cells within the malignant neoplasm. The cancer was DNA microsatellite stable despite the finding of tumour infiltrating lymphocytes.ConclusionsThere is evidence for the origin of colorectal neoplasia from dome epithelium in both experimental models and microreconstruction studies of early adenomas in nonpolypotic human colorectal mucosa. It is suggested that the lymphocyte‐rich subset of colorectal cancer that expresses MUC1 but not MUC2 may be differentiating as dome epithelium of gut‐associated lymphoid tissue.
Overexpression of HER2/neu in solid tumours: an immunohistochemical survey
Authors: Koeppen H K W , Wright B D , Burt A D , Quirke P , McNicol A M , Dybdal N O , Sliwkowski M X , Hillan K J 
Published: March 2003

Aims:Using a standardized immunohistochemical assay we have evaluated 575 primary neoplasms of different histogenesis to determine the incidence of HER2 overexpression in some of the most common categories of human solid neoplasms. This study addresses the variable incidence of HER2 overexpression previously published for some tumour types.Methods and results:The immunohistochemical staining was performed on paraffin sections of surgical specimens and a well‐defined scoring system based upon numbers of HER2 receptors expressed on the cell surface was applied. Overexpression of HER2 as defined as a HER2 score of equal or greater than 2 was seen in breast cancer (22%), pulmonary adenocarcinoma (28%), colorectal adenocarcinomas (17%), pulmonary squamous (11%) and gastric adenocarcinomas (11%). As expected, the proportion of cases with a HER2 score of 3 was highest in breast cancer. Contrary to published results prostate and pancreas adenocarcinomas showed a very low incidence of HER2 overexpression.Conclusions:Overexpression of HER2 is detected immunohistochemically in a proportion of epithelial neoplasms of diverse histogenesis in addition to ductal breast cancer. The standardized format of the assay will allow comparative analyses of studies performed at different institutions.
Dirofilariasis due to Dirofilaria repens in Italy, an emergent zoonosis: report of 60 new cases
Authors: Pampiglione S , Rivasi F , Angeli G , Boldorini R , Incensati R M , Pastormerlo M , Pavesi M , Ramponi A 
Published: March 2003

Aims: Sixty new cases of human dirofilariasis due to Dirofilaria repens, occurring in Italy between 1990 and 1999, are presented. This is the most extensive case study of this zoonosis reported worldwide by a single study group. The aim is to utilize this large experience to characterize the different histopathological findings in the parasitic lesions in man.Methods and results: Diagnosis was performed on histological sections of the nematode enclosed in the nodules excised at biopsy or surgery. The nematode was located in the subcutaneous tissue (49 cases), the epididymis (two cases), the spermatic cord (two cases), the lung (two cases), the breast (two cases), the omentum (two cases) and under the conjunctival tissue (one case). The majority of cases (46) were from Piedmont; the remainder were from Emilia‐Romagna, Sardinia, Sicily, Tuscany, Apulia and Lombardy. The histopathological features of the lesions are described and the clinical and epidemiological aspects of the zoonosis are discussed. The prevalence in Italy in general and in the area of Piedmont in particular, comprising the provinces of Alessandria, Asti, Novara and Vercelli, which is one of the most severely affected areas of the world, is emphasized. The evident increase in the number of cases in the last few years is a clear indication that it is an emergent zoonosis.Conclusions: We recommend that each and every case observed be recorded, to enable the true extent of human dirofilariasis in Italy to be assessed, and that a reference centre be set up in the area to collate the data. The importance of the histopathologist's role in the diagnosis is stressed.
Pulmonary artery dissection in patients without underlying pulmonary hypertension
Authors: Inayama Y , Nakatani Y , Kitamura H 
Published: March 2003

Pulmonary artery dissection in patients without underlying pulmonary hypertension Aims: Pulmonary artery (PA) dissection is a rare event which usually occurs in patients with underlying pulmonary hypertension. We describe two patients who developed PA dissection without pre‐existing pulmonary hypertension and present an extensive review of the literature. Methods and results: In the first patient (a 59‐year‐old woman), acute‐onset dyspnoea was initially thought to have been caused by pulmonary thrombosis, and thromboendarterectomy was performed. Histologically, pulmonary dissection without external rupture was evident, chiefly in the right main PA. In the second patient, an 85‐year‐old man who had hypergammaglobulinaemia of unknown cause and died from a haemorrhagic gastric ulcer, arterial dissection was detected at autopsy. There was no underlying pulmonary hypertension in either patient. Although the true reason for the development of dissection is unclear, pre‐existing inflammation was considered to be related to its formation, at least in the second case. Conclusions: A literature review indicated that idiopathic and inflammation‐related PA dissection is extremely unusual. Since PA dissection is very rare, it is important to be aware of its features in order to make a correct diagnosis.
Oncocytic papillary carcinoma with lymphoid stroma (Warthin‐like tumour) of the thyroid: a distinct entity with favourable prognosis
Authors: Ludvíková M , Ryška A , Korabečná M , Rydlová M , Michal M 
Published: March 2003

Oncocytic papillary carcinoma with lymphoid stroma (Warthin‐like tumour) of the thyroid: a distinct entity with favourable prognosis Aims: We report the clinicopathological and immunohistochemical characteristics of 12 cases of a recently recognized entity, oncocytic papillary thyroid carcinoma (PC) with lymphoid stroma (Warthin‐like tumour). Methods and results: The cases were retrieved from the surgical pathology files of our departments. There were 11 female patients and one male patient; they ranged in age from 45 to 85 years (mean 64.2 years). The immunohistochemical profile demonstrated positivity of tumour cells for cytokeratins, thyroglobulin, Leu‐M1 and anti‐mitochondrial antigen. S100 protein‐positive stromal dendritic/Langerhans cells were uniformly present. Polymerase chain reaction, in situ hybridization, and immunohistochemistry for Epstein–Barr virus (EBV) detection revealed no significant positive signal. MIB‐1 labelling index was low, compatible with that of ‘classical’ PC. Conclusions: Warthin‐like tumour is a rare variant of PC, occurring predominantly in elderly women. Its histological features are distinct and well recognizable, differentiating this tumour from a more aggressive tall‐cell variant of PC. The apparent indolent behaviour seems to be consistent with the presence of dendritic/Langerhans cells and with low proliferative activity. A possible role of EBV in pathogenesis of this lesion was not proven. Further studies are necessary to determine the prognosis and metastatic potential of this neoplasm.
Melanosis of the appendix: common in the paediatric age group
Authors: Graf N S , Arbuckle S 
Published: March 2003

Melanosis of the appendix: common in the paediatric age group Aims: To investigate the incidence of melanosis of the vermiform appendix in a paediatric population, and look for correlations with season, apoptotic rate and inflammation as possible causes. Methods and results: We examined 300 appendices removed for abdominal pain and incidentally during other procedures over the period January 1996 to March 1999. Melanosis was present in 46% of adequate specimens with an even distribution between sexes and age groups. The two older age groups had a relatively higher incidence of severe involvement compared with the younger age group, although the difference was not statistically significant. We attempted to correlate the presence of melanosis with the season of the year and the peak incidences of paediatric gastrointestinal disease but could find no relationship. No statistically significant correlation was found between apoptotic rate and the presence of melanosis. Conclusions: The findings suggest melanosis of the appendix is relatively common. It is probably due to apoptosis associated with increased epithelial cell turnover due to many differing causes including infection, with purgative ingestion probably involved in only a minority of paediatric cases.