Acid phosphatase in melanosome formation: a cytochemical study in normal human melanocytes.

A cytochemical study of acid phosphatase (AcPase) activity was conducted in normal epidermal melanocytes from both sun-exposed and sun-protected human skin to define the relationship between enzyme activity and melanosome formation. In the perikarya of melanocytes of both sun-exposed and sun-protected skin, it was determined that only a small proportion of stage 1 and 2 melanosomes had AcPase activity (20-33% and 9-26%, respectively). The proportion of AcPase-positive melanosomes in perikarya increased in stage 3 (39-56%), reaching a maximum in stage 4 (67-84%). In the dendrite of melanocytes, where melanosomes were mostly in stages 3 and 4, the vast majority of melanosomes demonstrated AcPase activity (79-87% and 88-93%, respectively). The preferential incorporation of AcPase in the later stages of melanogenesis is more consistent with a possible role for this enzyme in the degradation or transfer of melanosomes, rather than as an essential component in the early process of melanization.

The PUVA lentigo: an analysis of predisposing factors.

Pigmented macules appearing in sun-protected sites of psoriatic patients treated chronically with oral methoxsalen photochemotherapy (PUVA) have been characterized as a lentiginous proliferation of relatively large, sometimes cytologically atypical, melanocytes (i.e., PUVA lentigines). In 1380 psoriatic adults followed prospectively, PUVA lentigines of any degree (slight, moderate, or extensive) were noted on the buttocks of 53% of patients at the most recent examination (an average of 5.7 years after starting PUVA). The frequency of moderate or extensive buttock lentigines at the most recent examination was positively associated with a greater number of PUVA treatments, an older age at starting PUVA, and male sex, and negatively associated with skin types V and VI. Moderate or extensive buttock lentigines were present in 17% of 693 patients who had not had PUVA for 1-2 years or longer. According to a regression analysis, the persistence of buttock lentigines was related in greatest measure to the total number of PUVA treatments received and was relatively independent of the time interval from the last PUVA treatment to the most recent examination or to "other" UV radiation therapy (predominantly UVB) received after PUVA was discontinued. Until the long-term course of PUVA lentigines is known, individuals who develop "fixed" pigmented lesions while on PUVA should be monitored continually for melanocytic dysplasias, including melanoma.

Morphologic alterations of epidermal melanocytes and melanosomes in PUVA lentigines: a comparative ultrastructural investigation of lentigines induced by PUVA and sunlight.

Ultrastructural studies were conducted in order to determine morphologic and functional differences in melanocytes and melanosomes in PUVA lentigines and solar lentigines, and light-protected buttock skin. Compared to melanocytes in solar lentigines from 7 subjects and light-protected buttock skin from 5 subjects (none of these subjects had received UV radiation therapy), melanocytes in PUVA lentigines from 6 subjects generally had longer and more numerous dendrites, and showed more active melanogenesis. Basal keratinocytes in PUVA lentigines had a significantly increased frequency of large, single melanosomes, and revealed significantly larger individual melanosomes within compound melanosomes. Other findings in some PUVA lentigines included the close apposition of Langerhans cells to melanocytes, and atypical nuclear, cytoplasmic and melanosomal alterations, including melanosomal pleomorphism and melanin macroglobules. The presence of relatively large and predominantly single melanosomes in basal keratinocytes of PUVA lentigines suggests more active melanogenesis and/or an irreversible somatic alteration. It will be important to determine the clinical course and ultrastructural findings of PUVA lentigines that persist long after PUVA is discontinued.

Increased intraepidermal melanocyte frequency and size in dysplastic melanocytic nevi and cutaneous melanoma. A comparative quantitative study of dysplastic melanocytic nevi, superficial spreading melanoma, nevocellular nevi, and solar lentigines.

Dysplastic melanocytic nevi (DMN) are distinguished histologically by a hyperplasia of variably atypical intraepidermal melanocytes in a lentiginous epidermal pattern. In order to further characterize the intraepidermal melanocytes of DMN, 4 representative specimens each of DMN, acquired nevocellular nevi (NCN), solar lentigines (SL), and superficial spreading melanoma (SSM) were selected on the basis of predetermined criteria, confirmed in a blind histologic assessment, and compared in a quantitative morphologic study using 6 micron-thick hematoxylin and eosin stained sections of L-dihydroxyphenylalanine (dopa) preincubated vertical tissue slices of lesion and adjacent normal skin. The average melanocyte frequency, expressed as the percent of dopa-reactive perikarya among 600 consecutive basal unit cells, was significantly greater in DMN (60 +/- 23%) than in NCN (18 +/- 3%), SL (25 +/- 7%), and adjacent skin (14 +/- 3%), but similar to that in SSM (71 +/- 11%). The average mean diameter of 200 consecutive epidermal basal unit melanocytes was significantly larger in DMN (11 +/- 2 microns) than in NCN (7 +/- 0.4 microns), SL (6 +/- 0.1 microns), and adjacent skin (6 +/- 0.4 microns), but significantly smaller than in SSM (16 +/- 3 microns). The observed similarities of intraepidermal melanocytes in selected DMN and SSM, as well as distinct differences from melanocytes in selected NCN and SL, support the hypothesis that some varieties of DMN may represent potential precursors of cutaneous melanoma.

Disseminated intravascular coagulation and purpura fulminans in a patient with Candida sepsis. Biopsy of purpura fulminans as an aid to diagnosis of systemic Candida infection.

Disseminated intravascular coagulation and purpura fulminans developed in association with septicemia and meningitis due to Candida tropicalis in an 18-year-old female immunosuppressed renal allograft recipient. Although systemic Candida infection was initially suspected, blood cultures showed no growth of this organism until after its identification in the dermis of a skin biopsy specimen obtained from the site of purpura fulminans. This case illustrates the association between Candida sepsis and purpura fulminans, and demonstrates the usefulness of skin biopsy of purpura fulminans in the early diagnosis of Candida sepsis.

Familial aggregation of small congenital nevomelanocytic nevi.

We investigated the genetic aspects of congenital nevomelanocytic nevi (CNN) by comparing the prevalence rate of CNN in sibs of probands to that of CNN in newborn infants. Probands included all individuals with small (less than 40 mm) CNN registered photographically during 1982 in a children's hospital dermatology service. A CNN was defined on the basis of gross appearance and presence (according to parents) within the first 2 weeks of life. The 39 probands with small CNN had a total of 65 sibs. Eight of the 65 (12.3%) also had one or more small CNN. This prevalence rate in sibs is 11 times the population-based prevalence rate of CNN in newborn infants (1.1%) based on a published report surveying newborn infants in the same city within the past decade. In five of our 39 study families we also detected an affected parent with CNN. We conclude that small CNN may aggregate in families. Autosomal dominant inheritance with incomplete penetrance or multifactorial determination could account for this observation.

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.

Congenital arrector pili hamartoma. A case report and review of the spectrum of Becker's melanosis and pilar smooth-muscle hamartoma.

Congenital pigmented arrector pili hamartomas are unique malformations of epidermis and pilar apparatus usually appearing as localized, lightly pigmented, hairy plaques. Characteristic microscopic features include smooth-muscle proliferation similar to irregularly disposed arrectores pilorum, and slight elongation of epidermal rete with hypermelanosis of the basal unit. An otherwise normally developed child who had this hamartoma at birth is described in an attempt to clarify the relationship between pilar smooth-muscle hamartomas and Becker's melanosis. We propose that these two entities belong at different poles of the same developmental spectrum of hamartomatous change.

A histologic comparison of congenital and acquired nevomelanocytic nevi.

A reliable microscopic differentiation of nevomelanocytic nevi (NMNs) as congenital or acquired would be useful in defining a histogenic relationship between cutaneous melanoma and congenital NMN. In order to delineate histologic differences between congenital NMN and acquired NMN, a standardized assessment was conducted blindly, using a sample of consecutive surgical specimens of NMN submitted to a children's hospital pathology file. Despite significant histologic differences between congenital NMN and acquired NMN, the lack of a reliable prevalence rate for the proportion of congenital NMNs among all NMN specimens submitted for pathologic examination precludes a precise estimate of predictive value for diagnosing a given NMN as congenital or acquired based on histologic features alone. The results of this study can be used neither to support nor to refute a histologic association between cutaneous melanoma and congenital NMN.

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.

Melanocytic precursors of cutaneous melanoma. Estimated risks and guidelines for management.

There are several recognizable melanocytic precursors of cutaneous melanoma. These precursors include lentigo maligna, dysplastic melanocytic nevi, congenital nevi (of any size), and darkly pigmented lesions of acral surfaces and mucous membranes. Lentigo maligna is an uncommon melanocytic dysplasia, present in 3 per 1000 individuals over the age of 50 years and accounting for 4 percent of all cutaneous melanomas. Dysplastic melanocytic nevi are present in 2 per cent of white adults, and may account for at least a fifth of cases of cutaneous melanoma. Congenital nevomelanocytic nevi are present in 1 per cent of newborns; the vast majority of congenital nevi are smaller than 3 to 4 cm in diameter, while very large congenital nevi are present in 1 in 20,000 to 1 in 500,000 newborns. Very large congenital nevi account for less than 0.1 percent of cutaneous melanomas, whereas small varieties of congenital nevi may account for 15 percent of cutaneous melanomas. If individuals with lentigo maligna live long enough, possibly a third to a half are said to develop melanoma. This figure may be biased high. Persons with dysplastic melanocytic nevi in the familial melanoma setting have an estimated lifetime risk of developing melanoma approaching 100 per cent. Persons with dysplastic melanocytic nevi in other settings may have a lifetime melanoma risk of 18 per cent. Persons with congenital nevi of any size may have a lifetime melanoma risk of at least 5 per cent. Early recognition of these precursor melanocytic tumors, particularly in high-risk individuals (i.e., those with a personal or family history of melanoma), and careful photographic follow-up or prophylactic excision of these lesions may be the most effective means of reducing the morbidity and mortality of cutaneous melanoma. The impact of routine screening and excision of presumed melanoma precursors is unknown. Clinical judgment is required to balance the theoretical risk of melanoma associated with a given precursor and the known risks of surgery and anesthesia for a given individual. It must be kept in mind that the vast majority of acquired melanocytic nevi in adults are harmless. Probably even the majority of dysplastic nevi and small congenital nevi will remain unchanged throughout life. The simple recognition of the existence of melanoma precursors will heighten suspicion for these lesions and raise awareness of the earliest signs of malignant change.(ABSTRACT TRUNCATED AT 400 WORDS)

Nonepidermal origin of malignant melanoma associated with a giant congenital nevocellular nevus.

We report an adult who developed primary malignant melanoma arising in association with residual nevus cells in the pectoralis muscle under an intact skin graft 13 years following the partial excision of a giant congenital nevocellular nevus (GCNN). The case serves to emphasize the malignant potential of GCNN, for which we estimate a lifetime risk of at least 6.3 percent and an approximate 17-fold risk for melanoma when compared with the general population. This case supports previous observations that melanoma may arise in nonepidermal components of a GCNN and suggests the need to consider excision of the GCNN to muscle fascia or deeper if nevus cells extend beyond this anatomic zone. We estimate the risk of death from general anesthesia during the first year of life to be substantially less than the risk of malignant degeneration during the same time period. The decision to excise the GCNN as soon as the problem is recognized should depend on the general health of the infant and the risk of surgical complications.

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.

Twenty-nail dystrophy of childhood: a sign of localized lichen planus.

A 9 1/2-year-old girl was seen with 20-nail dystrophy. Lichen planus was suspected and further examination revealed other lesions localized to the oral mucosa. The diagnosis was confirmed as lichen planus by biopsy of tissue from the oral lesions. Careful examination of all mucocutaneous surfaces is recommended before accepting the diagnosis of so-called isolated 20-nail dystrophy of childhood.