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Association of specific p53 polymorphisms with keratosis in individuals exposed to arsenic through drinking water in West Bengal, India.

Although, more than six million people are endemically exposed to inorganic arsenic in West Bengal, India by drinking heavily contaminated groundwater, only about 300,000 people show arsenic induced skin lesions. This suggests that genetic variability plays an important role in arsenic induced skin lesions and skin cancers. Arsenic induced keratosis is considered as a possible precancerous state of in situ carcinoma. Several reports have suggested the role of p53 polymorphisms as potential marker for risk assessment of different types of cancers. This prompted us to study the association of three p53 polymorphisms with arsenic induced keratosis in a population exposed to arsenic through drinking water. A total of 366 unrelated individuals (177 individuals with arsenic induced keratosis and 189 individuals with no arsenic induced skin lesions) were recruited from North 24 Parganas, Nadia and Murshidabad districts between January 2003 and February 2005 for the study of the genotypic distribution of three p53 polymorphisms (16bp duplication at intron 3, codon 72 Arg/Pro and G>A at intron 6 [nt 13,494]) by PCR-RFLP. The arginine homozygous genotype at codon 72, and homozygous genotype of no duplication polymorphism at intron 3 were over represented in the individuals with keratosis compared with individuals with no skin lesions (OR=2.086; 95% CI=1.318-3.299 and OR=2.086; 95% CI=1.257-3.457, respectively). This study indicates that individuals carrying the arginine homozygous genotype at codon 72, and/or no duplication homozygous genotype at intron 3 are at risk for the development of arsenic induced keratosis.

Adult↗

[Palpebral seborrheic keratosis: a case study].

INTRODUCTION: Seborrheic keratosis is the most frequent palpebral tumor, observed for the most part in the second half of life. It may be confused clinically with a basal cell carcinoma or a melanoma. The histopathological study confirms the diagnosis. OBSERVATION: A 69-year-old man presented with a giant superior palpebral tumor leading to ptosis of the eyelid, which had evolved over 5 years. Examination found a pigmented cerebriform multilobed granulated mass, with a smooth surface and a more or less seborrheic aspect, pedicled in places, covering the entire eyelid but sparing the internal angle. This aspect suggested melanoma, basal cell carcinoma or seborrheic keratosis. Histological biopsy revealed basal cell carcinoma. Excision with palpebral reconstitution using palpebral flaps was performed. The histopathological analysis of the tumor concluded in seborrheic keratosis. DISCUSSION: Seborrheic keratosis is a frequent tumor of the face and eyelids. Its highly pigmented clinical aspect can be confounded with a nevus or a melanoma, whereas the histological aspect can suggest basal cell carcinoma or squamous cell carcinoma, but the basal membrane is always intact. Several treatments have been proposed, including electrocoagulation, cryotherapy, dermabrasion, as well as CO2 laser treatment. However, when there is doubt with regard to the histological nature, surgery is preferred. CONCLUSION: This was a case of seborrheic keratosis, atypical in that it covered the entire upper eyelid and produced a highly disfiguring aspect and functional problems, requiring surgical treatment with eyelid reconstruction.

Aged↗

Complications of keratosis obturans.

Three patients with extensive keratosis obturans were treated during a 12-month period. One presented with an idiopathic sensorineural hearing loss and was found to have keratosis obturans in the contralateral, asymptomatic ear. The disease process had resulted in a horizontal semicircular canal fistula in what was now, effectively, the only hearing ear. The second patient had an extensive dehiscence of the tegmen tympani. The third presented with a facial palsy. An automastoidectomy cavity was present, with circumferential skeletonization of the descending facial nerve over a length of 1.5 cm and dehiscence of the temporomandibular joint and jugular bulb. All three patients were successfully treated by surgical formalization of their automastoidectomy cavities. They appeared to represent cases of keratosis obturans rather than external auditory canal cholesteatoma, on the basis of previously published reports.These complications and patterns of bone erosion have not previously been described in keratosis obturans. The third patient is believed to have the most extensive case of keratosis obturans yet described.

Aged↗

Melanoma and seborrheic keratosis differentiation using texture features.

PURPOSE: To explore texture features in two-dimensional images to differentiate seborrheic keratosis from melanoma. METHODS: A systematic approach to consistent classification of skin tumors is described. Texture features, based on the second-order histogram, were used to identify the features or a combination of features that could consistently differentiate a malignant skin tumor (melanoma) from a benign one (seborrheic keratosis). Two hundred and seventy-one skin tumor images were separated into training and test sets for accuracy and consistency. Automatic induction was applied to generate classification rules. Data analysis and modeling tools were used to gain further insight into the feature space. RESULT AND CONCLUSIONS: In all, 85-90% of seborrheic keratosis images were correctly differentiated from the malignant skin tumors. The features correlation_average, correlation_range, texture_energy_average and texture_energy_range were found to be the most important features in differentiating seborrheic keratosis from melanoma. Over-all, the seborrheic keratosis images were better identified by the texture features than the melanoma images.

Diagnosis, Differential↗

Irritated seborrheic keratosis of the external ear canal.

Although a seborrheic keratosis is not rare on the skin of the trunk, extremities, head and neck of an elderly person, it is uncommon to originate in the external ear canal. Even rarer, an irritated subtype may arise in this location. We report the case of a 63-year-old man with an irritated seborrheic keratosis arising in the right external ear canal, who first presented with a bloody discharge from his right ear canal 3 years and 10 months before the subsequent operation. Macroscopically, a dome-like, black elevation was found at the anterior wall of the right external ear canal. A biopsy showed an exophytic papillomatous, hyperkeratotic growth of basaloid cells which revealed some nuclear atypism and mitosis. Squamous eddies and moderate inflammatory infiltrate were noted. Some cellular atypism made us suspect an irritated seborrheic keratosis. Because the patient hated the extirpation, he remained untreated for 3 years and 3 months following his first presentation. The biopsy and a surgical resection of his second presentation confirmed the diagnosis of irritated seborrheic keratosis. Immunohistochemical analysis of Ki-67, p53 and papillomavirus was performed to elucidate its character. We emphasize that irritated seborrheic keratosis does occur in the external ear canal and may cause some diagnostic difficulty. Pathologists should be aware of this fact and avoid overdiagnosis.

Ear Canal↗

Clonal nature of seborrheic keratosis demonstrated by using the polymorphism of the human androgen receptor locus as a marker.

We evaluated the clonality of seborrheic keratoses using a polymorphism due to the random inactivation of one of two X chromosomes in females. Thirty-eight seborrheic keratoses obtained from the skin of females with polymorphism of the human androgen receptor (HUMARA) locus were examined by a fluorescent polymerase chain reaction procedure, which allowed accurate measurement of the peak intensities of each HUMARA allele. The epithelial portion of seborrheic keratosis and normal control epidermis adjacent to the seborrheic keratosis were removed by laser capture microdissection. As biopsied specimens of seborrheic keratoses contained small amounts of normal epidermis, the effect of digestion by a restriction enzyme (HhaI) recognizing the nonmethylated active sites was compared between seborrheic keratoses and normal control epidermis in only five seborrheic keratosis cases. Disappearance or significant reduction in intensity of one of two HUMARA alleles was observed after HhaI digestion in seborrheic keratoses, but not in the normal control epidermis. Although the skewing of the polymorphism was not corrected by the normal control epidermis in the remaining 33 seborrheic keratosis cases, one of two HUMARA peaks practically disappeared after HhaI digestion in 20 of 33 seborrheic keratosis cases. In total, 25 of 38 seborrheic keratoses were considered to be monoclonal. The histologic type of seborrheic keratoses did not affect clonality.

Adult↗

P27 and mib1 expression in actinic keratosis, Bowen disease, and squamous cell carcinoma.

The histologic boundary between actinic keratosis, Bowen disease, and invasive squamous cell carcinoma is not clear in many cases. We determined nuclear expression of p27 (a protein associated with cellular quiescence) and Ki-67 (a marker of proliferation) immunohistochemically in actinic keratosis, Bowen disease, and squamous cell carcinoma to see if differential patterns of expression for p27 exist and how these might correlate with Ki-67 expression. We determined a labeling index for p27-stained nuclei and assessed the pattern of Ki-67 expression. The student's t test was used to evaluate the p27 labeling index. The p27 labeling index was decreased in invasive aggregates of squamous cell carcinoma (76.9+/- 1.1%) when compared with those of normal epidermis (97.2+/- 2.4%), actinic keratosis (95.3 +/- 1.4%), and Bowen disease (98.0+/- 0.5%). Ki-67 was expressed in a scattered to confluent linear pattern in the basal/parabasal cell layer of normal epidermis and actinic keratosis. Keratinocytes in squamous cell carcinoma exhibited Ki-67 in the peripheral layers of the neoplasm and frequently within the tumor aggregates. Ki-67 was observed in nuclei throughout the full thickness of the epidermis in Bowen disease. The staining pattern of Ki-67 in Bowen disease separated this entity from others under study. The combination pattern of p27 and Ki-67 staining can be used to support differentiation of actinic keratosis, Bowen disease, and squamous cell carcinoma.

Biomarkers, Tumor↗

Ultraviolet-induced dna repair synthesis in lymphocytes from patients with actinic keratosis.

Actinic keratosis is an epidermal cancer in situ. Extensive exposure to sunlight is considered as a contributing factor to the etiology of this tumor. Ultraviolet (UV) light of solar radiation induces structural damage in DNA, which may give rise to mutations and transformed cells if the damage is not repaired. Repair of UV-induced DNA lesions is an essential property of human cells. The conditions so far reported to have defective DNA repair are all associated with an increased incidence of malignancy. Do patients with actinic keratosis also exhibit a reduced capacity to repair UV-induced DNA lesions? DNA repair synthesis in peripheral leukocytes was studied in 10 patients with actinic keratosis and 10 healthy subjects of corresponding age. After irradiation with various doses of UV light the leukocytes were incubated for 2 hr with [3H]thymidine in the presence of hydroxyurea. A dose-response relationship for the UV-induced DNA repair synthesis was established for each individual. The average repair capacity in the patients with actinic keratosis was about 30% below that of the controls. The difference is statistically significant (p less than 0.02). Reduced DNA repair synthesis may therefore be an important factor in the etiology of actinic keratosis.

Aged↗

[Lichenoid keratosis].

Lichenoid keratosis is a usually solitary skin lesion occurring in sun-exposed areas. It is macroscopically uncharacteristic, resembles actinic keratosis, basal cell epithelioma, Bowen's disease, or flat seborrheic keratosis, but shows histologically the typical pattern of lichen planus. Lichenoid keratosis should be differentiated from the lichenoid variant of actinic keratosis.

Aged↗

Invasive cutaneous squamous cell carcinoma associated with actinic keratosis: a case with orbital invasion and meningeal infiltration.

BACKGROUND: It is suggested that most squamous cell carcinomas in sun-exposed areas arise from preexisting solar keratosis. Actinic keratosis is thought of as being a precursor to squamous cell carcinoma. This form of squamous cell carcinoma has been considered to be a relatively benign lesion. We report a case of invasive squamous cell carcinoma associated with actinic keratosis leading to orbit destruction and meningeal infiltration. OBJECTIVE: To demonstrate that well-differentiated tumors can act extremely aggressively with the potential toward infiltrative growth patterns. METHODS: Histologically controlled surgery along with multiple radiation therapy was performed. RESULTS: The tumor progressed inducing perineural invasion, orbit infiltration, osseous destruction, and meningeal invasion. CONCLUSION: The association of squamous cell carcinoma and actinic keratosis supports the concept of a causal relation. Excision with histologic examination of actinic keratosis seems to be useful for accurate diagnosis. Squamous cell carcinoma can represent an aggressive tumor with infiltrative growth pattern and should not be considered a benign lesion.

Aged↗

Effect of a 1-week treatment with 0.5% topical fluorouracil on occurrence of actinic keratosis after cryosurgery: a randomized, vehicle-controlled clinical trial.

BACKGROUND: No long-term randomized controlled clinical trial has compared the efficacy of cryosurgery alone vs cryosurgery following fluorouracil applications for the treatment of actinic keratosis. OBJECTIVE: To determine the 6-month outcome of a 1-week course of 0.5% fluorouracil followed by cryosurgery. DESIGN: Prospective, multicenter, randomized, double-blind, vehicle-controlled clinical trial performed in community and academic outpatient clinics. PATIENTS: A total of 144 patients with 5 or more visible or palpable actinic keratoses on the face. INTERVENTIONS: Topical 0.5% fluorouracil or vehicle once daily for 7 days. At the 4-week follow-up visit, residual lesions were treated with cryosurgery. MAIN OUTCOME MEASURE: Reduction in facial actinic keratoses from baseline to 4 weeks and 6 months. RESULTS: At 4 weeks, mean actinic keratosis lesion count was reduced by 62.4% in the 0.5% fluorouracil group vs 28.8% in the vehicle group (P<.001), and complete clearance was achieved in 16.7% of patients in the 0.5% fluorouracil group vs 0% of those in the vehicle group (P<.001). At 6 months, mean lesion count was reduced by 67.0% in the 0.5% fluorouracil plus cryosurgery group vs 45.6% in the vehicle plus cryosurgery group (P =.01), and significantly more patients in the 0.5% fluorouracil plus cryosurgery group than in the vehicle plus cryosurgery group had complete clearance (30% vs 7.7%; P<.001). CONCLUSIONS: A 1-week course of topical 0.5% fluorouracil before cryosurgery is significantly more effective in reducing patients' numbers of actinic keratosis lesions 6 months after treatment than cryosurgery alone. The high occurrence rate of actinic keratosis lesions at 6 months suggests a need for follow-up.

Administration, Cutaneous↗

Metastatic cutaneous squamous cell carcinoma derived from actinic keratosis.

BACKGROUND: Squamous cell carcinoma (SCC) with histologically contiguous actinic keratosis has long been thought of as a tumor with minimal risk for metastasis. The objective of this study was to determine if contiguous actinic keratosis is present in the original tumors of metastatic cutaneous SCC and to describe the histologic features of these tumors. METHODS: The primary lesions of 22 patients with metastatic cutaneous SCC were examined using light microscopy. RESULTS: Contiguous actinic keratosis was present histologically in 44% of the original lesions of cutaneous SCC that metastasized. The average tumor thickness was 6.6 mm. Greater than 66% of the tumors were well or moderately differentiated. The skin adjacent to the tumors showed solar degeneration in almost all instances. CONCLUSIONS: The histologic presence of contiguous actinic keratosis is not a useful predictor of the metastatic behavior of cutaneous SCC. Increased tumor thickness and depth of invasion are the most consistent histopathologic features of cutaneous SCC that metastasize.

Carcinoma, Squamous Cell↗

Antikeratin 14 monoclonal antibody staining in psoriasis and seborrhoeic keratosis: immunofluorescence and two colour FACS studies.

A monoclonal antibody (ES3A) was raised against a mouse graft-versus-host reaction (GVHR) model. This antibody was against basal cell cytoplasm and reacted with an acidic (pI 6.2) 50 kDa keratin of human epidermis. However, ES3A reacted with several lower layers of epidermal cells in psoriasis and seborrhoeic keratosis. Acanthotic seborrhoeic keratosis showed varying patterns even in a single lesion. If combined with FACS analysis, ES3A-positive cells could be quantified. Normal skin showed 28%, while psoriasis and seborrhoeic keratosis showed 44% and 51%, respectively. ES3A-positive compartments of the acanthotic type of seborrhoeic keratosis were larger than those of the hyperkeratotic type. ES3A may be suitable for quantification of germinative or proliferative cells.

Animals↗

Immunohistochemical examination of tumor-suppressor gene p53 product and pyrimidine dimer in solar keratosis.

In order to find biomarkers to measure the effects of UV irradiation, we examined the accumulation of p53 protein and pyrimidine dimers in 18 solar keratosis specimens. Frozen or AMeX-fixed solar keratosis specimens were immunohistochemically stained by anti-p53 mouse monoclonal antibody, pAb1801 and polyclonal anti-(pyrimidine dimer) antibody. Nuclear accumulation of p53 protein was found in 5/18 (28%) solar keratosis lesions. The percentage of cases showing nuclear p53 protein varied according to the histological type; in the bowenoid type it was 4/7 (57%); in the atrophic type it was 1/7 (14%). Nuclear pyrimidine dimers were not stained in solar keratosis, although the skin of UV-irradiated nude mice was positive. Accumulation of p53 protein is a good marker for early precancerous change caused by UV exposure.

Aged↗

The transformation of laryngeal keratosis into invasive carcinoma.

Although 93.0% to 97.0% of all laryngeal carcinomas are diagnosed on the first biopsy, 3.0% to 6.7% of them occur in patients who have what is initially diagnosed as "laryngeal keratosis." To study this phenomenon, we examined data from 1,019 patients with laryngeal keratosis seen between 1962 and 1981. Eleven patients with keratosis and initially undetected cancer at different laryngeal sites were excluded, as were 87 outside referrals for whom no records were available beyond the histologic report. The remaining 921 patients were classified on the basis of the initial histologic findings into groups comprising 604 patients with keratosis without atypia (group 1), 204 patients with mild atypia (group 2), 23 patients with moderate atypia (group 3), and 90 patients with severe atypia (group 4). All 921 were followed for from 5 to 25 years. Invasive carcinoma of the larynx developed in 18 patients from group 1 (3.0%), 15 from group 2 (7.4%), four from group 3 (17.4%), and 25 from group 4 (27.8%). Fifty-seven patients (91.9%) developed invasive carcinoma after less than 10 years but only five (8.1%) did so after 10 years or more.

Adolescent↗

Human papillomavirus infection in actinic keratosis and bowen's disease: comparative study with expression of cell-cycle regulatory proteins p21(Waf1/Cip1), p53, PCNA, Ki-67, and Bcl-2 in positive and negative lesions.

We examined the presence of human papillomavirus (HPV) DNA in tissues of premalignant skin lesions, i.e., actinic keratosis (n = 13) and Bowen's disease (n = 62), taken from 69 Japanese immunocompetent and renal transplant recipient patients. Detection and typing of HPV DNA were performed using polymerase chain reaction (PCR) and sequence analysis or restriction fragment length polymorphism (RFLP) analysis, respectively. The positivity rates of HPV DNA in tissues of actinic keratosis and Bowen's disease were 77% and 65%, respectively. Twenty-seven HPV types were detected in 50 (67%) premalignant skin lesions, in which Z95963 (accession no. in the EMBL Databank), Z95968, AJ010823, and AJ000151 have been described as partial sequences of unknown HPV types. Furthermore, 2 unknown types, HPVX1 and HPVX2, were found in specimens of actinic keratosis. Sequence analysis showed that HPVX1 is related to HPV-37 (86.1% sequence homology) and that HPVX2 is related to HPV-38 (79.7%). These results indicate that various mucosal and epidermodysplasia verruciformis-related HPV types are associated with the pathogenesis of actinic keratosis and Bowen's disease. In addition, 24 specimens of HPV-positive or HPV-negative premalignant skin lesions were examined immunohistochemically for proliferating cells to determine biological differences between HPV-positive and HPV-negative lesions. Immunohistochemistry for p21(Waf1/Cip1), p53, proliferating cell nuclear antigen (PCNA), Ki-67, and Bcl-2 revealed that there was no significant difference in the cell proliferation activity between HPV-positive and HPV-negative lesions, suggesting that HPV infection alone does not induce cell proliferation in those lesions.

Adult↗

Seborrheic keratosis of conjunctiva simulating a malignant melanoma: an immunocytochemical study with impression cytology.

OBJECTIVE: Seborrheic keratosis on the conjunctiva appears to have never been reported in the literature. The authors report here a well-documented case of seborrheic keratosis of conjunctiva clinically simulating a malignant melanoma. DESIGN: Case report. METHODS: A 66-year-old man presented with a juxtalimbal pigmented tumor involving the temporal conjunctiva of his left eye. Because of the rapid enlargement of the mass within a period of 5 months, a clinical diagnosis of malignant melanoma was made. Cytopathologic examinations were performed by impression cytology before the patient underwent a wide en-block excision of the tumor. MAIN OUTCOME MEASURES: Cytologic features were studied by impression cytology with periodic acid-Schiff-Papanicolaou stain. Immunochemical characteristics of tumor cells were studied by immunochemical stain of cytokeratin and HMB-45. Tumor morphology was observed by histopathologic examination. RESULTS: Impression cytology disclosed basaloid cells intermixing with squamoid cells, and these cells demonstrated positive immunoreactivity to cytokeratin and no reactivity to HMB-45. Histopathologic examination of the tumor specimen established the diagnosis of seborrheic keratosis, and the results of immunohistochemical staining were consistent with those of the impression cytology with immunocytochemical staining. CONCLUSION: The authors describe the first case report of conjunctival seborrheic keratosis and present its immunocytochemical and immunohistochemical characteristics. Such a benign lesion can clinically mimic a malignant melanoma.

Aged↗

Topical tretinoin in actinic keratosis and basal cell carcinoma.

In several studies between 1962 and 1978, topical tretinoin was proved capable of producing complete regression of actinic keratosis and basal cell carcinoma. But because its efficacy is not comparable to that of other modalities, topical tretinoin is currently used only as an adjunct to topical 5-fluorouracil in the treatment of actinic keratosis. One recent report found topical tretinoin ineffective in the chemoprevention of actinic keratosis. Although the oral synthetic retinoids isotretinoin and etretinate have been used in the prevention and treatment of cutaneous malignancy, the potential exists for chronic toxicity from the prolonged systemic therapy that appears necessary for maintaining the chemopreventive effect. For this reason, it may be appropriate to study further the preventive as well as therapeutic effects of topical tretinoin and other retinoids for actinic keratosis and skin cancer. If they prove safe and effective, the use of topical retinoids in the prevention and treatment of cutaneous tumors may be the most significant clinical application of these drugs.

Basal Cell Carcinoma↗