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PubMed1984

Keratosis punctata palmaris et plantaris and adenocarcinoma of the colon. A possible familial association of punctate keratoderma and gastrointestinal malignancy.

We report a patient with keratosis punctata palmaris et plantaris who developed adenocarcinoma of the colon. Family history revealed at least seven other individuals with punctate keratoderma. The patient's mother had punctate keratoderma and carcinoma of the colon, and his maternal grandfather had punctate keratoderma and carcinoma of the pancreas. This is the third reported family, to our knowledge, in which hereditary palmar and plantar hyperkeratosis appears to be associated with gastrointestinal carcinomas.

Adenocarcinoma↗
PubMed1994

Genetic linkage evaluation of twenty-four loci in an eastern Canadian family segregating Darier's disease (keratosis follicularis).

BACKGROUND: Darier's disease (keratosis follicularis) is known to have a genetic cause as evidenced by its autosomal dominant transmission in families. The gene causing this disease has not been discovered. OBJECTIVE: During an ongoing linkage study of schizophrenia, a family segregating Darier's disease was found. This family is being studied in an attempt to locate prospective regions that may contain the Darier's disease gene. METHODS: Two genetic strategies are being employed: (1) testing candidate genes for the disorder and (2) scanning the entire genome with polymerase chain reaction-based microsatellite markers. RESULTS: Thirty-nine marker systems located on chromosomes 1, 2, 4, 5, 6, 9, 11, 12, 16, 17, 22, X, and Y have been genotyped. Slightly positive lod scores were achieved between six markers and Darier's disease. The remaining 33 markers were nonsegregating or indeterminate, or revealed an obligate recombinant. CONCLUSION: Linkage analysis can lead to localization of the gene causing Darier's disease. In these preliminary studies low positive lod scores were obtained, potentially pointing to the chromosomal location of the Darier's disease gene.

Chromosome Mapping↗
PubMed1998

Immunohistochemical staining for desmogleins 1 and 2 in keratinocytic neoplasms with squamous phenotype: actinic keratosis, keratoacanthoma and squamous cell carcinoma of the skin.

Desmosomes are intercellular junctions that have been shown to be down-regulated in certain types of carcinoma and that may play a role in suppression of invasion and metastasis. This paper describes an immunohistochemical study of three types of epidermal neoplasms with monoclonal antibody to desmoglein in order to determine how desmosomal staining correlates with the clinical, biological and histopathological features of these neoplasms. Actinic keratosis (AK) is the most common keratinocytic premalignant neoplasm that was reported to have a 10-20% rate of malignant transformation into squamous cell carcinoma (SCC). Keratoacanthoma (KA) is a benign neoplasm that involutes spontaneously after a few months of rapid growth. SCC is a malignant tumour capable of metastasis. Electron microscope studies of KA and SCC showed significantly reduced staining for desmosomes in SCC but not in KA. We have examined staining for desmoglein using the monoclonal antibody 33-3D, a mouse IgM monoclonal antibody, that recognizes the cytoplasmic domains of desmoglein (Dsg)1 and Dsg2 on frozen sections. Immunohistochemical staining of normal skin with this antibody revealed strong pericellular localization of the antigen, outlining the cell membranes of the keratinocytes. A series of 30 AKs, 12 KAs and 24 SCCs was stained immunohistochemically with 33-3D monoclonal antibody. All examined KAs showed extensive pericellular staining for Dsg. By contrast, juxtanuclear staining for Dsg was noted in 12 SCCs, and completely negative staining in seven SCCs. The five remaining SCCs showed focal pericellular staining for the Dsg marker. The most common finding in AK was focal pericellular staining for Dsg, with complete absence of staining in dysplastic areas (25 cases). In five cases negative pericellular staining in dysplastic areas was associated with juxtanuclear accumulation of the Dsg marker. A strong negative correlation between Dsg staining and degree of dysplasia was obtained. The Dsg pattern in KA is similar to normal epidermis and shows a clear difference between KA and SCC. AK has a limited loss of Dsg expression in a SCC-like pattern that is congruent with its premalignant nature. As the stain works on frozen tissue, it may be helpful for rapid differentiation in selected cases in cutaneous oncology and Mohs micrographic surgery. This antibody may also have great potential for the detection of the effects of chemopreventive agents in skin cancer.

Animals↗
PubMed1993

Identification of the genetic locus for keratosis palmaris et plantaris on chromosome 17 near the RARA and keratin type I genes.

Familial keratosis palmaris et plantaris (KPPF) is characterized by extreme keratinization and desquamation of the skin of the palmar and plantar surfaces of the hands and feet. We have mapped the causative genetic defect to an 8 cM interval on 17q12-24 in or close to the acidic keratin (type I) gene cluster. We show that KPPF co-segregates with a rare, high molecular weight allele of an insertion-deletion polymorphism in the C-terminal coding region of the keratin 10 gene (Z = 8.36 at theta = 0.00) and segrates as a true autosomal dominant trait. Some pedigrees with familial hyperkeratosis of the palms and soles have co-inherited diseases such as congenital malformations and familial cancers. Our analysis provide a region which should be investigated for contiguous gene syndromes in such pedigrees.

Base Sequence↗
PubMed2001

Nitric oxide and endothelin-1,2 in actinic keratosis and basal cell carcinoma: changes in nitric oxide/endothelin ratio.

BACKGROUND: Nitric oxide (NO) is an inorganic free radical gas which has cytostatic/cytotoxic actions in tumoral tissues, including gynecologic, breast, and colon cancer. Nitric oxide is also a multifunctional signaling molecule active in many cells of the body, including endothelial cells, macrophages, monocytes, hepatocytes, mast cells, osteoblasts, and astrocytes. Endothelin-1 (ET-1) is a 21-amino acid peptide that stimulates the proliferation of vascular smooth muscle cells, fibroblasts, and keratinocytes, and plays a role in the expression of proto-oncogenes (c-myc, c-fos), which precedes cell proliferation. Similar to NO, ET is secreted by different cell types, including macrophages, monocytes, hepatocytes, endothelial cells, vascular smooth muscle cells, and various tumor cells. Elevated ET-1 levels are observed in pulmonary, hepatocellular, and prostate cancers. Actinic keratosis (AK) and basal cell carcinoma (BCC) are common skin tumors with accentuated hyperkeratinization, hyperpigmentation, and keratinocyte proliferation. AIM: To investigate plasma NOx (nitrite/nitrate -- the end products of NO metabolism), ET, and the NOx/ET ratio in patients with AK and BCC in comparison with healthy controls. METHODS: NOx, ET, and the NOx/ET ratio were measured in 13 patients with AK, 12 patients with BCC, and in 16 healthy controls. RESULTS: Data analysis indicated a significant increase in plasma NOx, ET, and NOx/ET values in BCC patients in comparison with controls (P < 0.001, P < 0.05 and P < 0.001, respectively). Plasma ET levels in AK were also increased in comparison with controls (P < 0.001). When the two study groups (AK and BCC) were compared, a significant increase (P < 0.001) in the NOx/ET ratio in BCC was found. CONCLUSIONS: The increased plasma ET and NOx levels in AK and, especially, BCC are probably the result of and/or reason for the accentuated hyperkeratinization, hyperpigmentation, and keratinocyte proliferation. The increased production of ET and NO by keratinocytes may function as growth and cytotoxic factors and potential mitogens, and may accelerate further proliferation of these skin tumors. In addition, the increased NOx/ET ratio probably reflects a disturbed equilibrium between these two substances, leading to cell damage and tumor promotion and proliferation.

Adult↗
PubMed2002

Keratosis pilaris atrophicans in mother and daughter.

We report two cases of keratosis follicularis spinulosa decalvans in a Caucasian family involving a 28-year-old woman and her mother. This is an unusual family in that no male relatives are similarly affected. Secondly, both patients have no significant eye changes but quite extensive scarring alopecia. To the best of our knowledge this is the second reported family in the UK.

Adult↗
PubMed2000

Ber-EP4-positive phenotype differentiates actinic keratosis from superficial basal cell carcinoma.

BACKGROUND: Well-defined histopathologic criteria exist to distinguish actinic keratosis (AK) from superficial basal cell carcinoma (BCC). A similar morphology of downwardly budding dysplastic keratinocytes may occur in both entities, creating potential for errors in diagnosis. A marker that could reliably distinguish these two lesions would overcome this difficulty in diagnosis. OBJECTIVE: To investigate whether Ber-EP4 staining is useful in distinguishing AK from superficial BCC, and to determine whether AK exhibits a cellular phenotype that is more consistent with BCC or squamous cell carcinoma (SCC). METHODS: We subjected tissue sections from superficial BCC, AK, and squamous intraepithelial neoplasia (SIN) demonstrating epidermal budding to immunohistochemical staining with monoclonal antibody Ber-EP4. RESULTS: Abnormal keratinocytes in all specimens of superficial BCC (5 of 5) were Ber-EP4 positive; all AK (10 of 10) and SIN (8 of 8) were Ber-EP4 negative. CONCLUSION: Ber-EP4 staining reliably distinguishes AK from superficial BCC. The lack of Ber-EP4 staining of AK supports the currently accepted pathogenetic dogma that SIN and SCC arise from AK, but BCC does not.

Antibodies, Monoclonal↗
PubMedDate not supplied

Cole disease: hypopigmentation with punctate keratosis of the palms and soles.

Cole disease is an uncommon disorder characterized by distinctive cutaneous hypopigmentation and punctate keratosis of the palms and soles. It is a congenital skin disease with an autosomal dominant inheritance pattern. We report two patients from a family with 15 members, 5 of whom were affected. One of the patients had both types of lesions since birth, while in the other they arose in the first months of life. We studied the pedigree, histopathology, immunohistochemistry, and electron microscopy findings of the hypopigmented macules with the patients' normal skin used as a control. The pedigree showed involvement of both genders, with a Mendelian autosomal dominant inheritance pattern with phenotypic variability in the family. Immunohistochemistry showed a reduction in the melanin pigment in the keratinocytes and normal pigmentation in the melanocytes. Ultrastructural studies showed a strong contrast between the large number of melanosomes in the body and dendrites of the melanocytes, in contrast with the small number of these organelles in the neighboring keratinocytes. These findings suggest that this disease is a primary congenital disorder of the transfer mechanisms of the melanosomes from melanocytes to keratinocytes in hypopigmented lesions, associated with abnormal epidermopoiesis in the punctate hyperkeratosis.

Biopsy, Needle↗
PubMedDate not supplied

Papular palmoplantar hyperkeratosis following chronic medical exposure to arsenic: human papillomavirus as a co-factor in the pathogenesis of arsenical keratosis?

This study presents the case of a 38-year-old patient from Pakistan with vitiligo, who developed multiple verrucous papules on the palms and soles several years after receiving "herbal treatment" from a travelling Indian doctor for a period of 12 months. Histopathological examination showed changes consistent with the diagnosis of arsenical keratosis. Molecularbiological examination of a skin biopsy detected an atypical human papillomavirus. This observation supports the concept of human papillomavirus as a co-factor in the pathogenesis of premalignant arsenic-induced skin tumours.

Adult↗
PubMed2004

Differentiation of hidroacanthoma simplex from clonal seborrheic keratosis--an immunohistochemical study.

Hidroacanthoma simplex (HS) is an uncommon poroid neoplasm confined within the epidermis. The clinical features of HS are not distinctive and histopathologically HS may be confused with clonal seborrheic keratosis (CSK) if cystic or ductal structure is not present. The purpose of our study was to differentiate HS from CSK by the immunohistochemical expressions of various cytokeratins, CEA, CD1a, and S-100 protein, as well as by the degrees of deposition of melanins and glycogen. Four cases of HS and seven cases of CSK were included in the research. In contrast with CSK, HS showed a very low density of Langerhans cells (19.9 +/- 7.7 versus 3.1 +/- 1.0 CD1a (+) cells/mm, P = 0.027) and sparse melanin deposition in the nests. However, HS could not be set apart from CSK by the expressions of cytokeratins. The nests of both HS and CSK showed very similar patterns of cytokeratin expression and seemed to be mainly composed of basaloid cells with focal differentiation toward epidermal suprabasal cells.

Acrospiroma↗
PubMed1994

Oral minocycline improved keratosis follicularis squamosa (Dohi) and related disorder: bacterial factors are possibly involved in abberant keratinization.

Three cases of keratosis follicularis squamosa (Dohi) and one case of papillomatose confluente et reticulee were successfully treated with oral minocycline (50-100 mg/day). The clinical effect first appeared at 2 weeks after the initiation of therapy and no recurrence was observed for more than 3 months without minocycline. Gram positive cocci were demonstrated inside the hair follicle and horny layers in all 4 case. Minocycline might modulate abberant keratinization through its bactericidal effects in these keratinizing disorders.

Administration, Oral↗
PubMedDate not supplied

Erythromelanosis follicularis faciei et colli associated with keratosis pilaris in two brothers.

Erythromelanosis follicularis faciei et colli is characterized by well-demarcated erythema, hyperpigmentation, and follicular papules. Since the original description, it has seldom been reported in the literature. We present two adolescent brothers who had this disorder associated with keratosis pilaris on the shoulders and the extensor surfaces of the arms. Dermatologic examination found brown-red pigmentation, erythema, and follicular papules on both maxillary, preauricular regions, and the cheeks. The lesions of the older brother were more prominent. Histopathologic examination of skin biopsy specimens taken from both brothers revealed hyperpigmentation of the basal layer, follicular plugging, dermal vascular dilatation and congestion, and perivascular inflammatory infiltration. We suggest that the coexistence of these two conditions in brothers implies a genetic inheritance and a possible relationship between the disorders.

Adolescent↗
PubMed1981

Darier's keratosis follicularis: an ultrastructural study during and after topical treatment with retinoic acid alone or in combination with 5-fluorouracil.

An ointment containing 0.05% retinoic acid (RA) was applied to the anterior surface of the chest in a patient suffering from Darier's keratosis follicularis. A mixture of two ointments containing equal amounts of 5% 5-fluorouracil (5-FU) and 0.05% RA was used on the dorsum of the same patient. Biopsies were taken 30 days and 70 days after treatment started. Retinoic acid gave rise to an initial disorganisation of desmosomes; the "corps ronds" and "grains" disappeared, the lacunae gradually decreased in size, and the epidermis was practically normal when the clinical manifestations of the skin had disappeared. The damage induced with the RA + 5-FU mixture was more serious, but when the skin lesions relapsed they did so later and in a less severe way than the recurrences observed after treatment with RA alone.

Darier Disease↗
PubMed1987

Mast cells containing melanin granules in sublingual keratosis.

In an ultrastructural study of 3 biopsies taken from the floor of the mouth of 2 patients suffering from sublingual keratosis, it was found that some of the mast cells appearing within the epithelium and connective tissue contained melanin granules which were found to be positive with Masson Fontana stain for melanin. These cells showed all the characteristic features of mast cells and not macrophages. The present results suggest that mast cells have phagocytosed melanin granules and therefore support those views suggesting that mast cells are capable of phagocytosis. They also suggest that not all the cells containing melanin granules and appearing in the lamina propria are the conventional melanophages but some of these may be mast cells.

Adult↗
PubMed1975

Inverted follicular keratosis.

Attention is drawn to a benign skin tumour which has escaped recognition in the British lieterautre. Inverted folliculr keratosis can be mistaken clinically for basal cell carcinoma and a variety of benign skin lesions. Pathologically it is easliy confused with squamous carcinoma, a serious error because this lesion occurs dominantly on the face. The lesion is thought to arise from the infundibulum of hair follicte.

Adult↗
PubMed1992

Keratosis follicularis spinulosa decalvans: a family study of seven male cases and six female carriers.

Keratosis follicularis spinulosa decalvans (KFSD) is a rare X linked disease which is characterised by follicular hyperkeratosis of the skin and corneal dystrophy. Seven male patients and six female carriers are described. Special attention has been paid to the dermatological and ophthalmic markers of KFSD in patients and carriers. The most prominent features present in the male patients were follicular hyperkeratosis, hyperkeratosis of the calcaneal regions of the soles, scarring alopecia of the scalp, absence of eyebrows and eyelashes, and corneal dystrophy accompanied by photophobia. They also had high cuticles on the fingernails which has not been described before. Carriers often have dry skin, minimal follicular hyperkeratosis, and mild hyperkeratosis of the calcaneal areas of the soles. Mild corneal dystrophy without photophobia was observed in one female carrier.

Adult↗