No abstract

The encapsulation of islets of Langerhans in alginate-poly-l-lysine has been proposed as a method for the immunoprotection of transplanted islets. Although several capsule compositions have been reported, there has been no published study concerning the effect of capsule composition on the severity of the foreign body reaction. Empty capsules were prepared from high mannuronic acid alginate and were coated with: (1) poly-l-lysine alone, (2) poly-l-lysine plus high guluronic acid alginate, or (3) poly-l-lysine plus high mannuronic acid alginate. The capsules were placed in the renal subcapsular space or the peritoneal cavity, and retrieved after three weeks of histological examination. The recipients were WAG/01a, nude (athymic), diabetic BB, and non-diabetes prone BB rats. The severity of reaction to the capsules was determined by measuring the thickness of the pericapsular cell infiltrate or by a scoring system. The severity of the reaction to the capsules was strain-dependent in both the renal and peritoneal sites, with the BB and nude rats displaying the most severe responses. The degree of response was not affected by capsule composition in the renal subcapsular space, but in the peritoneum, the high mannuronic acid alginate capsules provoked the weakest response, and this type of capsule will be used for future transplantation work. The infiltrating cells were characterised by immunohistochemistry and electron microscopy and found to be mostly fibroblasts and macrophages.

No abstract

We have assessed the degree of observer variation of both Breslow depth and Clark's level in a series of 50 thin malignant melanomas. Our findings are similar to those of previous international studies in the Breslow depth is the more reproducible measure. Significant intra- and inter-observer variation exists and in some cases it was up to +/- 0.86 mm. Even small differences will potentially affect patient management at our centre and this was analysed using kappa statistics. Good agreement was found between observers and this could be improved by comparing the mean of two or more measurements. This removes larger errors, but smaller observer errors and differences in subjective interpretation of the deepest malignant cell mean that agreement will never be more than 90 per cent. This is high compared with studies of observer variation in other pathological conditions, e.g., dysplasia of the cervix, but where surgical management is potentially disfiguring it is not high enough. We conclude that Breslow depth and Clark's level should not be the sole basis of wide excision protocols.

Highlights d Representative sequencing (Rep-Seq) is a new method for tumor molecular profiling d Rep-Seq homogenizes residual tumor tissue not taken for standard pathology d Representative sampling of tumors generates accurate tumor mutation burden scores d Rep-Seq detects more mutations and accurately resolves clonal from subclonal variants

A 33-year-old man with recessive dystrophic epidermolysis bullosa presented with a 3-month history of an enlarging mass within scarring on the posterior aspect of the right shoulder. The clinical appearance of the mass with an almost cobbled, verrucous surface, and its rapid evolution suggested the development of a squamous cell carcinoma (SCC) in a chronically scarred site. Histopathological examination of a biopsy taken from the lesion subsequently revealed it to be a verruciform xanthoma. This case shows that benign phenomena can mimic SCC and underlines the need for a biopsy to be taken promptly.

The lineage of Hodgkin and Reed-Sternberg cells is still unclear. Detection of both immunoglobulin light chains in Hodgkin and Reed-Sternberg cells by immunohistochemistry is a well-known phenomenon. However, up to now, in situ hybridization techniques have failed to demonstrate light chain messenger(m) RNA in Hodgkin and Reed-Sternberg cells. In this investigation, we have analysed 26 cases of Hodgkin's disease (nodular lymphocyte predominant Hodgkin's disease, mixed cellularity, and nodular sclerosis type) using digoxigenin-labelled oligonucleotide probes for kappa and lambda light chains by in situ hybridization. In nearly half of the cases of nodular lymphocyte predominant Hodgkin's disease and in one case of mixed cellularity type, mRNA for only one light chain could be clearly demonstrated in the lymphocytic and histiocytic cells, Hodgkin, and Reed-Sternberg cells. These results support the idea that at least some cases of Hodgkin's disease are B-cell neoplasms.

The value of pigmented lesion clinics (PLCs) for the early detection and treatment of malignant melanoma has been questioned. We have examined the effect of the introduction of a PLC on the referral interval between patients with melanoma presenting to their general practitioner (GP) and their attendance at hospital. The case notes of all patients presenting with melanoma in Leicestershire between 1984 and 1994 were reviewed. There was a significant initial reduction in the mean referral interval following the introduction of the PLC from 27.9 days (SEM = 6.6) in 1984 to 11.3 (2.3) days in 1987 (P < 0.01). However, the referral interval gradually rose over the following 7 years to a mean of 20.4 (4.4) days in 1994, which was not significantly better than the 1985/86 level. The increase in the referral interval was due to a greater percentage of melanomas being referred to clinics other than the PLC. Only 48% of melanomas were referred to the PLC in 1994 compared with 70% in 1987. We also reviewed the referral letters for those patients presenting in 1991 and 1994, and decided, on the basis of the content of the letter, whether the GP had suspected the diagnosis of melanoma. More than 50% of the melanomas were correctly diagnosed by the GP, but only half of these were then appropriately referred to the PLC. We believe that PLCs are of value in the early diagnosis and treatment of melanoma, but only if they are appropriately utilized by GPs.