The misdiagnosis of malignant melanoma.

Despite the increasing awareness of malignant melanoma over the last 40 years, clinical diagnostic accuracy remains disappointing. Malignant melanoma can masquerade clinically as benign lesions (false negatives), and benign pigmented lesions can clinically simulate malignant melanoma (false positives). Histologic examination of pigmented lesions is therefore important to ensure proper diagnosis and treatment. We review many of the published reports of benign lesions mimicking melanoma and melanoma masquerading as other entities as well as present additional cases of clinical misdiagnoses of melanoma.

The relationship of pregnancy, hormones, and melanoma.

There has been considerable interest in the relationship of pregnancy and melanoma. Since 1951, a number of case reports have suggested that pregnancy may induce or exacerbate melanoma. Likewise, there has been concern over the relationship between exposure to oral contraceptives (OCs) or hormone replacement therapy (HRT) and possible increased risk of melanoma. We critically reviewed: (1) controlled clinical trials to assess the effect of pregnancy on the prognosis of melanoma; and (2) epidemiological data to evaluate the risk of melanoma after exposure to OCs or HRT. Pregnancy before, during, or after the diagnosis of melanoma does not appear to influence 5-year survival rates. Exposure to OCs or HRT does not appear to increase the risk of melanoma.

Ocular melanomas and melanocytic lesions of the eye.

This article describes several melanocytic lesions of the eye. Benign and malignant lesions will be discussed as well as a review of the dysplastic nevus syndrome and its proposed association with ocular melanoma. Ocular melanomas arise from the same embryologically derived melanocytes as their cutaneous counterparts. However, ocular and cutaneous melanomas differ in many respects. The diagnosis and management of these ocular tumors rely heavily on the ophthalmologist. However, knowledge of melanocytic lesions will aid the dermatologist in detection and in proper referral of these patients.

The immune response in halo nevi.

The mechanism(s) responsible for halo nevus presents a provocative link with the immune response to melanoma. Although no direct demonstration of melanocyte killing has been observed by the immune effector cells found within the halo, the abundance of antigen-presenting cells in the regressing nevus and the presence of T lymphocytes at the site of depigmentation suggest that these cells participate in the halo phenomenon. Within the latter population of cells, evidence points to the involvement of CD8+ T cells as potential effectors in the destruction of nevomelanocytes. The break in tolerance that triggers migration and the presumed activation of these and other lymphocytes in the nevus in the apparent absence of disease remains unexplained. This brief overview reviews the evidence for the participation of the immune response in the genesis of the halo nevus.

Changes in size of melanocytic nevi during pregnancy.

BACKGROUND: The relation between pregnancy, melanocytic nevi, and malignant melanoma is ambiguous. It has been reported that nevi grow and darken during pregnancy. Several recent studies have shown that malignant melanomas diagnosed during pregnancy are thicker than those not associated with pregnancy. This may be partially due to a delay in diagnosis because of the opinion that benign nevi change during pregnancy. OBJECTIVE: Our purpose was to photographically document any change in size of melanocytic nevi during pregnancy. METHODS: Twenty-two women were entered into the study during the first trimester of pregnancy and examined again in the third trimester. All nevi 2 mm or larger on their back were documented and photographed. Photographs were then compared and nevi measured for change in diameter. RESULTS: Of 129 nevi, only eight nevi (6.2%) changed in diameter from the first to the third trimester. The mean change in size of all nevi studied was zero. Of the eight nevi that did change in size, four increased by 1 mm and four decreased by 1 mm. CONCLUSION: Our study suggests that pregnancy is not associated with any significant change in size of melanocytic nevi. Patient characteristics (age, pregnancy number, skin type) and nevi characteristics (location, number) did not correlate with any change in size.

Pregnancy and the prognosis of malignant melanoma.

The influence of pregnancy on the prognosis of malignant melanoma (MM) is unclear. Since 1951, a number of case reports have suggested that pregnancy may have an adverse effect on the clinical course of MM. We reviewed the literature on pregnancy and MM and focused on the well-controlled studies. Based on a limited number of controlled trials, pregnancy before, after, or during the time of diagnosis of stage 1 MM does not appear to affect survival. However, these data should be interpreted with caution because the duration of follow-up and number of patients may not be sufficient to observe a true effect.

Sun exposure of young children while at day care.

Sun exposure in childhood has been implicated as a risk factor for the development of melanoma and nonmelanoma skin cancers. As an increasing number of young children are cared for in day-care centers, we were interested in examining the sun-protection practices in this setting. In our study of day-care centers, we found that while most day-care center staff were aware of the adverse effect of excess sun exposure and the need for sun protection, the use of sunscreen and protective clothing and avoidance of midday sun were limited. We conclude that intensive education of day-care center staff and parents regarding sun exposure and sun protection is necessary if we are to attempt to reduce the frequency of melanoma and nonmelanoma skin cancer.

Recurrence rates of treated basal cell carcinomas. Part 4: X-ray therapy.

This is the fourth report in a series that reviews the experience in the Skin and Cancer Unit, from 1955 through 1982, with the treatment of basal cell carcinomas (BCCs). It concerns 862 primary (previously untreated) BCCs irradiated by a "standardized" x-ray therapy schedule. The overall 5-year recurrence rate for these lesions, as determined by the modified life-table method, was 7.4%. This rate was not significantly different from that experienced with 211 recurrent (previously treated) BCCs with a re-recurrence rate of 9.5% (P = .552). For the primary BCCs, multivariate analysis showed that increasing BCC diameter was the only independent risk factor for high recurrence rates (P = .003). The patient's age or sex, the duration of the BCC, the anatomic site of the BCC, or time-span treated (1955-1963, 1964-1972, 1973-1982) did not significantly affect the recurrence rate. Additional analysis showed that BCCs on the head less than 10 mm in diameter had a 5-year recurrence rate of 4.4% whereas those 10 mm or greater in diameter had a rate of 9.5%. Lastly, the proportion of recurrence-free treatment sites with a good or excellent long-term cosmetic outcome after x-ray therapy (63%) was lower than previous reports in this series with curettage-electrodesiccation (91%) and surgical excision (84%). Thus, if the long-term cosmetic outcome after treatment is not an overriding concern to the patient, x-ray therapy is an effective modality for many primary and recurrent BCCs.

Recurrence rates of treated basal cell carcinomas. Part 3: Surgical excision.

This is the third report in a series that reviews the experience in the Skin and Cancer Unit, from 1955 through 1982, with the treatment of basal cell carcinomas (BCCs). It concerns 588 previously untreated (primary) BCCs removed by surgical excision. The cumulative 5-year recurrence rate was 4.8%. This is a statistically significant lower recurrence rate (P = .034) than 135 previously treated BCCs that had a re-recurrence rate of 11.6%. For the primary BCCs, multivariate analysis showed that location on the head (P = .010) and being male (P = .004) were independent risk factors for recurrence. The patient's age, the duration of the BCC, its maximum diameter, or the time span (1955-1963, 1964-1972, 1973-1982) in which it was treated did not significantly affect the recurrence rate. The 5-year recurrence rate for BCCs excised from various anatomic sites were as follows: 1) neck, trunk, and extremities = 0.7%; 2) head--less than 6 mm in diameter = 3.2%; 3) head--6 to 9 mm in diameter = 8.0% (treated since 1964 = 5.2%); and 4) head--10 mm or more in diameter = 9.0%. Surgical excision is a highly effective method for removal of BCCs, and achieved a good to excellent cosmetic outcome in about 85% of the recurrence-free treatment sites.

Determination of preexcision surgical margins of melanomas from fixed-tissue specimens.

The shrinkage of cutaneous surgical specimens of 199 malignant melanomas was analyzed. A formula was derived that makes it possible to calculate the in vivo (preexcision) specimen diameter from the in vitro (fixed-tissue) specimen diameter. The age of the patient was found to significantly influence specimen shrinkage and was incorporated into this shrinkage formula. The calculated in vivo specimen diameter was then used to determine the width of the in vivo surgical margins with reasonable accuracy. Thus this method permits calculation of the width of surgical margins from fixed-tissue specimens.

Volume of malignant melanoma is superior to thickness as a prognostic indicator. Preliminary observation.

There are many clinical and histologic factors that are known to be valuable in predicting survival rates for patients with cutaneous malignant melanomas. Breslow thickness is considered to be the most reliable prognostic factor; however, thickness is a unidimensional measurement. A more accurate mensuration to predict biologic behavior might be one that takes into account the three-dimensional volume of the neoplasm. In a study of 35 primary malignant melanomas, the volumes of the dermal components of the tumors were calculated. Those patients with tumor volumes of 200 mm3 or less had a 91.4% 5-year disease-free survival rate, compared with survival rate of only 16.7% for those patients whose lesions had tumor volumes exceeding 200 mm3. On multivariate analysis, tumor volume exceeded thickness as a prognostic indicator. Thus, measurement of tumor volume proved to be of greater significance than thickness in predicting the outcome for patients with malignant melanomas.

Distinguishing benign and malignant melanocytic lesions with the AgNOR method.

A silver staining technique has recently been devised to aid in the differentiation between benign and malignant melanocytic lesions. This study showed a statistically significant difference between the staining of silver-nucleolar organizer regions (AgNORs) in melanocytic nevi and that of AgNORs in malignant melanomas.

Clinical features of dysplastic nevi.

The clinical features of 100 dysplastic nevi were tabulated. Although certain characteristics were present in most or all of these melanocytic nevi, there was a marked heterogeneity of other clinical features. The preponderant type of large (greater than or equal to 8 mm) melanocytic nevus in patients with classic dysplastic nevi is a papule or plaque with the following characteristics: multicoloration (various shades of tans, browns, reds, or black); slightly raised height for its broad diameter; mamillated surface; and lack of hypertrichosis. An atlas illustrates some of the clinical varieties of melanocytic nevi in this syndrome.

Recurrence rates of treated basal cell carcinomas. Part 1: Overview.

This is the first article in a series reviewing the extensive experience of the Oncology Section of the Skin and Cancer Unit, from 1955 through 1982, with 5755 basal cell carcinomas (BCCs) treated by curettage-electrodesiccation, surgical excision, or x-ray therapy. Recurrence rates were calculated by three methods for each of the treatment modalities: 1) by the raw recurrence rate method; 2) by the "strict" 5-year recurrence rate method; and 3) by modification of the life-table method. Our analyses show that the last method best approximates the true recurrence rate. Primary (previously untreated) BCCs had a 5-year recurrence rate of 10.6% (standard error 0.6%), and previously treated BCCs had a rate of 15.4% (standard error 1.3%) (P = .0002). The greatest risk for recurrence of treated primary BCCs occurred 1 to 4 years after therapy. It is concluded that recurrence rates of primary BCCs should be reported separately from those of previously treated BCCs and that the modified life-table method is best suited to calculate 5-year recurrence rates.

Recurrence rates of treated basal cell carcinomas. Part 2: Curettage-electrodesiccation.

This is the second article in a series that reviews the experience in the Skin and Cancer Unit, from 1955 through 1982, with the treatment of basal cell carcinomas (BCCs). This report deals with 2314 previously untreated (primary) BCCs removed by curettage-electrodesiccation. Multivariate analysis showed that increasing lesion diameter (P less than .001), high-risk anatomic sites (nose, paranasal, nasal-labial groove, ear, chin, mandibular, peri-oral, and peri-ocular areas) (P less than .001), middle-risk anatomical sites (scalp, forehead, pre- and post-auricular, and malar areas) (P less than .001), and time-span treated (1955 to 1963) (P = .012) were independent risk factors for high recurrence rates. The patient's age, sex, and lesion duration before treatment did not affect the recurrence rates. In order to best illustrate our current experience with BCCs, the last time-span (1973 to 1982) was examined in detail. For the low-risk sites (neck, trunk, and four extremities), BCCs of all diameters responded well to curettage-electrodesiccation with an overall 5-year recurrence rate of 3.3% (SE = 1.5%) determined by the modified life-table method. In the middle-risk sites BCCs less than 10 mm in diameter had a recurrence rate of 5.3% (SE = 2.7%). Finally, in the high-risk sites, lesions less than 6 mm in diameter had a recurrence rate of 4.5% (SE = 2.6%). Thus, BCCs less than 6 mm in diameter, regardless of anatomic site, as well as selected larger BCCs depending on their anatomic site, are effectively treated by currettage-electrodesiccation.

Prospective follow-up for malignant melanoma in patients with atypical-mole (dysplastic-nevus) syndrome.

A total of 357 white patients who had melanocytic nevi that fulfilled the clinical criteria for the "classic" atypical-mole (dysplastic-nevus) syndrome (100 or more melanocytic nevi; one or more melanocytic nevi 8 mm or larger in diameter; and, one or more melanocytic nevi with atypical features) were followed for the development of cutaneous malignant melanomas. Seventeen patients (4.8%) developed malignant melanomas during an average follow-up period of 49 months. One patient developed two malignant melanomas. Eight of the malignant melanomas detected were in situ and ten were invasive melanomas (less than 0.86 mm in Breslow thickness), implying an excellent prognosis. The number of malignant melanomas detected in these patients exceeded significantly the number expected to occur in age- and sex-matched white controls. All groups were shown to have an increased risk for the development of malignant melanomas. Total-body photographs were helpful in detecting changes in size, shape, and color that led to the diagnosis of malignant melanoma. These data support the concept that patients with this readily regionalized clinical presentation of classic atypical-mole syndrome are at an increased risk for malignant melanomas and, therefore, should be examined regularly.

Accuracy in the clinical diagnosis of malignant melanoma.

The computerized database (1955 through 1982) of the Oncology Section of the Skin and Cancer Unit of New York (NY) University Medical Center includes data on 13,878 lesions. Of these lesions, 214 were diagnosed clinically and histologically as malignant melanoma (MM). An additional 51 lesions, diagnosed clinically as other than MMs, were found histologically to be MM. Seventy-nine lesions were clinically diagnosed as MM but were found histologically to be other entities. An analysis of the clinical diagnostic accuracy showed some improvement over the three periods studied (1955 through 1963, 1964 through 1973, and 1974 through 1982). Although the diagnostic accuracy for the best period (1974 through 1982) was only 64%, the diagnosis of MM was made in 84.5% of the histologically proved cases of MM, reflecting a high degree of sensitivity.