S.S. Bleehen

Pigmented basal cell epithelioma. Light and electron microscopic studies on tumours and cell cultures.

Light and electron microscopic studies have been carried out on three pigmented basal cell epitheliomas and on cell cultures of two of these tumours, to determine the formation and transfer of pigment and the fine structure of the constituent cells. Scattered in the epithelial tumour buds were many functional melanocytes that contained melanosomes in various stages of development and whose morphology was essentially normal. Many melanophages were present in the dermal stroma, but few transferred melanosomes were to be found in the epithelial tumour cells.

The treatment of vitiligo with topical corticosteroids

Twenty patients with lesions of vitiligo were treated either with 0.1% betamethasone valerate (BV) or with 0.05% clobetasol propionate (CP) creams and similar control areas with placebo preparations.

Cellular fine structure in the invasive nodules of different histogenetic types of malignant melanoma.

Ultrastructural studies were carried out on the invasive nodule of forty malignant melanomas. The findings support the concept that the fine structure of lentigo maligna melanoma is often characteristic, and differs from that of superficial spreading and nodular melanoma. The melanosomes in lentigo maligna melanoma are usually ellipsoidal and resemble those of normal melanocytes, whereas the melanosomes in superficial spreading and nodular melanoma are most often spheroidal and abnormal in appearance. Superficial spreading and nodular melanomas cannot be distinguished reliably by their ultrastructure.

Mutant p53 oncogene expression in keratoacanthoma and squamous cell carcinoma

The tumour suppressor gene p53, located on the short arm of chromosome 17, encodes for a nuclear protein which regulates cell proliferation by inhibiting cells entering S‐phase. p53 mutations are alleged to be the commonest genetic abnormality in human cancer. We studied mutant p53 oncoprotein expression, using PAb1801 monoclonal antibody immunohistochemistry, in 25 ‘ideal’ keratoacanthomas and 26 well‐, 19 moderately and 18 poorly differentiated squamous cell carcinomas of the skin. While there was a highly significant trend in the proportion of p53 oncoprotein‐positive lesions from keratoacanthomas to poorly differentiated squamous cell carcinomas (χ2= 17·13, df=l, exact P=0·00003), p53 expression was inadequate for distinguishing keratoacanthoma from well‐differentiated squamous cell carcinoma (χ2= 2·55, df = 1, exact P = 0·18; corresponding to a sensitivity of 0·84 and a specificity of only 0·36).

Herpes gestationis: immunopathological and ultrastructural studies*

Eleven patients with the clinical picture of herpes gestationis were investigated. Biopsies were taken from involved and uninvolved areas of skin and the immunopathological and microscopic changes studied. Direct immunofluorescence showed a deposition of C3 and/or IgG at the basement membrane zone in the involved skin of nine patients and the uninvolved skin of five. Immuno‐electron microscopy using a multistep peroxidase antiperoxidase method revealed the in vivo deposition of IgG at the basal plasma cell membrane that extended into the lamina lucida. Light microscopy of urticarial and vesicular lesions showed a marked oedema of the papillary dermis with an inflammatory cell infiltrate that was mainly perivascular. There was spongiosis of the epidermis with oedema and necrosis of the basal cells and in several specimens sub‐epidermal clefts with bulla formation. Electron microscopy confirmed the marked degenerative and necrotic changes of the basal cells in the involved areas of skin.

Absence of Epstein-Barr viral encoded RNA (EBER) in primary cutaneous t-cell lymphoma.

Epstein‐Barr virus (EBV) has been associated with various extracutaneous lymphoproliferative diseases and it has been suggested that EBV may have a similar aetiological role in cutaneous T‐cell lymphoma. In this study, in situ hybridization was used to investigate the presence of EBV encoded RNAs (EBER‐1 and EBER‐2) in 37 biopsies from 28 cases of primary cutaneous T‐cell lymphoma originating from the U.K. The results showed that EBV had no demonstrable pathogenic role in the lymphomas studied, as EBER was not detected in any case.

Epstein‐Barr virus in cutaneous lymphomatoid granulomatosis

Epstein‐Barr virus (EBV) has been associated with various extra‐cutaneous lymphoproliferative diseases and it has been suggested that EBV may have a similar aetiological role in the skin. In this study, 10 biopsies from 7 cases of primary cutaneous lymphomatoid granulomatosis have been analyzed, using in situ hybridisation, for the presence of EBV encoded RNAs (EBER‐1 and EBER‐2). Only one case showed positive staining with the EBER probes and it is concluded that, in the skin, the relationship between EBV and lymphomatoid granulomatosis is variable. The role of EBV as an aetiological agent in primary cutaneous lymphomatoid granulomatosis appears less important than in primary respiratory disease.

Freckles induced by PUVA treatment

Azelaic (C9) and dodecandioic (C12) acids, to final concentrations of 100 and 200 /u,g/ml, were added to dispersed cultures of epidermal cells grown in Eagles MEM with HEPES salts, glutamine, and 18% fetal calf serum. At 7,10,15 and 20 days, control, and experimental cultures were processed for electron microscopy. Results were essentially similar with C9 and C12 acids. At 7,10 and 15 days, melanocytes of experimental cultures exhibited significantly increased melanogenic activity compared with controls. Disintegrating melanosomes were present in cells of both, but more numerous in experimental ones. At 20 days, control and experimental melanocytes were essentially similar, with poorly melanized melanosomes, but healthy. We conclude that dicarboxylic acids have an initial stimulatory effect on melanocytes of the original culture generation and that this may result in destruction of melanosomes. Their presence in the medium at present concentrations does not prevent growth of, nor cause damage to, a second generation of cells up to 20 days.

D‐penicillamine in the treatment of rheumatoid arthritis and progressive systemic sclerosis

D-Penicillamine (BB dimethylcysteine) is a drug widely known for its clinical therapeutic benefit in the treatment of Wilsons disease and cystinuria. A number of recent studies have demonstrated that penicillamine may be therapeutically active in other diseases including rheumatoid arthritis (RA), progressive systemic sclerosis (PSS), morphoea and active chronic hepatitis, as well as acting as a chelator of a number of heavy metals. The increasing number of therapeutic indications for D-penicillamine therapy need to be clearly defined and its ill effects plainly identified. This review will concentrate on the present value of this drug in the treatment of rheumatoid arthritis and progressive systemic sclero-

Lentigo-maligna melanoma: an ultrastructural study

specimens examined was small, and the conclusions may have been biased by observer knowledge of the tumour type. Forty surgically excised specimens of malignant melanoma were studied. Case summaries, clinical photographs and light histological material were sent to Glasgow (R.M. and A.C.) and the histogenetic type of each tumour determined. Electron-microscopy of tissue obtained from the invasive nodule was carried out in Edinburgh (J.H. and S.Z.) so that neither worker was aware ofthe histogenetic type of tumour being examined. At least two blocks from each tumour were studied, and a minimum of thirty random photographs taken. The electron micrographs were then analysed independently in Edinburgh (J.H.) and Sheffield (S.B.), both workers still being unaware of the tumour type. Particular attention was paid to melanosomal morphology. The code was then broken and the ultrastructural features correlated with the histogenetic type. Results. Types of tumour in series: LMM, 14; SSM, 14; NM, 9; metastatic skin deposit, 3. Most tumour cells contained melanosomes which were either ellipsoidal or spheroidal. The morphology of the ellipsoidal profiles was usually similar to that of normal melanosomes. Spheroidal melanosomes were of the abortive, granular or lamellar type (Clark et al., 1972). Tumour cells of LMM contained numerous ellipsoidal melanosomes whilst those of SMM, NM and metastatic deposits contained only occasional ones. All varieties of spheroidal melanosomes were seen in each histogenetic type, though granular profiles were less common in LMM. Thus the ultrastructural appearance of LMM is reasonably characteristic, but there are no obvious differences in melanosomal morphology in the nodules of SMM, NM and metastatic deposits. These results can be explained most easily on the basis of subcellular dedifferendation due to the malignant process.