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BACKGROUND The clinical appearance of amelanotic lentigo maligna melanoma (ALMM) is quite confusing and usually is not diagnosed prior to histopathologic examination. METHODS We have studied four new patients with ALMM whose correct diagnosis was not obtained from any one clinical finding. We arrived at the final diagnosis in an unexpected way, having had biopsied the lesions for diagnoses other than malignant melanoma. RESULTS ALMM presents as a nonspecific skin lesion with no single indicative characteristic. A search of the literature confirmed our difficulty in making the diagnosis. CONCLUSIONS To diagnose ALMM, one has to be cognizant of this condition and has to consider a constellation of findings that are unusual with melanocytic lesions. Questionable lesions must be biopsied for definitive histopathologic diagnosis. Cancer 1996;77:2052-7.

Six cases of malignant melanoma in children 14 years of age and younger are reported. The six cases were diagnosed among 850,000 consecutive skin biopsy specimens and consultation slides examined within a 32-year period. This series included an infant born with neurocutaneous melanosis, a child with malignant melanoma developing in a large congenital nevus at the age of 13 years, a superficial spreading malignant melanoma, Clark Level III, in a child with many dysplastic nevi, and three cases with primary nodular malignant melanoma, two of which showed histologic features of Spitz nevus. A review of the literature indicates that malignant melanoma in childhood is rare, and no large series have been investigated. It is not known whether the genetic and the environmental factors incriminated in the development of malignant melanoma in adults play a role in childhood melanomas. Data on the incidence of childhood melanoma in the population, the clinical and the histologic variations, and the prognosis are not adequate. A multiinstitutional study is needed to gather a large enough series to provide this information.

The mouse monoclonal antibody AFH1 was produced using formalin-fixed, sham paraffin-embedded human melanoma cell culture line A375 as immunogen. Reactivity of this antibody was assessed by immunohistochemical techniques against formalin- or acid alcohol-fixed paraffin-embedded tissue as well as formalin- or acid alcohol-fixed unembedded lesions. Ninety-seven nevomelanocytic lesions, neurofibromas, epithelial lesions, and a plasmacellular infiltrate were evaluated. AFH 1 was immunoreactive on 54 of 55 nevocytic lesions (98.2%), 15 of 16 primary melanomas (93.7%), a lentigo maligna, and nests in 21 of 21 dysplastic nevi (100%). Of 100 consecutive basal melanocytes of intraepidermal melanoma cells counted in each lesion, mean AFH1 immunoreactivity for nonnested basal melanocytes in nevocellular nevi was 3.8%; for dysplastic nevi, 13.8%; and for intraepidermal melanoma cells, 78.0%. When nonnested basal melanocytes were subdivided into cytologically normal and abnormal cell groups, AFH1 immunoreactivity was 9.4% and 72.6%, respectively. AFH1 recognition of the lentiginous portion of dysplastic nevi corresponds statistically to the appearance of abnormal melanocyte cytology, nest formation, or both. Using 50% immunoreactive nonnested melanocytes as the criterion, AFH1 seems to distinguish primary melanoma from dysplastic nevi with a sensitivity of 93.8% and a specificity of 95.8%.

Histologic studies have shown the evolution of lentigo senilis and have established the relationship between lentigo senilis, solitary lichen planus-like keratosis, and the reticulated form of seborrheic verruca. Histologic differentiation can be made between lentigo senilis and the early light-brown stage of lentigo maligna.

The normal and pathologic morphology and chemistry of elastic fibers in human skin have been subject of renewed investigation during the past decade (1, 2, 3). New staining reactions and the availability of certain enzymes (4) that will attack elastic fibers comprise additional tools of investigation.

In an address delivered before the Section of Dermatology of the Royal Society of Medicine in London in 1924, A. Civatte (1) described what he considered the primary histological lesion of psoriasis and seborrheic eczema. He advocated separating the two diseases and including seborrheic dermatitis in the “eczema” group, because the histologic events, while similar, included spongiosis in seborrheic derma-tisis, but not in psoriasis.According to Civatte, the primary histologic event is exudate of polymorphonuclear leukocytes and serum from the tip of the capillary loop into the supra-papillary layer of the epidermis followed by parakeratosis.Civatte's work has not found many followers and is rarely referred to at present. There are few modern investigations on seborrheic dermatitis and recent interest in the pathology and biochemistry of psoriasis has centered on the epidermis (2). Most authors consider the epidermis as the primary seat of the disease (3).

The present study was brought about by the casual observation of a common intradermal nevus which had developed around fts perimeter a narrow, yellowish halo. The puzzling histological picture was mainly characterized by elastic fiber hyperplasia and neoplasia obliterating the nevus cell nests and suggesting, at first sight, the diagnosis of a connective tissue nevus such as juvenile elastoma or nevus elasticus Fig. (1). In review of major articles on the histopathology of benign nevi and malignant melanoma, only few and short references were found in regard to specific changes of the elastic fibers in these lesions.

The development of elastic fibers within the fibrous stroma of basal cell epithelioma has previously been reported (1). Because these cases only included material from sun-exposed regions, the influence of actinic exposure on elastic fibers could not be eliminated. It was therefore thought necessary to review a series of basal cell epitheliomas from areas not exposed to actinic irradiation and observe the elastic fibers. periphery of solid epithelial nestsf (Figure 1A). In the two other cases, the thin elastic fibers were found lying in a brush-like arrangement at the periphery of the epithelial nests within the stroma (Figure IB). DISCUSSION The study of elastic fibers in cases of superficial basal cell epithelioma from sun-protected areas was TABLE Elastic fibers in superficial basal cell epithelioma-sun protected areas Case Number Age and Sex Duration of Tumor Anatomical Location Pattern of Elastic Fibers within the Tumor 1 70 F-W 1 year Upper Chest Sheaths of elastic fibers surrounding tumor nests 2 64 F-W 20 years Upper Thigh Sheath like 3 42 F-W 1 month Upper Back Sheath like 4 50 F-W 4 years Breast Sheath like 5 40 F-W 6 months Lower Back Sheath like 6 40 F-W 4 years Posterior Leg Sheath like 7 70 M-W 10 years Midback Sheath like 8 35 M-W 1 year Upper Thigh Brush like pattern of elastic fibers 9 60 F-W Unknown Posterior Hip Brush like MATERIALS AND OBSERVATIONS One hundred cases of superficial basal cell epitheliomas on unexposed areas were reviewed. Sections were stained with acid orcein and Giemsa. The series included 43 men and 57 women with the average age of 55 years. Newly-formed elastic fibers were found in nine cases. The clinical data on these nine cases are given in the Table. The newly-formed elastic fibers in the fibrous stroma of basal cell epithelioma are much thinner than those of the surrounding normal corium. They are found in two different patterns. In seven cases, the thin orceinophilic fibers formed sheaths at the done mainly to supplement the previous work. In the present study no evidence of solar elastosis was present in the skin at the periphery of the tumor. Formation of elastic sheaths surrounding the epithelial nests in basal cell epithelioma resembles those seen at the periphery of normal hair follicles. This resemblance may be explained if one considers basal cell epithelioma as a monstrous attempt in adnexogenesis in post-embryonal incompetent skin (2, 3). Solar exposure seems to play no definite role in the formation of elastic fibers. Newly-formed elastic fibers were seen in nine of the hundred cases of superficial basal cell epithelioma on non-solar-exposed areas. The pattern f A similar pattern was seen in the previous study of basal cell epithelioma from sun-exposed areas.

A monoclonal antikeratin antibody, EKH4, was produced from a hybridoma cell line which was established by fusing P3X63SAg8 mouse myeloma cells with spleen cells of mice immunized with human trichilemmoma cells. Immunoblot analysis showed that EKH4 antibody reacts predominantly with 50 kilodalton keratin polypeptide in normal epidermis. By indirect immunofluorescence and immunoperoxidase techniques, EKH4 antibody reacted with the lower 2–3 cell layers of the epidermis as well as most cells of pilosebaceous follicle of human and animal skin. Tumor cells of human basal cell epitheliomas and squamous cell carcinomas were also stained with this antibody. The staining was much more regular and intense compared with an available monoclonal antikeratin antibody, AE1. In the lesion of epidermal proliferative disorders, such as psoriasis and actinic keratosis, the entire epidermis instead of the lower layers was stained with EKH4 antibody. Normal skin overlying or adjacent to epithelial tumors also showed positive staining in the entire epidermis. By using indirect immunoperoxidase technique, EKH4 also stained alcohol-fixed, paraffin-embedded tissue sections.

Under dermal elastosis J. Graham Smith (1) has recently classified a group of skin diseases characterized by definite increase of elastic tissue in the corium. The elastic fibers in many of these pathologic conditions are similar to the fibers present in normal skin. However, in several instances they may exhibit morphologic and staining variations. The elastic fibers in pseudoxanthoma elasticum are short and curled and resemble ravelled wool. The elastic fibers penetrating to the surface epidermis in elastosis perforans serpiginosa are distinctly eosinophilic. Some variations in thickness and length of the fibers may be noticed in normal skin and in pathologic conditions. The subject of this study is to see if there is any variation in susceptibility to enzyme digestion of the elastic fibers in several dermal elastoses.