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Tretinoin, or retinoic acid, is a compound related to vitamin A which has improved skin that has been aged by sun exposure. Of 30 patients who participated in a four-month study, 21 continued tretinoin treatment for 10 months, and 16 continued for 22 months. Patients who did not continue treatment cited inconvenience or objection to further biopsies, but not lack of effectiveness, as the reason. Evaluation of patients receiving the more prolonged treatment showed that improvement of skin appearance and structure continued in spite of reductions in the dosage or frequency of treatment. Most improvements occurred during the first 6 to 10 months of therapy. Besides continued improvement of skin wrinkling and texture, 71 percent of liver spots disappeared. Other notable changes associated with treatment were increased skin pinkness, which was not adverse, and skin dryness with a red, flaking dermatitis, which diminished with continued treatment. There was no difference in adverse effects at different doses of tretinoin. Anatomic changes and the persistence of improvement for two months after therapy was discontinued indicate that tretinoin alters basic skin structure rather than causing a transient, superficially beneficial, swelling of the skin. The study suggests that tretinoin is likely to benefit sun-aged skin. (Consumer Summary produced by Reliance Medical Information, Inc.)

• Daily application of 1% fluorouracil cream to normal white skin results in definite morphologic alterations of the epidermis. Although clinical changes were not present, electron microscopic examination of the tissue demonstrates changes especially pronounced in the epidermal keratinocytes. These changes consist of cytoplasmic vacuoles, alterations in the mitochondria, Golgi complex, and endoplasmic reticulum, as well as widened extracellular spaces.(Arch Dermatol 111:1301-1306, 1975)

• Epidermodysplasia verruciformis (EV) is a rare disease characterized by the early onset and unremitting progression of wart-like lesions and frequent association of cutaneous carcinomas. We report two siblings with EV. Immunologic study of both patients demonstrated normal immunoglobulin levels, normal numbers of T-lymphocytes and B-lymphocytes, but markedly depressed in vitro blastogenic reactivity to mitogens and antigens. Cutaneous anergy to a variety of common skin test antigens was noted. These observations may reflect an inherited abnormality in immune function, or the depressed immune function may result from the viral infection of EV.(Arch Dermatol 113:495-499, 1977)

• Biopsy specimens of normal skin and lentigines from an 82-year-old man with multiple lentigines syndrome were examined with light and electron microscopes. Giant melanosomes were found in dermal melanophages, melanocytes, and keratinocytes in all epidermal layers. Morphologic characteristics of these melanosomes are described, and other conditions in which they have been found are discussed.(Arch Dermatol 113:491-494, 1977)

• Localized brown to blue-black discoloration of the skin occurred in three patients receiving long-term minocycline hydrochloride therapy. Abundant perivascular pigmented material was present at all levels of the dermis below the upper papillary portion. Histochemical studies demonstrated reactivity with the Prussian blue stain and the Fontana-Masson silver technique. The granules were brightly refractile by dark-field illumination. Ultrastructurally, there were membranebound dense intracellular inclusions differing from melanin and iron but identical to those known to occur in the thyroid glands of minocycline-primed laboratory animals. The abnormal pigment most likely represents a metabolic derivative of minocycline.(Arch Dermatol 116:1262-1265, 1980)

We studied three patients having cerebriform intradermal nevus (CIN), a cause of cutis verticis gyrata that can be diagnosed by clinical and histopathologic findings. Histologically and ultrastructurally, CIN has the appearance of a very large nevus-cell type of dermal nevus. Complications of CIN, including the development of malignant melanoma, are the basis for prognosis and for therapeutic approach.

In the past two years there have been several reports dealing with the unusual discoloration present in the sunexposed sites of patients receiving prolonged and high doses of chlorpromazine. The general consensus has been that it is due to a melanin or a melanin-plus-drug combination. Electron-microscopic examination of both normal and involved skin from these patients, as well as examination of extracts and residues of normal and involved skin of these patients following the extraction of chlorpromazine from the tissue, strongly suggests that the peculiar blue-gray color presented by these patients is due to a combination of both the drug and melanin rather than to melanin by itself.

Qualitative as well as quantitative studies, including direct counting of cells and linear scanning of electron micrographs, to determine volume ratios for epidermal dendritic cells revealed an increase in melanocyte number and an essential absence of Langerhans' cells following two weeks of daily ultraviolet irradiation. These findings suggest some form of relationship between the melanocyte and the Langerhans' cell.

In an electron microscopic study of the pigmented basal cell epithelioma, the high degree of activity of the dendritic cell is pointed out. The melanocyte is increased in size and the nucleus is multilobed. The cell is richly dendritic, and is producing an abundance of melanosomes. The granules produced accumulate in the dendritic tips of the melanocytes and are not passed to any great extent to the neoplastic epithelial cells. Thus, most of the pigment within the tumor is found in the large dendritic cells. The symbiotic relationship of epidermal cells and melanocytes is stressed.

Congenital phlebectasia was first described under the title cutis marmorata telangiectatica congenita. The vascular pattern in this disease is established essentially at birth, but there may be some extension of involvement in the first one or two weeks of life. This abnormality has been confined to the skin and has not been associated with other abnormalities, and nearly all patients show improvement as they get older.

Study of cultured fibroblasts on consecutive days of growth demonstrated them to be polymorphic cells capable of many forms and functions. On the fourth day of growth there is the formation of a well-developed endoplasmic reticulum and a marked folding of the cell membrane. Subsequently, filaments form intracellularly and are later released from the cell through the folds in the cell membrane. Following this, the filaments line up laterally and longitudinally in the extracellular space, thus giving rise to the striated collagen fibers.

The so-called "epidermal sweat duct unit"1 has long been a subject of controversy. The intraepidermal portion of the eccrine sweat duct has been considered by some to have a specialized epithelium, while others have felt that this portion of the duct is lined by typical epidermal cells. Physiologically, a final clarification of this matter would be of great importance. Charles,2 in an electron microscopic study of the eccrine sweat gland, mentioned the epidermal sweat duct. He did not depict the orifice in the stratum corneum, but in summary, stated that "as the duct ascends to the epidermis the large lumen first becomes surrounded by a dark, papillate cuticle, and then becomes completely occluded, the only channel left for the passage of sweat being between closely adpressed papillae. Within the epidermis the cuticle appears to keratinize and an unspecialized pore is formed."A study was undertaken, using the electron

Since Pauling (1949) mentioned that abnormalities of hemoglobin formation may be genetically determined, there has been a tremendous impetus for the study of both normal and abnormal hemoglobin patterns. The medical literature has become voluminous on the various hemopathic syndromes, although little is to be found in the dermatologic journals. Thalassemia, or Mediterranean anemia, is being seen and recognized with increased frequency by dermatologists; hence a review of the syndrome seems indicated.Cooley and Lee (1925) first described a disorder occurring in children of Mediterranean descent and characterized by anemia, hepatosplenomegaly, Mongoloid appearance, and discoloration of the skin and sclerae. Laboratory examinations showed there was bile in the urine and increased resistance of the patient's erythrocytes to hypotonic solutions. In addition, leukocytosis and nucleated red blood cells, chiefly of the normoblastic variety, were present in the blood. Roentgenograms showed enlargement of the cranial and

Tyrosinase activity was studied in dermal nevus cells using a modification of the ultrastructural DOPA technique. Tyrosinase was localized to melanosomes and premelanosomes in nevus cells of the superficial dermis. Nevus cells in the middermis and deep dermis, in addition to having melanosomal tyrosinase activity, also demonstrated linear accumulations of DOPA-melanin in the smooth endoplasmic reticulum. Nevus cells having a neuroid appearance also contained this linear reaction product after incubation in DOPA, suggesting a pigment cell origin similar to other dermal nevus cells. The absence of tyrosinase activity in the smooth endoplasmic reticulum of the superficial dermal nevus cells may be related to auto-phagic breakdown of melanin with the information of melanosome complexes. The findings of this study support the hypothesis that premelanosomes can be formed directly from the smooth endoplasmic reticulum without prior processing by the Golgi apparatus.

Removal of the stratum corneum of human epidermis wih cellophane tape stimulated tyrosinase activity in basal melanocytes. An edematous condition surrounding the melanocytes, also a result of the stripping, inhibited the passage of melanosomes to keratinocytes. Consequently, melanosomes were packaged into autophagic vacuoles within the melanocytes. Melanocytes in the upper layers of the epidermis had autophagic vacuoles in their cytoplasm. Some melanocytes on or near the basal lamina possessed vacuoles which contained parts of Langerhans cells, demonstrating the phagocytic capability of the melanocyte.