Whole-mount Histological Sections Research Articles

Patterns of Caudate Lobe Invasion of Hilar Cholangiocarcinoma: A Panoramic Histologic Study of Liver.

At present, caudate lobectomy (CL) in hilar cholangiocarcinoma (HCCA) was controversial. Our study was designed to investigate the features of caudate lobe invasion (CLI) by whole-mount histologic large sections (WHLS). A total of 46 HCCA patients underwent hemihepatectomy or trisectionectomy combined with CL were included. Serial WHLS (120 mm × 100 mm) were collected, and the relationship between caudate lobe and tumor was retained to determine the incidence of CLI. Hematoxylin and eosin (HE) and immunohistochemical (IHC) staining were completed to further explore the pathway of CLI. The whole region of the Glisson system in caudate lobe and hilar area can be clearly displayed by WHLS, and 32 (32/46 69.6%) patients were identified with CLI. There were three different pathways of CLI with panoramic IHC staining. The most common pathway is through the fibrous connective tissue along Glisson system (20/32 62.5%, without carcinoma in bile ducts). The Bismuth type, tumor size, vascular invasion, pathological type, and hepatic invasion were related to the CLI (p < 0.05). The incidence and distribution of CLI provided histologic evidence for CL in HCCA. Based on the invasion pathway, it is necessary to assess the fibrous connective tissue in Glisson system of caudate lobe in pathological research and practice.

Characteristic of Perineural Invasion in Hilar Cholangiocarcinoma Based on Whole-Mount Histologic Large Sections of Liver.

Background & ObjectivePerineural invasion is an important biological feature of hilar cholangiocarcinoma (HCCA). We developed a whole-mount histologic large sections (WHLS) of the liver to evaluate peripheral nerve invasion (PNI) of HCCA.MethodsUsing sampling, fixation, dehydration, embedding, sectioning, hematoxylin and eosin (H&E) and immunohistochemical (IHC) staining, and scanning, the characteristics of intrahepatic and extrahepatic PNI in 20 patients with Bismuth type III and type IV HCCA were analyzed with WHLS. Correlation between the characteristics of nerve invasion and tumor size, vascular invasion (artery, portal vein), degree of differentiation, microvascular invasion (MVI), carbohydrate antigen19-9 (CA19-9), and differentiation degree of HCCA was statistically evaluated.ResultsThe WHLS of the liver was successfully established, which enabled us to observe intrahepatic and extrahepatic distribution of HCCA and whether surrounding tissues including nervous, blood, and lymph vessels were infiltrated. Extrahepatic and intrahepatic PNI were identified in 20 (100%) patients and 1 (5.0%) patient, respectively. Vessel density decreased in most invaded nerves presented by CD-34, which correlated with 100% of poorly differentiated and 83% of moderately differentiated tumors (P<0.008).ConclusionThis study established a WHLS of the liver that can be used for clinical diagnosis and research, and confirmed that extrahepatic PNI is prevalent, but intrahepatic nerve invasion is rare and does not accompany the invasion scope of bile ducts in types III and IV HCCA. In addition, moderately and poorly differentiated malignant tumors are more prone to PNI, independent of blood supply.

Short-duration dynamic [18F]DCFPyL PET and CT perfusion imaging to localize dominant intraprostatic lesions in prostate cancer: validation against digital histopathology and comparison to [18F]DCFPyL PET/MR at 120 minutes

PurposeLocalized prostate cancer (PCa) in patients is characterized by a dominant focus in the gland (dominant intraprostatic lesion, DIL). Accurate DIL identification may enable more accurate diagnosis and therapy through more precise targeting of biopsy, radiotherapy and focal ablative therapies. The goal of this study is to validate the performance of [18F]DCFPyL PET and CT perfusion (CTP) for detecting and localizing DIL against digital histopathological images.MethodsMulti-modality image sets: in vivo T2-weighted (T2w)-MRI, 22-min dynamic [18F]DCFPyL PET/CT, CTP, and 2-h post-injection PET/MR were acquired in patients prior to radical prostatectomy. The explanted gland with implanted fiducial markers was imaged with T2w-MRI. All images were co-registered to the pathologist-annotated digital images of whole-mount mid-gland histology sections using fiducial markers and anatomical landmarks. Regions of interest encompassing DIL and non-DIL tissue were drawn on the digital histopathological images and superimposed on PET and CTP parametric maps. Logistic regression with backward elimination of parameters was used to select the most sensitive parameter set to distinguish DIL from non-DIL voxels. Leave-one-patient-out cross-validation was performed to determine diagnostic performance.Results[18F]DCFPyL PET and CTP parametric maps of 15 patients were analyzed. SUVLate and a model combining Ki and k4 of [18F]DCFPyL achieved the most accurate performance distinguishing DIL from non-DIL voxels. Both detection models achieved an AUC of 0.90 and an error rate of < 10%. Compared to digital histopathology, the detected DILs had a mean dice similarity coefficient of 0.8 for the Ki and k4 model and 0.7 for SUVLate.ConclusionsWe have validated using co-registered digital histopathological images that parameters from kinetic analysis of 22-min dynamic [18F]DCFPyL PET can accurately localize DILs in PCa for targeting of biopsy, radiotherapy, and focal ablative therapies. Short-duration dynamic [18F]DCFPyL PET was not inferior to SUVLate in this diagnostic task.Clinical trial registration number: NCT04009174 (ClinicalTrials.gov).

Comparing radiomic classifiers and classifier ensembles for detection of peripheral zone prostate tumors on T2-weighted MRI: a multi-site study

BackgroundFor most computer-aided diagnosis (CAD) problems involving prostate cancer detection via medical imaging data, the choice of classifier has been largely ad hoc, or been motivated by classifier comparison studies that have involved large synthetic datasets. More significantly, it is currently unknown how classifier choices and trends generalize across multiple institutions, due to heterogeneous acquisition and intensity characteristics (especially when considering MR imaging data). In this work, we empirically evaluate and compare a number of different classifiers and classifier ensembles in a multi-site setting, for voxel-wise detection of prostate cancer (PCa) using radiomic texture features derived from high-resolution in vivo T2-weighted (T2w) MRI.MethodsTwelve different supervised classifier schemes: Quadratic Discriminant Analysis (QDA), Support Vector Machines (SVMs), naïve Bayes, Decision Trees (DTs), and their ensemble variants (bagging, boosting), were compared in terms of classification accuracy as well as execution time. Our study utilized 85 prostate cancer T2w MRI datasets acquired from across 3 different institutions (1 for discovery, 2 for independent validation), from patients who later underwent radical prostatectomy. Surrogate ground truth for disease extent on MRI was established by expert annotation of pre-operative MRI through spatial correlation with corresponding ex vivo whole-mount histology sections. Classifier accuracy in detecting PCa extent on MRI on a per-voxel basis was evaluated via area under the ROC curve.ResultsThe boosted DT classifier yielded the highest cross-validated AUC (= 0.744) for detecting PCa in the discovery cohort. However, in independent validation, the boosted QDA classifier was identified as the most accurate and robust for voxel-wise detection of PCa extent (AUCs of 0.735, 0.683, 0.768 across the 3 sites). The next most accurate and robust classifier was the single QDA classifier, which also enjoyed the advantage of significantly lower computation times compared to any of the other methods.ConclusionsOur results therefore suggest that simpler classifiers (such as QDA and its ensemble variants) may be more robust, accurate, and efficient for prostate cancer CAD problems, especially in the context of multi-site validation.

Radiological Wheeler staging system: a retrospective cohort analysis to improve the local staging of prostate cancer with multiparametric MRI.

The knowledge of tumor location and extension can allow a modulated radical prostatectomy in order to minimize positive surgical margins and reduce functional morbidity after surgery in patients with prostate cancer (PCa). Multiparametric (mp) magnetic resonance imaging (MRI) could allow the assessment of tumor extension and of its relationship with external structures. Aim of this study is to propose a new radiological Wheeler (rW) staging system applied to mp-MRI, based on the pathologic staging system (pW) for the local assessment of PCa. This retrospective single-center multi-reader study included consecutive patients with PCa and preoperative mp-MRI, who underwent non-nerve sparing radical prostatectomy. Three radiologists reported on all examinations and classified each selected lesion according to imaging criteria following rW. Whole-mount histological sections were used as the reference standard. An experienced pathologist classified the extent of prostatic capsular invasion of each PCa according to the pW. Each histological section was scanned for comparison with mp-MRI findings. The rate of PCa correctly classified by radiologists using the pW was assessed. To evaluate the accuracy of mp-MRI in the discrimination between T2 and T3 PCa, the AUC was computed. One-hundred and five patients with a total of 195 PCa foci were included in the study. 130/195 tumors with a clear overlap between mp-MRI and surgical specimens were selected. The sensitivity of the most experienced reader was lower than that of the other two readers (48.6% vs. 68.6% and 62.9%, P>0.09) while specificity and PPV were higher (95.8% vs. 79.0% and 57.9%, P<0.001; 81.0% vs. 54.6% and 35.5%, P<0.041; respectively). The AUC values for the most and the intermediate experienced readers in the detection of extracapsular extension were in the range 0.72-0.74. The rW staging system has low accuracy in predicting each single pW class, while accuracy was over 80% for experienced readers in the identification of organ-confined (T2 stage class) tumors and non-organ confined cases (T3 stage class).

The role of side-specific biopsy and dominant tumor location at radical prostatectomy in predicting the side of nodal metastases in organ confined prostate cancer: is lymphatic spread really unpredictable?

The aim of this study was to evaluate the correlation between the location of prostate cancer (PCa) either at biopsy or at radical prostatectomy (RP) specimens and the side of positive lymph nodes (LNs). Furthermore, we assessed the risk of contralateral LN metastasis (LNMs) in patients with unilateral positive biopsy and/or dominant lesion at RP. We reviewed retrospectively our prospectively maintained database of patients with LNM treated with robot-assisted RP and bilateral robot-assisted extended pelvic lymph node dissection (EPLND) for PCa from January 2014 to May 2018 at a surgical high-volume center. All men with a suspicion for PCa underwent a 12-cores prostate biopsy. In case of a first negative biopsy but the persistence of suspicion, all the patients underwent prostate multiparametric magnetic resonance imaging (mpMRI) and subsequently either fusion targeted biopsy (TBx) or systematic standard biopsy (SBx), in case of positive or negative mpMRI, respectively. All patients underwent a robot-assisted RP. Whole-mount histological sections resected from the RP specimens were used as reference standards. Eighty-seven patients were enrolled for the study. Median number of LNs retrieved per patient was 26, specifically 13 and 12, on the left and right side, respectively. Seven of 24 (29.1%) right lobe positive biopsy showed positive LNs on the left side (one exclusively left, 6 bilateral LNMs). Again, 12 of 26 (46.1%) left lobe positive biopsy showed positive LNs on the right side (one exclusively right, 11 bilateral LNMs). No significant differences of performance to predict the side of LNMs were recorded in the SBx and TBx groups. Concerning RP specimens, only five of 22 (22.7%) right lobe dominant cases showed positive LNs on the left side (two exclusively left, 3 bilateral LN metastases). Again, none of 16 left lobe dominant cases showed positive LNs on the contralateral side (15 exclusively right, 1 bilateral LNMs). Our results suggest confirmed that a unilateral LN dissection limited to the tumor-bearing side of the gland evaluated by biopsy specimens should not be recommended due to the substantial risk of missing contralateral LNMs.

MR measurement of luminal water in prostate gland: Quantitative correlation between MRI and histology.

To determine the relationship between parameters measured from luminal water imaging (LWI), a new magnetic resonance imaging (MRI) T2 mapping technique, and the corresponding tissue composition in prostate. In all, 17 patients with prostate cancer were examined with a 3D multiecho spin echo sequence at 3T prior to undergoing radical prostatectomy. Maps of seven MR parameters, called N, T2-short , T2-long , Ashort , Along , geometric mean T2 time (gmT2 ), and luminal water fraction (LWF), were generated using nonnegative least squares (NNLS) analysis of the T2 decay curves. MR parametric maps were correlated to digitized whole-mount histology sections. Percentage area of tissue components, including luminal space, nuclei, and cytoplasm plus stroma, was measured on the histology sections by using color-based image segmentation. Spearman's rank correlation test was used to evaluate the correlation between MR parameters and the corresponding tissue components, with particular attention paid to the correlation between LWF and percentage area of luminal space. N, T2-short , Along , gmT2 , and LWF showed significant correlation (P < 0.05) with percentage area of luminal space and stroma plus cytoplasm. T2-short and gmT2 also showed significant correlation (P < 0.05) with percentage area of nuclei. Overall, the strongest correlation was observed between LWF and luminal space (Spearman's coefficient of rank correlation = 0.75, P < 0.001). Results of this study show that LWF measured with MRI is strongly correlated with the fractional amount of luminal space in prostatic tissue. This result suggests that LWI can potentially be applied for evaluation of prostatic diseases in which the extent of luminal space differs between normal and abnormal tissues. 1 Technical Efficacy: Stage 1 J. MAGN. RESON. IMAGING 2017;46:861-869.

A fully automatic computer aided diagnosis system for peripheral zone prostate cancer detection using multi-parametric magnetic resonance imaging

Multiparametric (mp)-Magnetic Resonance Imaging (MRI) is emerging as a powerful test to diagnose and stage prostate cancer (PCa). However, its interpretation is a time consuming and complex feat requiring dedicated radiologists. Computer-aided diagnosis (CAD) tools could allow better integration of data deriving from the different MRI sequences in order to obtain accurate, reproducible, non-operator dependent information useful to identify and stage PCa. In this paper, we present a fully automatic CAD system conceived as a 2-stage process. First, a malignancy probability map for all voxels within the prostate is created. Then, a candidate segmentation step is performed to highlight suspected areas, thus evaluating both the sensitivity and the number of false positive (FP) regions detected by the system. Training and testing of the CAD scheme is performed using whole-mount histological sections as the reference standard. On a cohort of 56 patients (i.e. 65 lesions) the area under the ROC curve obtained during the voxel-wise step was 0.91, while, in the second step, a per-patient sensitivity of 97% was reached, with a median number of FP equal to 3 in the whole prostate. The system here proposed could be potentially used as first or second reader to manage patients suspected to have PCa, thus reducing both the radiologist's reporting time and the inter-reader variability. As an innovative setup, it could also be used to help the radiologist in setting the MRI-guided biopsy target.

Detection of prostate cancer index lesions with multiparametric magnetic resonance imaging (mp-MRI) using whole-mount histological sections as the reference standard.

To evaluate the sensitivity of multiparametric magnetic resonance imaging (mp-MRI) for detecting prostate cancer foci, including the largest (index) lesions. In all, 115 patients with biopsy confirmed prostate cancer underwent mp-MRI before radical prostatectomy. A single expert radiologist recorded all prostate cancer foci including the index lesion 'blinded' to the pathologist's biopsy report. Stained whole-mount histological sections were used as the reference standard. All lesions were contoured by an experienced uropathologist who assessed their volume and pathological Gleason score. All lesions with a volume of >0.5mL and/or pathological Gleason score of >6 were defined as clinically significant prostate cancer. Multivariate analysis was used to ascertain the characteristics of lesions identified by MRI. In all, 104 of 115 index lesions were correctly diagnosed by mp-MRI (sensitivity 90.4%; 95% confidence interval [CI] 83.5-95.1%), including 98/105 clinically significant index lesions (93.3%; 95% CI 86.8-97.3%), among which three of three lesions had a volume of <0.5mL and Gleason score of >6. Overall, mp-MRI detected 131/206 lesions including 13 of 68 'insignificant' prostate cancers. The multivariate logistic regression modelling showed that pathological Gleason score (odds ratio [OR] 11.7, 95% CI 2.3-59.8; P = 0.003) and lesion volume (OR 4.24, 95% CI 1.3-14.7; P = 0.022) were independently associated with the detection of index lesions at MRI. This study shows that mp-MRI has a high sensitivity for detecting clinically significant prostate cancer index lesions, while having disappointing results for the detection of small-volume, low Gleason score prostate cancer foci. Thus, mp-MRI could be used to stratify patients according to risk, allowing better treatment selection.

Why prostate tumour delineation based on apparent diffusion coefficient is challenging: An exploration of the tissue microanatomy

Background. Focal boosting of prostate tumours to improve outcome, requires accurate tumour delineation. For this, the apparent diffusion coefficient (ADC) derived from diffusion-weighted MR imaging (DWI) seems a useful tool. On voxel level, the relationship between ADC and histological presence of tumour is, however, ambiguous. Therefore, in this study the relationship between ADC and histological variables was investigated on voxel level to understand the strengths and limitations of DWI for prostate tumour delineation. Material and methods. Twelve radical prostatectomy patients underwent a pre-operative 3.0T DWI exam and the ADC was calculated. From whole-mount histological sections cell density and glandular area were retrieved for every voxel. The distribution of all variables was described for tumour, peripheral zone (PZ) and central gland (CG) on regional and voxel level. Correlations between variables and differences between regions were calculated. Results. Large heterogeneity of ADC on voxel level was observed within tumours, between tumours and between patients. This heterogeneity was reflected by the distribution of cell density and glandular area. On regional level, tumour was different from PZ having higher cell density (p = 0.007), less glandular area (p = 0.017) and lower ADCs (p = 0.017). ADC was correlated with glandular area (r = 0.402) and tumour volume (r = −0.608), but not with Gleason score. ADC tended to decrease with increasing cell density (r = −0.327, p = 0.073). On voxel level, correlations between ADC and histological variables varied among patients, for cell density ranging from r = −0.439 to r = 0.261 and for glandular area from r = 0.593 to r = 0.207. Conclusions. The variation in ADC can to a certain extent be explained by the variation in cell density and glandular area. The ADC is highly heterogeneous, which reflects the heterogeneity of malignant and benign prostate tissue. This heterogeneity might however obscure small tumours or parts of tumours. Therefore, DWI has to be used in the context of multiparametric MRI.

Multimodal wavelet embedding representation for data combination (MaWERiC): integrating magnetic resonance imaging and spectroscopy for prostate cancer detection

Recently, both Magnetic Resonance (MR) Imaging (MRI) and Spectroscopy (MRS) have emerged as promising tools for detection of prostate cancer (CaP). However, due to the inherent dimensionality differences in MR imaging and spectral information, quantitative integration of T(2) weighted MRI (T(2)w MRI) and MRS for improved CaP detection has been a major challenge. In this paper, we present a novel computerized decision support system called multimodal wavelet embedding representation for data combination (MaWERiC) that employs, (i) wavelet theory to extract 171 Haar wavelet features from MRS and 54 Gabor features from T(2)w MRI, (ii) dimensionality reduction to individually project wavelet features from MRS and T(2)w MRI into a common reduced Eigen vector space, and (iii), a random forest classifier for automated prostate cancer detection on a per voxel basis from combined 1.5 T in vivo MRI and MRS. A total of 36 1.5 T endorectal in vivo T(2)w MRI and MRS patient studies were evaluated per voxel by MaWERiC using a three-fold cross validation approach over 25 iterations. Ground truth for evaluation of results was obtained by an expert radiologist annotations of prostate cancer on a per voxel basis who compared each MRI section with corresponding ex vivo wholemount histology sections with the disease extent mapped out on histology. Results suggest that MaWERiC based MRS T(2)w meta-classifier (mean AUC, μ = 0.89 ± 0.02) significantly outperformed (i) a T(2)w MRI (using wavelet texture features) classifier (μ = 0.55 ± 0.02), (ii) a MRS (using metabolite ratios) classifier (μ = 0.77 ± 0.03), (iii) a decision fusion classifier obtained by combining individual T(2)w MRI and MRS classifier outputs (μ = 0.85 ± 0.03), and (iv) a data combination method involving a combination of metabolic MRS and MR signal intensity features (μ = 0.66 ± 0.02).

Elastic registration of multimodal prostate MRI and histology via multiattribute combined mutual information

By performing registration of preoperative multiprotocol in vivo magnetic resonance (MR) images of the prostate with corresponding whole-mount histology (WMH) sections from postoperative radical prostatectomy specimens, an accurate estimate of the spatial extent of prostate cancer (CaP) on in vivo MR imaging (MRI) can be retrospectively established. This could allow for definition of quantitative image-based disease signatures and lead to development of classifiers for disease detection on multiprotocol in vivo MRI. Automated registration of MR and WMH images of the prostate is complicated by dissimilar image intensities, acquisition artifacts, and nonlinear shape differences. The authors present a method for automated elastic registration of multiprotocol in vivo MRI and WMH sections of the prostate. The method, multiattribute combined mutual information (MACMI), leverages all available multiprotocol image data to drive image registration using a multivariate formulation of mutual information. Elastic registration using the multivariate MI formulation is demonstrated for 150 corresponding sets of prostate images from 25 patient studies with T2-weighted and dynamic-contrast enhanced MRI and 85 image sets from 15 studies with an additional functional apparent diffusion coefficient MRI series. Qualitative results of MACMI evaluation via visual inspection suggest that an accurate delineation of CaP extent on MRI is obtained. Results of quantitative evaluation on 150 clinical and 20 synthetic image sets indicate improved registration accuracy using MACMI compared to conventional pairwise mutual information-based approaches. The authors' approach to the registration of in vivo multiprotocol MRI and ex vivo WMH of the prostate using MACMI is unique, in that (1) information from all available image protocols is utilized to drive the registration with histology, (2) no additional, intermediate ex vivo radiology or gross histology images need be obtained in addition to the routinely acquired in vivo MRI series, and (3) no corresponding anatomical landmarks are required to be identified manually or automatically on the images.

Three-dimensional Analysis of Supracricoid Hemilaryngopharyngectomized Hypopharyngeal Cancer

The aims of this study were to demonstrate the technical aspects of processing high-resolution three-dimensional (3D) images and to describe the value of this approach for studying partially removed hypopharyngeal cancer. Supracricoid hemilaryngopharyngectomy was conducted in three sinus-type hypopharyngeal cancers as a salvage operation. A histopathologic study was conducted in order to fully examine the resection margin of the surgical specimens and to ensure the credibility of our case selection. The morphological features of each specimen were analyzed and demonstrated using 2D and 3D settings. Whole-mount serial histological sections were developed from the surgical specimens and 3D images were reconstructed based on these sections. In each case the 3D images demonstrated the characteristic patterns of cancer extension, such as superior extension under the intact epithelium and the formation of multiple skip lesions. The overall resection margin was proven to be free of cancer in all three cases. In conclusion, 3D study was useful for evaluating the overall resection margin of surgical specimens and provided valuable information for use in future follow-up. Using this technique, the morphological findings from serial sections are more comprehensive and impressive. 3D reconstruction is and will be a crucial modality for studying the morphological behavior of hypopharyngeal cancer.

Nuclear changes in the normal-looking columnar epithelium adjacent to and distant from prostatic intraepithelial neoplasia and prostate cancer. Morphometric analysis in whole-mount sections.

Subtle morphological changes and molecular alterations have been reported in normal-appearing tissue in prostates with high-grade prostatic intraepithelial neoplasia (PIN) and prostate cancer (PCa). The severity and the distribution of these changes and alterations within the prostate gland have not been addressed in previous publications. The aim of this study was to investigate morphometrically the nuclear changes of the normal-looking columnar epithelium adjacent to and distant from high-grade PIN and PCa. Karyometry was performed on the whole-mount histological sections of three radical prostatectomy (RP) specimens. Two concentrical lines, one corresponding to the outer surface (or capsule) of the prostate and the other corresponding to one centimeter towards the center, were drawn with a black pen on each whole-mount section. The part of the prostate tissue between these two boundaries was then divided into twelve equal sectors or regions. The part within the inner line was divided into two regions. The analysis was also performed on the slides of the apex and base of the prostate. One prostate contained normal-looking epithelium only (case no. 1). Another contained both high-grade PIN and PCa, the former occupying larger areas than the latter (case no. 2). Both high-grade PIN and PCa were present in the third sample, in which PCa was more widely distributed than PIN (case no. 3). The lesion measured in each region was always the most severe, e.g., either high-grade PIN or PCa. When neither were identifiable, then the normal-looking columnar epithelium was analyzed. For each sector, the mean and standard deviation of the nuclear area, maximum nuclear diameter, nuclear roundness factor, and nucleolar area were calculated. In normal-looking columnar epithelium, the mean of the mean nuclear area of the sectors of case no. 1 was 35.19 microm2 (SD 4.14). The mean nuclear areas in cases no. 2 and no. 3 were 37.94 microm2 (SD 4.65) and 37.31 microm2 (SD 4.36), respectively. The mean of the mean nuclear area of the sectors with high-grade PIN of case no. 2 was 49.85 microm2 (SD 8.44), whereas it was 54.26 microm2 (SD 2.91) in case no. 3. The mean of the nuclear area values obtained in the sectors of cases no. 2 and no. 3 with PCa was 56.74 microm2 (SD 6.56) and 61.17 microm2 (SD 8.13), respectively. When considering the normal-looking tissue of the second and third case, 79% and 90%, respectively, of the regions showed nuclear area values greater than 34.94 microm2 (e.g., the 50th percentile of the mean nuclear area values of the regions of the first case). Sectors with normal-looking epithelium, whose nuclear area was above this threshold, were both adjacent to and at a distance of more than 1 cm from those with PIN or PCa. The other nuclear features showed a similar trend of value changes. This study demonstrates that the normal-looking ducts and acini from prostate harboring preneoplastic and neoplastic lesions show morphological nuclear abnormalities that are not seen by the human eyes but that can be detected with image analysis. Such changes may be of diagnostic importance, especially in cases where clinical suspicion for cancer prevails after a negative biopsy.

Mosaic pattern of hepatocellular carcinoma: histologic basis for a characteristic CT appearance.

The mosaic pattern is a characteristic CT appearance for hepatocellular carcinoma (HCC). This study was designed to assess the tissue composition responsible for the CT mosaic pattern. Gross and whole-mount histologic sections of 10 HCC tumors from eight patients were prepared at identical levels as preoperative CT sections. CT features of the mosaic tumor pattern were spatially registered with the corresponding pathologic sections. CT of mosaic HCC demonstrated enhancing nodules (9/10), low attenuation areas (9/10), and internal septa (3/10). Spatial registration of CT and microscopic sections showed that enhancing tissue was viable tumor in nine of nine. Low attenuation areas were either necrotic (4/9) or of mixed tissue (5/9), including areas of necrosis, fibrosis, and hemorrhage. The variable tissue composition of HCC accounts for the mosaic CT pattern. In most patients, enhancing nodules indicate viable tumor cells, and low attenuation areas represent necrosis, fibrosis, or hemorrhage.

Prostate cancer: Comparison of pre-operative 0.35 T MRI with whole-mount histopathology

Magnetic resonance imaging of the prostate was performed in eight patients prior to radical prostatectomy. The results of the imaging studies were then directly compared to histopathologic findings from whole-mount histologic sections. Magnetic resonance imaging identified 82% of cancers greater than 5 mm in minimal diameter. Cancers were identified as areas of decreased signal intensity compared to the high signal intensity peripheral zone on long TR TE sequences. Cancers were best detected when they involved the middle level of the gland and the posterior half of the prostate. Of the individual tumors identified by imaging, the amount of tumor involvement was underestimated by 37% and overestimated by 22% by MRI. We conclude that magnetic resonance imaging can identify prostate cancer, but has limitations as a screening modality and in accurately assessing the amount of involvement of the prostate gland by cancer.

Morphologic Alterations of the Subchondrall Bone in Advanced Degenerative Arthritis

A series of 535 femoral heads surgically excised at the time of total hip arthroplasty for degenerative arthritis were analyzed by gross photography, specimen roentgenograms, and whole-mount histologic sections. Limited regenerative capacity was apparent in the chondrous tufts in the exposed bone of the osteoarthritic joint surface. The mechanism for the formation of subchondral cysts was interpreted to be the proliferation of viable myxomatous cells within the bone marrow. Osseous remodeling adjacent to the cysts was secondary to expansion of the soft tissue contents of the early cysts and later vascularization with fibrosis in the older cysts. Stress fracturing was a focal feature secondary to the remodeling of live bone. Advanced degenerative arthritis demonstrated focal osteocytic necrosis in the exposed osseous surface. Bone necrosis was also observed when small segments of the surface were undermined by cysts. Finally, bone necrosis was occasionally observed as focal infarcts of the joint surface (2-6 mm). In all three instances, bone necrosis in degenerative arthritis appeared to be a secondary reaction, presumably related to local disruption of blood supply.

Early phase acute myocardial infarct size quantification: Validation of the triphenyl tetrazolium chloride tissue enzyme staining technique

Gross histochemical delineation of myocardium which has lost dehydrogenase enzyme activity has been shown to facilitate macroscopic recognition of necrotic myocardium. The present study was undertaken to assess the accuracy of the triphenyl tetrazolium chloride (TTC) technique for quantitating myocardial infarct size very early after coronary occlusion. In 16 closed-chest dogs the left anterior descending coronary artery was occluded with an intra-arterial balloon. Twelve dogs were killed 6 hours after occlusion, their hearts excised, cut from apex to base into 1 cm thick slices, and incubated in TTC. Whole-mount histologic sections of each slice were prepared. Myocardial infarct size was measured by planimetry of photographs of each gross slice and histologic section using classical criteria of necrosis. Myocardial infarct size determined in 54 slices by the TTC technique and histologically was similar (25 ± 16% vs 27 ± 16% of the left ventricular mass, mean ± SD) with close correlation between the two methods ( r = 0.91). Four dogs were killed 3 hour after occlusion and TTC stained and unstained myocardium was studied by electron microscopy. When the TTC technique identified necrosis so did electron microscopy. Areas identified by the TTC technique as non-necrotic were either normal or only ischemic by electron microscopy. Thus, using TTC, necrosis can be quantitated reliably 6, and even 3 hours after coronary occlusion, before histologic changes are clearly diagnostic. This technique represents a reliable, practical means for quantitation of recent infarction and for studying the evolution of ischemic injury in its early phase.