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Rarely, different variants of porokeratosis may coexist in an individual patient or their family members. A patient with the linear form of porokeratosis present since birth subsequently developed the disseminated superficial actinic form at a later age. A review of the literature pertaining to the coexistence of variants of porokeratosis suggests a significant association between the linear and disseminated superficial actinic forms. Genetic linkage between different variants and the basis for their association is discussed.

Nine tumors of squamous cell carcinoma developed in a 61-year-old Japanese woman with linear porokeratosis. She had disseminated superficial porokeratosis, but a linear arrangement of pronounced lesions was found only on the left side of the body, and all of the tumors arose on the linear lesions on the left side of the body. Some of her family members had disseminated superficial porokeratosis. This case may represent a type 2 segmental manifestation of disseminated superficial porokeratosis showing a systematized pattern of involvement and pronounced cancer proneness.

A 73-year-old man presented with typical lesions of disseminated superficial porokeratosis (DSP) and multiple seborrhoeic keratoses on his face, trunk and extremities, and later developed a keratoacanthoma on his lip. He belonged to a cancer-prone pedigree susceptible to colonic, uterine and other internal cancers, and had a personal history of early gastric cancer and advanced adenocarcinoma of the descending colon without adenomatous polyps at age 59 years. Polymerase chain reaction amplification of skin samples for seven separate microsatellite polymorphisms revealed microsatellite instability (MSI) at multiple loci in five of six seborrhoeic keratoses and the keratoacanthoma, strongly suggesting underlying defects in DNA mismatch repair. Although no germline mutations in two mismatch repair genes hMSH2 and hMLH1 were found, our patient was recognized as having hereditary non-polyposis colorectal cancer (HNPCC) based on the family history and the findings of the microsatellite analysis of skin tumours. This confirmed the usefulness of detection of MSI in prevalent and readily accessible skin lesions, including non-sebaceous non-dysplastic tumours such as seborrhoeic keratosis in the screening of HNPCC families. Although DSP may also be inherited as an autosomal dominant condition, this particular skin disease appeared to be sporadic in our patient and, to our knowledge, no association of DSP or other forms of porokeratosis with HNPCC has previously been reported. In contrast to the seborrhoeic keratoses and keratoacanthoma, no MSI was observed in two samples from DSP lesional epidermis examined.

Disseminated superficial actinic porokeratosis is an autosomal dominant cutaneous disorder characterized by many uniformly small, minimal, annular, anhidrotic, and keratotic lesions. The genetic basis for this disease is unknown. Using a genomewide search in a large Chinese family, we identified a locus at chromosome 12q23.2-24. 1 responsible for disseminated superficial actinic porokeratosis. The fine mapping study indicates that the disseminated superficial actinic porokeratosis gene is located within a 9.6 cM region between markers D12S1727 and D12S1605, with a maximum two-point LOD score of 20.53 (theta = 0.00) at D12S78. This is the first locus identified for a genetic disease where the major phenotype is porokeratosis. The study provides a map location for isolation of a gene causing disseminated superficial actinic porokeratosis.

A 73-year-old man with porokeratosis palmaris, plantaris et disseminata is presented. He had punctate, guttate and annular hyperkeratotic papular lesions widespread on his body with thorn-like hyperkeratosis on the palms and soles. Lesional skin did not show mutations of TP53 exons 5-6, 7, 8., (Copyright 2000 S. Karger AG, Basel)

A concept of dichotomous types of segmental involvement of autosomal dominant skin disorders has recently been proposed. Among the different types of porokeratosis, disseminated superficial actinic porokeratosis is known to be an autosomal dominant skin disorder, and linear porokeratosis represents the segmental form of the disease. We intended to exemplify the type 2 segmental manifestation within this concept. Clinical and histopathologic aspects of porokeratotic lesions of 2 patients were investigated. The family history was studied in both cases. Linear porokeratosis superimposed on disseminated superficial actinic porokeratosis was observed in both patients. These 2 cases of linear porokeratosis associated with disseminated superficial actinic porokeratosis can be taken as further examples of a type 2 segmental involvement occurring in an autosomal dominant skin disorder.

We report on the occurrence of coronal craniosynostosis, anal anomalies, and porokeratosis in two male sibs. A third male sib was phenotypically normal as were the parents. The occurrence of these three clinical features has, to our knowledge, not been reported before. Cutaneous or anal anomalies or both have been reported in a number of syndromes associated with craniosynostosis, including Crouzon, Pfeiffer, Apert, and Beare-Stevenson syndromes. These syndromes are associated with mutations in the fibroblast growth factor receptor genes FGFR1, FGFR2, and FGFR3. They are inherited in an autosomal dominant fashion. In contrast, the cases we report do not carry any of the common FGFR mutations and the pedigree suggests autosomal or X linked recessive inheritance.

In this and previous studies, we have shown p53 overexpression immunohistochemically in 14 of 17 porokeratotic specimens obtained from 14 lesions of nine cases, and in all six specimens of squamous cell carcinoma (SCC) arising on porokeratotic lesions of two cases. We screened mutations in exons 5 to 10 of the p53 gene in all these specimens by polymerase chain reaction-single strand conformation polymorphism analysis. Mutations of the p53 gene were detected in two of the six SCCs but not in any of the 17 porokeratotic specimens. These two mutations were C to T transitions at codons 146 and 175 in exon 5, which were a nonsense mutation at a dipyrimidine site and a missense mutation at a CG site, respectively. To our knowledge, neither of these mutations has been identified in skin cancers before. Our observations indicate that mutations of the p53 gene are not the major molecular etiology for porokeratosis, but are related to its skin carcinogenesis, and that p53 overexpression in porokeratosis is not due to p53 gene mutations.

Background: It is well known that porokeratosis, a genetically heterogeneous disorder characterized by the histopathological feature of the cornoid lamella, shows an increased proneness to develop carcinoma. On the other hand, a significant mechanism in the origin of many forms of cancer is loss of heterozygosity or allelic loss., Objective: Because it has recently been proposed that linear porokeratosis may result from allelic loss, one might expect that linear porokeratosis is especially prone to malignant degeneration. In order to test this hypothesis, a review of case reports was performed., Method: Cases of cancer-associated porokeratosis were collected from the European language literature and assigned to one of 5 different types [plaque type of Mibelli (PM); disseminated actinic superficial porokeratosis (DSAP); porokeratosis palmaris, plantaris et disseminata (PPPD); porokeratosis punctata palmaris et plantaris (PPPP); linear porokeratosis (LP)]., Results: Malignant or premalignant lesions were reported in 9 cases of PM, 15 cases of DSAP, 3 cases of PPPD, 1 case of PPPP and 21 cases of LP., Conclusion: This analysis supports the view that among the various forms of porokeratosis, the linear type is particularly susceptible to malignant degeneration. Arguments are presented in favor of the assumption that the genetic mechanism of allelic loss giving rise to LP may represent an initial step in the development of cancer.

We report a family with hyperkeratotic lesions on palms and soles. The lesions became evident in the second to third decade, and there is an autosomal dominant mode of transmission. Skin biopsy specimens show a central epidermal depression filled by a compact hyperkeratotic plug of columnar parakeratosis, like a broad cornoid lamella. The lesions resemble porokeratosis plantaris discreta clinically and histologically. The cornoid lamella is a broad, solid keratin plug rather than a centrifugally enlarging annular or serpentine ridge as can been seen in other types of porokeratosis. Perhaps the lesions of porokeratosis plantaris discreta should not be classified as a true porokeratosis but as porokeratotic plantar keratoderma discreta. We have therefore called the lesions in our patients porokeratotic palmoplantar keratoderma discreta, and suggest that porokeratotic palmoplantar keratoderma discreta is a variant of porokeratosis plantaris discreta.

Introduction: Erythropoietic protoporphyria was generally assumed to be an autosomal dominant disease with variable penetrance. The determination of the ferrochelatase activity and the biological molecular studies have shown that both autosomal dominant and recessive patterns of inheritance are possible., Case Report: Is reported the case of a 17 years-old male patient with erythropoietic protoporphyria and porokeratosis. There are some hepatic biochemical abnormalities without cholelithiasia and without pathological change of the liver biopsy. Leucocyte ferrochelatase activity is decreased to 5 p. 100 of the normal mean level. In both the parents, without photosensitivity, the enzyme activity is reduced to 40 p. 100 of the normal values., Discussion: The patients with severe ferrochelatase defect have no more important clinical manifestations than in the usual form of erythropoietic protoporphyria. For clarify the exact mode of inheritance, the determination of the ferrochelatase activity and the identification of the mutations in the patient and his parents are necessary. In our patient the porokeratosis should be in relation with the protoporphyrin induced phototoxic reaction which facilitate the emergence of a mutant cellular clone of epithelial cells.

Introduction: Mibelli's porokeratosis is uncommon in black persons. We report two brothers who had two different clinical presentations., Case Report: The brothers were seen at the ages of 16 and 19 years. Both had Mibelli's porokeratosis, one with a papulo-verruciform presentation located on the scrotum, the anus, the gluteal area and the back of the hand, and the other with a superficial disseminated eruption involving the face and the forearm., Discussion: The incidence of Mibelli's porokeratosis in the black population at Cotonou is approximately 0.3 per 10.000. The presence of the disease in two uterine brothers confirms the monogenic and familial nature of Mibelli's porokeratosis. Dominant transmission cannot be easily demonstrated when the parents of the patients are phenotypically healthy.

We report on a family with porokeratosis plantaris, palmaris et disseminata with a very unusual clinical manifestation. The father showed an association of multiple filiform hyperkeratosis on the trunk with sparing of the palms and soles. In addition, this patient featured secondary nail dystrophy owing to porokeratosis. The daughter had an unusual course: the disease started on the trunk and did not spread to the palms and soles until later. In general the reverse is true.

Disseminated superficial actinic porokeratosis (DSAP) is a cutaneous disorder, usually inherited in an autosomal dominant fashion, characterized by numerous annular papules with subtle raised hyperkeratotic borders and slightly atrophic centers. While the precise pathophysiologic mechanisms underlying the development of DSAP are unknown, one hypothesis is multifocal expansion of atypical clones of keratinocytes, perhaps unmasked by actinic damage, as implied by its name. Although primarily of cosmetic concern, there is an increased risk of squamous cell carcinoma of the skin developing within DSAP lesions, which often show histologic keratinocytic atypia centrally. Immunosuppression, which is a significant risk factor for secondary malignancies including cutaneous squamous cell carcinoma, is also a well-documented precipitant of porokeratosis. We report a 62-year-old man who developed DSAP in a widely and rapidly progressive manner within days of receiving total body radiation and high-dose induction chemotherapy as planned preparative therapy for an autologous peripheral blood stem cell transplant for relapsed high grade lymphoma. Our patient's eruption of DSAP highlights a little recognized cutaneous manifestation of aggressive bone marrow transplant induction therapy.

Porokeratosis (PK) is a rare genetic skin disorder inherited as an autosomal dominant trait and regarded as a disease predisposing to cancer. To evaluate chromosomal radiosensitivity of PK cells, we examined chromosome aberration frequency after X-irradiation of cultured skin fibroblasts derived from PK patients and controls. Without X-ray exposure, frequencies of chromosome-type aberrations (exchanges or deletions) were not different between the patients and controls. Following X-ray irradiation, frequencies of deletions in the patient group were significantly increased, whereas those of exchanges were not elevated. No differences in chromatid-type aberration frequency were found between the patients and controls with or without exposure to X-ray. The observed radiosensitivity, though not as high as in ataxia telangiectasia (AT) cells, agrees well with the previously reported higher radiosensitivity of PK fibroblasts in survival analysis.

Background: p53 is a tumor suppressor nucleoprotein. Mutations of the p53 gene have been found in a variety of malignant neoplasms. Wild-type p53 has a short half-life, possibly only 20 to 30 minutes, and is not present in the nucleus at levels that are detectable with routine immunohistochemical techniques. Mutant p53 has a longer half-life, and is readily detectable with immunoperoxidase staining., Results: We studied 17 specimens from patients with either porokeratosis of Mibelli or actinic porokeratosis, using immunoperoxidase staining with an antibody directed against the p53. There was staining of lesional keratinocyte nuclei in 16 of 17 specimens, limited in most cases to the zone between cornoid lamellae. Staining for proliferating cell nuclear antigen was increased above background levels in only six of 13 specimens., Conclusions: The finding of p53 immunoperoxidase staining in porokeratosis suggests genetic mutation, as occurs in other cutaneous keratinocytic neoplasms, and the lack of corresponding proliferating cell nuclear antigen expression in many specimens indicates that p53 overexpression is not simply a reflection of increased cellular proliferation.

Disseminated superficial actinic porokeratosis (DSAP), skin lesions of which are known to be induced by ultraviolet (UV) light, does not develop into skin cancer as frequently as other types of porokeratosis (PK). To establish the cellular basis of this characteristic of DSAP, we examined the colony-forming ability of UVC light- or X-ray-irradiated cultured fibroblasts derived from DSAP patients' skin. Sensitivity to the lethal effects of UV light was not significantly different between 3 DSAP and 5 control cell strains. In contrast, DSAP cell strains were significantly hypersensitive to the lethal effects of X-radiation, although the sensitivity was less than that of cell strains from other types of PK patients. The results indicate that the actinic character of DSAP is not reflected in the cellular response to the lethal effects of UV light, but suggest that DSAP shares X-ray sensitivity, which is probably associated with the cancer-prone nature of PK.