Arthur R. Rhodes

The malignant potential of small congenital nevocellular nevi: An estimate of association based on a histologic study of 234 primary cutaneous melanomas

In order to assess a relationship between small congenital nevocellular nevi and cutaneous melanoma, histologic features commonly associated with congenital nevi were sought in 234 melanomas. The detection of one or more histologic features of congenital nevi in 8.1% (19/234) of melanoma specimens was directly related to the number of slides and tissue sections with melanoma available for review, the predominance of superficial spreading melanoma (SSM) and the historic relationship to a preexisting pigmented nevus at the tumor site. The histologic association was inversely related to melanoma thickness and tumor location on the lower extremities. The observed frequency of histologic association was estimated to be approximately 4,000 to 13,000 times greater than expected on the basis of surface area by chance alone. These findings suggest that small congenital nevi may be precursors for at least some cases of cutaneous melanoma. The strength of histologic association is highly dependent on the specificity of methods used for detecting congenital nevi in melanoma specimens.

Mucocutaneous lentigines, cardiomucocutaneous myxomas, and multiple blue nevi: The “LAMB” syndrome

We describe a 13-year-old girl with a cardiocutaneous syndrome characterized by an atrial myxoma, pigmented lesions of the skin and genital mucosa, and opalescent papules and dermal nodules of the skin and tongue. Her pigmented lesions included black macules of the face and vulva, brown macules of the lips and perioral skin, multiple blue nevi, and a congenital nevomelanocytic nevus. The black and brown macules of the face and vulva consisted of lentiginous proliferations of large, intensely dopa-reactive melanocytes. The opalescent papules and dermal nodules had histologic, ultrastructural, and histochemical characteristics of myxomas. During follow-up, the patient developed thyroid nodules, which were composed of mixed papillary and follicular hyperplasia. This case emphasizes the necessity of a cardiac evaluation for a potentially fatal (and surgically treatable) atrial myxoma in individuals with multiple melanocytic and myxomatous tumors of the skin and mucosa.

Small congenital nevocellular nevi and the risk of cutaneous melanoma

The relative risk of melanoma associated with small congenital nevi was estimated by comparing the published frequency of histologically documented nevocellular nevi in newborn infants with the frequency of: (1) congenital nevi at the tumor site, ascertained by history in 134 patients with melanoma; and (2) tumor-associated nevi with congenital features in 234 melanoma specimens. A 21-fold increase in melanoma risk was estimated for persons with small congenital nevi when nevi were ascertained by history, and a three- to tenfold increase in risk when nevi were ascertained by histology. Based on these approximations of relative risk from historic and histologic methods of detection, persons with small congenital nevi who live to age 60 are estimated to have cumulative risks for melanoma of 4.9/100 and 0.8 to 2.6/100, respectively. The increased risk is related presumably to the markedly increased probability of melanoma arising in association with small congenital nevi. In other words, small congenital nevi may represent precursors for at least some cases of cutaneous melanoma. The estimated risk are highly dependent on the specificity of methods used for ascertainment of congenital nevi.

Dysplastic melanocytic nevi in histologic association with 234 primary cutaneous melanomas

Dysplastic melanocytic nevi (DMN) are irregularly pigmented lesions characterized by (1) atypical melanocytic hyperplasia in a lentiginous epidermal pattern (AMHL), (2) one or more dermal mesenchymal changes, and (3) frequently a dermal nevocellular nevus. In order to determine an association between DMN and cutaneous melanoma, the dominant histologic feature of DMN (namely, AMHL) was sought in histologic contiguity with 234 primary melanomas. Of these 234 cases, 9 were lentigo maligna melanomas. Of the remaining 225 cases, 49 (21.8%) were associated with AMHL in the same histologic section as (but beyond the most lateral margin of) intraepidermal and invasive melanoma. AMHL was directly associated with the presence of dermal nevocellular nevi in histologic contiguity with melanoma, and a greater number of histologic slides with melanoma available for review. AMHL was inversely associated with nodular melanoma. Most of the AMHL cases were not associated with familial melanoma, but the total number of familial cases was low. The histologic association between AMHL and melanoma in one fifth of cases in this series supports the hypothesis that at least some cutaneous melanomas may have an origin in DMN.

Enumeration of T cell subsets in atopic dermatitis using monoclonal antibodies

Peripheral blood lymphocytes from 22 patients with atopic dermatitis, 17 age-matched healthy controls, 10 patients with other skin diseases, and 14 patients with either asthma or allergic rhinitis were characterized by reactivity with monoclonal antibodies to the surface antigens of helper-inducer (T4) and suppressor-cytotoxic (T8) T cell subsets and to a common T cell antigen (T3). In contrast to healthy controls and controls with other skin diseases or respiratory allergic disease, patients with atopic dermatitis had a reduced percentage of T3-positive (T3+)cells (p less than 0.01) and T8-positive (T8+) cells (p less than 0.001) but not of T4-positive cells (T4+)op less than 0.05). A selective increase in the ratio of T4+ cells over T8+ cells was observed in 17 of 22 patients with atopic dermatitis but not in any of the controls. Thus there is a loss of circulating suppressor-cytoxic T cells in the majority of patients with active atopic dermatitis.

The PUVA-induced pigmented macule: A lentiginous proliferation of large, sometimes cytologically atypical, melanocytes

Eleven PUVA-induced pigmented macules (PM) obtained from seven psoriatic adults 4 to 6 years after starting PUVA therapy were compared to eight sun-induced pigmented macules (SM) and five specimens of light-protected skin (LPS) from twelve nonpsoriatic control subjects who had not received ultraviolet radiation therapy. Unlike SM, many PM were darkly or irregularly pigmented. In a blind histologic assessment using routine and L-dihydroxyphenylalanine (dopa)-incubated tissue sections, both PM and SM were lentigines. Three of eleven PM had slight melanocytic atypism, compared to none of eight SM. When compared to SM and LPS, PM had a significantly increased proportion of hypertrophic melanocytes. These observations demonstrate that chronic PUVA induces pigmented macules characterized by a lentiginous proliferation of large melanocytes which, in some cases, may be slightly atypical. PUVA-treated individuals require continual monitoring for atypical melanocytic lesions.

Urticaria associated with acute viral hepatitis type B: studies of pathogenesis.

To determine whether skin deposition of circulating immune complexes contributes to prodromal urticaria of acute hepatitis B, we studied two patients with hepatitis B who presented with urticaria and fever. During the urticarial prodrome but not thereafter, we found activation of both classic and alternative complement pathways. Hepatitis B surface antigen (HBsAg)-antibody complexes were identified (by electron microscopy) in cryoprecipitates from both patients and IgG (by immunodiffusion) in cryoprecipitates of one patient during urticaria. Light and electron microscopy of involved urticarial skin revealed necrotizing venulitis in both patients. Immunofluorescence microscopy showed fibrin within involved cutaneous vessel walls in one patient and C3, IgM, and HBsAg, which were not detected in simultaneously obtained uninvolved skin, in both patients. Our findings suggest that deposition of circulating immune complexes containing HBsAg is important in the pathogenesis of urticaria associated with acute hepatitis B virus infection.

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.

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.

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.