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R L Barnhill

Publications and source records attributed to R L Barnhill.

At least 55 records · Page 3Linked to original sources

Theoretical and empirical arguments in relation to elective lymph node dissection for melanoma.

Nearly a century of clinical inquiry has failed to incontrovertibly resolve the question of whether elective lymph node dissection is therapeutically beneficial in the management of clinically localized melanoma. The controversy has been renewed by a recent interim update from the Intergroup Melanoma Surgical Program, sponsored by the National Cancer Institute, which has indicated a small survival benefit in a narrowly defined subgroup of patients with primary melanoma. That report stimulated this review of the data, which are presented in the historical context that originally prompted the Intergroup study. Case selection bias has intractably hindered firm conclusions from the numerous nonrandomized studies of elective lymphadenectomy. The two original randomized trials that were executed during the 1970s failed to uncover any significant effect of the procedure on survival. Definitive conclusions from the recent Intergroup report are limited by the likelihood that the observed therapeutic benefits are a chance occurrence resulting from uncorrected multiple subgroup comparisons. It remains uncertain whether elective lymphadenectomy can be therapeutically beneficial in the management of melanoma. Nevertheless, it is clear that the procedure, or preferably sentinel lymphatic mapping with selective lymphadenectomy, can provide clinically relevant prognostic information, as well as the staging data requisite to adjuvant interferon alfa-2b therapy or enrollment into other adjunctive trials for patients at high risk of clinical relapse.

Elective Surgical Procedures↗

Loss of the p16INK4a and p15INK4b genes, as well as neighboring 9p21 markers, in sporadic melanoma.

Although homozygous deletions of the cyclin-dependent kinase inhibitor 2 gene p16INK4a on 9p21 have been reported frequently in metastatic melanoma cell lines, and intragenic mutations within the p16INK4a gene have been detected in familial melanoma kindreds, specific targeting of this gene in the development of sporadic melanoma in vivo remains controversial. Southern analyses were performed in this study to initially assess the frequency of hemi- or homozygous losses of p16INK4a, as well as its neighboring family member, p15INK4b, and other candidate regions within 9p21, in sporadic melanoma. Overall, 22 of 40 (55%) uncultured sporadic melanoma DNAs were determined to harbor deletions of 1-11 markers/genes located on 9p21. This included 10 tumors (25%; 10 of 40) with homozygous deletions limited to either the p16INK4a gene only (20%; 2 of 10), both the p16INK4a and p15INK4b genes (10%; 1 of 10), another novel 9p21 gene, FB19 (10%; 1 of 10), or all three of these genes plus surrounding markers (60%; 6 of 10). In subsequent single-strand conformation polymorphism and sequencing analyses, intragenic mutations in the p16INK4a gene were also revealed in two (10%; 2 of 21) melanoma DNAs that retained one copy of this locus. By comparison, the frequency of pl6INK4a and p15INK4b homozygous deletions, as well as p16INK4a mutations, in melanoma cell lines (analyzed in parallel) was 2-3-fold higher at 61 (23 of 38) and 24% (9 of 38), respectively. These findings indicate that (a) p16INK4a is inactivated in vivo in over one-fourth (27.5%; 11 of 40) of sporadic melanomas; (b) mutation/deletion of p16INK4a may confer a selective growth advantage in vitro; and (c) other 9p21 tumor suppressor genes could be targeted during the development of melanoma.

Carrier Proteins↗

Malignant melanoma risk factors by anatomic site: a case-control study and polychotomous logistic regression analysis.

This population-based case-control study systematically examined reported malignant melanoma risk factors by anatomic site. Study subjects consisted of 548 invasive melanoma cases diagnosed in Connecticut during 1987-1989 and 494 randomly selected controls. Multivariate polychotomous logistic regression was used to determine whether risk factors differed across anatomic sites. Risk factors examined included demographic and pigmentary characteristics, sun exposure-related factors, anatomic site-specific sunburn, recreational water activity clothing habits and number of nevi. A pattern of site-specificity was observed for sunburn. A history of sunburn at an anatomic site was specifically related to the development of malignant melanoma at that site more so than at other sites. This site-specificity was consistent with a direct role for intense, intermittent sun exposure in the development of melanoma. Age and gender were the only risk factors that differed significantly in effect across anatomic sites. The age difference was explained by differences in histologic subtype across sites. The gender difference could not be explained by sex differences in anatomic site-specific sunburns or in recreational water activity clothing habits. Alternative explanations include sex differences in behavioral patterns of sun exposure that we did not measure and as yet unelucidated differences in susceptibility to melanoma according to sex and anatomic site.

Adult↗

Predicting five-year outcome for patients with cutaneous melanoma in a population-based study.

BACKGROUND: In numerous studies tumor thickness has been shown to be the most important prognostic factor for patients with localized cutaneous melanoma. However, to our knowledge there are no population-based studies analyzing the prognosis of patients living in the United States with cutaneous melanoma. METHODS: A prognostic model was developed with death as an outcome for 548 patients from Connecticut with localized cutaneous melanoma. Only patients with invasive melanoma who either died of the disease or were followed-up at least five years were studied. Fourteen pathologic parameters (histologic type of melanoma, Clark level, microscopic satellites, histologic regression, tumor thickness [Breslow], ulceration, vascular invasion, mitotic rate per mm2, tumor-infiltrating lymphocytes, radial vs. vertical growth phase, solar elastosis, co-existing nevus, lymphocytic response, and pigmentation) and three clinical variables (age, sex, and anatomic site) were analyzed using logistic regression. RESULTS: After univariate analysis, 10 pathologic variables showed prognostic significance: histologic type (nodular and "other" types only), Clark level, microscopic satellites, regression (protective), tumor thickness, ulceration, vascular invasion, mitotic rate, vertical growth phase, and solar elastosis (protective). In the final model employing multivariate analysis, only tumor thickness and mitotic rate continued to have independent predictive value. CONCLUSIONS: In this population-based study of 548 patients in Connecticut, tumor thickness was the most significant prognostic factor for survival of patients with localized cutaneous melanoma. Other prognostic factors studied to date have not been conclusively verified as providing any additional information beyond that of tumor thickness.

Adult↗

Constitutive expression of B7-1 (CD80) on mouse keratinocytes does not prevent development of chemically induced skin papillomas and carcinomas.

Expression of the B7-1 (CD80) costimulatory molecule in a variety of tumor cell lines leads to an enhanced CD8+ T cell response to tumor Ags. We used transgenic mice constitutively expressing B7-1 on keratinocytes (K14/B7-1 line) to determine whether keratinocyte B7-1 expression would inhibit the development of papillomas and carcinomas following two-stage chemical carcinogenesis in skin. FVB inbred mice carrying the K14/B7-1 transgene and controls were initiated with 25 micrograms of 7,12-dimethylbenz[a]anthracene and promoted weekly with 5 micrograms of 12-O-tetradecanoylphorbol-13-acetate for 20 wk. Expression of the B7-1 transgene did not result in statistically significant decreases in the mean number of papillomas or carcinomas compared with controls. The incidence of carcinomas in both transgenic and control mice reached 90% or greater by 60 wk after initiation. Carcinoma cell lines established from the K14/B7-1 mice maintained expression of B7-1 and Kq. These B7-1 expressing carcinomas grew progressively following intradermal injection into syngeneic FVB mice, further demonstrating their inability to evoke protective tumor immunity. These same carcinoma cell lines were rapidly rejected by minor alloantigen-mismatched SWR mice, confirming their susceptibility to immune effector mechanisms. The failure of constitutive B7-1 expression on keratinocytes to prevent the growth of squamous cell papillomas and carcinomas may reflect the limited immunogenicity of tumors arising after initiation-promotion carcinogenesis. Our results in this transgenic model system are further evidence that B7-1 gene therapy alone may not be sufficient to induce protective immunity to some types of tumors.

Animals↗

Screening for cutaneous melanoma by skin self-examination.

BACKGROUND: Although some evidence indicates that early detection protects against the development of lethal melanoma, no randomized clinical trials have been conducted to measure the efficacy of early detection (or screening) in preventing death from this disease. Since melanoma incidence in the United States is relatively rare, a randomized clinical trial to test the efficacy of screening would be extremely expensive. PURPOSE: As an alternative to a randomized clinical trial, we conducted a population-based, case-control study to investigate whether early detection through skin self-examination (SSE) is associated with a decreased risk of lethal melanoma (includes the presence of advanced disease with distant metastases in addition to death from melanoma). METHODS: SSE (conducting a careful, deliberate, and purposeful examination of the skin) was assessed in all subjects by use of a structured questionnaire and personal interviews. The major exposure variable, SSE, was defined following focus-group interviews with melanoma patients and healthy control subjects. The final study population consisted of 1199 Caucasian residents of the state of Connecticut enrolled from January 15, 1987, through May 15, 1989; 650 individuals were newly diagnosed with cutaneous melanoma, and the remaining 549 individuals were age- and sex-frequency matched control subjects from the general population. During the study interviews, nevi on the arms and backs of subjects were counted. In 5 years of follow-up (through March 1994), 110 lethal cases of melanoma were identified. The study design allowed separate estimation of the impact of SSE on reduced melanoma incidence (primary prevention) and survival among incident cases (secondary prevention). Odds ratios (ORs) were used to measure the associations between SSE and melanoma and between SSE and lethal melanoma. RESULTS: SSE, practiced by only 15% of all subjects, was associated with a reduced risk of melanoma incidence (adjusted OR = 0.66; 95% confidence interval [CI] = 0.44-0.99; comparing case patients with control subjects). The data indicated further that SSE may reduce the risk of advanced disease among melanoma patients (unadjusted risk ratio = 0.58; 95% CI = 0.31-1.11); however, longer follow-up is required to confirm this latter estimate. If both estimates are correct, they suggest, in combination, that SSE may reduce mortality from melanoma by 63% (adjusted OR = 0.37; 95% CI = 0.16-0.84; comparing lethal cases with general population controls). CONCLUSIONS AND IMPLICATIONS: SSE may provide a useful and inexpensive screening method to reduce the incidence of melanoma. SSE may also reduce the development of advanced disease. The results of this study need to be replicated before strategies to increase the practice of SSE are further developed and promoted.

Adult↗

Expression of platelet-derived growth factor (PDGF)-A, PDGF-B and the PDGF-alpha receptor, but not the PDGF-beta receptor, in human malignant melanoma in vivo.

There has been considerable interest in the potential role of growth factors in the initiation and development of cutaneous malignant melanoma (CMM). Platelet-derived growth factor (PDGF) has been shown to be secreted by melanoma cell lines and by metastatic melanoma in vivo. PDGF also has been reported to stimulate the development of tumour stroma and new blood vessels. We studied the expression of PDGF and its receptors by both immunohistochemistry (IHC) and in situ hybridization (ISH) in primary and metastatic melanoma and in normal skin specimens. Cryostat sections were incubated with 35S-labelled riboprobes and antibodies for PDGF-AA, PDGF-alpha receptor, PDGF-BB and PDGF-beta receptor. Both primary and metastatic melanoma exhibited significant expression of PDGF-AA, PDGF-BB and PDGF-alpha receptor by both IHC and ISH, compared with only background expression in normal skin. We did not observe expression of PDGF-beta receptor in melanoma. Our results suggest that PDGF may function as an autocrine growth factor, as well as an angiogenesis factor, in CMM tumour development. This expression of the PDGF-alpha receptor rather than the beta receptor may be unique among solid tumours.

Humans↗

Borrelial fasciitis: diffuse fasciitis and peripheral eosinophilia associated with Borrelia infection.

We present four cases of diffuse fasciitis (DF) associated with peripheral eosinophilia in which spirochetal organisms were identified. Two patients had borderline positive results on serologic evaluation for Borrelia burgdorferi. Deep biopsy showed dermal sclerosis associated with variable degrees of perivascular mononuclear inflammation. Diffuse fasciitis, septal panniculitis, and myositis with mononuclear cell infiltrates and varying numbers of eosinophils were observed. All cases showed a striking lymphocytic vasculopathy associated with atypical reactive endothelial cells. Using modified Dieterle and Steiner silver stains, multiple organisms were seen in one specimen, a single unequivocal organism detected in two specimens. In one case, no organisms were detected on silver stain; however, organisms were demonstrated using rabbit polyclonal antibodies against B. burgdorferi. B. burgdorferi-specific DNA was identified in one patient by the polymerase chain reaction. These results indicate that some cases of eosinophilic fasciitis are an expression of Lyme disease. We have previously proposed the more specific term "borrelial fasciitis" to describe such lesions.

Adult↗

Efficacy of an elective regional lymph node dissection of 1 to 4 mm thick melanomas for patients 60 years of age and younger.

OBJECTIVE: A prospective multi-institutional randomized surgical trial involving 740 stage I and II melanoma patients was conducted by the Intergroup Melanoma Surgical Program to determine whether elective (immediate) lymph node dissection (ELND) for intermediate-thickness melanoma (1-4 mm) improves survival rates compared with clinical observation of the lymph nodes. A second objective was to define subgroups of melanoma patients who would have a higher survival with ELND. METHODS: The eligible patients were stratified according to tumor thickness, anatomic site, and ulceration, and then were prerandomized to either ELND or nodal observation. Femoral, axillary, or modified neck dissections were performed using standardized surgical guidelines. RESULTS: The median follow-up was 7.4 years. A multifactorial (Cox regression) analysis showed that the following factors independently influenced survival: tumor ulceration, trunk site, tumor thickness, and patient age. Surgical treatment results were first compared based on randomized intent. Overall 5-year survival was not significantly different for patients who received ELND or nodal observation. However, the 552 patients 60 years of age or younger (75% of total group) with ELND has a significantly better 5-year survival. Among these patients, 5-year survival was better with ELND versus nodal observation for the 335 patients with tumors 1 to 2 mm thick, the 403 patients without tumor ulceration, and the 284 patients with tumors 1 to 2 mm thick and no ulceration. In contrast, patients older than 60 years of age who had ELND actually had a lower survival trend than those who had nodal observation. When survival rates were compared based on treatment actually received (i.e., including crossover patients), the patients with significantly improved 5-year survival rates after ELND included those with tumors 1 to 2 mm thick, those without tumor ulceration, and those 60 years of age or younger with tumors 1 to 2 mm thick or without ulceration. CONCLUSION: This is the first randomized study to prove the value of surgical treatment for clinically occult regional metastases. Patients 60 years or age or younger with intermediate-thickness melanomas, especially with nonulcerative melanoma and those with tumors 1 to 2 mm thick, may benefit from ELND. However, because some patients still are developing distant disease, these results should be considered an interim analysis.

Female↗

Chromosome 17 allelic loss and NF1-GRD mutations do not play a significant role as molecular mechanisms leading to melanoma tumorigenesis.

Allelic loss in human cutaneous melanoma has been detected on chromosomes 1p, 6q, 9p, 10q, and 11q. Chromosome 17 contains important tumor suppressor genes such as p53, NM23, and neurofibromatosis type 1 (NF1), which have been implicated in melanoma tumorigenesis. The role of p53 has already been studied by a number of laboratories, showing contrasting results. In the present study, two restriction fragment length polymorphism (RFLP) probes for the NM23 and NF1 genes, together with five other RFLP and four variable number of tandem repeat chromosome 17 probes, were investigated at the loss of heterozygosity (LOH) level in a Southern blot-based assay. The NF1 gene was also tested for LOH by a polymerase chain reaction (PCR)-based approach in two different experiments, using a dinucleotide repeat polymorphic probe at locus D17S250 (17q11.2-q12), and an Alu probe intragenic to the NF1 gene (17q11.2). A PCR single-strand conformation polymorphism assay was included in the study for mutation detection at the NF1-GTPase-activating protein-related domain (GRD). A total of 68 melanocytic tumors were analyzed. LOH was detected in 9 of 87 informative cases (10%). LEW301 (17p11.2-pcen) presented the highest LOH frequency (22%). NM23 showed LOH in 17% of the informative cases, while NF1 did not show either LOH in the Southern blot- and PCR-based experiments or mutations at the NF1-GRD. These results are in concordance with those of previous smaller studies, but when compared with higher LOH frequencies obtained from other chromosomes, these findings indicate that the LOH values found in our study can most likely be attributed to background effect. Thus, chromosome 17 LOH is likely to play and unimportant role as a genetic event in melanoma tumorigenesis. Nevertheless, NF1 merits further study, since homozygous deletions have been detected at this locus in melanoma cell lines.

Alleles↗

Expression of basic fibroblast growth factor in desmoplastic melanoma.

Basic fibroblast growth factor (bFGF) is an established growth factor for melanocytes and a potent angiogenic factor. The expression of bFGF was investigated in 23 desmoplastic melanomas. (DM) (12 males, median age 64 years, and 11 females, median age 54 years) by immunostaining of formalin-fixed, paraffin-embedded sections with high-affinity purified antibody raised against recombinant human bFGF (Scios Nova, Inc.). The tumors were characterized by level II invasion in 1 case (5%), level IV invasion in 11 cases (48%), level V invasion in 8 cases (35%), and indeterminate in 3 cases. bFGF expression was observed in 22 of 23 tumors (95%), either immune localized to tumor cell nuclei in 17 of 22 tumors (77%), or to the cytoplasm of tumor cells in 5 of 22 tumors (23%). Also in these cases, bFGF was strongly expressed in the nuclei of vascular endothelial cells. Maximal expression was noted in the peripheral blood vessels of 20 tumors (91%) versus intratumoral vessels of 13 DM (59%). In conclusion, the expression of predominantly nuclear bFGF by tumor cells in DM suggests a role in mediating the desmoplastic phenotype. In addition, the localization of bFGF to vascular endothelium, particularly at the periphery of the tumor, may be relevant to tumor angiogenesis.

Adult↗

A factual, not arbitrary, basis for choice of resection margins in melanoma.

Try as some might, it has proved exceedingly difficult to dispel the notion that primary melanoma should be treated by arbitrarily wide resection margins. There was never any substantive scientific foundation for the traditional 5-cm margin, but for much of this century it nevertheless found favor in medical folklore. Current opinions concerning melanoma management in the dermatologic literature, while careful to point out the limitations of supportive data, have continued the tradition of offering arbitrary guidelines for resection margins. The last 2 decades have witnessed the acquisition of sufficient experimental evidence to warrant further scrutiny of the practice.

Decision Making↗

Cutaneous melanoma and atypical Spitz tumors in childhood.

BACKGROUND: Malignant melanoma in childhood is rare. As a result, the biology and natural history of melanoma in this age group is still poorly understood. Although the majority of Spitz nevi are benign regardless of atypical features, a particular problem is the continued confusion of Spitz nevi with atypical features with melanoma and the lack of specific criteria for their distinction. The latter discrimination is perhaps not so difficult when Spitz nevi are minimally atypical; however, the greater the atypia, the more challenging is this discrimination. METHODS: All cases of malignant melanoma referred to Children's Hospital (Boston, MA) and to one of the authors were examined during the period of 1959-1995. Criteria for inclusion in the study included: (1) age up to 15 years; (2) availability of microscopic slides; and (3) availability of demographic data. RESULTS: There were 11 males and 12 females, ranging in age from 2 to 15 years (mean age, 9.4 years). Histopathologically, the 23 tumors were categorized into four subgroups: (1) small cell melanoma (5); (2) adult-like melanoma (6); (3) Spitz-like melanoma (3), and (4) atypical Spitz tumors (9). The small cell melanomas were notable for localization to the scalp, significant thickness, and fatal outcome. The adult-like melanomas resembled typical tumors occurring in adults. The one fatal Spitz-like melanoma was located on the neck of a 14-year-old male. Two tumors in this group metastasized to regional lymph nodes, but were not associated with further aggressive disease on follow-up despite treatment with surgical excision only. The atypical Spitz tumors were characterized by significant thickness and abnormal features including prominent cellularity and mitotic activity. CONCLUSIONS: Anatomic site and cell type may be important prognostic factors in addition to tumor thickness for childhood melanoma, but these tumors require further study. In addition, the biologic potential of atypical Spitz tumors has not been characterized sufficiently.

Adolescent↗

Desmoplastic neurotropic melanoma. A clinicopathologic analysis of 28 cases.

BACKGROUND: Desmoplastic neurotropic melanoma (DNM) is a rare variant of malignant melanoma, the natural history and histogenesis of which still are being defined. METHODS: The clinical and histologic features of 28 cases of DNM were studied. All published cases of DNM to date were reviewed. Paraffin sections from 26 cases were investigated with a panel of 10 tissue markers. The ultrastructural features of seven cases were evaluated. RESULTS: A comparison of this study's findings with that of other published cases revealed many similarities regarding clinical and pathologic findings and outcome. The patients were white (15 men:13 women; mean and median age, 59 years; range, 22-83 years). Most tumors were located on the head and neck (75%) and were nonpigmented (57%). An associated intraepidermal melanocytic proliferation was identified in 85% of the patients (lentigo maligna in 56%). Histologically, the dermal tumors were composed of tapered, nonpigmented spindle cells in peripheral nerve sheath patterns resembling neuromas, schwannomas, neurofibromas, and perineurial proliferations accompanied by variable neurotropism and desmoplasia; desmoplasia was the most notable feature in most tumors. The mean depth of tumor invasion was 4.1 mm (range, 0.32-9.0 mm). Tumors with continuity between the epidermal and dermal components had a significantly thinner depth of invasion and a more extensive intraepidermal melanocytic proliferation than those tumors with a grenz zone between the two components (2.3 mm vs. 4.6 mm, P = 0.015). Mitotic activity ranged from 0/HPF in 10 cases, 1-6/high power field (HPF) in 12 cases, and to greater than 6/HPF in 4 cases. An ulcer was present in 5/27 tumors, regression in 4/27, a microsatellite in 1, and brisk and had nonbrisk tumor infiltrating lymphocytic responses in 2 and 14, respectively. Vimentin was uniformly positive and keratins AE1.3 and Cam 5.2 and Leu-7 were uniformly negative. S100 protein, also uniformly positive, had patchy reactivity in most tumors that expressed EMA (43%). Smooth muscle actin (52%), neuron-specific enolase (42%), and FXIIIa (30%) had patchy positivity. HMB-45 was reactive only in the epidermal and superficial papillary dermal component in 21% of cases. Ultrastructurally, the common features were long, often intertwining cellular processes, intercellular junctions, and discontinuous basal lamina. Melanosomes were not identified. Follow-up data available on 26/28 patients (mean, 36 months; median, 24 months; range, 5-132 months) showed 20 (70%) alive without disease, 2 alive with disease and 3 dead from disease. Seven patients had recurrent local tumor (multiple in four); four had lymph node metastases, and three had visceral metastases. Patients with recurrent disease of any type had significantly thicker tumors (5.4 mm vs. 3.4 mm, P = 0.046) and were more likely to have an ulcerated tumor (P = 0.03). Actuarial 5-year survival for tumors with greater than a 4-mm thickness was 72%, which was greater than that for other types of melanoma with greater than a 4-mm thickness. CONCLUSIONS: Desmoplastic neurotropic melanomas are neuroectodermal tumors that usually arise from an intraepidermal melanocytic proliferation but rarely develop de novo in the dermis. Schwannian and perineurial differentiation may account for the desmoplasia and neurotropism encountered in these neoplasms. Desmoplastic neurotropic melanomas present at a more advanced stage locally and may be associated with a better survival than associated with conventional melanomas of similar depth of invasion.

Adult↗

Histologic features of congenital melanocytic nevi in infants 1 year of age or younger.

BACKGROUND: Congenital melanocytic nevi (CMN) occur in approximately 1% of the white population. These lesions are often surgically excised prophylactically because of increased melanoma risk. OBJECTIVE: In this study 87 CMN of all sizes from infants 12 months of age or younger (mean age, 6.6 months) were examined histologically. METHODS: Each lesion was evaluated for depth of nevus cell involvement, overall epidermal and dermal pattern, and cytologic atypia. RESULTS: Most CMN involved the lower half of the reticular dermis (89%), and 51% infiltrated the subcutaneous tissue. Depth of nevus cell infiltration was positively correlated with size of the lesion. The predominant dermal pattern was diffuse interstitial infiltration (63%). Patchy nevus cell patterns were observed in 37% of the CMN and were associated with smaller lesions (p < 0.001). Most of the CMN displayed no cytologic atypia (70%), and we found no cases of melanoma. Atypia was not significantly associated with either size or location of the nevus. CONCLUSION: These results indicate that depth and pattern of nevus cells are directly related to size of CMN in infants.

Female↗

Familial cutaneous melanoma.

Family history is an important risk factor for cutaneous malignant melanoma. We evaluated the clinical characteristics of patients with cutaneous familial melanoma. A chart review was conducted, including all patients who presented to Massachusetts General Hospital Pigmented Lesion Clinic over an 8-year period. A total of 102 patients from 49 families were confirmed with shaving cutaneous melanoma. Eighty-two per cent had a personal and/or family history of dysplastic naevi. Within families, subsequent affected patients had thinner primary lesions with substantially lower median thickness than those diagnosed first. Seventeen per cent had multiple primary melanomas, with the median thickness of subsequent primaries being much lower than that of the first primary lesions. The mean thickness of primary lesions in patients with one primary lesion was marginally significantly greater than that in patients with multiple primaries. Verification of family history is essential given the implications of a positive family history. Screening family members of all patients with cutaneous melanoma and surveillance examinations for all patients with cutaneous melanoma is recommended.

Adolescent↗

Increased thickness of pregnancy-associated melanoma.

The effects of pregnancy on the pathophysiology of melanoma remain unclear. Although a gender-specific advantage for women vs. men is seen for characteristics such as stage at presentation, site of primary tumour, and survival time, an adverse effect of pregnancy on melanoma development and progression has been reported. In a retrospective study, we investigated the tumour characteristics of women who developed pregnancy-associated melanoma, and compared them with melanomas arising in non-pregnant women of child-bearing age. The patient records of the Massachusetts General Hospital Pigmented Lesion Clinic were reviewed, and 465 women of reproductive age (16-45 years) who developed melanoma were identified. Of these, in 45 women (age 21-42 years) there was a close temporal relationship between diagnosis of the tumour and pregnancy. Clinical and histological characteristics of the primary tumours were recorded. Differences in tumour thickness, site and histological type were analysed. The mean thickness of pregnancy-associated melanomas was significantly greater than that of non-pregnancy-associated tumours (2.28 vs. 1.22 mm, respectively; P < 0.007). No differences in histological type (P = 0.64) or site (P = 0.74) of the primary tumours were found between the two patient groups. Not surprisingly, multivariate analysis revealed that tumour thickness was a statistically significant variable in determining prognosis (P = 0.001). An unexpected finding, on multivariate analysis, was a possible pregnancy-associated prognostic advantage (P = 0.08). Melanomas arising during pregnancy are thicker, but are not necessarily associated with a less favourable prognosis than tumours arising in non-pregnant women of child-bearing age.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗