Tyrosine phosphate in melanoma progression.

BACKGROUND: Cellular tyrosine phosphorylation is regulated by two large families of enzymes. Protein tyrosine kinases (PTK) mediate addition, and protein tyrosine phosphatases (PTP), removal of phosphate from protein substrates. PTKs are oncogenes and PTPs have been hypothesized to function as tumour suppressor genes. OBJECTIVES: To determine changes in tyrosine phosphate and PTP activity that occur during melanoma progression. METHODS: Immunohistochemistry was used to study phosphotyrosine in melanocytic lesions. In addition, PTP activity of normal melanocytes and melanoma cell lines was measured using an enzyme-linked immunosorbent assay-based system. RESULTS: Melanocytes in normal skin and most (67%) benign naevi were not immunostained. Neither were early malignant lesions (80% of malignant melanoma in situ and radial growth phase melanomas) stained. However, most advanced melanomas (100% of vertical growth phase, and 90% of metastatic melanomas) were immunoreactive. When total PTP enzyme activity was assayed in normal melanocytes and malignant melanoma cell lines, there was a significant increase in activity associated with melanoma progression. CONCLUSIONS: Taken together, the data suggest increased phosphotyrosine signalling occurs during melanoma progression at the stage when cells first become competent for metastasis.

Expression of beta-catenin in basal cell carcinoma.

Background beta-Catenin is a crucial member of the E-cadherin/catenin complex, which plays a major role in cell-cell adhesion. beta-Catenin is also known to be involved in signal transduction pathways. Many studies have demonstrated changes in the expression of beta-catenin in colorectal carcinomas, suggesting a role for beta-catenin in neoplastic development. Objectives Basal cell carcinoma (BCC) is a locally invasive tumour. The various subtypes show differences in biological behaviour. This study aimed to investigate the presence of differences in the immunoprofile of beta-catenin among histological variants of BCC. Methods Eighty BCCs were studied (32 nodular, 7 micronodular, 24 superficial and 17 infiltrative and morphoeic). Formalin-fixed, paraffin-embedded tissue sections were stained for beta-catenin using the avidin/biotin immunodetection technique. Results All the nodular BCCs showed membranous and weak cytoplasmic staining. Nuclear staining was seen in 15 of 32 (47%) cases, being stronger at the periphery of the nodules in 11 of 15 (73%) of these cases. In superficial BCCs the membranous staining was variable and cytoplasmic staining was increased. Nuclear staining was seen in 16 of 24 (67%) cases, being more notable at the periphery in 8 of 16 (50%) of these cases. All micronodular BCCs showed strong membranous staining, weak cytoplasmic and no nuclear staining. In the infiltrative and morphoeic BCCs membranous staining was completely lost at the advancing margins of the invading cell strands, with a marked increase in cytoplasmic staining; nuclear staining was observed in all these tumours. Conclusions The expression of beta-catenin varied between different types of BCC. Nuclear localization was most notable in the infiltrative and morphoeic variants, followed by the superficial variant, and seen least in nodular BCC. Its prominence at tumour margins suggests that this may be associated with more aggressive types of invasion.

Transepidermal elimination of urate-like crystals: a new perforating disorder?

We report two men who developed a transient perforating disorder characterized by transepidermal elimination of negatively birefringent needle-shaped crystals similar to monosodium urate. This striking clinical presentation has not previously been described and we propose that it be added to the group of diseases known as the primary perforating disorders.

Up-regulation of ephrin-A1 during melanoma progression.

Ephrin-A1, formerly called B61, is a new melanoma growth factor; it is angiogenic and chemoattractant for endothelial cells. EPH-A2, or ECK (a receptor for ephrin-A1), is ectopically expressed in most melanoma cell lines; the pathology where this expression is first manifested and the possible role of the receptor in tumor progression are unknown. To determine these, we studied the expression of this ligand and receptor in biopsies of benign and malignant melanocytic lesions. EPH-A2 was not detected in normal melanocytes, benign compound nevi or advanced melanomas, though it was found in 2 of 9 biopsies of malignant melanoma in situ. Ephrin-A1 was present in occasional early lesions and in advanced primary melanomas (43%) and metastatic melanomas (67%). Expression of ephrin-A1 was induced in melanoma cells by pro-inflammatory cytokines. Our findings are consistent with 2 possible roles for ephrin-A1 in melanoma development: it may promote melanocytic cell growth or survival and induce vascularization in advanced melanomas. Both effects may be potentiated by inflammatory responses. Our data are consistent with earlier observations that an inflammatory infiltrate is associated with poor prognosis in thin primary melanomas.

Lichen planus associated with milia.

The formation of milia is well recognized in both bullous and inflammatory dermatoses. There are several reports of milia developing in a rare variant of lichen planus pilaris known as lichen planus follicularis tumidus (LPFT), but the association of milia with other types of lichen planus (LP) has not been documented in the literature. We report five patients who developed milia during the course of either drug-induced or idiopathic LP and one in whom milia developed in a lichenoid tattoo reaction. Milia were noted to occur transiently during the resolving phase of LP. Most cases were severe enough to warrant treatment with systemic steroids. The association of milia with LP is not restricted to the rare clinical variant LPFT. We speculate that a severe lichenoid reaction with basal layer degeneration may precipitate the formation of milia in some cases of LP.

Cutaneous malignant melanoma in Scotland: incidence, survival, and mortality, 1979-94. The Scottish Melanoma Group.

OBJECTIVE: To determine the changing incidence of and mortality from cutaneous malignant melanoma in Scotland from 1979 to 1994. DESIGN: Detailed registration of clinical and pathological features, surgical and other treatment, and follow up of all cases of cutaneous malignant melanoma diagnosed from 1979 to 1994 and registered with specialist database for Scotland. SETTING: Scotland. SUBJECTS: 6288 patients with invasive primary cutaneous malignant melanoma diagnosed between 1 January 1979 and 31 December 1994. RESULTS: The annual age standardised incidence of cutaneous malignant melanoma rose significantly from 3.5 to 7.8 per 100,000 per year in men and from 6.8 to 12.3 per 100,000 per year in women (P < 0.001 for both). World standardised rates increased from 2.7 to 6.0 per 100,000 per year in men and 4.6 to 8.50 per 100,000 in women. The incidence of melanoma continued to increase significantly in men of all ages during the study, but the rate stabilised in women after 1986. Mortality from cutaneous malignant melanoma was 1.3 per million per annum in men in 1979, rising to 2.3 per million per annum in 1994 (P < 0.01); it was 2.4 per million per annum in women in 1979, falling to 1.9 per million per annum in 1994 (P = 0.09). The underlying mortality trends showed a continuing rise for men but a downward trend for women that was not significant (P = 0.09). In men, melanoma free survival was 69% at 5 years and 61% at 10 years; in women the corresponding rates were 82% and 75%. Younger patients had higher survival rates, which were not entirely explained by thinner tumours. Over the 15 year period, survival rates improved by 12% overall, only partly owing to thinner tumours. CONCLUSIONS: In Scotland the incidence of melanoma in women has stabilised, while mortality associated with melanoma in women shows a downward trend.

Cutaneous manifestations of fucosidosis.

Angiokeratoma corporis diffusum (ACD) is still often thought to be synonymous with Anderson-Fabry disease, a deficiency of alpha-galactosidase. It is important, however, to consider other possible enzyme deficiencies in patients with ACD. We report an 8-year-old boy with neurodevelopmental delay who was diagnosed as having fucosidosis following recognition of ACD in the dermatology department. Other cutaneous features in this patient included distal transverse purple nail bands, acrocyanosis and a naevus anaemicus. Histology and electron microscopy of skin papules was consistent with angiokeratoma. Skeletal survey demonstrated dysostosis multiplex. The diagnosis was confirmed by leucocyte oligosaccharide enzyme analysis. There are only three previous reports of fucosidosis in the U.K.

Papular mucinosis: is the inflammatory cell infiltrate neoplastic? The presence of a monotypic plasma cell population demonstrated by in situ hybridization.

Papular mucinosis is a condition reported to be associated with abnormal serum paraproteins and plasma cell dyscrasias. We report a patient with papular mucinosis, without a serum paraprotein or bone marrow plasmacytosis, in whom the affected skin contained a prominent perivascular plasma cell infiltrate. Using in situ hybridization, for kappa and lambda light chain mRNA, these plasma cells were demonstrably monotypic for lambda light chain and, therefore, presumably monoclonal and putatively neoplastic. We suggest that the absence of a serum paraprotein and marrow plasmacytosis does not exclude the existence of a plasma cell neoplasm in patients with papular mucinosis. Such plasma cell populations may exist in the affected skin, although their true nature and behaviour remains to be determined.

Localized argyria caused by silver earrings.

We report a patient with localized cutaneous argyria following the wearing of silver earrings in pierced ears.

Expression of NM23 in human melanoma progression and metastasis.

NM23 is a putative metastasis-suppressor gene for some human cancers. Here we have studied NM23 expression during melanoma progression using Northern blotting and immunocytochemistry. There was no significant difference in the average amounts of NM23 mRNA between cell lines derived from metastatic and primary melanomas. The level of NM23 mRNA was also determined for three pairs of poorly metastatic parental (P) and their highly metastatic variant (M) cell lines; the ratios for M/P were 1.2, 0.98 and 0.80. Next we used immunocytochemistry to study NM23 protein in normal skin, benign naevi and primary and metastatic melanomas. Melanocytes in all normal skin and benign samples were positive for NM23; however most primary melanomas (7/11) were not stained by the antibody. All metastatic melanoma samples (5/5) were positively stained. Findings were similar with an antiserum reactive with both forms of NM23 (H1 and H2), and with an antibody specific for NM23-H1. No relationship was apparent between NM23 immunoreactivity in primary tumours and their aggressiveness or prognosis. Hence, in contrast to the situation described for murine melanoma, the amount of NM23 mRNA or protein in human melanoma did not correlate inversely with metastasis.

Evidence based assessment?

There have been many calls recently for a more 'evidence based' approach to clinical dentistry. This article argues the need for a similar approach to be adopted by the private dental schemes when setting criteria for practice inspection. The author recognises the laudable attempt to revise the 'quality' of dental practice but questions whether the methods adopted to date are justifiable.

Sebaceous carcinoma of the periorbital and extraorbital regions.

Sebaceous carcinomas are uncommon amongst cutaneous malignancies. These lesions can broadly be classified into 2 groups; (i) periorbital, which behave aggressively, and (ii) extraorbital, which are reported to metastasize rarely. A retrospective review has identified 12 cases of primary sebaceous carcinoma treated at Canniesburn Hospital over the decade from mid-1983 to mid-1993. Out of 7 cases with periorbital primary lesions, one patient died from metastatic disease and another developed local recurrence which was successfully excised. The series included an unusual case of metastasizing primary extraorbital sebaceous carcinoma.

Aneuploidy in atypical fibroxanthoma: DNA content quantification of 10 cases by image analysis.

It has recently been reported that atypical fibroxanthoma (AFX) is a predominantly diploid lesion in contrast to malignant fibrous hystiocytoma (MFH) which is usually aneuploid. To test this hypothesis, DNA content quantification was undertaken on Feulgen-stained cytology and tissue section preparations from 10 cases of AFX by image analysis. The large atypical cells which characterize AFX were aneuploid in each case. Smaller spindle-shaped cells found in this lesion were diploid. The results suggest that AFX is indistinguishable from MFH by DNA content estimation and highlight an advantage of image analysis over flow cytometry.