Comparison of the microvasculature of basal cell carcinoma and actinic keratosis using intravital microscopy and immunohistochemistry.

BACKGROUND: Angiogenesis is a prerequisite for growth of invasive tumours. We hypothesized that angiogenesis would be present in invasive basal cell carcinoma (BCC) but not in a noninvasive tumour such as actinic keratosis (AK). OBJECTIVES: To investigate both types of tumour for evidence of angiogenesis. METHODS: Patients with BCC or AK underwent intravital videocapillaroscopy. Three regions were examined: the tumour, perilesional skin and a control site. Microvessel width, area fraction and length density were determined from capillaroscopy images. Biopsies were stained for CD34 and a microvessel count was performed. RESULTS: Capillaroscopy demonstrated a grossly disorganized tumour microcirculation in BCC. Compared with control skin, microvessel width was increased 2.4-fold, area fraction was increased 4.9-fold and length density was increased 5.9-fold. In AK, microvessel width was increased 1.7-fold, area fraction 2.5-fold and length density 3.4-fold. Vessel width and area fraction were significantly greater in BCC than AK. Biopsies showed significant increases in microvessel length density for both BCC and AK compared with control skin, with BCC significantly greater than AK. CONCLUSIONS: Angiogenesis was demonstrated in BCC in humans in vivo, and to a lesser extent in AK.

Impact of skin cancer education on medical students' diagnostic skills.

Skin cancer is increasingly common, and the skills involved in its diagnosis should be promoted in UK medical schools. However, there has been no scientific evaluation of the teaching methods employed by dermatology departments. The aim of this study was to evaluate, using traditional audiovisual methods, the impact of an illustrated booklet on skin cancer, coupled with a lecture, on undergraduates' diagnostic skills. The ability of 27 final-year medical students to recognize a variety of skin lesions, using projected images from clinical slides, was assessed. They were tested without warning on two occasions. Immediately after the first test, students were given an illustrated booklet on skin tumours and pigmented lesions which was supplemented with a lecture based on the booklet. Two weeks later, a second test was employed using a series of slides deemed to be of equal diagnostic difficulty. Our results showed a significant increase in the median number of correct diagnoses between the first and second tests (P < 0.001). However, there remained wide variation at the second test in the percentage of correct answers (30 to 80%) amongst students. Our study highlights the need to develop effective methods for improving the diagnostic skills of undergraduates in dermatology, and the importance of evaluating teaching methods. The methods of evaluation, such as ours, can be simple and inexpensive.

Impact of skin cancer education on general practitioners' diagnostic skills.

Seventeen general practitioners (GPs) were evaluated to assess their ability to recognize malignant, borderline and benign skin lesions before and after a novel, cheap and quick skin cancer educational programme. They were tested without prior warning on two occasions using two sets of 30 clinical slides. Between each test the GPs were given a lecture based on an illustrated booklet of similar lesions. The results showed an improvement in the GPs' diagnostic skills (P < 0.05), but nevertheless a wide variation in diagnostic ability between GPs remained. Our study highlights a simple, effective and inexpensive method for teaching GPs the diagnostic clinical features of skin cancer. Further work is needed to improve their diagnostic accuracy in the long term.

The treatment of urticaria pigmentosa with the frequency-doubled Q-switch Nd:YAG laser.

Urticaria pigmentosa is a chronic benign proliferation of mast cells in the skin that presents considerable cosmetic disability, for which there is no current successful treatment. We describe a 30-year-old woman with urticaria pigmentosa in whom treatment with the Nd:YAG laser produced a significant improvement in the clinical appearance of the eruption, with some recurrence after 9 months. This procedure has not previously been described, and we propose this as a potential new treatment modality for urticaria pigmentosa.

Basal cell carcinoma--an in-vivo model of human tumour microcirculation?

The role of angiogenesis in tumour growth and metastasis is well established. However, investigations of tumour microcirculation to date have used either biopsy material from human tumours, or animal models in vivo. We have studied the tumour microcirculation in vivo in human skin cancers using video-microscopy to examine 12 basal cell carcinomas (BCCs) on the head and neck of 11 patients, and compared the vessels with those seen in the peri-lesional skin, and in normal control skin on the opposite side of the body. The vessels seen within the BCCs were markedly abnormal qualitatively, forming bizarre, disorganized patterns. Quantitative analysis revealed that the mean diameter (+/-standard deviation) of the largest vessel was significantly greater within the BCC (0.086+/-0.029 mm) than that in the control skin (0.034+/-0.012 mm) (P<0.001). The area fraction, a measure of the area of tissue occupied by vessels, was increased highly significantly within the BCCs (0.158+/-0.038) compared with both peri-lesional skin (0.029+/-0.012) and control skin (0.027+/-0.010) (P<0.001). Length density, the length of blood vessel per unit area of tissue, was also highly significantly greater within the lesion (210.22+/-66.05 cm(-1)) compared to peri-lesional (27.10+/-15.67 cm(-1)) and control skin (28.27+/-15.81 cm(-1)) (P<0.001). This is the first study to have demonstrated that BCCs possess a distinct tumour microcirculation which can be observed directly, and assessed quantitatively. Prospective studies of tumour progression, possibly after intervention with angiogenesis inhibitors, are possible.

An in vivo study of the microlymphatics in psoriasis using fluorescence microlymphography.

Angiogenesis is a recognized event in psoriasis. Previous ultrastructural studies have demonstrated lymphatic capillaries extending high into the dermal papillae. Using the novel method of fluorescence microlymphography which permits visualization of upper dermal initial lymphatics in vivo we tested the hypothesis that lymphangiogenesis exists within plaque psoriasis. Six patients underwent fluorescence microlymphography with fluorescein isothiocyanate-dextran administered intracutaneously within a psoriatic plaque on the leg. Stereological analysis permitted quantification of the lymphatic network opacified both within (lesional) and without (perilesional) the plaque. Results showed a greater spread of tracer from the depot into perilesional skin than into the plaque (P < 0.006). The mean length of lymphatics per unit area at increasing distance from the centre of the depot was also increased for the perilesional skin, 10.5 +/- 1.9/cm2 (mean +/- SEM), compared with lesional skin, 3.06 +/- 0.8/cm (P < 0.001). The cumulative lymphatic length was also greater in perilesional, 22 +/- 7.3 cm2, compared with lesional skin, 3.6 +/- 0.3 cm (P < 0.006). Fluorescence microlymphography has proved to be an effective in vivo technique for the assessment of the dermal microlymphatics in psoriasis. Stereology provided quantitative analysis of the lymphatic network visualized. Overall, there is a greater network of lymphatics in perilesional compared with lesional skin in patients with plaque psoriasis. This finding is at odds with the accepted view that the lymphatic dermal vessels are increased within the psoriatic plaque.

Extensive naevoid eccrine spiradenoma.

We describe a 19-year-old girl with a painful naevoid eccrine spiradenoma affecting the right side of the body. This represents an extremely rare variant of this benign eccrine sweat gland tumour, and is the most extensive lesion described in the U.K. to date.

Axillary acne agminata (lupus miliaris disseminatus faciei).

Acne agminata is a papulo-pustular eruption typically affecting the face of young adults and characterized histologically by the presence of caseating granulomata in the dermis. We now describe two adults who developed the condition in the axillae.

Pyoderma gangrenosum in a child with congenital partial deficiency of leucocyte adherence glycoproteins.

Congenital deficiency of beta 2 integrin leucocyte adhesion molecules is a rare immunodeficiency and is often fatal. Neutrophils are unable to bind to ligands on the endothelium, and so cannot leave the circulation during inflammation or infection. When leucocyte adhesion deficiency (LAD) is caused by abnormally low expression of beta 2 integrins, it is termed LAD type 1. We describe a 5-year-old girl with a history of recurrent bacterial infections since early childhood who developed necrotic skin ulcers resembling pyoderma gangrenosum and a persistent circulating neutrophilia. Histologically, the lesions showed deep ulceration with a diffuse lymphohistiocytic infiltrate, but with a relative sparsity of neutrophils. Subsequent investigation revealed a complete absence of CD11a/CD18 beta 2 integrins on the surface of the patient's neutrophils, confirming the diagnosis of LAD type 1. The ulcers responded to treatment with oral prednisolone and colchicine.

Congenital superficial angiomyxoma.

Superficial angiomyxomas are rare, benign, dermal and subcutaneous tumours. We describe a 12-year-old girl who presented with a nodular swelling in the midline of her scalp that had been present since birth. Histological examination revealed an ill-defined myxoid lesion within the dermis, comprising spindle cells, blood vessels and occasional multi-nucleate giant cells. Immunohistochemical staining was negative for S-100, cytokeratin and smooth muscle actin, but focally positive for CD34. Our patient is unusual in that the angiomyxoma was present at birth, which has not previously been described. The importance of screening patients with cutaneous myxomas for cardiac lesions is discussed.

Dowling-Degos disease associated with hidradenitis suppurativa.

A case of Dowling-Degos disease coexisting with hidradenitis suppurativa is described. We propose that the follicular occlusion inherent in Dowling-Degos disease may predispose to the development of hidradenitis suppurativa.

Two unusual neurological presentations of granulocytic sarcoma in Philadelphia positive chronic myeloid leukaemia.

Granulocytic sarcoma (GS) is a rare extramedullary tumour consisting of immature myeloid precursors. It occurs most commonly in association with myeloid leukaemias and myeloproliferative disorders. Rarely there may be no evidence of haematological malignancy. We describe neurological presentations of GS in two patients with Philadelphia (Ph) positive chronic myeloid leukaemia (CML). In both cases the bone marrow was in chronic phase at the time of presentation of the GS, but there was rapid subsequent transformation into the blastic phase.

Technetium (99mTc)-labelled white cell scanning, 51Cr-EDTA and 14C-mannitol-labelled intestinal permeability studies: non-invasive methods of diagnosing acute intestinal graft-versus-host disease.

We describe a case of a 38-year-old female who presented with diarrhoea and abdominal pain 27 days after a second 'top-up' allogeneic marrow infusion for acute myeloid leukaemia (AML) in first remission. A clinical diagnosis of gut graft-versus-host disease (GVHD) was made. Technetium (99mTc)-labelled white cell scanning and intestinal permeability studies using 51Cr-EDTA and 14C-mannitol were undertaken to confirm the diagnosis. The 99mTc white cell scan showed extensive uptake in the small bowel and the urinary excretion of 51Cr-EDTA was increased, the results being consistent with intestinal inflammation and gut GVHD. 99mTc white cell scanning and intestinal permeability studies may assist in the diagnosis of gut GVHD and in assessing its extent and response to treatment.

Autoreactivity to hepatocellular antigens in primary biliary cirrhosis and primary sclerosing cholangitis.

To investigate the possible involvement of autoimmune reactions in the periportal hepatocellular damage that is often seen in primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC), sera from 35 patients with PBC and 31 with PSC were tested for autoantibodies against the liver-specific lipoprotein preparation, LSP, and against one of its liver-specific constituents, the asialoglycoprotein receptor (ASGP-R), and compared with results in 24 untreated patients with autoimmune chronic active hepatitis (AI-CAH). Anti-LSP antibodies were found in 48.5% of the PBC and 10% of the PSC patients, vs. 100% of those with AI-CAH, while anti-ASGP-R was found in 23% of PBC, 10% of PSC and 96% of AI-CAH patients. In PBC (but not in PSC) these antibodies correlated with severity of periportal inflammation and piecemeal necrosis but tended to be associated with the later stages of the diseases and both seropositivity for, and titres of, anti-LSP and anti-ASGP-R were significantly influenced by the presence of HLA DR3 (positively) and DR2 (negatively) in these patients. DR3 was also associated with significantly higher, and DR2 with lower, serum IgG concentrations in PBC. The findings suggest that, in PBC, DR2 and DR3 may be associated, respectively, with one or more genes that code for down-regulation or for elevation of overall immunoresponsiveness and that autoreactivity to hepatocellular antigens in PBC is more likely to be a consequence than a cause of hepatocellular injury. Periportal liver damage in PSC seems to involve different mechanisms.