A. Fletcher

WNT5A expression increases during melanoma progression and correlates with outcome.

Purpose: Wnt ligands play a major role in development and are important in cancer. Expression microarray analysis correlates one member of this family, WNT5A, to a subclass of melanomas with increased motility and invasion. There are no large studies of clinical samples primarily addressing the importance of WNT5A in melanoma progression or outcome. Therefore, this study aimed to assess the protein expression of WNT5A during melanoma progression and its effect on outcome. Experimental Design: Expression of WNT5A was determined in a series of 59 primary melanomas with matched metastases. To provide a benchmark of progression against which to assess WNT5A, expression of p16ink4a was analyzed, as this has been previously well documented in melanoma. The effect of WNT5A protein expression on outcome was assessed in 102 melanomas. Results: Cytoplasmic WNT5A showed a trend of increasing expression with melanoma progression (P = 0.013), whereas there was diminishing p16ink4a expression (P = 0.006). Nevi showed relatively strong WNT5A expression. Strong cytoplasmic WNT5A was an independent risk factor for reduced metastasis-free and overall survival in multivariate analysis (P = 0.001 and 0.003, respectively). Conclusion: Cytoplasmic WNT5A increases with melanoma progression and strong expression is associated with poor outcome.

Epidermal cytokeratin and immunocyte responses during treatment of psoriasis with calcipotriol and betamethasone valerate

Changes in epidermal immunocytes and cytokeratins were investigated during treatment of psoriasis with calcipotriol and betamethasone valerate. Skin biopsies were obtained from 10 subjects on each treatment from lesional and non‐lesional skin at baseline, and from treated lesions after 4 weeks. In each subject, changes in expression of cytokeratins K5, K10 and K16, and changes in epidermal immunocyte counts were assessed. Responses were compared with a separate histological parameter of improvement, epidermal thickness.

An immunohistochemical study of the dermal infiltrate and epidermal staining for interleukin 1 in 12 cases of Sweet's syndrome.

Summary Interleukin 1 (IL‐1) has been proposed as a possible mediator in Sweets syndrome. We examined all cases of Sweets syndrome (M = 12) presenting to the department over a 10‐year period, from 1982 to 1992, for the presence IL‐l and also assessed the nature of the dermal inflammatory infiltrate in those cases. Staining for IL‐1α and TL‐1β was stronger in control tissues than in Sweets syndrome. This may possibly be explained by the release of IL‐1α and IL‐1β into the dermis in Sweets syndrome. Contrary to recent reports, we found that neutrophils predominated in all cases examined, although histiocytes were present in increased numbers indicating their possible role in the pathophysiology of Sweets syndrome.

Amelanotic superficial spreading malignant melanoma mimicking Bowen's disease

A 67‐year‐old woman presented with a scaly, erythematous plaque, for which a clinical diagnosis of Bowens disease was made. However, incisional biopsy established the diagnosis of amelanotic superficial spreading malignant melanoma. Biopsy thus avoided the use of inappropriate destructive therapy, such as cryotherapy or cautery. This case illustrates the importance of obtaining a histological diagnosis, prior to treatment, in suspected cases of Bowens disease.

Is poor prognosis really related to HLA‐DR expression by malignant melanoma cells?

HLA‐DR expression was examined in 50 consecutive primary cutaneous malignant melanomas with a Breslow depth > 2 mm using two well‐characterized monoclonal antibodies which detect fixation‐resistant epitopes. In 31 of these cases (62%) a subpopulation of tumour cells was reactive, although there was considerable heterogeneity. Positive labelling did not correlate with depth but was associated with a reduced likelihood of developing early metastatic disease and a tendency for better overall survival, particularly in male patients. These findings contrast with earlier studies using cryostat sections and one study on paraffin‐embedded tissue in which HLA‐DR expression was shown to be a poor prognostic factor, but are consistent with the findings in other malignant tumours studied. The significance of HLA‐DR expression as a marker of prognosis may depend on the type of tissue preparation, the sensitivity of the immunocytochemical techniques used and the method of assessment.

Thymoma-associated cutaneous graft-versus-host-like reaction

A 47‐year‐old man presented with diarrhoea, acquired hypogammaglobulinaemia and a cutaneous graft‐versus‐host‐like reaction in association with a spindle cell thymoma. Graft‐versus‐host reactions usually occur following allogeneic transplantation or transfusion of immunocompetent lymphoid cells but have been described rarely in the context of a thymoma.

Demonstration of the distribution of Coxsackie virus RNA in neonatal mice by non-isotopic in situ hybridization

A simple method for the demonstration of Coxsackie virus RNA by in situ hybridization is described. Oligonucleotides complimentary to conserved sequences of Coxsackie B genome were synthesised and labelled with digoxigenin using commercially available reagents. In addition to detecting all five Coxsackie B strains examined, six strains of Coxsackie A were also demonstrated by these probes. Using one of the oligonucleotides separately it was possible to distinguish Coxsackie A strains from the strains of Coxsackie B virus examined. This study demonstrates the presence of viral RNA in mice tissues showing morphological evidence of damage, confirming the suspected tropisms of these viruses. The method described is directly applicable to the study of the presence of these viruses in human tissue from diseases where a viral aetiology is suspected.

Regressing cutaneous lymphomas of T-cell and B-cell lineage

We report two cases of regressing cutaneous lymphoma. The first case is a CD30‐positive T‐cell lymphoma with immunogenetic evidence of clonality. The second case is a diffuse large‐cell non‐Hodgkins lymphoma of B‐cell lineage in which clonality was established by immunogenetic analysis and in situ hybridization for light‐chain mRNA.

Absence of Coxsackie viruses in idiopathic inflammatory muscle disease by in situ hybridization.

The role of coxsackie virus infection in the pathogenesis of idiopathic inflammatory muscle disease (HMD) has been investigated by many workers with conflicting results. This study uses in situ hybridization, with digoxigenin–labelled oligonucleotide probes complementary to the coxsackie B virus genome, to investigate the presence of virus RNA in muscle biopsies from 26 patients with HMD. In the five cases of inclusion body myositis studied, there was focal probe–binding to nuclei and cytoplasm, and in nine cases probe–binding to mast cells was seen. In both of these instances probe–binding was non–specific and not due to hybridization. None of the cases showed the presence of coxsackie virus RNA within muscle and it is concluded that lytic infection of myocytes by coxsackie virus does not occur in IIMD.