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PubMed2004

Histological determinants of survival in completely resected T1-2N1M0 nonsmall cell cancer of the lung.

BACKGROUND: The histologic determinants of survival after surgical resection of stage II nonsmall cell lung cancer are poorly understood. We analyzed the prognostic significance of a number of histologic features after complete resection of T1-2N1M0 nonsmall cell cancer of the lung. METHODS: The case notes and histology of all patients who underwent a potentially curative surgical resection for T1-2N1M0 nonsmall cell carcinoma of the lung between 1991 and 1997 were reviewed retrospectively. The following histologic factors were recorded: histologic type of tumor; number of nodes with metastatic deposits together with their nodal station; the presence of vascular invasion, visceral pleural involvement, and cellular necrosis; and grade of tumor. The results from 98 patients were analyzed. Univariate and multivariate analyses were performed to identify prognostic factors. RESULTS: Univariate analysis showed that only three factors had a statistically significant correlation with a poor prognosis: vascular invasion (p = 0.002), nonsquamous histology (p = 0.005), and visceral pleural involvement (p = 0.002). Multivariate analysis revealed that all three factors were significant independent adverse prognostic indicators. CONCLUSIONS: Visceral pleural involvement, nonsquamous histology, and vascular invasion are all significant adverse prognostic factors after surgical resection of T1-2N1M0 nonsmall cell cancer of the lung. These findings conflict with previously published reports, and we advocate a prospective, large-scale study in order to clarify the prognostic significance of histologic characteristics in stage II disease.

Carcinoma, Non-Small-Cell Lung↗
PubMed2004

Evaluation of epicardial microwave ablation lesions: histology versus electrophysiology.

BACKGROUND: Pulmonary vein isolation is a hallmark in current surgical ablation for atrial fibrillation. However, validation of isolation remains cumbersome. We evaluated electrophysiologic and not histologic means to test isolation. METHODS: In 16 mongrel dogs, robot-assisted epicardial beating-heart microwave ablation (FLEX 10) was performed around the pulmonary veins. Electrophysiologic isolation was tested by pacing at 4 times threshold values inside and outside the pulmonary veins (exit and entrance block). The histology of lesions was studied for transmurality and continuity of the lesion lines. In 5 dogs, lesions were studied at various time intervals. RESULTS: Histologic evaluation of the lesions showed incomplete (48% +/- 20%) circumferential myocardial damage in all dogs with acute lesions. Electrophysiologic evaluation showed completion of the box (entrance and exit block) in 8 dogs and in another 5 dogs after repeated ablation (p < 0.01 compared with histologic evaluation). Electrophysiologic evaluation of the dogs with chronic lesions showed completed lesions in 4 of 5 dogs directly after ablation. At follow-up (1 to 3 weeks), the isolations remained electrophysiologically complete. Histologic evaluation of the lesions 1 to 3 weeks after ablation showed complete (100%) circumferential lesions in all 4 dogs (p < 0.001 compared with the histology of dogs with acute lesions). CONCLUSIONS: Directly after treatment, ablation lesions are best evaluated electrophysiologically, because complete (transmural and circumferential) lesions are not shown by histologic evaluation in the acute stage. After 1 to 3 weeks, the histology is in accordance with the electrophysiology. To obtain a complete isolation, online electrophysiologic evaluation during pulmonary vein microwave ablation is necessary to optimize the results.

Animals↗
PubMed2004

Change in histological grade in locally recurrent soft tissue sarcomas.

Histological examination of locally recurrent soft tissue sarcomas usually reveals an appearance similar to that of the original tumour. Occasionally, however, recurrent sarcomas appear more or less malignant histologically than the initial lesion. The goals of this paper were to identify the frequency with which this phenomenon occurs, factors that predict for a change in grade and to determine if this change is associated with a different prognosis from other patients with local recurrence. From a large sarcoma database, 124 patients with local recurrence were identified. These patients were distributed into groups who had no change in histological grade, increased histological grade or decreased histological grade on local recurrence. Increased grade occurred approximately 20% of the time, whereas decreased grade occurred in 7% of cases. A histological diagnosis of myxofibrosarcoma was predictive of an increase in histological grade on local recurrence. An increase in histological grade with local recurrence was not associated with a poorer survival.

Adult↗
PubMed2004

[Histological diagnosis after Pap smears detecting cancer or high-grade lesion of the cervix].

OBJECTIVE: The aim of the study is to analyze the histological-cytological correlations for Pap smears having detected cancer or high-grade squamous intra-epithelial lesion (HSIL) of the cervix. PATIENTS AND METHOD: The study about 311 women is retrospective. The average age is 36.4 years. Group 1 (histological diagnosis of high-grade or invasive lesion) includes 244 women (77.5%). Group 2 (histological diagnosis other than high-grade or invasive lesion) includes 37 women (11.9%) with a presumed diagnosis of HSIL. Group 3 (absence of histological follow-up) includes 30 women (9.6%) with a presumed diagnosis of HSIL. RESULTS: In group 1, the presumed cytological diagnosis is HSIL in 229 cases, squamous carcinoma in 11 cases and adenocarcinoma in two cases. In this group, the average delay between the Pap smear and the first histology is equal to two months. It is longer than 6 months in seven cases. The diagnosis of cancer or high-grade lesion is confirmed histologically on a first biopsy of the cervix in 196 cases, a second or a third biopsy in 10 cases, an endocervical curettage in six cases and a surgical specimen in 32 cases. In the group 2, the histological diagnosis is normal-benign in 14 cases (presumed cytological false positives) and condyloma-CIN 1 in 23 cases (presumed overevaluations). DISCUSSION AND CONCLUSION: Results highlight benefits of interactive exchanges between clinicians and pathologists, and the necessity of review of discordant cases by several pathologists in due time, with written comments and coding of the conclusions of the review. Histological follow-up is late or not done in some women.

Adolescent↗
PubMed2004

Histological score for cells with irregular nuclear contours for the diagnosis of reflux esophagitis in children.

Histological criteria for the diagnosis of reflux esophagitis include basal zone hyperplasia, stromal papillae elongation, and inflammatory infiltrate. However, endoscopic esophageal biopsy specimens may include little or no lamina propria. Intraepithelial T lymphocytes, seen in hematoxylin and eosin-stained sections as cells with irregular nuclear contours (CINC), may have a higher density in children with esophagitis. We evaluated the diagnostic accuracy of a numerical score built up by grading the "classical" parameters and its correlation with CINC density in grasp biopsy specimens obtained from children undergoing esophagogastroduodenoscopy with and without esophagitis. We analyzed esophageal biopsy specimens from 349 children (median age, 5 years) subdivided in 4 groups according to the previous routine histology report: group 1, 144 children with esophagitis; group 2, 65 controls; group 3, 51 children with dubious esophagitis; and group 4, 75 children with esophagitis on endoscopy but a normal histology report. A numerical value was assigned to each parameter; the sum of these values represented the histological score. We also evaluated intraepithelial CINC density (ie, number of CINC per high-power field). We separately analyzed histological sections with and without lamina propria. For both total score and for CINC density, we calculated a cutoff using a receiver operating characteristic curve. Cutoffs of 6 for score and of 4 for CINC density provided the best sensitivity and specificity. Sensitivity of the histological score was better in biopsy specimens containing lamina propria (94%) than in those without lamina propria (4%). Sensitivity of CINC density was satisfactory in both specimens with (78%) and without (75%) lamina propria. Specificity was satisfactory for both parameters. In conclusion, when lamina propria was present in sections of endoscopic esophageal biopsy specimens, histological score provided a better diagnostic accuracy for the diagnosis of esophagitis. However, when no lamina propria was present, as was the case in 67% of our children, CINC density had better sensitivity. In addition, this latter parameter showed esophageal mucosa damage in 34% of previously dubious cases or cases with esophagitis at endoscopy but a previous routine histology report of normal mucosa.

Adolescent↗
PubMed2006

Etiology of lingual nerve injuries in the third molar region: a cadaver and histologic study.

PURPOSE: It has been suggested that different etiologies of lingual nerve damage in the third molar area will produce a different clinical and histologic appearance in the nerve. If the clinical and histologic pictures were different, it could result in different treatments being recommended. MATERIALS AND METHODS: Eight preserved cadavers (16 lingual nerves) were used for this study. As far as possible, the nerves were left in situ and damaged in a way that could be envisaged during third molar surgery. In each case, the damaged sections of nerve were photographed, resected, embedded in paraffin wax, sectioned in 5 mum sections, stained with hematoxylin-eosin, and examined histologically. RESULTS: The scalpel clinically produced a clean wound with sharply defined edges; this was confirmed histologically with minimal disruption to the fascicles. The 702 fissure bur produced a ragged stretch-type injury clinically, and histologically this was confirmed with an irregular-edged border to the lesion and stretching and internal damage to the fascicles immediately adjacent to the wound. The crush injury clinically caused considerable apparent damage to the nerve, which was confirmed histologically with crushing and disruption of the fascicles and reduction to approximately 25% of their preinjury thickness. The stretch injury clinically showed no damage, but histologically showed irregular internal disruption of the fascicles over the whole area subject to stretching movements. CONCLUSION: It does appear that different modalities in nerve injury produce a different type of injury both clinically and histologically. This information has implications for both natural clinical recovery and the indications for surgical intervention. Clinical recovery may occur best with close approximation of a sharp scalpel-type wound or excision of a crushed area of nerve with reapproximation of the nerve endings, but a ragged wound caused by a fissure bur may require excision back to healthy nerve with subsequent reapproximation, whereas with the stretching injury it may be difficult to ascertain the edges and limits of the wound, and difficult to repair, and it may be most appropriate to rely on a natural healing process for the best results.

Cadaver↗
PubMed2006

Pelvic lymph node count is an important prognostic variable for FIGO stage I and II endometrial carcinoma with high-risk histology.

OBJECTIVE: To determine whether pelvic lymph node count is associated with patterns of recurrence or survival in patients with FIGO stage I and II endometrial cancer. METHODS: Single institution retrospective study of 467 patients with FIGO stage I and II endometrial cancer treated with primary surgery including lymph node dissection. Analysis included pelvic lymph node count, histology, stage, age, race, BMI, year of surgery, depth of myometrial invasion, and adjuvant radiation. Kaplan-Meier life-tables were used to calculate survival; the Cox proportional hazards model was used to identify prognostic factors independently associated with survival. RESULTS: Mean pelvic lymph node count was 12.6 (SD +/- 8). Distant recurrence was associated with decreased pelvic lymph node count, high-risk histology, and postoperative pelvic radiation. Pelvic lymph node count was not associated with survival by univariate analysis, however, overall (OS) and progression-free (PFS) survival were significantly better with pelvic lymph node counts >or=12 among women with high-risk histology (P < 0.001), but not among women with low-risk histology. Multivariable Cox proportional hazards regression identified increasing age, non-Caucasian race, and high-risk histology as independent negative prognostic factors for both OS and PFI. Among patients with high-risk histology, pelvic lymph node count remained an independent prognostic factor for both overall (OS) and progression-free survival (PFS) in the model, with hazard ratios of 0.28 and 0.29, respectively, when >or=12 pelvic lymph nodes were identified. Pelvic lymph node count had no association with OS or PFS in women with low-risk histology. CONCLUSION: Pelvic lymph node count >or=12 is an important prognostic variable in patients with FIGO stage I and II endometrial cancer who have high-risk histology. Most likely, the association of survival and lymph node count in this group is the result of improved staging among patients with higher pelvic lymph node counts.

Adult↗
PubMed2000

Serum laminin and type IV collagen are accurate markers of histologically severe alcoholic hepatitis in patients with cirrhosis.

BACKGROUND/AIMS: Severe alcoholic hepatitis occurs mainly in patients with cirrhosis, and has a high death rate. Corticosteroid therapy has been particularly advocated as reducing mortality in patients with severe histologic lesions. However, identification of these patients is difficult, requiring transvenous liver biopsy. Extracellular matrix serum markers have been proposed as non-invasive diagnostic tools in alcoholic liver disease. The aim of this study was to determine the accuracy of 5 extracellular matrix serum markers, i.e. laminin (Lam), N-terminal peptide of type III procollagen (PIIINP), type I (CI), type III (CIII) and type IV (CIV) collagens in identifying patients with severe histologic alcoholic hepatitis from among those with cirrhosis and suspected alcoholic hepatitis. METHODS: We studied 80 consecutive patients with alcoholic cirrhosis and clinical suspicion of alcoholic hepatitis referred for transvenous liver biopsy. Clinical severity of alcoholic hepatitis was assessed according to Maddrey's score. Histological severity was scored using the sum of the 3 following items: polynuclear infiltration (0-3); hepatocytes alterations (0-3); Mallory bodies (0-2). According to this score, patients were divided into 3 groups: mild (1-3), moderate (4-6), and severe (7-8) alcoholic hepatitis. Serum levels of the 5 extracellular matrix serum markers were measured at the time of biopsy using radioimmunoassays. Diagnostic value for histologically severe alcoholic hepatitis of the 5 extracellular matrix serum markers was assessed using receiver operating characteristic curves. RESULTS: Histological alcoholic hepatitis was present in 67 patients (mean alcoholic hepatitis score: 3.4+/-2.3). Maddrey's score was 66% sensitive and 69% specific for the diagnosis of severe histologic alcoholic hepatitis. The serum Lam and CIV concentrations were the most accurate in identifying correctly patients with severe histologic alcoholic hepatitis. At a cut-off of 4.1 UI/ml, Lam was 90% sensitive and 77% specific, whereas at a cut-off of 150 ng/ml, CIV was 89% sensitive and 77% specific. Combination of markers did not result in improved diagnostic value. CONCLUSION: In patients with cirrhosis, determination of serum Lam or CIV could represent a simple and accurate non-invasive method for identification of patients with histologically severe alcoholic hepatitis eligible for corticosteroid treatment.

Adult↗
PubMed1999

The influence of age and extensive intraductal component histology upon breast lumpectomy margin assessment as a predictor of residual tumor.

PURPOSE: Young age and extensive intraductal component (EIC) histology have been shown to be associated with increased local recurrence in women treated with breast conservation therapy. This study was conducted to determine if the status of the lumpectomy specimen margin consistently predicted for residual tumor burden risk irrespective of these variables. METHODS AND MATERIALS: As part of an institutional prospective approach for breast conservation therapy (BCT), 265 cases with AJCC Stage I/II carcinoma with an initial excision margin that was < or =2 mm or indeterminate were subjected to reexcision. The probability of residual tumor (+RE) was evaluated with respect to tumor size, histopathologic subtype (invasive ductal carcinoma, invasive ductal carcinoma with an EIC, and invasive lobular carcinoma), relative closeness of the measured margin, and the extent of margin positivity graded as focal, minimal, moderate, or extensive. The amount of residual tumor was graded as microscopic, small, medium, or large. All variables were analyzed for patient age < or =45 or >45 years. RESULTS: There was no significant difference in the incidence of a +RE according to age < or =45 versus >45 years when the margin was >0 < or =2 mm. Of the patients aged < or =45 years, the incidence of a +RE with a margin that was positive as compared to >0 < or =2 mm was 71% vs. 23%, respectively (p = 0.002). For women >45 years old, the difference in the incidence of +RE comparing margins that were positive or >0 < or =2 mm was not significant at 50% vs. 40%, respectively (p = 0.23). For all cases in aggregate, age < or =45 years was associated with a greater incidence of +RE as compared to patients aged >45 years with the discrepant incidence of a +RE by age strata most pronounced for focally positive margins (60% vs. 18%;p< or =0.05). In a logistic regression analysis, age (per year, as a continuous variable) and an EIC histology were significantly associated with the probability of a +RE (odds ratio [OR] = 0.80, p = 0.05 and OR = 1.9, p = 0.01, respectively). Tumor size was not significant (p = 0.23). In patients with an EIC histology, margin status is generally less predictive for differences in the incidence of a +RE. Further, the overall magnitude of difference in the incidence of a +RE related to age appears to be minimized when an EIC histology is present. In contrast, for cases classified as having non-EIC histology, there is a near-linear relationship for both age strata with respect to margin status and the incidence of a +RE. When histology is classified as non-EIC, age < or =45 years is consistently associated with a greater risk of residual tumor for all margin status categories. When the extent of margin positivity was graded as focal or minimal, residual tumor was semiquantitatively estimated as a medium/large amount in 33% versus 26% of cases aged < or =45 or >45 years, respectively (p = 0.62). CONCLUSION: For positive lumpectomy specimen margins, younger age is associated with an increased residual tumor risk. An EIC histology appears to be associated with an elevated risk of residual tumor irrespective of age and may undermine the predictive utility of margin status. Therefore, age and an EIC histology should be factored into risk assessments for residual tumor that rely upon margin assessment.

Adult↗
PubMed2002

Does the histological subtype of high-grade central osteosarcoma influence the response to treatment with chemotherapy and does it affect overall survival? A study on 570 patients of two consecutive trials of the European Osteosarcoma Intergroup.

Large randomised trials are mandatory when one wants to examine the effects of different aspects (such as the treatment modality) of a pathological condition on the overall outcome. This is especially true when studying a disease in which there is a multifactorial influence on progression and outcome such as osteosarcoma. Data on 570 patients with biopsy-proven primary central osteosarcoma of an extremity included in two consecutive studies of the European Osteosarcoma Intergroup (EOI) were analysed in order to evaluate if the histological subtype of the biopsy specimen correlated with the subtype of osteosarcoma represented in the resected specimen, if there was a relationship between the histological subtype and overall survival and if there was a relationship between the histological subtype and histological response to chemotherapy. High-grade osteosarcoma, as defined by established criteria, was subtyped as either conventional, chondroblastic, teleangiectatic, small cell, fibroblastic, osteoclast rich, anaplastic and sclerotic/osteoblastic well differentiated. A panel of experienced pathologists with a special interest in bone pathology was appointed to review the histological diagnosis and to assess the tumour response to chemotherapy on the resected specimen of each patient entered into the trials. Subtyping on the biopsy specimen proved to be highly representative for the subtype of the whole tumour. In 102 patients for which subtyping was performed on the biopsy and the resected specimens, there were only two discrepancies. Of the 568 patients for whom subtype was available, 404 (71%) were of the conventional type, 54 (10%) were chondroblastic, 53 (9%) had fibroblastic tumours and the remainder consisted of rare subtypes. A good response to preoperative chemotherapy was defined as 90% or more necrosis. The proportion of patients responding well to chemotherapy differed significantly between subtypes (Chi-square test statistics=11.44, P=0.01 on 3 degrees of freedom (d.f.)). In comparison with the conventional subtype, there was a higher proportion of good responders in the fibroblastic group and a lower proportion of good responders in the chondroblastic group. Good responders had a significantly better survival than patients who responded poorly to the pre-operative chemotherapy (logrank statistic=25.20, P<0.01 on 1 df). Survival did not differ significantly according to subtype (logrank statistic=2.72, P=0.44 on 3 df), although there was a suggestion that patients with chondroblastic tumours experienced a better long-term survival. This large set of prospectively-collected data provides important information on the relationship between pathological subtype, histological response and survival. Histological response has a known prognostic effect on survival, and we have shown that the rates of response differ by subtype. There is some evidence from this study that the specific histological subtypes, i.e. the chondroblastic subtype, experience better survival. However, despite this large multi-institutional study, we have insufficient numbers of non-conventional tumours to examine this unambiguously for these subsets.

Adolescent↗
PubMed1994

Gallbladder wall thickening: an in vitro sonographic study with histologic correlation.

RATIONALE AND OBJECTIVES: We compared histologic sections with in vitro sonographic images for 40 resected gallbladder specimens to correlate the histopathologic processes with the sonographic appearance of the gallbladder wall. METHODS: In vitro sonographic images and histologic specimens were obtained by use of a specimen container with a micropositioner. An 8.5-MHz transducer and a scalpel were attached to the micropositioner to obtain the sonographic image and the histologic section. The sonographic images were analyzed for wall thickness and the number and echo texture of the visualized layers and then were correlated with the histologic sections. Each histologic specimen was interpreted as being normal or showing mild, chronic, acute, or gangrenous cholecystitis. RESULTS: One to four sonographic layers were observed in the gallbladder wall specimens. The number of wall layers was fairly evenly distributed among the different types of gallbladder wall inflammation. One to three sonographic layers were observed for most of the different types. In nearly all instances, the findings were attributable to either similar pathologic processes in two or more histologic layers or different pathologic processes in a single histologic layer. The gallbladder wall measured less than or equal to 3 mm in 89% of gallbladders with normal or mild inflammation, greater than 3-6 mm in 71% of cases of chronic cholecystitis, greater than 3 mm in 83% of cases of acute cholecystitis, and greater than 6 mm in 50% of cases of gangrenous cholecystitis. CONCLUSIONS: The sonographic layers in the inflamed gallbladder wall are determined by the pathologic changes present rather than by the normal histologic boundaries. However, because of the overlap of pathologic changes, we cannot predict the type of gallbladder wall pathology on the basis of the sonographic appearance. We found a trend toward gallbladder wall thickening for severely inflamed gallbladder walls.

Acute Disease↗
PubMed2001

Assessment of liver histology in chronic alcoholics with and without hepatitis C virus infection.

Patients with alcoholic liver disease have a high prevalence of hepatitis C virus (HCV) infection. The histological appearances of the liver in patients with alcoholic liver disease and HCV infection are well described. However, liver histology in individuals with dual pathology, both chronic alcohol abuse and HCV infection, is less well understood. The purpose of the present study was to examine this issue and to determine if there is any correlation between specific histological features and the serum biochemical abnormalities seen in these patients. Eighty-six chronic alcoholics, 65 with HCV infection and 21 uninfected subjects, were included in the study. All patients had history of heavy alcohol abuse (consuming 80 g or more of ethanol a day for at least 10 years). The following data were collected on each patient: demographic information (age, gender, race), the amount and duration of alcohol intake, biochemical results, and liver biopsy abnormalities including the histological activity index (HAI) score. HCV-infected alcoholics were younger (P = 0.05) and were more often African American than Caucasian (P < 0.01). Alcohol consumption was significantly greater in uninfected alcoholics compared to those with HCV infection (P < 0.05). Liver histology in subjects with HCV infection showed higher HAI scores for intralobular necrosis (P = 0.008) and periportal inflammation (P = 0.004). Features of "chronic hepatitis" and focal lymphoid aggregates were more frequent in HCV-infected alcoholics (P = 0.001 for each). By contrast, cirrhosis was present in a higher proportion of uninfected alcoholics compared to those with HCV infection (P = 0.05). Histological findings of hepatic fibrosis and total HAI score showed a significant correlation with serum albumin and platelet count in HCV-infected alcoholics. Chronic alcoholics with HCV infection have specific histological appearances that can usually help distinguish these patients from uninfected alcoholics. Correlation analysis indicates that of the various laboratory tests, serum albumin and platelet counts are the best predictors of the severity of liver damage at histology. In chronic alcoholics, the development of cirrhosis is related more to the amount of alcohol consumed than to the presence of HCV infection.

Alcoholism↗
PubMed2003

Assessment of histologic criteria in the diagnosis of mycosis fungoides.

BACKGROUND: The histologic diagnosis of early mycosis fungoides (MF) can be difficult to establish in many instances because the subtle changes observed in patches of MF are also present in many inflammatory dermatoses. METHODS: To assess the frequency and significance of many of these histologic parameters, we retrospectively reviewed 50 slides from patients with documented MF in patch, plaque, and tumor stages. The diagnosis of MF was unequivocally established either by the progression of patients to advanced stages of the disease or by indubitable histologic findings. In the second phase of the study, we compared the histologic parameters observed in 24 patch stage MF patients with those in 24 non-MF patients. The non-MF group were patients whose pathologic pattern was suspicious for MF, but who definitely did not have MF on clinical grounds. The two groups were matched by histologic pattern. Two different observers evaluated the slides and the intensities of 32 histologic parameters were graded on a four-point scale to minimize the subjective variability in the histologic reports. RESULTS: On univariate analysis, the following parameters achieved significance in distinguishing MF from non-MF: Pautrier's microabscesses, haloed lymphocytes, disproportionate epidermotropism, epidermal lymphocytes larger than dermal lymphocytes, hyperconvoluted lymphocytes in the epidermis and dermis, absence of dyskeratosis, and papillary dermal fibrosis. None of these features proved to have additional discriminating power on multivariate analysis. CONCLUSIONS: The efficacy of single histologic features in the diagnosis of early MF is generally poor and, to discriminate MF from its inflammatory simulators, a combination of cytologic and architectural features must be used.

Adolescent↗
PubMed2002

Validity and reproducibility of histologic diagnosis and grading for adult soft-tissue sarcomas.

Soft-tissue sarcomas in adults show great variations in histologic type and grade. A valid and reproducible prognostication system is needed to select patients with soft-tissue sarcomas who could benefit from adjuvant chemotherapy. This study was conducted to assess the validity and reproducibility of diagnosis of the histologic type, MIB-1 grade, and mitosis grade, as well as of the 3 components of these grading systems. MIB-1 grade is a recently proposed grading system for predicting the prognosis of patients with adult soft-tissue sarcomas on the basis of 3 criteria (tumor differentiation, necrosis, and MIB-1 score) and replaces the mitotic count in the French system with MIB-1 immunohistochemical staining. Four surgical pathologists from 4 institutions who had experience in diagnostic soft-tissue tumor pathology reviewed 130 cases of soft-tissue sarcoma and independently determined histologic type and grade. The validity of histologic diagnosis was measured by sensitivity and specificity, and that of grading was measured by kappa statistics and percentage agreement with the diagnosis of the expert panel at the National Cancer Center, which was defined as a gold standard. Interobserver reproducibility was measured by kappa and by percentage agreement between the diagnoses of the 4 pathologists. The validity of the diagnosis of histologic type was high for synovial sarcoma, small round-cell sarcoma, and liposarcoma (sensitivity 89% to 100%; specificity, 98% to 100%) but low for malignant fibrous histiocytoma (MFH) and spindle-cell sarcoma (73% to 75%; 93% to 95%). For the grading, the validity of the MIB-1 grade was substantial (kappa = 0.68; agreement, 79%) and higher than that of the mitosis grade (0.54; 69%). The most valid component was tumor differentiation (kappa = 0.79), followed by tumor necrosis (0.66), MIB-1 score (0.59), and mitotic score (0.37). Interobserver reproducibility of histologic diagnosis was high for small round-cell sarcoma, synovial sarcoma, and liposarcoma (kappa = 0.92, 0.90, 0.87; percentage agreement = 99%, 97%, 96%, respectively); for grading, reproducibility was highest for tumor differentiation (0.78; 87%) and second highest for MIB-1 grade (0.68; 79%). We conclude that diagnosis of the type of soft-tissue sarcoma for synovial sarcoma, small round-cell sarcoma, and liposarcoma and the MIB-1 grading system based on tumor differentiation are highly valid and reproducible among Japanese pathologists who are familiar with the grading system, whereas re-evaluation of histologic criteria is essential for other histologic types such as MFH and spindle-cell sarcoma.

Antigens, Nuclear↗
PubMed2001

Topographic analysis of K- ras mutations in histologically normal lung tissues and tumours of lung cancer patients.

Mutations in the K- ras gene are very common in lung tumours and are implicated in the development of lung cancer, but the timing of their occurrence remains poorly understood. We investigated K- ras mutations in cell samples microdissected by laser capture microscopy at multiple sites from lung tissue sections representing tumour tissue and matched histologically normal tissue obtained from 48 lung cancer patients. K- ras mutations were detected in cell samples from 10 of 38 (26.3%) lung adenocarcinomas and in none of the histologically normal or tumour cell samples taken from 10 lung squamous cell carcinomas. Of the K- ras mutation-positive adenocarcinomas, in 4 cases a mutation was found in only the tumour tissue, in 1 case a mutation was found only in the histologically normal tissue, and in 5 cases mutations were found in both the tumour tissue and histologically normal tissue. Among these 5 cases, 2 had identical mutations in both the tumour tissue and histologically normal tissue, 2 had 1 mutation in the tumour tissue and 2 mutations in the histologically normal tissue, 1 of which was identical to the mutation found in the tumour, and 1 case had 2 codon 12 mutations in tumour tissue and 2 mutations, in codons 9 and 11, in histologically normal tissue. These results showed that K- ras mutations are frequent in histologically normal cells taken from outside lung adenocarcinomas and suggest that some of these mutations may represent early events which could pave the way of lung carcinogenesis.

Adenocarcinoma↗
PubMed2000

[Clinical and histologic features of 141 primary basal cell carcinomas of the periocular region and their rate of recurrence after surgical excision].

BACKGROUND: The aim of this study was to assess clinical and histologic features of primary basal cell carcinomas of the periocular region and to calculate the rate of recurrence of these tumors after surgical excision without intraoperative frozen section control. METHODS: All primary basal cell carcinomas of the periocular region which were treated by surgical excision at the University Eye Hospital and Clinic of Ulm between 1993 and 1998 were reviewed and special attention was paid to age and sex of the patient and localization and histology of the tumor. The recurrence rates were calculated depending on whether the margins were free or involved on histologic examination of the excised specimens. RESULTS: We could include 137 patients with 141 tumors into this study. In 92 patients with 95 tumors, follow-up data of at least 3 months was available with a mean follow-up period of 31.3 months. The mean age of the patients was 68.9 years, range 28.7-91.3 years. The tumor was located at the lower eyelid, medial canthus, upper eyelid and lateral canthus in 63.1%, 29.8%, 5.7% and 1.4%, respectively. The solid (53.9%) and the solid-cystic (17.7%) type were the most common encountered histology followed by the mixed type with sclerosing foci (12.1%) and the morphea or sclerosing type (10.6%). A free margin on histologic examination was achieved in only 47.6% of cases. The overall recurrence rate was 9.5% [definite recurrences: 6 cases (6.3%); questionable recurrences: 3 cases (3.2%)]. With histologically complete excision the recurrence rate was only 2.3% (1 case) and in the case of an incomplete excision definite recurrent tumors were observed in 11.8% (6 cases) and questionable recurrences in 3.9% (2 cases) of cases during the follow-up period. CONCLUSIONS: Surgical excision of basal cell carcinomas of the periocular region without utilizing intraoperative frozen section control or Mohs' micrographic surgery is associated with a high rate of positive tumor margin on histologic examination. However, our study showed that this is only infrequently followed by local recurrences. This result may raise the question whether simple surgical excision is still an option in the case that more cumbersome methods such as Mohs' micrographic surgery or intraoperative frozen section control are not available. However, with positive tumor margin on histologic examination of the excised tissue or with the presence of a sclerosing type regular follow-up is mandatory.

Adult↗
PubMed2003

Increasing sensitivity of morphological diagnosis in hepatocellular carcinoma (HCC) by combination of cytological and fine-needle histological examination after ultrasound guided fine needle biopsy.

UNLABELLED: Increasing sensitivity of morphological diagnosis by combination of cytological and fine-needle histological examination after ultrasound guided fine needle biopsy in hepatocellular carcinoma (HCC). AIM: We investigated the factors which may affect the sensitivity of morphological diagnostics (cytology and fine-needle histology) in HCC after ultrasound guided biopsy. METHOD: In 62 patients, an ultrasound guided cytological (n = 62) and fine-needle histological (n = 45) biopsy was performed. In addition, the smears were investigated by cytophotometry (n = 62). RESULTS: Considering each method separately, the sensitivity of both cytological and histological diagnostics was about 80%. The sensitivity could be raised to 89% by combining the two methods. In seven patients, the HCC could not be primarily confirmed morphologically. In nine patients, the result of histological and cytological investigation was not congruent. With regard to the size of the biopsied lesion, tumor stage, cytophotometric finding and survival these 16 patients (group A) were compared with the 46 patients in whom the HCC could be primarily confirmed morphologically (group B). The statistical analysis did reveal a significantly lower percentage of tumors with diploid or tetraploid (euploid) cells in group B. Euploid tumors were significantly more highly differentiated. In patients with euploid tumors, the sensitivity of the cytological investigation was 67% and respectively 75% of the histological investigation. The sensitivity could be raised to 82% in this population by combining the two investigations. On the other hand in aneuploid tumors, the sensitivity could only be increased from 93% and 88% respectively to 97% by combining cytology and fine-needle histology. SUMMARY: Our investigations show that the sensitivity of morphological diagnostics can be raised especially in the highly differentiated HCC with a physiological DNA content by combination of cytological and fine-needle histological investigations.

Adult↗
PubMed2005

Outcome of neonates less than 30 weeks gestation with histologic chorioamnionitis.

The purpose of this study was to determine the short-term outcome of newborns less than 30 weeks gestation when there is definite placental histologic chorioamnionitis. A retrospective analysis was performed of records of all neonates delivered at our institution from January 1989 through January 1999. This information was retrieved from our perinatal database and pathology database. The population was stratified according to the presence or absence of histologic chorioamnionitis. Statistical analysis was performed using student t-test and Mann-Whitney method. Logistic regression was used to control for potential confounding variables. There were 392 neonates less than 30 weeks gestation delivered during this time period. Complete placental histology was available for 342 patients (87.4%). Histologic chorioamnionitis was identified in 140 (40.9%) cases. Those with histologic chorioamnionitis delivered sooner (26.3 versus 27.5 weeks), were of lower birth weight (920.1 versus 1029.8 g), and had lower 5-minute Apgarscores. Neonatal septicaemia and pneumonia were strongly associated with underlying histologic chorioamnionitis. There was a significant reduction in the incidence of respiratory distress syndrome (RDS) when histologic chorioamnionitis was present. Severe histologic chorioamnionitis increases the risk of premature delivery and is strongly associated with neonatal sepsis. There is a significant reduction in the incidence of RDS and neonatal mortality.

Chorioamnionitis↗