bromochloroacetic-acid and Hyperpigmentation

Pigmented extramammary Paget disease (PEMPD) is a rare intraepithelial carcinoma which can clinically resemble other pigmented neoplasms. Similarities to melanoma on dermoscopy, histopathology, and reflectance confocal microscopy (RCM) increase the risk of misdiagnosis and, consequently, mismanagement. Here, we describe a case of a 67-year-old African American woman with a large, pigmented axillary patch that exhibited features of melanoma on RCM, guiding the clinician to perform an excisional biopsy. While traditional histopathology resembled melanoma, immunohistochemistry staining was performed and revealed PEMPD. We highlight an uncommon clinical presentation of PEMPD disease and identify morphologic mimickers of melanoma on RCM-as well as differentiating features.

Topics: Aged; Axilla; Biopsy; Black or African American; Dermoscopy; Diagnosis, Differential; Diagnostic Errors; Female; Humans; Hyperpigmentation; Hyperplasia; Immunohistochemistry; Keratins; Melanocytes; Melanoma; Microscopy, Confocal; Paget Disease, Extramammary

We present a case of a patient with long-standing hyperpigmented macules and erythematous papules over his chest, abdomen, back and arms, suggestive of Dowling-Degos disease (DDD). In addition, there were hyperkeratotic papules, alternating red and white nail-bed discolouration, and V-shaped nail notching consistent with Darier disease (DD). Histology showed findings consistent with DDD and DD on separate specimens. The lack of acantholysis in areas of filiform hyperpigmented rete ridges ruled out Galli-Galli disease (GGD). DDD results from mutations in the genes encoding keratin 5 (KRT5), protein O-glucosyltransferase 1 (POGLUT1) or protein O-fucosyltransferase 1 (POFUT1), while DD results from mutations in the ATP2A2 gene. Both genes are present on chromosome 12. In this case, the patient presented with features of both DDD and DD, which suggests that either a cooperating mutation or a mutation in an unrelated gene locus may underlie the findings in this patient.

Topics: Acantholysis; Acneiform Eruptions; Chromosomes, Human, Pair 12; Darier Disease; Humans; Hyperpigmentation; Keratins; Male; Middle Aged; Mutation; Nail Diseases; Pedigree; Skin Diseases, Genetic; Skin Diseases, Papulosquamous

The purpose of our study was to describe clinical and histopathological features of sixty one patients with histological diagnosis of syringoma over four year period in our dermatology clinic in Korea. Female:male ratio was 6.6:1 with onset of age during 2nd and 3rd decades in more than half of the patients in our study. The most frequently involved site was eyelids (43 cases, 70.5%) and the most common color of lesion was skin-color (30 cases, 49.2%). In 34 cases, characteristic tad-pole appearances (55.7%) were observed. Basal hyperpigmentation was observed more frequently in brown-colored lesion (p=0.005). Fibrosis was observed more frequently in erythematous lesion (p=0.033). Keratin cyst was observed less frequently in genital involved group (p=0.006). We also performed immunohistochemical stain for the presence of progesterone receptor (PR) and estrogen receptor (ER) in fifty six cases with negative results.

Topics: Adolescent; Adult; Aged; Child; Eyelids; Female; Fibrosis; Humans; Hyperpigmentation; Immunohistochemistry; Keratins; Korea; Male; Middle Aged; Receptors, Estrogen; Receptors, Progesterone; Sweat Gland Neoplasms; Syringoma; Treatment Outcome

Naegeli-Franceschetti-Jadassohn syndrome and dermatopathia pigmentosa reticularis are autosomal dominant ectodermal dysplasias characterized by the absence of dermatoglyphics, reticulate hyper pigmentation of the skin, hypohidrosis, and heat intolerance. Palmoplantar keratoderma, nail dystrophy, and enamel defects are common in Naegeli-Franceschetti-Jadassohn syndrome, whereas diffuse alopecia is only seen in dermatopathia pigmentosa reticularis. We studied a large Swiss family with Naegeli-Franceschetti-Jadassohn syndrome originally described by Naegeli in 1927 and assessed linkage to chromosome 17q, which was proposed to harbor the Naegeli-Franceschetti-Jadassohn syndrome gene. Our results considerably narrow the Naegeli-Franceschetti-Jadassohn syndrome gene region from 27 cM to 6 cM flanked by D17S933 and D17S934 with a maximum multipoint LOD score of 2.7 at marker locus D17S800. In addition, we studied a small family with dermatopathia pigmentosa reticularis, and our linkage data suggest that dermatopathia pigmentosa reticularis may map to the same chromosomal region. The Naegeli-Franceschetti-Jadassohn syndrome critical interval spans approximately 5.4 Mb and contains a minimum of 45 distinct genes. We scrutinized 13 new prime candidates in addition to five genes previously examined, established the genomic organization of 10 of these genes, and excluded all of them by mutation analysis. Moreover, we identified a cDNA (KRT24) encoding a new keratin protein that bears high similarity to the type I keratins and displays a unique expression profile. No pathogenic mutations were identified in this novel gene either, however. In summary, our results substantially refine the Naegeli-Franceschetti-Jadassohn syndrome region and will aid in identifying a gene that is critical for ontogenesis of multiple ectodermal tissues.

Topics: Amino Acid Sequence; Chromosome Mapping; Chromosomes, Human, Pair 17; DNA, Complementary; Ectodermal Dysplasia; Gene Expression; Haplotypes; Humans; Hyperpigmentation; Keratins; Keratins, Type I; Keratoderma, Palmoplantar; Lod Score; Molecular Sequence Data; Pedigree

Epidermolysis bullosa simplex with mottled pigmentation (EBS-MP) is a rare dermatologic disorder of autosomal dominant inheritance with intraepidermal blistering after minor trauma, reticular hyperpigmentation unrelated to the blistering, nail dystrophy, and mild palmoplantar keratosis. Keratin 5 and keratin 14 are known to be essential for the basal keratinocyte cytoskeleton and are defective in several forms of epidermolysis bullosa simplex. Recently, a 71C-->T transition in the keratin 5 gene (KRT5) causing a P24L substitution was identified in some patients with EBS-MP. We present a family with three affected members and a sporadic patient with EBS-MP. They exemplify clinically mild expression with intrafamilial variability and the possibility of improvement with time. In all of them, mutation analysis of the KRT5 gene showed the P24L mutation. So far, other mutations in the same or in other genes have not been reported in patients with EBS-MP.

Topics: Adult; Base Sequence; Child; DNA; DNA Mutational Analysis; Epidermis; Epidermolysis Bullosa Simplex; Female; Genes, Dominant; Humans; Hyperpigmentation; Infant; Keratins; Male; Microscopy, Electron; Point Mutation

Nevoid hyperkeratosis of the nipple and areola is a rare dermatosis with unknown etiology, (Perez-Izquierdo JM, Vilata JJ, Sanchez JL, et al. Retinoic acid treatment of nipple hyperkeratosis. Arch Dermatol 1990;126:687-688). Only 40 cases have been reported until 1997 (Alpsoy E, Yilmaz E, Aykol A. Hyperkeratosis of the nipple: report of two cases. J Dermatol 1997;24:43-45). The disease has a benign course and may only be a cosmetic problem. Different modalities have been used in the treatment of NHNA. In our case treatment with topical retinoic acid induced an acceptable response.

Topics: Administration, Cutaneous; Adult; Breast Diseases; Female; Humans; Hyperpigmentation; Keratins; Keratolytic Agents; Keratosis; Nipples; Tretinoin; Warts

We postulate that wound healing is an orderly process mediated by a programmed expression of cytokines and growth factors. We suggest that these factors are produced in a consistent sequence, in regulated quantities and eliminated when their function is complete. We report here the results of studies on several cytokines, growth factors and the intercellular adhesion molecule expressed during the healing of grafts were visible clinically around 3-5 days post-graft and were completed by 4 weeks post-graft. During the 1st 2 weeks, we observed the following. (i) K-14 keratin was prominent throughout the entire epidermis. Thereafter it was limited to basal cell layers. (ii) Langerhans cells were not detectable with anti-human CD1a antibodies during the first week of healing but were clearly detectable 2 weeks post-graft. (iii) DOPA (dihydroxy phenylalanine) positive melanocytes gradually increased with time. The epidermis 21 to 28 days post-graft clinically and histologically seemed to be morphologically intact. Interleukin-1 (IL-1) was clearly detected in some basal cells of the epidermis, especially in melanocytes and some keratinocytes during the early stage of healing. Transforming growth factor-alpha (TGF-alpha) was detected in epidermis first in melanocytes and some keratinocytes shortly after grafting and again in the late stage of healing. It was also found in some dermal cells. Its expression coincided with keratinocyte proliferation and melanocyte migration. TGF-beta was strongly expressed in the epidermis and dermis after the first week post graft. (iv) ICAM-1 was transiently expressed only at the onset of healing. We previously reported that pro-opiomelanocortin and its derivatives MSH/ ACTH are expressed strongly during the healing of human xenografts. The 4 additional molecules which are the subject of this report all are expressed in healing human skin in a predictable sequence and quantity (intensity of stain). Together these data support our hypothesis that healing is a highly regulated process mediated by numerous cytokines.

Topics: Animals; Antigens, CD1; Cytokines; Dihydroxyphenylalanine; Epidermal Growth Factor; Epidermis; Humans; Hyperpigmentation; Intercellular Adhesion Molecule-1; Interferon-gamma; Interleukin-1; Keratins; Langerhans Cells; Mice; Mice, Inbred BALB C; Mice, Nude; Mice, SCID; Skin Transplantation; Transforming Growth Factor alpha; Transforming Growth Factor beta; Transplantation, Heterologous; Tumor Necrosis Factor-alpha; Wound Healing

A new patient with CHILD syndrome (congenital hemidysplasia, ichthyosiform erythroderma, and limb defects), the thirtieth in the literature, was observed for over three years. Initially, the right-sided lesion spared the breast area. At 10 months of age the trunk lesion extended to cover the entire area of the right chest. At age 20 months the patient developed linear, bandlike, keratotic, brown-black lesions on her left thigh that subsided within six weeks, leaving a slight hyperpigmentation. This patient was studied by routine histologic methods as well as with markers of keratinization and electron microscopy. In hematoxylin and eosinstained sections, parakeratosis and orthokeratosis alternated. In some parakeratotic areas, large granular cells, and in others, ghost granular cells, were present. The latter showed basophilic cytoplasm, and palestaining or vacuolated nucleus and were seen either above the normal granular layer or without it. Although regional variations existed, basal cell-type keratins as recognized by AE1 continued to be expressed in suprabasal layers. Filaggrin- and involucrin-positive layers were expanded, particularly the latter, down to the lower prickle cell layer. Ultrastructurally, numerous lamellar or membranous structures were found in upper layers of the epidermis, both intracellulary and intercellularly. Normal cementsomes coexisted with these abnormal lamellar structures, and it was thought that the latter represent modified cementsomes because the discharge of those from the cell periphery was often detected.

Topics: Arm; Epidermis; Female; Filaggrin Proteins; Follow-Up Studies; Humans; Hyperpigmentation; Ichthyosiform Erythroderma, Congenital; Infant; Infant, Newborn; Intermediate Filament Proteins; Keratinocytes; Keratins; Keratosis; Leg; Lichenoid Eruptions; Protein Precursors; Syndrome