D. W. K. Cotton

Nucleolar organizer regions in spitz nevi and malignant melanomas

Nucleolar organizer regions (NOR) are loops of DNA that transcribe ribosomal RNA; they can be easily identified in formalin fixed paraffin embedded tissue using a silver (Ag) method. It has been suggested that the number of AgNOR per cell can differentiate between benign and malignant melanocytic lesions of skin. We have studied 29 Spitz nevi (SN) and 39 invasive malignant melanomas (MM) by the same silver method. SN showed between 1.0 and 1.6 AgNOR per cell with a mean of 1.2. MM counts ranged from 1.2 to 4.2 with a mean of 2.0. It is concluded that the AgNOR method cannot reliably differentiate SN from MM; however, a count of more than 2.0 AgNOR per cell would favor a diagnosis of MM rather than SN.

AgNORs in Benign, Dysplastic, and Malignant Melanocytic Skin Lesions

Nucleolar organiser regions (NORs) are loops of DNA situated on the short arms of acrocentric chromosomes 13, 14, 15, 21, and 22; they can be demonstrated in formalin-fixed paraffin-embedded sections by a one-step silver technique, the resulting black structures being termed AgNORs. We have applied the technique to 30 benign “banal” nevi (BN), 30 dysplastic nevi (DN), and 30 malignant melanomas (MM). AgNORs in 200 nuclei were scored and the means calculated. Counts were as follows: BN showed a mean of 1.3 AgNORs per nucleus within a range of 1.1–1.6; DN showed a mean of 1.2 within a range of 1.0–1.6; and MM showed a mean of 2.1 within a range of 1.2—4.2. A significant difference existed between counts for MM and those for BN and DN, despite some overlap. There was no statistically significant difference between BN and DN. Although still within the field of research, the AgNOR technique may prove to be of value in helping to differentiate MM from DN, but is unlikely to be of help in separating DN from BN.

Fractal and integer-dimensional geometric analysis of pigmented skin lesions

&NA; 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 &kgr; 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.

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.

Recurrent solitary giant trichoepithelioma located in the perianal area; a case report

A case of giant solitary trichoepithelioma of the perianal region is described. Following excision the lesion recurred with a similar histological appearance. This is the first report, to our knowledge, of recurrence of such a lesion.

On the nature of clear cell acanthomas

Five clear cell acanthomas were studied using a panel of immunohistological markers. The results were compared with those from basal cell papillomas, with and without clear cell change, and with lesions of psoriasis and lichen planus. The results do not support the contention that these lesions are variants of basal cell papillomas nor that they are true neoplasms.

Flow cytometric comparison of keratoacanthoma and squamous cell carcinoma

The adaptor (Fig. i) is constructed from a staitiless steel core which has a screw thread and a hollow centre at one end (a), and a solid end to plug into the Hyfrecator handle at the other end (b). The core is insulated with a nylon sheath (c) which extends distally to cover the hub of the needle, protecting the user from accidental contact with it. Standard fitting metal hub dental needles are screwed into the end of the adaptor (Fig, 2). I have used this adaptor with 27 and 30 g dental needles. In addition to providing a readily changeable sterile electrode, the small needle tip has the advantage that it can be used on even the smallest lesions and can be inserted just within a lesion or small vessel providing a more localized action. I have used this technique with success on both spider naevi and skin tags. One important aspect of using the smaller tips is that the current density is higher than normal. When using the high output channel of the Hyfrecator a lower setting should be selected initially.

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.

Assessment of osteopenia at autopsy.

Osteoporosis is a common problem for the pathologist in the elderly female population where pathological fractures particularly of the neck of femur are frequent. Yet how should we assess osteoporosis at autopsy? This study reports on autopsy assessment of osteopenia, comparing our subjective findings of rib fracturability and vertebral compressibility with histological and histomorphometric assessment on a bone biopsy. We have shown a poor correlation between gross autopsy and histological techniques. There is good correlation between two gross autopsy techniques and these methods have been shown to be reproducible between observers. We believe that the most useful test of whether a patients bones are likely to break is to assess the fracturability of the ribs (and possibly the vertebral bodies) at autopsy. This should be supplemented with undecalcified histology sections from the iliac crest where possible. Further studies are clearly warranted in this area.

(25) Skin surface markings: an aid to diagnosis in dysplastic naevi and malignant melanoma

A number of distinct clinical entities are characterized by subepidermal blisters in association with linear deposition of immune reactants at the basement membrane zone (BMZ) of skin and mucous membranes. In addition to the clinical differences, further divisions are made on the basis of class of immunoreactants and the ultrastructural site of the immune deposits in relation to the BMZ, i.e. whether in the lamina lucida or below the lamina densa. We present Western blotting studies on patients with bullous pemphigoid (BP) (53), cicatricial pemphigoid (CP) (20), pemphigoid gestationis (PG) (34), linear IgA disease (LAD) of children (18), and adults (five), epidermolysis bullosa acquisita (EBA) (four) and lichen planus pemphigoides (LPP) (six). These 140 patients were classified clinically and by direct immunofiuorescence (IMF) and indirect IMF on intact and i M NaCl split skin prior to blotting. All the lamina lucida bullous diseases showed heterogeneity and overlap of epidermal antigens. Sera from the majority of typical BP patients (39%) reacted with the previously described 220 kDa BP glycoprotein, a significant minority (8%) reacted with antigens of 180 kDa (shared with PG) (6%) and 309 kDa (2%). The majority of PG sera reacted with a 180 kDa antigen (21%) and a minority also with the 220 kDa BP antigen (9%). Lichen planus pemphigoides sera also demonstrated reactivity with the 180 kDa antigen (66%) and a unique 200 kDa antigen (66%). Cicatricial pemphigoid sera also reacted with the 220 kDa antigen. Distinctive dermal antigens were identified for EBA/type VII collagen (250 kDa) and LAD (285 kDa). The molecular overlap as regards the target antigen in the blistering diseases with IgG antibodies in the lamina lucida may explain the clinical similarities. The heterogeneous nature of the antigens may also account for the diverse clinical presentations of BP. Although EBA may present clinically as BP it does not share a common antigen and no overlap with LAD has been observed. However, the antigen alone is not the sole determinant of the clinical presentation, and the host response must also be of major importance.