Search

SUMMARY We examined the effect of incisional biopsy on the subsequent histology of 15 benign melanocytic naevi. In all cases the histology of the residual lesion within the second specimen was unchanged apart from the presence of a surgical scar, and in general the definitive excision specimen showed a reduction in melanocytes at the dermo-epidermal junction overlying the scar. In no case were there any features suggestive of melanoma.

Controversy exists concerning the necessary margin of excision for cutaneous melanoma 2 mm or greater in thickness.We conducted a randomized clinical trial comparing 1-cm and 3-cm margins.Of the 900 patients who were enrolled, 453 were randomly assigned to undergo surgery with a 1-cm margin of excision and 447 with a 3-cm margin of excision; the median follow-up was 60 months. A 1-cm margin of excision was associated with a significantly increased risk of locoregional recurrence. There were 168 locoregional recurrences (as first events) in the group with 1-cm margins of excision, as compared with 142 in the group with 3-cm margins (hazard ratio, 1.26; 95 percent confidence interval, 1.00 to 1.59; P=0.05). There were 128 deaths attributable to melanoma in the group with 1-cm margins, as compared with 105 in the group with 3-cm margins (hazard ratio, 1.24; 95 percent confidence interval, 0.96 to 1.61; P=0.1); overall survival was similar in the two groups (hazard ratio for death, 1.07; 95 percent confidence interval, 0.85 to 1.36; P=0.6).A 1-cm margin of excision for melanoma with a poor prognosis (as defined by a tumor thickness of at least 2 mm) is associated with a significantly greater risk of regional recurrence than is a 3-cm margin, but with a similar overall survival rate.

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.

Summary Schwannomas are benign encapsulated tumours arising from the sheaths of peripheral nerves. They present as slowly enlarging solitary lumps, which may cause neurological defects. Multiple lesions are rare, but occur in patients with neurofibromatosis type 2 or schwannomatosis. Positive outcomes have been reported for surgical excision in solitary schwannomas. However, the role of surgery in patients with multiple lesions is less clear. The risk of complications such as iatrogenic nerve injury and the high likelihood of disease recurrence mean that surgical intervention should be limited to the prevention of progressive neurological deficit. We report a case of a 45 year old male who presented with multiple enlarging masses in the upper limb and sensory deficit in the distribution of the ulnar nerve. The tumours were found to be related exclusively to the ulnar nerve during surgical exploration and excision, a rare phenomenon. The masses were diagnosed as schwannomas following histopathological analysis, allowing our patient to be diagnosed with the rare entity segmental schwannomatosis. One year post-operatively motor function was normal, but intermittent numbness still occurred. Two further asymptomatic schwannomas developed subsequently and were managed conservatively.

Two cases of autoimmune bullous skin diseases in HIV-positive men are described. One man had bullous pemphigoid limited to his legs and the second man developed pemphigus herpetiformis. The possible association between autoimmune bullous diseases and HIV infection is discussed.

Summary To assess the effect of a pigmented lesion clinic on referral patterns and thickness of melanoma at presentation, we have compared data from the centralized pathology services of the adjacent health authorities of Wandsworth, and Merton and Sutton. Both districts were the subject of a CRC public awareness campaign in 1987, but only Wandsworth is served by a pigmented lesion clinic. All patients presenting with malignant melanoma were included; from 1981 to 1990 for Wandsworth, and from 1984 to 1990 for Merton and Sutton. The Breslow thickness and clinic source of all melanomas was documented. Approximately equal numbers of melanomas were seen in the two districts, with no obvious difference in the numbers of thin (

Eosinophilic folliculitis is a recognized skin manifestation of human immunodeficiency virus (HIV) disease. Five cases of eosinophilic folliculitis occurring in HIV-negative patients treated for haematological malignancy are reported. In four cases this self-limiting, pruritic eruption, affecting the head and upper trunk, occurred 3 months after bone marrow transplantation, and the fifth case was a patient undergoing chemotherapy for Waldenström's macroglobulinaemia. This suggests that eosinophilic folliculitis is a consequence of disturbances of immune function, and is not specific for HIV infection.

Summary In many centres the wide excision and split-skin grafting remains the standard therapy for primary cutaneous melanoma. One-hundred and thirty-seven primary cutaneous melanomas were seen in our department during a 3-year period; 25 patients were subsequently subjected to re-excision of scar following the initial excision biopsy. Lymphatic permeation, field change in the epidermal melanocytes and micrometastases were sought in the re-excision specimens in order to examine the pathological basis for this therapy. Two of the 25 primary melanomas included in this study were known to have been incompletely excised at the time of initial biopsy and both re-excision specimens included a few nests of atypical melanocytes adjacent to one edge of the biopsy wound. Examination of the re-excision specimens failed to demonstrate evidence of direct lymphatic permeation by melanoma, or of a field change in the epidermal melanocytes adjacent to the melanomas, although five specimens from sun-exposed sites showed slight melanocyte atypia. One re-excision specimen did include a single small group of melanocytes, less than 120 μm in size, in the dermis within 2 mm of the initial excision biopsy site of a melanoma 8.4 mm in thickness. These results support the view that more extensive local therapy than complete excision of primary cutaneous melanoma with a narrow margin of adjacent normal skin, is unlikely to benefit the patient.

Summary Basal melanocytes were counted and atypia assessed on an arbitrary scale in punch biopsies from the sun-exposed extensor aspect of the forearm of normal skin and from the covered skin of the buttock of patients with pigmented naevi and control subjects. The difference in melanocyte counts and in the presence of atypia between sun-exposed and covered skin was statistically highly significant. The only other difference was between melanocyte counts in covered skin from those with multiple atypical naevi and all other groups; the counts in the former were greater than those in the latter. No further difference was attributable to sun exposure, skin type or diagnostic group. Some degree of melanocyte atypia was seen in approximately half of the biopsies of sun-exposed skin, but atypia was seen in only six of 84 biopsies of covered skin. In each case atypia was present in the corresponding forearm biopsy and all six subjects had pigmented lesions (four with melanoma and two with multiple atypical naevi). It seems possible that while increased melanocyte counts in covered skin could correlate with the presence of atypical naevi, atypia of covered epidermal melanocytes could possibly relate to melanoma risk.

One hundred seventy-five consecutive patients with soft tissue sarcoma of the limb and limb girdle were studied using univariate and multivariate analysis. The most important factor determining risk of local recurrence was the quality of treatment of the primary tumor, with wide or radical surgery plus radical radiotherapy obtaining the best local control. Tumor size, site, and histologic grade were not predictive of local recurrence. The important tumor variables predicting survival were tumor size at first presentation and histologic grade. Tumors with greater than 10 cm greatest diameter and high-grade tumors carried a poor prognosis. Local recurrence was significantly associated with reduced survival, but only when (correctly) considered as a time-dependent variable in multivariate analysis. Irradiation was also significantly associated with poor survival. Review of the literature indicates that local recurrence is believed to have little influence on survival. Since the relevant randomized controlled trials have been small, the evidence is inconclusive.

Eosinophilic pustular folliculitis is a rare disorder previously reported predominantly in Japanese people who are otherwise healthy. Recently, the disorder has been noted in patients with acquired immune deficiency syndrome, as has eosinophilic folliculitis, a similar but distinct entity. The authors report a patient with eosinophilic folliculitis who was immunocompromised after high dose chemotherapy and bone marrow autograft for treatment of non-Hodgkin's lymphoma.

In primary cutaneous malignant melanoma, the vascularity of the dermis immediately deep to the lesion may relate to tumour aggressiveness and to prognosis. These newly formed dermal vessels are incorporated into the melanoma to form the tumour microcirculation. We have assessed the percentage vascular volume in a series of primary melanomas in order to investigate the relationship between tumour vascularity and maximum tumour thickness. For the 64 melanomas included in this study, there appeared to be a significant relationship between the percentage vascular volume and the maximum tumour thickness. This relationship was not influenced by the presence of necrosis, vascular invasion, regression, or lymphocytic infiltrate, nor by the growth phase of the tumour. However, the percentage vascular volume was very low in the occasional thick melanoma, at least one of which was associated with prolonged survival. It seems possible that a low tumour vascularity could correlate with a relatively favorable outcome in cutaneous melanoma.

Using Ulex europaeus I lectin (UEA1) to demonstrate endothelial cells, we have previously shown that frequency of capillary invasion correlates closely with maximum tumor thickness in primary cutaneous melanoma. UEA1 demonstrates both vascular and lymphatic capillaries; however, only vascular capillaries possess basement membranes. In order to ascertain whether these capillaries were lymphatic or vascular, we employed a double staining technique, using UEA1 in conjunction with a monoclonal anti-type IV collagen antibody. We studied 21 primary cutaneous melanomas. Seven of the 21 included lymphatic capillaries, while 14 did not. These lymphatic capillaries were very sparse and appeared to be residual dermal lymphatics rather than a result of lymphangiogenesis. Lymphatic permeation by melanoma was not seen in any of the tumors studied. There was no apparent association among tumor thickness, level of invasion, growth phase, necrosis, regression or mitotic index, and presence of lymphatics within the melanomas. Although scanty lymphatics are present in some primary cutaneous melanomas, this study does not suggest that lymphatic permeation plays a major role in the spread of melanoma to locoregional lymph nodes.

The role of vascular invasion as a prognostic indicator in melanoma has not been fully evaluated, mainly due to difficulty in differentiating between capillaries and artefactual spaces caused by shrinkage in routine histological sections. However, immunohistochemical staining using Ulex europaeus I (UEA-I) permits accurate identification of tumor capillaries, thus facilitating recognition of vascular invasion. Sixty-six primary cutaneous melanomas were included in this study. Sections of each case were stained with UEA-I; then, vascular invasion at the level of the tumor capillary bed was sought. Hematoxylin-and-eosin-stained sections were reviewed; the thickness of each lesion was measured and the level of invasion and the growth phase of the tumors were also assessed. The frequency of vascular invasion was found to increase with increasing tumor thickness and with increasing level of invasion. Vascular invasion was seen in only one of 29 horizontal growth phase melanomas, whereas it was identified in 28 of 37 vertical growth phase tumors. Although these results would seem to indicate that vascular invasion within melanomas is unlikely to be an independent prognostic variable, they may partly explain the deteriorating prognosis associated with increasing tumor thickness. They also lend support to the concept of "horizontal" and "vertical" growth phase in melanoma.

A novel method for grading intestinal metaplasia, with general applicability, is described. Highly significant agreement was found by kappa analysis both for intra-observer (k = 0.90) and for inter-observer (k = 0.85) variation, confirming the reproducibility of the method. The ranks derived by this method were correlated with gastric tissue levels of the enzymes beta-glucuronidase, lactic dehydrogenase (LDH), and %m-LDH. A significant (P less than 0.05) positive correlation was found between intestinal metaplasia and %m-LDH, but there was no correlation between intestinal metaplasia and beta-glucuronidase or LDH.

The vasculature of B16, a murine melanoma and Mel-mo, a human melanoma, was studied using intravital staining of patent capillaries by the fluorescent bisbenzamine dye Hoechst 33342. Capillaries were numerous at the edge of tumours in both the lines studied, but were scarcer within the nodules. Vascular volume as a proportion of total tumour volume was estimated by means of point counting. In both B16 and Mel-mo, the percentage vascular volume was inversely related to log tumour weight. Tumour necrosis, which increased with tumour size, was inversely correlated with percentage vascular volume, emphasizing the central under-perfusion of these experimental tumour nodules. This pattern of perfusion, with greater density of functioning capillaries at the periphery of tumour nodules, was seen in both the tumour lines examined despite differences in the degree and pattern of necrosis.