Dimorphic immunohistochemical staining in ocular sebaceous neoplasms: a useful diagnostic aid.

PURPOSE: We studied whether patterns of immunostaining in formalin-fixed, paraffin-embedded tissue could help to distinguish between sebaceous neoplasms of the eyelid and other eyelid neoplasms. METHODS: We applied antibodies to human milk fat globule-1 (HMFG1), cytokeratins (PKK1 and MNF116), epithelial membrane antigen (EMA) and carcino-embryonic antigen (CEA) to normal eyelid tissue and to a range of sebaceous lesions of the eyelid; these included sebaceous hyperplasia, sebaceous adenoma and sebaceous epithelioma, in addition to well to poorly differentiated sebaceous carcinoma. RESULTS: The central and peripheral cellular components of normal sebaceous glands and neoplastic sebaceous lesions showed a distinctive dimorphic staining pattern with the antibody panel used. The central foamy 'sebaceous' cells expressed HMFG1 and EMA, but not PKK1 or MNF116, whereas the smaller, peripheral basal and ductal cells expressed PKK1 or MNF116 but not HMFG1 or EMA. CEA expression in sebaceous cells was unhelpful diagnostically. CONCLUSION: Normal sebaceous glands and all sebaceous neoplasms show a dimorphic cell population that can be identified using a small panel of antibodies on formalin-fixed, paraffin-embedded tissue. This distinctive staining pattern can be assessed retrospectively, even in small biopsies, and largely removes the need for fat stains on frozen sections to differentiate sebaceous lesions from other ocular neoplasms. The results also support the suggestion that ocular sebaceous neoplasms arise from a common stem cell, rather than from either sebaceous or basal/ductal cells.

Clinician beliefs underlying autopsy requests.

The aim of the study was to use psychological theory to identify and evaluate factors influencing clinical autopsy requests. A series of pilot interviews were conducted with 20 clinicians to identify beliefs about the benefits and drawbacks, social groups and circumstances influential in the decision to make an autopsy request. The most common beliefs, together with measures of intention to request autopsies, were incorporated into a questionnaire which was distributed among all appropriate clinicians in four hospitals. Statistical analyses identified which beliefs had the most influence on clinicians' intentions to request autopsies. A total of 145 clinicians returned the questionnaire, a response rate of 42%. Clinicians were significantly more likely to request autopsy the more they thought that the outcome of requesting would be of educational value, would confirm clinical diagnoses, would not distress relatives, would not be time-consuming and that the request itself would receive support from their consultant. An autopsy request was unlikely in circumstances where clinicians felt uncomfortable when requesting relatives' permission and when the patients were elderly. The fear of causing distress to relatives and the degree of support from the clinician's consultant were found to be the strongest predictors of intention to request autopsies. These are two areas in which intervention could help to increase autopsy request rates.

Pilomatrix carcinoma and multiple pilomatrixomas.

Pilomatrixoma is the only skin appendage tumour showing predominantly hair matrix differentiation. Rarely, aggressive or malignant variants are reported in the literature. We report a case of a 44-year-old male with multiple pilomatrixomas, one of which grew rapidly, recurring several times. Histological examination of this tumour showed predominantly hair matrix differentiation but also abortive hair follicle formation with pilar keratinization reminiscent of a trichoepithelioma. Numerous mitoses and moderate cellular pleomorphism were present, associated with infiltration of subcutaneous skeletal muscle and vascular invasion.

Fractal and integer-dimensional geometric analysis of pigmented skin lesions.

Accurate in vivo diagnosis of pigmented skin lesions is required to identify and excise malignant melanomas but to avoid unnecessary excision of benign lesions; the published rates of clinical diagnostic accuracy are about 65%. This study investigates whether fractal geometric analysis of pigmented skin lesions can improve the rate of diagnostic accuracy. Forty-two pigmented skin lesions (15 malignant melanomas, 21 melanocytic naevi, and 6 basal cell papillomas) on patients attending a dermatology clinic were photographed, excised, and sent for histopathological examination. The fractal dimension of the boundary of the lesions was measured using a box-counting method implemented on a microcomputer-based image analysis system. Euclidean geometric parameters were also measured. The fractal dimension of all the lesions was greater than the topological dimension (one), indicating that there is a fractal element to their structure. Using all measured parameters together, multivariate linear discriminant analysis produced a confusion matrix in which 45% of the lesions were assigned to the correct diagnostic group with a kappa statistic of 0.33. There was no significant difference between the fractal dimension of melanocytic naevi and that of malignant melanomas (p = 0.18). Although pigmented skin lesions have a fractal element to their structure, the fractal dimension of their boundaries is not a useful morphometric discriminant between the diagnostic groups of malignant melanomas and benign melanocytic naevi.

How do clinicians learn to request permission for autopsies?

A postal survey of 434 clinicians at four local hospitals was undertaken in order to identify the methods by which clinicians learn how to request permission for hospital autopsies and to assess the preferred techniques and timing of relevant communication skills training. The majority of 128 responding clinicians had learnt through personal experience with some assistance from senior colleagues and peers. Few clinicians appeared to have learnt through formal training. The preferred methods for the provision of communication skills training were training in small groups (such as seminars or tutorials) and observation of clinicians at work. The most desirable time for the provision of this training was considered to be between the beginning of the final undergraduate year and the end of the pre-registration house officer year. The communication skills training provided within medical education is in need of improvement. More emphasis should be given to clinical-task- or situation-specific applications such as requesting permission for autopsies.

Fractal geometric analysis of the renal arterial tree in infants and fetuses.

Fractal geometry is a useful method of quantitating the space-filling properties of complex objects and has a particular advantage in pediatric pathology because it is independent of organ size. The fractal dimensions of angiographic images of 44 renal arterial trees from 23 consent pediatric autopsies were measured by the box-counting method. The mean fractal dimension was 1.64 and all values were greater than the topological dimension (one), indicating that the renal arterial tree in fetuses and infants has a fractal element to its structure. There was no significant association with size of the kidneys, confirming the size-independent nature of the fractal dimension. There was no significant association with age of the subject, and the mean value was not significantly different from values obtained in studies of adult kidneys, suggesting that the degree of branching, at a lobar and lobular level, does not increase after about the 21st week of gestation. The results are compatible with a diffusion-limited aggregation model of development.

Measuring fractal dimensions. Sensitivity to edge-processing functions.

The fractal dimension is a useful tool in quantitative histology and cytology, and its measurement is easily implemented on computerized image analysis systems. However, the optimal conditions for capture of images and the effect of image-processing functions on the measurement of the fractal dimension have not been reported. Edge-processing functions were applied to images of Euclidean (square) and fractal (Koch island, renal angiogram) objects. The fractal dimension of processed images was measured using implementation of the box-counting method, and the area of thresholded image was also recorded. The method was shown to be accurate, with errors of < 1.5% for objects with known fractal dimensions, and highly reproducible, with a reliability coefficient of 0.972 (95% confidence limits of 0.868-0.987). The fractal dimension of the fractal images showed a marked (> 15%) reduction when a binary noise reduction function was applied with the minimum neighbors limit set above 3. In contrast, the fractal dimension of the Euclidean square was unchanged by this function. The reduction in fractal dimension was due to the erosion of complex convolutions at the edge of the fractal objects. Edge-processing functions should be avoided when manipulating images of fractal objects.

Chaos and antichaos in pathology.

Deterministic chaos is a pattern of fluctuations that may seem to be stochastic (caused by random external forces) but is actually produced, in a determined manner, by the action of nonlinear dynamic processes. The existence of this phenomenon has important implications for pathologists because it means that experimental data with apparently random fluctuations may be caused by a deterministic process. The patterns noted in deterministic chaos are very sensitive to variation in initial conditions, so if chaotic processes do occur in pathology then methods of predicting biological behavior (prognosis) of lesions, such as tumors, will have to be modified. This review shows the properties of deterministic chaos using a simple mathematical model of tumor growth and describes the methods that may be used to analyze experimental data for the presence of such chaos illustrating these with some clinical data. Established applications in medicine are reviewed and antichaotic mechanisms are discussed.

Fractal geometric analysis of material from molar and non-molar pregnancies.

Histological sections from 25 non-molar pregnancies, nine partial hydatidiform moles, and 16 complete hydatidiform moles were examined (diagnosis was taken as the consensus of seven experienced histopathologists) and the fractal dimension was measured using a box-counting method implemented on a microcomputer-based image analysis system. The fractal dimensions of the different diagnostic categories were normally distributed with a mean of 1.50 for non-molar pregnancies, 1.44 for partial moles, and 1.42 for complete moles. All the measured fractal dimensions were greater than the topological dimension (1), demonstrating that the specimens had a fractal element to their structure. There was a significant difference between the fractal dimensions of non-molar pregnancies and complete moles (P = 0.0005), but not between partial moles and non-molar pregnancies (P = 0.0823) or complete and partial moles (P = 0.4400). Using the fractal dimension to predict the histopathological diagnosis assigned 56 per cent of the cases to the correct category with a kappa statistic of 0.26, so the fractal dimension, used alone, is not a useful morphometric discriminant in the diagnosis of molar and non-molar pregnancy.

Fractal geometric analysis of colorectal polyps.

Colorectal polyps have a subjectively self-similar structure which suggests that these structures may have fractal elements and that the fractal dimension may be a useful morphometric discriminant. The fractal dimensions of images from haematoxylin and eosin-stained sections of 359 colorectal polyps (214 tubulovillous adenomas, 41 'pure' tubular adenomas, 29 'pure' villous adenomas, 68 metaplastic polyps, and 7 inflammatory polyps) were measured using a box-counting method implemented on a microcomputer-based image analysis system. Results were assessed using polychotomous logistic regression, confusion matrices, and kappa statistics. All examined polyps were shown to have a fractal structure in the range of scales examined. The fractal dimension was significantly different between different diagnostic categories (P < 0.0001) and was a useful discriminant between these categories (kappa statistic 0.60 for the confusion matrix with size as the other variable). The fractal dimension did not shown any significant correlation with the grade of epithelial dysplasia (P > 0.05). This study shows that colorectal polyps have a fractal structure over a defined range of magnification and Euclidean morphometric measurements will be invalid outside precisely defined conditions of resolution and magnification. The fractal dimension is a better way of quantitating the polyp shape and is a useful morphometric discriminant between diagnostic categories.

Are hip fractures caused by falling and breaking or breaking and falling? Photoelastic stress analysis.

The distribution of stress in the heads of femurs has been assessed using an engineering technique known as photoelastic stress analysis. The aim of the investigation was to locate and evaluate the probable sites of structure failure in femurs with various axes of loading. The analysis shows that the maximum stress in the upper femur occurs in the cervical region during vertical loading. Lateral loading does not produce significant stress patterns at the sites of extracapsular hip fracture. It is concluded that cervical hip fractures in individuals suffering from osteoporosis result from a combination of fatigue damage and axial muscular compression, rather than forces generated by a fall. This has significance for the medico-legal interpretation of the cause of death following femoral neck fracture.

The meta-autopsy: changing techniques and attitudes towards the autopsy.

The contribution of new techniques to the performance, evaluation and future development of the autopsy as a quality assurance technique are reviewed. Particular emphasis is placed upon psychological techniques and studies that attempt to delineate the attitudes of those concerned with autopsies in various capacities including: medical students; junior doctors; senior clinicians; trainee pathologists and Coroners and their officers. The conclusions are considered in the light of the continuing decline in "hospital" autopsy rates.

Quantitation of the renal arterial tree by fractal analysis.

To determine whether the renal arterial system has a fractal structure, the fractal dimension of renal angiograms from 52 necropsy cases was measured using an implementation of the box-counting method on an image analysis system. The method was validated using objects with known fractal dimensions. The method was accurate with errors of less than 1.5 per cent and reproducible with initial values within 1.2 per cent of the mean of ten sets of measurements (reliability coefficient 0.968, 95 per cent confidence limits 0.911-0.984). In the 36 satisfactory angiograms the mean fractal dimension was 1.61 (SD 0.06), which was significantly greater than the topological dimension of 1 (P < 0.0001), indicating that the renal arterial tree has a fractal structure. There was no significant relationship between age (P = 0.494), sex (P = 0.136), or systolic (P = 0.069) or diastolic (P = 0.990) blood pressure, but two congenitally abnormal kidneys (hypoplastic dysplasia and renal artery stenosis) had fractal dimensions at the lower end of the normal range (third percentile). Since the renal arterial tree has a fractal structure, Euclidean geometric measurements, such as area and boundary length, are invalid outside precisely defined conditions of magnification and resolution.

Trabecular bone does not have a fractal structure on light microscopic examination.

The fractal dimension of the boundary of trabecular bone in 62 biopsies was measured on histological sections using a box-counting method implemented on a microcomputer image analysis system. The calculated fractal dimension had a mean value of 0.99 with a normal distribution. Since this value is not greater than the topological dimension, trabecular bone, when examined by light microscopy, does not have a fractal structure. Conventional Euclidean dimensions will continue to be the most useful measurements in bone histomorphometry.