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To the Editor.— Byrd et al 1 presented a good description of what Birt and Davis 2 and we 3,4 call hereditary polymorphic light eruption (HPLE) of the American Indian. By not making this distinction, the authors overlooked some interesting aspects of a disorder that is unique for Native Americans of North, Central, and South America. 4 The large group of Finnish patients described by Jansen 5 exhibited such characteristic HPLE symptoms as autosomal dominant transmission, seasonal springtime onset, and a high incidence of cheilitis. 6 The frequent occurrence of cheilitis, often as the only presenting symptom of HPLE, has been reported in Canada, 7 the United States, 4 and Honduras. 8 Jansen did not cite cheilitis as the initial symptom in any of his patients, but its appearance in 47 (46%) of 103 persons leads one to wonder about a remote ancestral association with the American Indian. Although the

The Leser-Trelat sign is the sudden appearance and rapid increase in size and number of seborrhoeic keratoses in association with cancer. Twenty cases of this unusual phenomenon have so far been reported in the world literature. More than half involve adenocarcinomas and none was shown to be familial. We report a unique example of a 41-year-old black female and her 74-year-old black mother, both of whom have demonstrated classical clinical-pathological evidence of the Leser-Trelat sign and adenocarcinoma of the breast. The remainder of the family history was negative for cutaneous lesions and cancer. The aetiological and pathogenetic significance of the Leser-Trelat sign in association with carcinoma of the breast in this mother and daughter remains obscure.

A flexible system of classifying topical corticosteroid proprietaries is proposed to help the clinician understand the relative antiinflammatory potency of these products. This system has the advantage of indicating not only the relative potency of a specific proprietary preparation but also noting the number of divisions in the classification. It allows for new product development and keeps the clinician informed of the change by the number of divisions being used. The system also has the potential for the classification of relative severity of both local and systemic side effects of corticosteroids.

This review provides a comprehensive coverage of hereditary malignant melanoma with emphasis upon its heterogeneity as well as newly developed biomarker investigations. The recently described familial atypical multiple mole melanoma (FAMMM) syndrome is featured. Particular attention has been given to findings of increased hyperdiploidy observed as an in vitro phenomenon in cultured skin fibroblasts from high-risk and FAMMM-affected subjects. The FAMMM genotype is complex in that it predisposes a patient not only to melanoma (cutaneous and intraocular malignant melanoma) but also to other histologic varieties of cancer, including cancer of the lung, pancreas, and breast. Attention is given to cancer surveillance and management programs for patients at increased risk for the several forms of hereditary malignant melanoma. This approach capitalizes advantageously upon employment of a knowledge of genetics and hereditary cancer syndrome identification, with particular attention to tumor associations.

Clinical-pathologic-genetic studies were performed on 3 kindreds showing the familial atypical multiple mole-melanoma syndrome (FAMMM). Findings showed vertical transmission, including father-to-son, of cutaneous malignant melanoma and/or FAMMM moles with no sex predilection. A broad spectrum of clinical signs characterizing the phenotype ranged from an apparent lack of disease expression through minimal, moderate, and florid manifestations. An extreme example was a patient with 9 separate primary melanomas in 18 years. The FAMMM moles were histologically compound nevocellular nevi with varying degrees of dysplasia of the melanocytes, an increased occurrence of fibroplasia, and chronic inflammation within the papillary dermis. Of further interest was marked variation in the degree of dysplasia in moles between and within families. These observations, when coupled with recent reports by others, are consistent with an autosomal dominant gene showing markedly variable expressivity. Management of these patients is difficult, as one cannot be certain which moles require biopsy and then, following histological study, which will require wider excision. Studies of the FAMMM syndrome should deal carefully with its natural history, including the patient's lifelong susceptibility to multiply malignant melanomas, and the possibility that cancer of other anatomic sites may be integral components of this hereditary cancer syndrome. Images Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 8 Fig. 10

PreviewTopical glucocorticoids constitute an important and often incorrectly used class of drugs. Drs Fusaro and Kingsley offer not only a great deal of valuable information to help physicians prescribe these drugs correctly and educate patients to their correct use, but also a rational potency classification designed to avoid the emerging confusion concerning the relative potency of the various preparations available.

The topical sunscreen, dihydroxyacetone/lawsone (DHA/lawsone), was tested on 18 patients with photosensitivity disorders. Separate sequential application of the components increased sunlight tolerance in these patients twelvefold, thus providing four times greater protection against sunlight than did the previous technique employing mixtures of the components. This sunscreen, which is chemically bound to the stratum corneum, provides both long and short ultraviolet photoprotection.

The recent increase in incidence of malignant melanoma in many of the "sun belts" of the world has focused intense interest on its etiology. Although sunlight is an important factor, only a fraction of those individuals exposed to significantly large amounts of sunlight develop malignant melanoma. Genetic susceptibility undoubtedly plays an important etiologic role. We have put forth a multifaceted hypothesis, which we believe provides unification for the genetic-environmental interaction in the etiology of malignant melanoma. Genetic heterogeneity in the familial atypical multiple mole melanoma (FAMMM) syndrome and other single gene disorders that predispose to malignant melanoma are particularly stressed. The possibility of polygenic or multifactorial factors in the etiology of malignant melanoma remains to be elucidated.

Familial atypical multiple mole melanoma (FAMMM) syndrome, a cancer-associated genodermatosis, is a dominantly inherited heterogeneous disorder with variable expressivity of both its cutaneous and cancer phenotypes. By using a verified historical review technique of cancer documentation (idout patient health records, pathology reports/slides, autopsy reports/slides, and death certificates) of all anatomic sites in all members of a modified nuclear pedigree (first-degree relatives plus maternal and paternal grandparents, aunts, and uncles) over several generations, we showed that the FAMMM syndrome is similar to the majority of autosomal dominant inherited cancer-associated genodermatoses and has excessive risk for cancer of multiple anatomic sites. With respect to the FAMMM syndrome, these cancers involved the breast, respiratory tract, gastrointestinal system, the eye (intraocular melanoma), and the lymphatic system. These FAMMM pedigrees showed some of the following distinctive characteristics of hereditary cancer: 1) integral patterns of cancer within and between pedigrees; 2) early age of onset of cancer; 3) prolonged survival of some pedigree members with cancer; and 4) an excess of multiple primary melanomas and cancers of variable anatomic sites. The presence of these features indicates that these cancers of variable anatomic sites may be etiologically associated with the FAMMM syndrome. Heterogeneity should be investigated in FAMMM pedigrees with attention to consistent differences in size and distribution of atypical lesions, age at cancer onset, and pattern of tumor occurrences. The occurrence of FAMMM pedigrees in the general population or among pedigrees of probands with atypical nevi is not known. The occurrence of systemic cancers in these FAMMM pedigrees requires the development of cancer surveillance programs that are specifically modified to the particular cancer pattern of each pedigree.

The Familial Atypical Multiple Mole-Melanoma Syndrome (FAMMM) is characterized by an autosomal dominantly inherited susceptibility to multiple atypical naevi. Patients with this hereditary phenotype show a strong susceptibility to cutaneous malignant melanoma (CMM). Our investigation of an extended Dutch kindred showing the FAMMM phenotype revealed a proband with bilateral intraocular malignant melanoma (IOM) and multiple CMM. The family revealed an array of tumours which included carcinoma of the lung, skin, larynx, and breast in addition to CMM and IOM, which were transmitted vertically through 3 generations. There was male-to-male transmission, and the number of affected males and females was about the same, which was consistent with an autosomal dominant inheritance. Thus the FAMMM syndrome not only indicates a potential for CMM, but a susceptibility to other systemic cancers as well. These observations, though limited to a single kindred, merit a painstaking evaluation of cancer of all anatomical sites in other kindreds showing the FAMMM syndrome. Such studies could yield clues to cancer aetiology, pathogenesis, and control. Images Fig. 2 Fig. 3 Fig. 4

The authors quantitated T-rosette-forming cell (TRFC) and T-cell subsets (T mu, T gamma) in the peripheral blood of twenty patients with lepromatous leprosy. The results obtained in their studies are as follows: (1) They reconfirmed the low levels of TRFC in patients with lepromatous type of leprosy; (2) T-cell subsets, both T mu (helper) and T gamma (suppressor) cells, showed lower levels in all patients with lepromatous leprosy than mean values of normal healthy controls; (3) The degree of decreased levels of T mu cells (96%) was more severe than other parameters TRFC (70%) and T gamma cells (47%) in all patients with lepromatous leprosy; and (4) It may be concluded that the alteration of the T-cell subset, T mu-cells, reflects a more fundamental abnormality than TRFC aberration in demonstrating the impairment of cell-mediated immunity in patients with lepromatous leprosy.

Dihydroxyacetone (DHA) chemically induces long ultraviolet (UV) and/or visible photoprotection into the stratum corneum as demonstrated by (a) long UV protection of albino rats which were psoralen-photosensitized to black fluorescent light and (b) sunlight protection of five patients with long UV and/or visible photosensitivity. Previously, DHA treatment of skin was considered to provide no protection against UV. For clinical use, the combination of DHA and lawsone (2-hydroxy-1,4-naphthoquinone) is preferred to DHA alone, because it provides rapid, positive protection over a range extending from short UV into the visible region of sunlight.

For almost two decades we have followed a kindred with the familial, arypical, multiple-mole menlanoma (FAMMM) syndrome. We first evaluated the proband's 14-year-old daughter when she was age 5 years. We documented the evolution, both clinically and histologically, of the FAMMM phenotype in this girl for eight years.

1. 1. The enzymic techniques employed for the analysis of animal liver carbohydrate were applied to rabbit skeletal muscle, and quantitative and statistical data are presented. 2. 2. Glycogen determination based on direct analysis of neutralized KOH muscle digest is evaluated. 3. 3. A simple technique for oligoglucoside assay by analysis of deproteinized tissue homogenate is outlined. 4. 4. Glucose, oligoglucoside, and glycogen contents of rabbit muscle specimens obtained under a variety of experimental conditions are presented, and the implications of the observed changes in carbohydrate distribution are discussed briefly. 5. 5. Practical aspects of enzymic glycogen assay and its adaptability to microdetermination are discussed.

In the preceding publications in this series we have discussed the use of the Alcian Blue technic for the histochemical demonstration of acid substances in human skin (1), the correlation between results of comparison of Alcian Blue (AB) staining and the periodic acid-Schiff (PAS) reaction (2), the results of the application of these two technics to sections of normal human skin (3), and to tumors of ecerine gland origin (4), as well as to basal cell epitheliomas (5). It has been shown that these technies are useful for the demonstration of carbohydrate substances in tissue sections. They have the advantage over other histologic technic for carbohydrates in that they are relatively simple and give highly reproducible results. Furthermore, their actual chemistry is reasonably well known, in contrast to many other commonly used teehnies. To summarize, the PAS reaction is known to stain all substances containing 1—2 glycol linkages (in the main, hexoses), as well as related substituted amines, and possibly certain unsaturated lipids. Two color reactions appear in histologic sections, magenta and red (2). With the significant exception of glycogen, those substances stained magenta by PAS are positive to AB, while those substances stained red by PAS are AB negative. It is our opinion that the former are possibly made up of certain acid mueopolysaccharides and acidic mucoproteins, while the latter consist in large part of neutral mueopolysaccharides, neutral mucoproteins, and glycoproteins. On the other hand, many acidic substances, such as nuclear DNA, as well as certain acid mucopolysaccbarides, are AB positive but PAS negative.

We treated four leprosy patients with intravenous infusions of leukocytes from normal blood donors. Within the short period of 2–3 months, the patients showed remission of their clinical, histologic and bacterial findings. During the subsequent 4-month follow-up period, the patients remained in clinical remission.

A convenient enzymic method has been developed for the quantitative determination of glycogen. Using this method, we have obtained consistent, reproducible results for glycogen solutions in the concentration range of 6 to 18 μg glycogen/ml of test solution. The enzyme mixture has been shown to effect 92–96% conversion of glycogen to glucose, and shows little species differentiation between rabbit liver and human liver glycogen.

Since 1948 when Robert (1) reported serum protein patterns in several dermatoses examined with the macroelectrophoretic method of Ti-selius, there have been numerous reports dealing with serum protein changes in dermatologie disorders (2-5). After the development of paper electrophoresis serum proteins were further characterized in these diseases. It was anticipated that these methods would be of some diagnostic value in differentiating closely allied diseases when clinical and histologic data were insufficient. These expectations have not been fully realized since specific patterns have not been found for various diseases and the electrophoretic patterns have not been diagnostic (6). However, non-specific but characteristic changes of the serum protein fractions have been found in certain diseases or disease states such as acute pemphigus vulgaris (6-10). In dermatitis herpetiformis (D.H.) most authors have found minimal changes in the electrophoretic patterns of the serum proteins. Robert (1) reported electrophoretic analysis of 2 cases of D.H. which showed a slight decrease in the serum albumin and a slight increase in the alpha and beta globulin fractions, with normal total proteins. Lever et al (2) examined 5 patients with the same disease and found no significant abnormalities in any of the serum electrophoretic patterns. His reported values for total proteins were normal with the exception of mild hypoproteinemia in one case. Rochl and Jaroschka (9) described 6 cases of D.H. which showed very minor changes in the protein fractions : the alpha globulin fractions were slightly increased, especially in those cases with widespread eruptions and secondary infection; again the total proteins were normal. Haensch (4) investigated 5 patients with D.H. and found a slight increase in beta globulin but it was not consistent in all cases. He also found that the gamma globulins were slightly increased. The total serum proteins were normal. He felt that the marked protein changes in pemphigus vulgaris might be used as a diagnostic aid in the differential diagnosis of this disorder from D.H. However in mild cases of pemphigus vulgaris the protein fraction alterations were slight as Lever et al (6) had previously reported. Bonelli and Da-voto (7) studied 7 cases of pemphigus vulgaris, 8 cases of D.H., and 3 cases of herpes gesta-tionis (H.G.). They found in D.H. an increase in the alpha and gamma globulin fractions, a decrease in the concentration of albumin and normal total proteins, but they often found similar values in all 3 diseases. Pozzo and Hoffman (11) reported approximately the same findings in a series of 13 patients with D.H, 3 with H.G. and 10 patients with pemphigus vulgaris. Madras and Stoberl (10) examined 4 cases of D.H. and found a slight decrease in albumin, a slight increase in alpha-1 globulin and a pronounced increase in alpha-2 globulin. There were no significant changes in the beta and gamma globulins. They also felt as Haensch (4) and Leinbrock (8, 12) that electrophoresis could be of help in the differential diagnosis between pemphigus and dermatitis herpetiformis. Alexander (13) analyzed serum from 16 patients with the adult type of D.H. and from 17 patients who were under control by dapsone therapy. His results showed “that in adult dermatitis herpetiformis there is a significantly lower than normal level of al protein after treatment with dapsone and a level of al glycoproteins significantly below normal in active cases of this disorder, which are further lowered by treatment.

A technique for the enzymic determination of oligoglucosides in liver homogenate has been described and evaluated. Examples were cited to illustrate the utility of determining glucose and oligoglucoside contents in the investigation of in vivo and in vitro liver carbohydrate metabolism. The reliability of routine application of the analytical methods employed in this investigation was evaluated by performing repeat assays of several homogenates. Although numerous liver homogenates with high glycogen and low oligoglucoside contents have been analyzed, detectable quantities of oligoglucosides were present in each specimen.

A rabbit antiserum was prepared against a lens fraction which constituted 20% of the soluble bovine lens protein. Immunoelectrophoresis demonstrated that the antiserum formed numerous precipitin arcs against lens, none against serum, a single characteristic arc against erythrocyte hemolysate, and at least five against epidermis. The results of an immunoelectrophoretic survey of soluble cross reacting antigenic determinants between lens and other bovine organs are enumerated. Osserman immunoelectrophoretic identity reactions were conducted between epidermal antigens resolved by electrophoresis, and those of various tissues. In addition to at least two obvious identity reactions in several tissues, a tentative one is defined as a change in shape of an epidermal arc. These conclusions are supported by treatment of lens antisera with kidney and liver powders, which indicate that some of the determinants contained in the epidermis cross react with those of the two powders. The advantage of using the identity reaction, in conjunction with absorption studies, to establish the immunologic identity or nonidentity of antigens in two tissues is discussed.

An earlier report described a technique for assessing long ultraviolet (UV) phototoxicity, based on measurement of increased paw weight of psoralen-sensitized rats after exposure to black light. The procedure was modifled and employed to demonstrate that dihydroxyacetone/naphthoquinone (DHA/lawsone) protects sensitized rats against light. The observed effectiveness of DHA/lawsonein the animal model agreeswith our clinical success in protecting photosensitive patients against long UV light.

Preliminary to a study of benign appendageal tumors of the skin, the results of which will be published separately, the following study of normal apocrine and eccrine glands was undertaken. The use of the periodic acid-Schiff (PAS) and Alcian Blue (AB) stains separately on tissue sections and the clarification of the two color reactions of the PAS stain by Alcian Blue (1) has lead to a better histochemical characterization of some of the structures of normal human eccrine and apocrine glands.

This report arose out of the application of the Alcian blue staining technic to the study of epithelial and appendageal tumors. In the course of those investigations it became necessary to make a detailed study of normal skin as a baseline for interpretation of abnormal findings.

This, to authors' knowledge, is the first report in the United States of Tinea pedis caused by Trichophyton violaceum in a recent Southeast Asian immigrant. Because of the recent entry into this country of refugees from an area of the world where T. violaceum is endemic, this anthropophilic dermatophyte may become a significant cause of dermatophytosis in the United States.

Parapsoriasis with poikiloderma and transformation in mycosis fongoides Parapsoriasis poikilodermique avec transformation en mycosis fongoide

The concept of a cutaneous glucose tolerance test has been reported several times (1—4). It seems reasonable to assume that skin, like blood, can dispose of an extracellular carbohydrate load in an orderly manner. TJrbach, et at (2—4) described a cutaneous glucose tolerance technic which they used to study the ability of the skin to deal with a sudden glucose load after a fasting patient was given 100 gm of dextrose orally. If the fasting skin sugar level was above 68 mg%, the patient was considered abnormal. If the blood glucose tolerance test was normal and the skin glucose value was abnormal, the patient had "skin diabetes" or "hyperglycodermia without hyperglycemia." TJrbach's concept of a cutaneous glucose tolerance test appeared to be reasonable, but the analysis of their data was unreliable because of a number of undeterminable variables in their technic. Since the dextrose is given orally, the same variables which affect the blood glucose tolerance test also affect the cutaneous glucose tolerance test. The variables in the blood glucose tolerance test following oral ingestion of dextrose have been discussed by several authors (5—7). The major source of error is that the dextrose is introduced to the body orally. It has been shown (5, 6) that variable amounts (as much as 70%) of orally administered dextrose may remain in the stomach up to two hours after the start of the test; therefore, glucose enters the blood at an unknown rate and consequently the blood glucose levels are dependent upon this variable factor. Another undetermined variable in the oral glucose tolerance test is the effect of the liver on the glucose absorbed from the gastrointestinal tract. Scow and Cornfield (8) have shown that in rats 67% of the portal vein glucose was retained in the liver, and 33% entered the general systemic

A plastic straw and wood applicator stick serve as a simple, inexpensive, and disposable inoculation unit for fungal studies. The method gives a uniform and intact inoculum. The technique is especially useful because a large number of agar plates can be inoculated rapidly.

The familial atypical multiple mole-melanoma syndrome (FAMMM) is characterised by an autosomal dominantly inherited susceptibility to multiple atypical moles which show variable colouration ranging from black to brown, tan, red, or pink, with occasional variegation. These compound naevi may be macular or papular, with regular or irregular borders, and measure 1 cm or more in size. They may be few in number or absent or may exceed 100 in a given patient. They are located predominantly on areas not exposed to the sun. Dysplastic changes in melanocytes, fibroplasia, focal chronic inflammatory cell infiltrate, and new blood vessel formation of the papillary dermis characterise their histopathology. These findings are not uniformly present. Because of these distinctive features, coupled with their propensity for transformation to cutaneous malignant melanoma, little attention has been given to the possibility of either minimal or absent cutaneous expression of the phenotype or more diverse neoplastic involvement in this disease. These latter phenomena, which we ascribe to the pleiotropic effects of the cancer-prone FAMMM genotype, were observed in a single FAMMM kindred, the subject of this report.

Dihydroxyacetone (DHA), a browning agent, protects photosensitive rats and humans against long ultraviolet radiation (UVA, 320–400 nm) and visible (blue) light. The photoprotective efficacy of DHA and structurally similar compounds was assessed as prevention of edema in the paws of psoralen-sensitized rats, after exposure to blacklight fluorescent lamps. Methylglyoxal produced a yellow-brown color and provided nearly the same protection as DHA, whereas monohydroxyacetone did not color the skin and afforded little or no protection. Glyceraldehyde provided a moderate amount of protection, which was enhanced by prior exposure of the agent to alkaline pH. A solution of 5-hydroxymethylfurfuraldehyde was yellow and provided minimal protection by staining the skin rather than browning it. We conclude that the ability to produce a brown color in skin is a useful criterion for screening compounds for photoprotective efficacy against UVA radiation.

Genetic analysis was performed on four kindreds with clinical and pathological verification of the FAMMM syndrome. There were 80 affected or at risk members in these families. A segregation ratio of 0.47 was observed, which is consistent with an autosomal dominant mode of inheritance. Three obligate gene carriers who lacked any FAMMM phenotypic manifestations were observed and the rate of penetrance for the FAMMM gene was calculated to be 0.93. Cancer at all anatomical sites (exclusive of cutaneous malignant melanoma and intraocular malignant melanoma) showed a five-fold increase (p less than 0.004) in risk for gene carriers when age corrected and compared to the population expectation. Although there was an apparent excess of carcinoma of the lung, pancreas, and breast, the number of family members studied with specific organ cancer was too small; therefore, a larger sample size will be needed to verify this apparent excess. Our findings warrant further investigation in additional FAMMM kindreds.