Cutaneous melanoma: patient surveillance and tumor progression.

BACKGROUND: The goal of surveillance examinations (SVE) in patients at high risk for cutaneous melanoma (CM) is to diagnose premetastatic tumors. OBJECTIVE: We attempted to determine whether SVE before CM diagnosis influences the histopathologic features of tumor progression. METHODS: A retrospective review was conducted of consecutive patients who presented with an intact primary CM during a 36 month period (1991 to 1994) in a university dermatology ambulatory setting. RESULTS: Thirty-nine intact CMs were diagnosed in 34 patients. Compared with 23 CMs in as many patients presenting at the first encounter, 16 CMs diagnosed in 11 patients during SVE had a smaller mean tumor diameter (P = .007) and tumor thickness (P = .002) and were more likely anatomic level I or II (P = .003) with microscopic thickness less than 0.76 mm (P = .01) and less than 0.50 mm (P = .002). CONCLUSION: Primary CMs are more likely to be smaller and thinner when diagnosed during SVE than at first encounter, features that are likely to have a positive impact on CM mortality.

Reliability of the histopathologic diagnosis of melanocytic dysplasia. The Dysplastic Nevus Panel.

OBJECTIVE: To determine the reliability of the histopathologic diagnosis of melanocytic dysplasia among diverse dermatopathologists who had no joint training, agreed to abide by predetermined criteria, and who were provided reference photomicrographs illustrative of the criteria. DESIGN, SETTING, AND PARTICIPANTS: A stratified random sample of 112 melanocytic tumors were chosen from the files of the pathology department of a large staff-model health maintenance organization. The original diagnoses included typical and dysplastic melanocytic nevi and melanoma. A single representative slide for each case was interpreted independently by each of the 5 panel dermatopathologists and 2 melanoma specialists. They had no prior knowledge of the original diagnosis or the diagnoses of the other panel members. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Interrater reliability was measured by intraclass and Pearson correlation coefficients. Each case was graded on a 5-point scale from no dysplasia to melanoma. RESULTS: The intraclass correlation among the panel members was 0.67 (95% confidence interval, 0.59-0.73). The Pearson correlations of each of the 5 panel dermatopathologists with the mean of the 2 melanoma specialists ranged from 0.67 to 0.84, and the correlations of the mean of the panel with the 2 melanoma specialists were 0.79 and 0.82; the mean reading of the melanoma specialists correlated 0.89 with the mean panel reading. Apparent protocol violations occurred in 6.5% of the readings. CONCLUSIONS: Agreement was substantial to excellent for the histopathologic diagnosis of 112 melanocytic tumors by dermatopathologists. Using predetermined criteria, melanocytic dysplasia can be reproducibly graded among diverse general dermatopathologists.

Congenital nevomelanocytic nevi: proportionate area expansion during infancy and early childhood.

BACKGROUND: The way in which congenital nevomelanocytic nevi (CNN) expand relative to anatomic region during growth is relevant to decisions about optimal timing for surgical excision and assessment for malignant change. OBJECTIVE: Our purpose was to determine how CNN area expands relative to anatomic region during infancy and early childhood. METHODS: Forty-one small CNN in as many subjects were studied from the newborn period. Relative area (CNN area/anatomic region area) was derived for each measure. Proportionate expansion (PE), defined as change in relative area per unit time as a proportion of initial relative area, was calculated. Relative to anatomic region, area expansion of CNN is greater when PE is greater than 0, less when PE is less than 0, and at least double when PE is +1.0 or greater. RESULTS: From the newborn period to last measure (2 to 71 months), PE ranged from -0.7 to +8.8 (median, +0.1). For 66% of CNN (27 of 41), PE was greater than 0. Nine of 39 CNN (15.4%) had PE values of +1.0 or greater during the first 6 months, compared with 1 of 26 cases (3.8%) for the interval beginning at or after 6 months. CONCLUSION: Disproportionately rapid area expansion of CNN may occur during early infancy, related to transient benign neoplasia, delayed pigmentation, and/or error of the methods used in the analysis.

Public education and cancer of the skin. What do people need to know about melanoma and nonmelanoma skin cancer?

Cutaneous melanoma (CM) and nonmelanoma skin cancer (NMSC) have a high chance for cure if detected in an early phase of development. Patients who have these tumors may now be treated in the outpatient setting with a minimum of discomfort, inconvenience, and cost. Most skin cancer deaths are caused by CM. Until recently, CM incidence in the United States has been increasing faster than any other potentially lethal cancer, attributable at least in part to aggressive case detection and greater public awareness about the significance of risk factors and early warning signs of evolving tumors, resulting in increased numbers of curable tumors. Most CMs are discovered by patients or close acquaintances. Most CM deaths are related to patient delay in seeking medical care. Patient delay is attributed mostly to lack of knowledge rather than to fear and denial. In the United States, primary prevention of CM and NMSC has focused on encouraging sensible sun-exposure behaviors, while secondary prevention consists of a yearly national campaign that promotes skin awareness and self-examination and free examinations to detect evolving tumors, sponsored by the American Academy of Dermatology and the American Cancer Society. More attention is needed to encourage timely consultation for evolving tumors and predisposing risk factors and to focus screening and surveillance efforts of those people at greatest risk. Public education must continue to promote personal responsibility in the intervention process to reduce the morbidity and mortality associated with CM and NMSC.

Mid-dermal elastolysis with inflammation.

A 71-year-old white woman had finely wrinkled, erythematous patches of skin that met the clinical and histologic criteria for mid-dermal elastolysis. In addition to the loss of mid-dermal elastin described in previous cases, histopathologic examination revealed a superficial and deep perivascular inflammatory infiltrate of lymphocytes and plasma cells and interstitial collections of multinucleated giant cells containing phagocytized elastin. These results support a previously postulated inflammatory pathogenesis for mid-dermal elastolysis.

Sun-induced freckles in children and young adults. A correlation of clinical and histopathologic features.

Sun-induced freckles are a risk factor for epidermal and melanocytic neoplasia. Whereas sun-induced freckles in children and older adults may be clinically indistinguishable, and sun-induced freckles in older adults usually consist of increased numbers of intraepidermal melanocytes, the histology of sun-induced freckles in children remains unsettled. Using L-3,4 dihydroxyphenylalanine (DOPA)-paraffin sections, the authors examined six sun-induced freckles and adjacent nonpigmented skin (ANP) in as many white male subjects, ages 10 to 23 years. Melanocyte frequency was expressed as the ratio of DOPA-reactive melanocytes to total epidermal basal unit cells. For each case, melanocyte frequencies in freckles were significantly greater than in ANP. Cellular atypia of melanocytes was noticed in four of six freckles. Reactivity of melanocytes for HMB-45 was noticed in two freckles studied, compared with no reactivity in three specimens of ANP studied. The authors conclude the sun-induced freckles in the young may consist of a hyperplasia of melanocytes (i.e., similar to solar lentigines in the elderly), sometimes with cellular atypia, and that these findings may be relevant to melanocytic neoplasia.

Cutaneous melanoma and bilateral retinoblastoma.

We report the case of an otherwise healthy 37-year-old man who had had bilateral enucleation during early childhood for bilateral retinoblastomas, in addition to two cutaneous melanomas (the first appearing at age 27 years). He also had dysplastic melanocytic nevi and a history of cutaneous melanoma in his mother. Retinoblastoma may aggregate in families and is associated with DNA abnormalities of chromosome 13. Recent reports have emphasized the appearance of second malignancies in retinoblastoma survivors. The second malignancies include osteosarcoma, soft tissue sarcoma, and cutaneous melanoma. Cutaneous melanoma also may aggregate in families, usually in the setting of dysplastic melanocytic nevi. The features of this case and of similar reported cases suggest that there may be a greater than expected association between retinoblastoma and cutaneous melanoma.

Combined immunodeficiency associated with xeroderma pigmentosum.

We report a 15-month-old boy with xeroderma pigmentosum, a history of repeated infections, and immune deficiency who developed a fatal pneumonia with parainfluenza type 1. Immunologic evaluation revealed a severe combined immunodeficiency with hypoglobulinemia, C3 deficiency, anergic response to skin testing, and an abnormal lymphocytic response to mitogens. We suggest that patients with xeroderma pigmentosum be evaluated carefully for immune deficiencies, should repeated infections occur.

Origin of cutaneous melanoma in a congenital dysplastic nevus spilus.

Cutaneous melanoma developed in contiguity with a congenital nevus spilus on the leg of a 79-year-old white woman. The unique features of the nevus spilus in this case were its relatively large size (diameter, 8 cm), irregular gross appearance, lifelong stability until the recent appearance of a tumor nodule, and the presence of intraepidermal melanocytic dysplasia appearing as multifocal elements within darkly pigmented speckles distributed throughout a lightly pigmented background of lentigo simplex. Based on this observation, we suggest that the presence of intraepidermal melanocytic dysplasia in nevus spilus may be a predisposing factor for the development of melanoma. The malignant potential of "dysplastic" nevus spilus requires further study.

Genital lentiginosis: a clinical and histopathologic study.

We studied the clinical and histopathologic characteristics of melanotic macules of the penis and vulva. The 10 lesions studied were relatively large (up to 2 cm), multifocal, irregular in outline, and had variegated pigmentation. Most were regarded as clinically atypical in appearance. Histologic examination of the lesions showed basal layer hyperpigmentation, slight melanocytic hyperplasia, epithelial hyperplasia, and stromal melanophages. No cytologic atypia of melanocytes was detectable. Information is insufficient at present to predict the natural history of genital lentiginosis or its relation to mucocutaneous melanoma.

Dysplastic melanocytic nevi and cutaneous melanoma: markers of increased melanoma risk for affected persons and blood relatives.

Dysplastic melanocytic nevi are potential precursors of cutaneous melanoma and markers of increased risk. This article presents representative case histories that illustrate the usefulness of careful follow-up of persons who have dysplastic melanocytic nevi or cutaneous melanoma, as well as examination of their blood relatives for the same lesions. Identification and periodic examination of such high-risk persons may result in the detection of melanoma in a curable phase. Our observations suggest that (1) dysplastic melanocytic nevi may aggregate in families of persons who have dysplastic melanocytic nevi or melanoma, even in the absence of a family history of dysplastic melanocytic nevi or melanoma and (2) formal genetic and natural history studies of persons who have dysplastic melanocytic nevi outside the familial melanoma setting are warranted.

Dysplastic melanocytic nevi: a reproducible histologic definition emphasizing cellular morphology.

Histologic criteria commonly used to diagnose dysplastic melanocytic nevi (DMN) have not been correlated adequately with biology nor subjected to rigorous reproducibility studies. To address these failings, we developed histologic definitions emphasizing cellular morphology based on the appearance of typical melanocytes in sun-protected buttock skin, fully-evolved atypia in the vertical component of metastasizing primary cutaneous melanomas, and slight and moderate degrees of atypia defined within these limits in selected varieties of DMN. Reproducibility of our histologic definitions were tested by using two pathologists working independently to assess single routine tissue sections of 19 melanocytic lesions on two occasions at least 6 mo apart. Lesions included five previously diagnosed primary invasive cutaneous melanomas, seven lesions selected for gross morphologic features characteristic of DMN, and four solar lentigines and three common acquired nevomelanocytic nevi preselected for typical appearance and stable growth history. For the primary pathologist using the grading scheme, agreement rates between first and second readings were 84% for final diagnosis and 79% for the highest degree of cellular atypia; for the secondary pathologist, agreement rates for first and second readings for both parameters were 84%. Agreement rates comparing second readings of final diagnosis and highest degree of cellular atypia by the two pathologists were 89% and 79%, respectively. Most of the architectural and host response features commonly associated with DMN were less reproducible. In conclusion, we demonstrated very good reproducibility of histologic definitions used to differentiate the intraepidermal component of DMN from that of melanoma and benign melanocytic and nevomelanocytic hyperplasias, based on a biologic correlation emphasizing cellular morphology. Reproducible histologic definitions are a requisite first step in defining a clinical-pathologic correlation for DMN.

Melanosomal alterations in dysplastic melanocytic nevi. A quantitative, ultrastructural investigation.

Abnormal-looking melanosomes are observed commonly in both intraepidermal melanocytes of cutaneous melanoma and dysplastic melanocytic nevi (DMN). This was investigated by using transmission electron microscopic examination to determine the percentage of abnormal melanosomes among 8267 melanosomes assessed in at least five solitary intraepidermal basal unit melanocytes from each of five specimens of DMN, superficial spreading melanoma (SSM), common acquired nevomelanocytic nevi (NMN), and normal skin (NS) adjacent to DMN. The percentage of abnormal melanosomes in DMN (mean + SD, 44 + 23%) was seven times greater than that in NMN (6 + 7%) and 22 times greater than that in NS (2 + 5% [P less than 0.001, both comparisons]), but only 80% that in SSM (57 + 19% [P less than 0.02]). Melanocyte area, nuclear area, and the ratio of nuclear area to cytoplasmic area did not account for the observed differences. Melanosomal alterations may be a useful marker of atypicality in melanocytic tumors.