High-definition endoscopy with iScan and Lugol's solution for the detection of inflammation in patients with nonerosive reflux disease: histologic evaluation in comparison with a control group.

Nonerosive reflux disease (NERD) is commonly diagnosed in patients with symptoms of reflux. The aim of the present study was to determine whether high-definition endoscopy (HD) plus equipped with the iScan function or chromoendoscopy with Lugol's solution might permit the differentiation of NERD patients from those without reflux symptoms, proven by targeted biopsies of endoscopic lesions. A total of 100 patients without regular intake of proton pump inhibitors and with a normal conventional upper endoscopy were prospectively divided into NERD patients and controls. A second upper endoscopy was performed using HD+ with additional iScan function and then Lugol's solution was applied. Biopsy specimens were taken from the gastroesophageal junction in all patients. A total of 65 patients with reflux symptoms and 27 controls were included. HD(+) endoscopy with iScan revealed subtle mucosal breaks in 52 patients; the subsequent biopsies confirmed esophagitis in all cases. After Lugol's solution, 58 patients showed mucosal breaks. Sensitivity for the iScan procedure was 82.5%, whereas that for Lugol's solution was 92.06%. Excellent positive predictive values of 100% and 98.3%, respectively, were noted. The present study suggests that the majority of patients with NERD and typical symptoms of reflux disease can be identified by iScan or Lugol's chromoendoscopy as minimal erosive reflux disease (ERD) patients.

[How should cytopathology be taught?]. / Wie soll Zytopathologie gelehrt werden?

Cytopathology is not excessively employed in the whole faculty of pathology in Germany, in contrast to some neighboring countries. Cytopathology also suffers from a lack of next generation cytologists, because experienced and interested specialists as well as assistants actively engaged in cytology (ZTA, cytological technical assistant and MTLA medical laboratory technical assistant) are only available in limited numbers. However, cytopathological expertise is urgently needed, not only in the diagnostics of gynecological cancer screening but also for assessment of many non-gynecological preparations, which have nowadays become more demanding and more complex particularly due to the technical developments in internal medicine. In addition, adjuvant methods have become incorporated into cytopathology, the interpretation of which must be carried out within this specialty.This article gives a review of the status quo of cytopathology in Germany and sketches how training and advanced education opportunities are organized and if necessary could be improved. The course of specialist medical training as well as the ZTA and MTLA training are described, also as a teaching concept (e.g. microscopy of current cases, microscopy of case collections and online microscopy). In order to provide cytopathology in Germany with a wider perspective, a paradigm shift in the internal approach to cytology is suggested so that the next generation can perceive this specialty not as a burden but as a chance.

[Pleural effusion cytology of asbestos-associated malignant mesothelioma and lung carcinoma in the diagnosis of occupational diseases by the statutory accident insurance funds]. / Zytopathologische Ergussdiagnostik in der berufsgenossenschaftlichen Begutachtung von Asbest-assoziierten malignen Mesotheliomen und Lungenkarzinomen.

Pleural effusion often represents the first clinical symptom of lung carcinoma and malignant mesothelioma. As pleural punctation is performed quite early in the diagnostic procedure, effusion cytology frequently gives the first evidence about the presence of tumour cells and tumor histogenesis. In this study, we report on seven cases which were evaluated in our institution for the Employers' Liability Insurance Association, based solely on cytology findings.The mean age of the seven patients with a given long-term asbestos exposure during their working life was 81.7 years. On average eight smears per patient were investigated. In addition to routine cytology, immunocytochemistry, DNA image cytometry, AgNOR-analysis and fluorescence in situ hybridization were applied in a case-specific way. The results were interpreted against the clinical and occupational history of the respective patient.Definitive diagnosis could be made in six cases. In three of them, the diagnosis of malignant mesothelioma was made. Two cases were diagnosed as malignant effusion due to metastatic lung cancer. In one case, cells of high-grade Non-Hodgkin's lymphoma (NHL) were diagnosed and a malignant mesothelioma was excluded. In the last case, malignant mesothelioma could not be diagnosed unequivocally by cytology. In all seven cases, our interpretation was accepted by Employers' Liability Insurance Association. The five mesothelioma or lung cancer cases were accepted as asbestos-associated occupational disease, while the NHL case was rejected. In the last case, malignant mesothelioma was diagnosed later by autopsy, and the case was retroactively accepted as occupational disease.Cytology-based tumor diagnosis including adjuvant methods is a useful and reliable approach in cases of asbestos-associated tumours. Acceptance of occupational disease on the basis of cytological diagnoses even by the Employers' Liability Insurance Association helps avoid invasive pleural or lung biopsies in cases with an unequivocally positive effusion cytology of lung cancer or malignant mesothelioma.

High definition colonoscopy combined with i-Scan is superior in the detection of colorectal neoplasias compared with standard video colonoscopy: a prospective randomized controlled trial.

INTRODUCTION: Colonoscopy is the accepted gold standard for the detection of colorectal cancer. The aim of the current study was to prospectively compare high definition plus (HD+) colonoscopy with I-Scan functionality (electronic staining) vs. standard video colonoscopy. The primary endpoint was the detection of patients having colon cancer or at least one adenoma. METHODS: A total of 220 patients due to undergo screening colonoscopy, postpolypectomy surveillance or with a positive occult blood test were randomized in a 1 : 1 ratio to undergo HD+ colonoscopy in conjunction with I-Scan surface enhancement (90i series, Pentax, Tokyo, Japan) or standard video colonoscopy (EC-3870FZK, Pentax). Detected colorectal lesions were judged according to type, location, and size. Lesions were characterized in the HD+ group by using further I-Scan functionality (p- and v-modes) to analyze pattern and vessel architecture. Histology was predicted and biopsies or resections were performed on all identified lesions. RESULTS: HD+ colonoscopy with I-Scan functionality detected significantly more patients with colorectal neoplasia (38 %) compared with standard resolution endoscopy (13 %) (200 patients finally analyzed; 100 per arm). Significantly more neoplastic (adenomatous and cancerous) lesions and more flat adenomas could be detected using high definition endoscopy with surface enhancement. Final histology could be predicted with high accuracy (98.6 %) within the HD+ group. CONCLUSIONS: HD+ colonoscopy with I-Scan is superior to standard video colonoscopy in detecting patients with colorectal neoplasia based on this prospective, randomized, controlled trial.

Osseointegration of one-piece zirconia implants compared with a titanium implant of identical design: a histomorphometric study in the dog.

OBJECTIVE: The aim of this study was to evaluate osseointegration of one-piece zirconia vs. titanium implants depending on their insertion depth by histomorphometry. MATERIAL AND METHODS: Four one-piece implants of identical geometry were inserted on each side of six mongrel dogs: (1) an uncoated zirconia implant, (2) a zirconia implant coated with a calcium-liberating titanium oxide coating, (3) a titanium implant and (4) an experimental implant made of a synthetic material (polyetheretherketone). In a split-mouth manner they were inserted in submerged and non-submerged gingival healing modes. After 4 months, dissected blocks were stained with toluidine blue in order to histologically assess the bone-to-implant contact (BIC) rates and the bone levels (BL) of the implants. RESULTS: All 48 implants were osseointegrated clinically and histologically. Histomorphometrically, BL in the crestal implant part did not differ significantly with regard to material type or healing modality. The submerged coated zirconia implants tended to offer the most stable crestal BL. The histometric results reflected the different healing modes by establishing different BL. The median BIC of the apical implant part of the zirconia and titanium group amounted to 59.2% for uncoated zirconia, 58.3% for coated zirconia, 26.8% for the synthetic material and 41.2% for titanium implants. CONCLUSIONS: Within the limits of this animal study, it is concluded that zirconia implants are capable of establishing close BIC rates similar to what is known from the osseointegration behaviour of titanium implants with the same surface modification and roughness.

pp32/PHAPI determines the apoptosis response of non-small-cell lung cancer.

During malignant transformation, cancer cells have to evade cell-intrinsic tumor suppressor mechanisms including apoptosis, thus acquiring a phenotype that is relatively resistant to clinically applied anticancer therapies. Molecular characterization of apoptotic signal transduction defects may help to identify prognostic markers and to develop novel therapeutic strategies. To this end we have undertaken functional analyses of drug-induced apoptosis in human non-small cell-lung cancer (NSCLC) cells. We found that primary drug resistance correlated with defects in apoptosome-dependent caspase activation in vitro. While cytochrome c-induced apoptosome formation was maintained, the subsequent activation of caspase-9 and -3 was abolished in resistant NSCLC. The addition of recombinant pp32/putative human HLA class II-associated protein (pp32/PHAPI), described as a putative tumor suppressor in prostate cancer, successfully restored defective cytochrome c-induced caspase activation in vitro. Conditional expression of pp32/PHAPI sensitized NSCLC cells to apoptosis in vitro and in a murine tumor model in vivo. Immunohistochemical analyses of tumor samples from NSCLC patients revealed that the expression of pp32/PHAPI correlated with an improved outcome following chemotherapy. These results identify pp32/PHAPI as regulator of the apoptosis response of cancer cells in vitro and in vivo, and as a predictor of survival following chemotherapy for advanced NSCLC.

High-definition endoscopy with i-Scan and Lugol's solution for more precise detection of mucosal breaks in patients with reflux symptoms.

BACKGROUND AND STUDY AIMS: Patients with gastroesophageal reflux disease are subdivided into non-erosive (NERD) and erosive reflux disease (ERD). The newly available EPKi processor enables high-definition resolution above HDTV standard (HD+). The aim of the study was to test the efficacy of HD+ esophagogastroduodenoscopy alone and in conjunction with i-Scan (newly developed postprocessing digital filter) and chromoendoscopy (Lugol's solution) for differentiation of reflux patients. METHODS: The distal esophagus of patients with heartburn was inspected with three imaging modalities. HD+ was followed by i-Scan and 15-mL Lugol's solution (1.5 %). The esophagus was evaluated for mucosal breaks (Los Angeles Classification [LA]). Small visible changes were also characterized, and targeted biopsies were performed. End points of the study were the presence and grade of esophagitis and the number of circumscribed changes. RESULTS: A total of 50 patients were included (female 29; mean age 54.7 years). HD+ identified nine patients with mucosal breaks (LA 7A; 2C), i-Scan was able to detect 12 patients (LA 8A; 2B; 2C; 0D) ( P = n. s.) and chromoendoscopy identified 25 patients (LA 16A; 7B; 1C, 1D) ( P < 0.01). Furthermore, a higher grade of esophagitis was recognized by using i-Scan and Lugol's solution in 19 patients. The number of circumscribed lesions could be increased from 21 (HD+) to 58 (i-Scan) ( P < 0.01), and up to 85 after Lugol spraying ( P < 0.01). CONCLUSIONS: Lugol's solution in conjunction with HD+ endoscopy significantly improves the identification of patients with esophagitis and reduces misclassification. The i-Scan filter and chromoendoscopy help to identify reflux-associated lesions.

Maxillary sinus grafting with a nano-structured biomaterial: preliminary clinical and histological results.

BACKGROUND: In this study the potential of a new and entirely synthetic, nano-structured hydroxyapatite-based biomaterial for sinus floor augmentation is evaluated. METHODS: 20 sinus floor elevations were carried out in a total of 20 patients. After a healing period of 6 months, in 10 cases cylinder-shaped bone biopsies were taken from the augmented maxillary region using trephine burs. RESULTS: The healing period progressed without any complications. General and specific histological analysis of the bone biopsies showed a high osteoclast activity at the margin of the biomaterial which was well integrated into the newly formed bone. CONCLUSION: This study demonstrates that new trabecular bone is formed after grafting with the nanocrystalline bone substitute after 6 months. Ongoing histomorphological studies are necessary to quantify the biomaterial-bone ratio and the exact amount of newly built bone in the augmented cavity after 6 months.

Differential diagnosis and evaluation of the clinical course of transurethrally resected T1G3 urothelial carcinoma of the bladder by DNA image cytometry.

The value of DNA image cytometry in the differential diagnosis of 106 T1G3 urothelial carcinomas of the bladder and the long-term prognosis (recurrence-free interval, survival) of the patients was tested in comparison with Ta/T1G1 (n=30) and Ta/T1G2 carcinoma (n=54). Monolayer smears were prepared from three 50-microm-thick sections by a cell separation technique and were stained according to Feulgen. The DNA content of 250 epithelial cells, chosen at random, was determined using a TV-image analysis system CM-1 (Hund, Wetzlar, Germany). The DNA content of 30 lymphocytes served as an internal standard for the normal diploid value in every individual case. Different DNA cytometric parameters and the mean nuclear area were calculated. In comparison with G1- and G2-cases, the mean values of all DNA cytometric variables were markedly increased in the group of T1G3 cases, most obviously for the 5cEE, the mean ploidy and the ploidy imbalance (0.0006 > or = p > or = 0.0001). However, a remarkable overlay of the data distribution had to be considered. An aneuploid DNA stemline ploidy was highly characteristic for T1G3 urothelial carcinoma (sensitivity: 92%), but not sufficiently specific (57%). However, if increased values for the mean ploidy, the 2cDI, the 5cEE or the 9cEE (specificity: 86%-89%) were present additionally, the diagnosis of a T1G3 urothelial carcinoma could be made cytometrically. Follow-up data for survival (recurrence) analysis was available for 90 (82) patients of the T1G3 group. Using the median value as threshold, significant differences in survival were found for the mean ploidy only (p=0.0353). The length of the recurrence-free interval was significantly different for the entropy (p=0.0205), the 2cDI (p=0.0309) and the mean ploidy (p=0.0442). In conclusion, DNA single cell cytometry represents a highly relevant tool in the objective identification of T1G3 urothelial carcinoma of the bladder, with a sufficient sensitivity and specificity. Further, this method enables prediction of tumor recurrence if suitable variables are chosen. The long-term survival of patients with T1G3 urothelial carcinoma can be estimated by DNA cytometry only in a limited manner, possibly due to the fact that the causes of death in the mostly elderly patients will be independent from the limited tumor disease.

Mitotic frequency as a prognostic factor in breast cancer.

Grading of tumor malignancy in breast cancer should contribute essential information both for the prospective outcome of the individual patient as well as for TNM staging. In a series of 104 breast cancer patients we tested the prognostic validity and reproducibility of mitotic figure counting compared with TNM staging, Bloom and Richardson grading, DNA single cell cytometry, and morphometry. Four-micrometer thick hematoxylin-eosin-stained routine slides were investigated. Mitotic figures were counted in representative areas of the tumor in 10 159-microns 2-sized high power fields (HPFs) at a 400X magnification; the median value was seven and the threshold for the 25th percentile was three. This value should replace the common but prognostically invalid threshold of 10. Univariate survival analysis showed that mitotic figure counting allows the identification of three groups of patients (< or = 3, 4 to 20, > 20 mitoses per HPF) with significantly different survival probabilities (P < .0001; P = .0178). Depending on the number of mitotic figures, length of survival was significantly different within the group of T1N0 tumors (P = .0082) and the group of T1N1 or T2N0 tumors (P = .0251). In a Cox stepwise regression model mitotic frequency counting added prognostic information to tumor size and was of higher prognostic significance than lymph node status, DNA ploidy, or mean nuclear area. The 95% confidence limit for interobserver reproducibility, tested in 20 cases, was plus/minus 8 mitoses. After quartilization an agreement of 75% was observed.

Experimental arterial stent placement. Comparison of a new Nitinol stent and Wallstent.

RATIONALE AND OBJECTIVES: To compare technical aspects and neointima formation of a new Nitinol stent and a Wallstent. METHODS: A Nitinol sten and a Wallstent were placed into the iliac arteries of 14 sheep (total of 28 stents) and followed angiographically. Seven sheep were killed after 1 month and 7 after 4.5 months. Examination of histologic specimen by light microscopy was performed to determine neointimal and medial thickness inside the stents. Measurements were analyzed statistically. RESULTS: Neointima was thicker in Nitinol stents (N) than in Wallstents (W) (P < 0.004), both adjacent to (W = 0.265 mm, N = 0.596 mm) and between the stent wires (W = 0.177 mm, N = 0.361 mm). Because of poor radiopacity and the Crochê releasing technique, delivery was more difficult with Nitinol stents. High-grade stenosis was found in two Nitinol stents at 1 and 4.5 months of follow-up, respectively. One Wallstent was insufficiently incorporated into the vessel wall. CONCLUSIONS: The observed difference in neointima formation that may be caused by differences in design, mechanical properties or the metal alloy of the stents probably is too insignificant to be relevant to patency of large arteries. However, it may be relevant in small vessels such as coronary arteries.

Polyploidy in non-neoplastic tissues.

AIM: To investigate the prevalence and amount of polyploidy in fine needle aspiration specimens of the liver, urinary cytospin preparations, and cytospin preparations from pleural and peritoneal fluid. METHODS: Cells from 44 liver smears, 48 urine specimens, and 46 pleural and peritoneal aspirations were examined. After Feulgen restaining the DNA content of 100 randomly selected nuclei was determined using a TAS-plus image analysis system, combined with an automated microscope. RESULTS: Polyploidy was observed up to 16c in the liver, and up to 8c in urothelium and mesothelium. Sixty eight per cent of the liver aspirates contained polyploid nuclei. The rate in urothelium was 20.8% and in mesothelium 6.5%. CONCLUSIONS: Polyploidy in the liver may be interpreted as being associated with tissue differentiation, but the findings in urothelium and mesothelium remain of unknown importance.

Improvement of breast cancer prognostication using cell kinetic-based silver-stainable nucleolar organizer region quantification of the MIB-1 positive tumor cell compartment.

Recently, it was stated that the proliferative activity (P) of a cell population could be indirectly calculated by multiplying the MIB-1 immunopositivity and silver-stainable nucleolar organizer region (AgNOR) features extracted exclusively in MIB-1 positive (pos.) nuclei: P=MIB-1 x AgNOR(MIB-1pos.). To study the prognostic significance of this hypothesis, MIB- immunohistochemistry and AgNOR staining were applied on a series of 89 cases of breast cancer with an 8-year follow-up period. The mean MIB-1 immunopositivity (MIB-1mean) was evaluated immunohistometrically on paraffin sections using a TV image analysis system CM-2 (Hund, Wetzlar, Germany). Later, a combined MIB-1/AgNOR staining was applied and evaluated using a TV image analysis system AMBA (IBSB, Berlin, Germany). The AgNOR features of 150 randomly chosen tumor nuclei were investigated, irrespective of their MIB-1 status (AgNOR count, AgNOR area). Later, a second measurement was performed on 100 MIB-1 positive tumor nuclei exclusively (AgNOR countMIB-1pos., AgNOR areaMIB-1pos.). AgNOR count and AgNOR countMIB-1pos. showed a different data distribution [2.7+/-0.7 (mean+/-SD) vs 3.9+/-1.1; r=0.315, P=0.014]. Similar results were obtained for AgNOR area and AgNOR areaMIB-1pos. (5.1+/-2.1 microm2 vs 7.5+/-2.4 microm2; r=0.501, P<0.001). Kaplan-Meier survival curves revealed significant differences for MIB-1mean (P=0.0018) and AgNOR areaMIB-1pos. (P=0.0340). In Cox models, both parameters provided independent prognostic information. Using their combination, the P, three groups of patients with statistically different survival could be separated (P=0.0014). Thus, the combination of MIB-1-immunopositivity and AgNOR measurements in MIB-1 positive nuclei appears to be more useful in breast cancer prognosis than the exclusive application of one of the two methods. By this combined application, probably effects of tumor biology are represented more precisely.

Expression of matrix metalloproteinases (MMP-2 and -9) and their inhibitors (TIMP-1 and -2) in prostate cancer tissue.

Matrix metalloproteinases (MMPs) have been implicated in progression and metastases of different tumours. The balance between the MMPs and their natural inhibitors (tissue inhibitors of matrix metalloproteinases; TIMP) seems to be an important factor related to this role. Here, the expression of MMP-2 and -9 along with TIMP-1 and -2 was examined in prostate cancer tissue. A total of 40 radical prostatectomy specimens were embedded in paraffin and immunohistochemical staining was performed to detect MMP-2 and -9, and TIMP-1 and -2. The immunoreactivity was assessed semiquantitively using routine light microscopy. The intensity of staining was correlated to preoperative PSA, T category, Gleason score and clinical parameters of the specimens. The imbalance of MMPs and TIMPs was recognised as a significant loss of TIMP-1 in malignant epithelium and an upregulation of MMPs. Palpable tumours (T2, T3) expressed significantly more MMP-2 and significantly less MMP-9 than T1c tumours. Our data are in accordance with other literature reports in that an imbalance of MMPs and TIMPs is found in malignant tumours. The observed imbalance of MMP and TIMP is mainly caused by a loss of TIMP-1. Furthermore, palpable tumours demonstrated significantly more MMP-2 and significantly less MMP-9 expression than nonpalpable tumours.

Absence of epidermal growth factor receptor expression in squamous cell carcinoma of the uterine cervix is an indicator of limited tumor disease.

The expression of growth factors is considered as an important diagnostic and prognostic feature in tumor pathology. We investigated the value of the immunohistochemical EGF-receptor expression (EGF-R) in 30 squamous cell carcinomas of the uterine cervix, treated by radical hysterectomy and lymphadenectomy according to the Wertheim-Meigs-Okabayashi technique. Immunohistochemical reactions were performed on 4 microm sections from paraffin-embedded tissue, using an indirect peroxidase method. The staining results were evaluated semiquantitatively as negative (n=9; 30%) or as slightly, moderately or severely positive (n=21; 70%). The EGF-R-negative tumors were found in less advanced tumor stages. None had invaded into the parametrium (100%), eight were staged as T1 (89%), seven as N0 (78%), and seven showed no evidence for lymphangiosis carcinomatosa (78%). The respective values for the EGF-R-positive tumors ranged from 52% to 67%. However, only the difference in parametral invasion (EGF-R-negative: 0%, EGF-R-positive: 38%) was statistically significant (p=0.0306), probably due to the small number of cases. The EGF-R-expression was not correlated to histomorphological tumor grading. The results of this study indicate an inverse correlation between EGF-R expression and tumor spread. Assuming that this trend could be confirmed by a larger group of patients, immunostaining for EGF-R in a tumor biopsy could be useful to adapt surgical strategies and adjuvant therapy in the individual patient. Moreover, the EGF-R is an interesting target for immunotherapeutic approaches in squamous cell cervical carcinoma.

Re-evaluation of prognostic mitotic figure counting in breast cancer: results of a prospective clinical follow-up study.

Some years ago we were able to confirm reports on the prognostic meaning of mitotic figure counting in breast cancer on a retrospective series of 104 breast cancer cases (Hum Pathol 26: 47-52, 1995). An independent influence of mitotic figure counting on prognosis could be proven in stage I and stage II tumors. Using the same methodological approach, the investigation has been repeated recently on a prospectively collected series of breast cancer patients (n = 108). A strong benefit for the patients' outcome was found for patients with stage II tumors (p = 0.0093), but not for patients with stage I tumors (p > 0.05). Regarding the differences between the two studies, most probably the effects of therapeutic changes between the late 1970s and the late 1980s and aspects of the patients' selection may be responsible.

Epidermal growth factor receptor-immunohistochemical detection and clinical significance for treatment of primary breast cancer.

Epidermal growth factor receptor is considered to play an important role in the carcinogenesis and progression of breast cancer, but its clinical significance remains controversial mainly due to different methods and methodical problems. We determined EGF-R expression by an immunohistochemical assay on paraffin-embedded primary breast cancer tissue by means of the anti EGF-R mab E30 (Merck, FRG) and streptavidin-peroxidase technique. Material and clinical data were available from 111 patients with a mean follow-up time of 75.4 +/- 1.1 months (range 61-90 months). 21 (18.9%) of the breast cancer specimens showed positive staining for EGF-R 5 year-overall survival in patients with EGF-R negative tumors was 61.7% compared with 41.6% of patients with EGF-R positive breast carcinomas. No correlation was found between the expression of EGF-R and other prognostic factors except an inverse relationship with the expression of the estrogen receptor (p < 0.05). Whereas EGF-R expression demonstrated prognostic significance in univariate analysis, this could not be confirmed by multivariate analysis. Immunohistochemical determination of EGF-R represents a reliable and simple method to obtain more data about the biological behavior of malignant breast disease with increasing impact on therapeutic procedures.

Principal component analysis. A factor analytical technique for the determination of interobserver variation in histomorphologic tumor grading.

The insufficient interobserver reproducibility limits the practical use of histomorphological tumor grading in daily routine pathology. In this study, the reasons for the quite low rates of agreement between different observers have been investigated by the application of a factor analytical technique, i.e. principal component analysis with varimax rotation, on a tumor grading system. Grading results from 44 cases of G1 and G2 giant cell tumors of the bone (GCT), graded by three different observers according to the five criteria of Jaffe, were taken as an example. It could be proven that the single criteria were used in an observer-specific way. Two criteria, for example, which are scored highly correlated by one observer, may be used independently by another. The resulting observer-specific different recognition patterns may provide an explanation for their quite different grading results, which were identical in only 48.6% to 54.1% (mean: 50.9%) of the cases. No correlation of GCT grading with recurrence was found in 31 cases which had been treated by intralesional surgery.