The 2016 International League of Dermatological Societies' revised glossary for the description of cutaneous lesions.

BACKGROUND: In order to facilitate effective communication in dermatology, a clearly defined glossary with precise descriptions is essential. The International League of Dermatological Societies' (ILDS) 'Glossary of basic dermatology lesions' was first published in 1987. A quarter of a century later, the ILDS made the decision to revise and expand this nomenclature. OBJECTIVES: Revision and expansion of an international nomenclature for the description of cutaneous lesions. METHODS: The ILDS nominated a committee on nomenclature. Based on a review of the literature and major textbooks, the committee assembled a list of terms and definitions. National member societies of the ILDS were then invited to participate in a Delphi voting exercise (two rounds for basic descriptive terms, one round for additional terms). The committee reviewed and consolidated comments and consented the final version. RESULTS: The revised and expanded version of the ILDS nomenclature includes 13 basic terms and over 100 additional descriptive terms. Forty-six and then 34 national member societies participated in the first and second voting rounds, respectively. CONCLUSIONS: A unifying nomenclature is crucial for effective communication among dermatologists and those who care for skin diseases. The next step will be a roll-out programme to national member societies of the ILDS that will include translations into languages other than English and adaptations reflecting local circumstances.

A spontaneous murine melanoma lung metastasis comprised of host x tumor hybrids.

Cells from a lung metastasis, arising from Cloudman S91 melanoma cells implanted s.c. in the tail of a BALB/c nu/nu mouse, were comprised chiefly of host x tumor hybrids. These lung metastasis cells showed: (a) 30-40% increased DNA content; (b) resistance to 10(-4) M hypoxanthine, 4 x 10(-7) M aminopterin, and 1.6 x 10(-5) M thymidine (HAT) + G418; and (c) the presence in genomic DNA of genes for both wt and albino tyrosinase, reflecting the DBA/2J (Cloudman S91) and BALB/c mouse genotypes, respectively. Individual clones of lung metastasis cells expressed enhanced pigmentation, motility, and responsiveness to MSH/IBMX, a behavior similar to that recently reported for artificially generated melanoma x macrophage fusion hybrids. These similarities suggested that the host fusion partner generating the lung metastasis hybrids might have been a macrophage, although formal proof for this was not possible. The results provide the first direct evidence that host x tumor hybridization could serve as an initiating mechanism for melanoma metastasis.

Role of computed tomography in the staging of primary melanoma.

PURPOSE: To evaluate the role of body computed tomography (CT) for the staging of patients with early melanoma. PATIENTS AND METHODS: A total of 151 new patients with American Joint Committee (AJC) clinical stage I, II, and III melanoma who received a CT scan of at least the chest and abdomen are the subject of this study. CT scans considered suspicious for metastases were reviewed again by one of the investigators (A.McB.C.). RESULTS: Of 151 patients, 63 had AJC clinical stage I, 61 stage II, and 23 stage III disease. In addition, one patient each had primary melanoma of the anal canal, esophagus, or vulva. Twenty-nine (19%) of 151 patients had a CT scan that was considered suspicious for metastases. The most common radiologic findings were single hepatic, and single or multiple pulmonary nodules. Of these 29 patients with suspicious scans, 24 subsequently proved to have benign processes by biopsy or follow-up studies, three had second primary tumors (well-differentiated lymphocytic lymphoma, Hodgkin's disease, and renal cell carcinoma), and only two were found to have metastatic melanoma. Of these two patients, one had regional nodal disease (unsuspected on physical examination) and one had distant nodal metastases. CONCLUSION: Body CT is not a useful imaging study in the detection of occult metastases in patients with primary melanoma. Although body CT commonly shows suspicious radiologic abnormalities in patients with early melanoma, these abnormalities most likely represent benign processes or a second primary tumor, rather than metastatic melanoma. The value of body CT in patients who present with nodal metastases needs further study.

Bazex syndrome (acrokeratosis paraneoplastica). An analytic review.

Bazex syndrome (acrokeratosis paraneoplastica) is characterized by a psoriasiform eruption that favors acral sites and has been associated with an underlying malignancy in all reported cases. Of the 93 patients in this series, 89 were male with a mean age of 60 +/- 8.5 years. Squamous cell carcinomas of the head and neck and squamous cell tumors of unknown primary with cervical lymph node metastases were the most commonly associated neoplasms, suggesting that the factor(s) responsible for the development of the syndrome are relatively specific for tumors of the upper aerodigestive tract. The cutaneous lesions were erythematous to violaceous in color and had associated scale; the most frequently observed sites of involvement were the ears, nose, hands, and feet, including the nails. In 63% of the cases, the cutaneous lesions preceded the initial symptoms or diagnosis of the tumor by an average of 11 months (range, 1-72) and, in general, the eruption was resistant to a variety of topical treatments. Occasionally, a reappearance of the papulosquamous lesions signaled the recurrence of the tumor (6 cases) or the appearance of skin lesions coincided with the development of metastatic disease (3 cases). In 91% (64/70) of the patients, the skin eruption either improved significantly following treatment of the underlying malignancy or did not improve in the setting of persistent tumor. However, even when all of the skin lesions cleared, the nail dystrophy often persisted. Fifteen of the patients developed vesicles, bullae, and crusts in addition to papulosquamous lesions. Possible explanations include the formation of an epidermal-dermal split via a bullous lichen planus-like mechanism, or the coexistence of two diseases; i.e., acrokeratosis paraneoplastica plus either porphyria cutanea tarda, bullous pemphigoid, or epidermolysis bullosa acquisita. One possible explanation for the development of the characteristic cutaneous eruption is an immune reaction, humoral or cellular, directed against a common antigen present on the tumor and the normal skin. Alternatively, tumor production of a keratinocyte growth factor such as TGF-alpha may be involved in the induction of the psoriasiform skin lesions.

Aging skin.

Aging of the skin is a composite of actinic damage, chronologic aging, and hormonal influences. The majority of changes associated with aging, such as wrinkles and solar lentigines ("liver spots"), are due to photoaging and reflect cumulative sun exposure as well as skin pigmentation. Classically, chronologic aging includes those cutaneous changes that occur in non-sun-exposed areas, such as the buttocks, and are observed in both men and women. A clinical example would be soft tissue sagging due to elastic fiber degeneration. In women, investigations into the effect of hormones on aging of the skin have concentrated on estrogens; in men, there have been a limited number of studies on the influence of testosterone. The latter have shown an age-dependent decrease in tissue androgens in pubic skin, but not scrotal or thigh skin. To date, age has not been shown to have an effect on androgen receptor binding, although a decrease in foreskin 5 alpha-reductase activity with increasing age has been described. In fibroblast cultures from foreskins, there have been conflicting results as to whether 5 alpha-reductase activity decreases in an age-dependent manner. Some of the skin changes that have been categorized as secondary to chronologic aging, such as decreased sebaceous gland activity and decreased hair growth, may actually represent a decline in the concentration of tissue androgens with increasing age. The influence of androgens on age-related changes in keratinocyte and fibroblast function remains speculative.

Cutaneous malignant melanoma and atypical moles associated with a constitutional rearrangement of chromosomes 5 and 9.

Hereditary cutaneous malignant melanoma (HCMM) with or without atypical moles has been described in several large kindreds worldwide. Despite numerous studies of these kindreds, the gene or genes responsible for this disorder has not yet been identified. Cytogenetic and molecular studies of melanoma tumor tissue and cell lines suggest that a gene involved in the pathogenesis of malignant melanoma lies on chromosome 9p. We describe a woman with atypical moles and multiple primary melanomas, who lacks a family history of HCMM, and, has a de novo constitutional unbalanced reciprocal translocation involving the short arms of chromosomes 5 and 9 with a cytogenetically visible deletion of 5p or 9p: [46,XX,-5,-9, +der(5)t(5;9) (p13.3 or 14.2;p13.3 or 21.2), +der(9)t(5;9)]. This finding supports the hypothesis that a gene predisposing to HCMM lies on the short arm of chromosome 9.

Reticulated black solar lentigo ('ink spot' lentigo).

BACKGROUND AND DESIGN: Pigmented lesions that are black and have an irregular outline are often considered suspicious for melanoma; however, these features may be seen in benign lesions. The reticulated black solar lentigo is such a lesion and is described in a clinicopathologic study of nine lesions in eight patients. RESULTS: The "ink spot" lentigo is distinguished clinically by its color and wiry or beaded, markedly irregular outline. It has a reticulated pattern and most resembles a spot of ink on the skin. In this series of patients, the lesions were limited to sun-exposed areas of the body and had a distribution pattern similar to that of solar lentigines. Although all the patients were of Celtic ancestry and had numerous solar lentigines, they usually had only one black lentigo (range, one to four; mean, 1.6; median, one). Histologic evaluation, including electron microscopy and dopa-incubated vertical sections, demonstrated lentiginous hyperplasia of the epidermis, marked hyperpigmentation of the basal layer with "skip" areas that involved the rete ridges, and a minimal increase in the number of melanocytes. CONCLUSIONS: Because of their dark color, irregular border, and limited number, reticulated black solar lentigines were of concern to patients and primary care physicians. However, the characteristic features of these lesions allow one to make the clinical diagnosis of a benign lentigo.

The impact of managed care on graduate medical education and academic medical centers.

The goal of this article is to examine the present and future impact of managed care on graduate medical education (GME) and academic medical centers. Obviously, the later 2 entities are closely intertwined and will share in the consequences of changes in our medical care systems. However, there are differences in the funding of medical schools as compared with GME provided by teaching hospitals, and an appreciation of the vital issues and concerns requires that each be discussed separately.

The melanocortin-1 receptor: red hair and beyond.

Although human pigmentation is genetically complex, to date polymorphism at only 1 locus, the melanocortin-1 receptor (MC1-R), has been associated with physiologic variation in hair and skin color. The MC1-R, a G protein-coupled receptor with 7 transmembrane-spanning domains, plays a key role in determining the type of melanin (eumelanin vs pheomelanin) that is produced within melanocytes. This article begins with an overview of melanocortin receptors, proopiomelanocortin-derived ligands, and the agouti antagonist, with particular focus on their functions in regulating eumelanin and pheomelanin synthesis, including UV-induced melanogenesis. A brief description of mouse-coat-color genetics is then followed by a discussion of human MC1-R variants, which are present in approximately 50% of white populations. We review the increasing evidence that loss-of-function MC1-R mutations largely account for the red hair phenotype in humans (which approximates an autosomal recessive trait) and also have a strong association with fair skin and a decreased ability to tan, with a significant heterozygote effect in individuals without red hair. Finally, we examine recent work showing that loss-of-function MC1-R variants may increase the risk of developing melanoma and nonmelanoma skin cancer beyond their effects on pigmentation phenotype.

Perifollicular hypopigmentation. A cause of variegate pigmentation and irregular border in melanocytic nevi.

BACKGROUND AND DESIGN: Clinical and histologic features of perifollicular hypopigmentation within melanocytic nevi are described. RESULTS: Perifollicular hypopigmentation was observed in congenital and acquired melanocytic nevi. When the area of hypopigmentation was found within the nevus, it was circular. When the hypopigmentation was located at the edge of the nevus, however, it formed a half circle that resulted in a notch in the outline of the lesion. The phenomenon occurred in nevi with terminal hairs as well as nevi with vellus hairs. In biopsy specimens from 15 melanocytic nevi, one or more of the following findings were observed around hair follicles when compared with the remainder of the nevus: decrease in the number of junctional melanocytes as nests and solitary units (n = 12), decrease in pigment within keratinocytes (n = 14), decrease in the number of melanocytes in the papillary dermis (n = 6), and decrease in the number of melanophages (n = 6). CONCLUSIONS: Perifollicular hypopigmentation is a cause of variegate pigmentation and irregular border in melanocytic nevi.

The significance of eccentric foci of hyperpigmentation ('small dark dots') within melanocytic nevi. Analysis of 59 cases.

BACKGROUND AND DESIGN: Fifty-nine melanocytic nevi with eccentric foci of hyperpigmentation ("small dark dots") that measured primarily 1 to 2 mm in diameter were prospectively examined to determine the histologic correlates of the dark dots. RESULTS: Forty-one (69%) of the dark dots were due to increased melanin in epidermal melanocytes and/or keratinocytes, usually accompanied by melanophages; of these 41, six (15%) were associated with slight or moderate melanocytic nuclear atypia. Fifteen (25%) of the dark dots were due to increased dermal pigment that was either superficial or deep. Three (5%) of the dark dots were due to melanoma arising within a nevus. CONCLUSIONS: A small percentage of "small dark dots" within melanocytic nevi are due to melanoma. Biopsy specimens of nevi with small dark dots should be sectioned to ensure histologic examination of this focus of hyperpigmentation.

Unilateral cutaneous emboli of Aspergillus.

A 40-year-old white woman with acute nonlymphocytic leukemia, which relapsed despite bone marrow transplantation and various chemotherapeutic regimens, developed fever and neutropenia. Her fever was unresponsive to broad-spectrum antibiotics, and on hospital day 53 she developed purpuric macules with necrotic centers on her left hand and forearm. Frozen sections of lesional skin were stained with Grocott's methenamine-silver and showed hyphae consistent with a species of Aspergillus; culture of the skin biopsy specimen yielded a pure culture of Aspergillus flavus. Localization of the emboli to the left upper extremity was subsequently explained by magnetic resonance imaging scan of the chest demonstrating invasion of the left subclavian artery by a pulmonary aspergilloma.

Speckled lentiginous nevus: within the spectrum of congenital melanocytic nevi.

BACKGROUND: Currently, there is disagreement as to whether speckled lentiginous nevi (nevi spili) are congenital or acquired pigmented lesions. Part of this controversy is related to the natural history of these lesions that often present at birth as hyperpigmented patches and then take several years to reach their more readily recognized spotted form. Arguments in favor of speckled lentiginous nevi as a subtype of congenital nevi include the following observations: multiple reports of lesions present at birth or noted soon thereafter; patterns of distribution reflecting embryonic development; hamartomatous behavior with various types of nevi (eg, junctional nevi, blue nevi, and Spitz nevi) presenting in the same lesion over time; and histologic features of congenital melanocytic nevi within the spots. Herein we present additional evidence for the congenital nature of speckled lentiginous nevi. OBSERVATIONS: Ten patients are described with congenital pigmented lesions that had the clinical appearance of speckled lentiginous nevi in whole or in part. These lesions either evolved and acquired an appearance more suggestive of "classic" congenital nevi, or they existed as "hybrid" lesions with portions appearing as classic congenital nevi adjacent to or admixed with portions appearing as speckled lentiginous nevi. On histologic examination, biopsy specimens from the spots within these lesions showed features of congenital melanocytic nevi. CONCLUSIONS: These 10 cases, along with the arguments outlined above, provide strong support for the hypothesis that speckled lentiginous nevi are a subtype of congenital melanocytic nevi.

Figurate and bullous eruption in association with breast carcinoma.

We describe a patient with two coexistent cutaneous eruptions: (1) trauma-induced bullae of the distal extremities and elbows and (2) multiple concentric gyrate lesions on the trunk and extremities, some of which became bullous. The gyrate lesions were stationary and nonpruritic. Biopsy of both types of lesions showed a subepidermal blister and a minimal inflammatory infiltrate. Direct immunofluorescence revealed linear deposition of IgG and C3 at the dermoepidermal junction and indirect immunofluorescence was negative. By immunoelectron microscopy, these immune deposits were localized to the lower lamina lucida. The eruption was not controlled despite high-dose (80 mg/d) oral administration of prednisone and required the addition of an oral administration of methotrexate (20 mg weekly). On further evaluation, an intraductal mammary carcinoma was detected. Following radiation therapy, the methotrexate and prednisone therapy were tapered without recurrence of the eruption during a follow-up period of 18 months.

Phakomatosis pigmentovascularis type IIb with iris mammillations.

BACKGROUND: Phakomatosis pigmentovascularis type IIb is a syndrome in which extensive nevus flammeus is associated with persistent aberrant mongolian spots. Herein, we describe a patient with phakomatosis pigmentovascularis who had numerous iris mammillations that were initially mistaken for the Lisch nodules of neurofibromatosis type I. OBSERVATIONS: A 5-year-old girl with phakomatosis pigmentovascularis type IIb was found to have bilateral melanosis oculi and numerous iris mammillations. The mammillations differed from Lisch nodules in their smaller size, stellate shape, darker color, increased number, and more regular distribution. Similar iris mammillations have been described in patients with melanosis oculi accompanying nevus of Ota. CONCLUSIONS: Patients with phakomatosis pigmentovascularis can present with the clinical manifestations of one or more of the following: Sturge-Weber syndrome, Klippel-Trenaunay syndrome, and melanosis oculi; our patient had clinical features of all three of these entities. In addition, the presence of iris mammillations in this patient can be explained by their known association with melanosis oculi.

Clinicopathologic findings in the Bannayan-Riley-Ruvalcaba syndrome.

BACKGROUND: The term Bannayan-Riley-Ruvalcaba syndrome has been proposed to reflect the clinical overlap of 3 conditions previously described as separate entities, each inherited in an autosomal dominant fashion. They are the Riley-Smith, Bannayan-Zonana, and Ruvalcaba-Myhre-Smith syndromes. OBSERVATIONS: We studied 2 kindreds with the Bannayan-Riley-Ruvalcaba syndrome. Characteristic cutaneous findings included multiple subcutaneous lipomas and vascular malformations, lentigines of the penis and vulva, verrucae, and acanthosis nigricans. Macrocephaly with normal ventricular size, mental retardation, central nervous system vascular malformations, intestinal polyposis, skeletal abnormalities, and thyroid tumors were the most common systemic featues. A striking clinical finding in 1 patient was widespread verrucous changes of both lips that histologically showed epidermal hyperplasia with papillomatosis and hyperkeratosis. Biopsy specimens of facial papules demonstrated the histological features of both syringomas and trichilemmomas. Lentiginous hyperplasia of the epidermis with increased pigment in the basal layer and a slight increase in the number of melanocytes were seen in biopsy specimens of the penile lentigines. CONCLUSIONS: The histologic findings of both the facial lesions and the pigmented macules of the penis in the Bannayan-Riley-Ruvalcaba syndrome have not, to our knowledge, been reported previously. The similarities between the Bannayan-Riley-Ruvalcaba syndrome and Cowden disease raise the possibility of a common genetic pathogenesis for these 2 diseases.

Periodic acid-Schiff-positive organisms in primary cutaneous Bacillus cereus infection. Case report and an investigation of the periodic acid-Schiff staining properties of bacteria.

Primary cutaneous Bacillus cereus infection frequently presents as a single necrotic bulla on the extremity of an immunocompromised patient. In lesional biopsy specimens and smears, the large gram-positive rods of B cereus may be mistaken for Clostridium species. This is a potentially serious error, as Bacillus species are resistant to penicillin and other beta-lactam antibiotics. We studied a case in which large periodic acid-Schiff-staining organisms were seen in the biopsy specimen from a necrotic bulla on the finger of a neutropenic patient with diffuse large cell lymphoma. The tissue biopsy specimen subsequently yielded a pure culture of B cereus. Staining with periodic acid-Schiff was then performed on a series of bacterial species in human tissue and from smears of culture colonies. The following bacterial species were found to be consistently periodic acid-Schiff positive after diastase digestion: B cereus, Corynebacterium diphtheriae, Propionibacterium acnes, Klebsiella pneumoniae, and Micrococcus luteus.

Skin changes in menopause.

Skin signs and symptoms were examined in 46 menopausal women prior to estrogen replacement therapy. Several symptoms such as pruritus, bruising, dryness and thinning were seen more frequently in sun-exposed skin emphasizing the contribution of photoaging. At the end of a 6-mth treatment period, no significant difference was observed in the prevalence or severity of the cutaneous signs and symptoms when patients receiving transdermal 17 beta-estradiol (Estraderm) were compared with controls (the only exception was cutaneous flushing). Elastic fibers from sun-protected (buttock) skin of menopausal women were studied by light and electron microscopy. In 3 women (ages 30-37) with a history of premature menopause, the elastic fibers had several degenerative changes including coalescence of cystic spaces into lacunae, peripheral fragmentation, granular degeneration and splitting of the fibers into strands. Similar age-related ultrastructural changes are normally found in individuals that are at least 20 yrs older than these patients. These findings are suggestive of a relationship between premature aging of the dermal elastic fibers and estrogen deprivation.

Ocular manifestations of pigmentary disorders.

Disorders of pigmentation can result from either an abnormal number of melanocytes, as in nevus of Ota and vitiligo, or an abnormal amount of melanin production, as in albinism. Melanin-producing cells are found in the skin, mucous membranes, uveal tract, and retinal pigment epithelium of the eye and the stria vascularis of the inner ear. Thus, many of the hereditary or congenital pigmentary disorders of the skin are associated with similar pigmentary abnormalities in the eye, such as iris heterochromia or changes in pigmentation of the fundus; however, more commonly, the associated eye finding is a defect in ocular motility, i.e., strabismus and nystagmus, suggesting a concomitant defect in neurologic development. In albinos, the observed neurologic abnormality in the visual pathway and foveal hypoplasia are hypothesized to be related directly to the lack of melanin in the pigment epithelium during development. In acquired disorders of pigmentation, in particular, vitiligo, Vogt-Koyanagi-Harada syndrome, and onchocerciasis, there is a frequent association with uveitis, suggesting an inflammatory cause for the cutaneous pigmentary changes.

Disorders of hypopigmentation in children.

The most common disorders of hypopigmentation in children are pityriasis alba, vitiligo, nevus depigmentosus, and tinea versicolor. Pityriasis alba usually presents as ill defined, scaly patches of hypomelanosis on the cheeks of children with an atopic diathesis. The face is also a favored site for vitiligo, but the distribution is periorificial, and the pigment loss is complete because of a destruction of melanocytes. Vitiligo is an acquired, progressive disorder in contrast to nevus depigmentosus, which is a stable, congenital leukoderma. The localized form of nevus depigmentosus must be distinguished from an ash leaf spot, the earliest cutaneous manifestation of tuberous sclerosis, whereas the systematized form may be confused with hypomelanosis of Ito, another neurocutaneous disorder. The lesions of tinea versicolor favor the upper trunk of adolescents, and potassium hydroxide examination of the associated scale reveals hyphal and yeast forms of P. orbiculare. Any inflammatory process in the skin such as dermatitis or psoriasis can resolve with areas of hypopigmentation.