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These very common lesions are pre-skin cancers. They are also known as solar keratosis linking it with the damaging effects of solar irradiation. They are especially predominant in fair skinned individuals occurring on sun-exposed areas. It is estimated that 10-20% will transform into squamous cell carcinomas if left untreated. Some important variants include hyperplastic, pigmented, and lichenoid. The usual appearance is a scaly, erythematous lesion. Under the microscope, there is parakeratosis overlying dysplastic epithelium, most pronounced in the basal layers of the epidermis. Extensive solar elastosis is usually present in the dermis. The diagnosis is usually straightforward although the pathologist is sometimes faced with deciding whether the lesion has progressed to a superficial squamous cell carcinoma. The general rule of thumb is protrusion of the aytpical keratinocytes into the reticular dermis with detachment of individual nests.


Reliability of Counting Actinic Keratoses Before and After Brief Consensus Discussion The VA Topical Tretinoin Chemoprevention (VATTC) Trial

Martin A. Weinstock, MD, PhD; Stephen F. Bingham, PhD; Gary W. Cole, MD; David Eilers, MD; Mark F. Naylor, MD; James Kalivas, MD; J. Richard Taylor, MD; Hayes B. Gladstone, MD; Daniel J. Piacquadio, MD; John J. DiGiovanna, MD

Arch Dermatol. 2001;137:1055-1058 Abstract quote

Objective To assess the reliability of counts of actinic keratoses (AKs) and the effect of a brief joint discussion of discrepancies on that reliability.

Design and Intervention Seven dermatologists independently counted AKs on the face and ears before and after a brief joint discussion of discrepancies.

Setting and Patients A volunteer sample of 9 patients from the ongoing VA (Department of Veterans Affairs) Topical Tretinoin Chemoprevention (VATTC) Trial. All participating individuals are veterans and have had 2 or more keratinocyte carcinomas (basal or squamous cell carcinoma) in the 5 years before enrollment in the study.

Main Outcome Measure Standard deviation of estimates of the Poisson regression parameter for the dermatologists.

Results Substantial variation was found among the dermatologists in their AK counts. The SD of the parameter estimates for the dermatologists decreased from 0.45 to 0.24 after the brief joint discussion, a 47% decrease (P = .076). The variation attributable to the dermatologists also decreased substantially (26 decrease, 94 to 12).

Conclusions Actinic keratoses are common, and there is a continuous spectrum of lesions that ranges from sun-damaged skin to squamous cell carcinoma in situ. Clinical distinguishing features may be difficult to delineate precisely. Counts of AK are commonly performed, but appear to be unreliable, even when performed by experienced dermatologists. Joint discussion of discrepancies may enhance the reliability of these counts, although substantial variation remains. Research that relied on these counts must be reevaluated in light of the marked variation among expert observers. Future studies should consider measures to assess and enhance reliability.



Comparative histochemical study of Bowen's disease and actinic keratosis: preserved normal basal cells in Bowen's disease.

Ishida H, Kumakiri M, Ueda K, Lao LM, Yanagihara M, Asamoto K, Imamura Y, Noriki S, Fukuda M.

Department of Dermatology, Fukui Medical University, Yoshida-Gun, Japan.

Eur J Histochem 2001;45(2):177-90 Abstract quote

The degree of DNA-instability as revealed by immunohistochemical staining with anti-cytidine antibody after acid hydrolysis (DNA-instability test) has been recently used as a marker of malignancy.

This technique was applied to examine 17 skin tissue samples of Bowen's disease, 47 of actinic keratosis, 15 of squamous cell carcinoma, 5 of seborrheic keratosis, and 10 of normal skin. All benign neoplastic cells of seborrheic keratosis and normal epidermal cells were negative. On the other hand, all cancer cells were positive with the DNA-instability test, indicating their malignancy, but all basal cells in Bowen's disease were completely negative. Compatible with this result, the basal cells in Bowen's disease were characteristically normal as evident in other histochemical examinations. Thus, they were negative with p53 immunohistochemistry, with normal signals of chromosome 17 in situ hybridisation and argyrophilic nucleolar organiser region, and showed slightly enhanced proliferative activity as revealed by proliferating cell nuclear antigen immunohistochemistry.

Immunohistochemical staining with 34 beta E12 (monoclonal antibody against cytokeratins 1, 5, 10, and 14), which stains all normal epidermal keratinocytes including basal cells, showed that only the basal cells of Bowen's disease stained strongly and homogeneously, while all cancer cells in the upper layers of Bowen's disease and all layers of actinic keratosis were only sporadically or weakly stained. Staining with 34 beta B4 (monoclonal antibody against cytokeratin 1), which recognises the whole epidermis except for the basal layer in the normal epidermis, showed that the basal cells in the Bowen's disease were completely negative, and lower layer cells in the actinic keratosis and upper layer cells in Bowen's disease were only sporadically stained positive, although the superficial layer cells in actinic keratosis stained strongly and homogeneously.

Our findings clearly indicate that the basal cells in Bowen's disease are normal. In support of this conclusion, the same cells showed normal morphology on electron microscopy with preserved basement membrane, although the latter was often damaged in actinic keratosis.



Histologic features of actinic keratoses in solid organ transplant recipients and healthy controls

Alan S. Boyd, MD Thomas Stasko, MD Gregory S. Cameron, PhD Mark Russell, MD Lloyd E. King Jr, MD, PhD

Nashville, Tennessee, Muncie, Indiana, and Charlottesville, Virginia

J Am Acad Dermatol 2001;45:217-21 Abstract quote

Background: Squamoproliferative lesions are common in patients who are immunosuppressed, particularly in recipients of solid organ transplants. Histologic features in such biopsy specimens may differ from those of otherwise healthy patients. Actinic keratoses (AKs) in transplant recipients may possess pathologic characteristics that suggest that they arose in an immunosuppressed host.

Objective: We evaluated 30 randomly selected AKs from 25 recipients of solid organ transplants and compared their histologic features to those of 50 AKs from 45 patients who were not immunosuppressed.

Methods: Tissue samples were categorized by sex, patient age, and site of biopsy. Sixteen separate histologic criteria were evaluated in a blinded fashion in each specimen. Statistical analysis was performed between the two groups with and without controlling for the age of the patient. Results: The transplant group was significantly younger (54.8 years) than the nontransplant group (70.0) and contained more men (88%) than women (51%). AKs from transplant recipients were statistically more likely to demonstrate bacterial colonization, confluent parakeratosis, hyperkeratosis, increased mitotic activity, and verrucous changes. After controlling for age only, hyperkeratosis failed to be more prevalent in the transplant group.

Conclusion: Certain histopathologic features are more common in AKs of immunosuppressed transplant recipients and may be used to distinguish between those removed from otherwise healthy persons.



Standardized AgNOR Analysis in Actinic Keratosis

Giovanni Tuccari, M.D.; Giuseppe Giuffrè, M.D.; Antonino Catalano, M.D.; Maria Lentini, M.D.; Dario Batolo, M.D.

From the Department of Human Pathology, Polyclinic Pad. D (G. T., G. G., M. L., and D. B.), Department of Surgical Specialties (A. C.), University of Messina, Italy.

Am J Dermatopathol 2001;23:407-412 Abstract quote

To assess if the quantity of silver-stained nucleolar organizer region (AgNOR) proteins predicts the behavior of actinic keratosis (AK), we performed a standardized AgNOR analysis on 51 cases of AK; in addition, 10 cases of squamous cell (SCC) and 10 cases of basal cell (BCC) carcinomas and 10 normal skin samples were also studied.

AgNOR analysis was performed on formalin-fixed and paraffin-embedded sections according to the guidelines of the Committee on AgNOR Quantification (1995), evaluating the mean area (m 2 ) of AgNORs per nucleus (NORA). A highly significant P value (< 0.001) was found in the comparison among NORA values of normal skin (1.869 m 2 ; SD + 0.332), AK (3.988 m 2 ; SD + 0.914), BCC (3.044 m 2 ; SD + 0.254), and SCC (5.286 m 2 ; SD + 0.920).

In AK, a progressive increase of mean NORA values was observed moving from Stage I (3.161 m 2 ; SD + 0.600) to Stage II (3.455 m 2 ; SD + 0.562), Stage III (4.360 m 2 ; SD + 0.295), and Stage IV (5.168 m 2 ; SD + 0.694); highly significant differences ( P < 0.001) were noted when Stages I or II were compared with Stage III or Stage IV or between these latter stages.

The AgNOR quantity may identify AKs with high proliferative activity and increased tendency to develop into invasive SCC.


Photodynamic therapy of actinic keratoses with topical aminolevulinic acid hydrochloride and fluorescent blue light Edward W. Jeffes, MD, PhD
Jerry L. McCullough, PhD
Gerald D. Weinstein, MD
Ross Kaplan, MD
Scott D. Glazer, MD
J. Richard Taylor, MD

Irvine and Long Beach, California, Miami, Florida, and Buffalo Grove, Illinois Sections

J Am Acad Dermatol 2001;45:96-104. Abstract quote

Background: Aminolevulinic acid hydrochloride (ALA, Levulan) applied topically to actinic keratoses (AKs) leads to accumulation of the photosensitizer protoporphyrin IX, which, when activated by exposure to light, eradicates AKs.

Objective: We examined the safety and efficacy of photodynamic therapy using topical 20% ALA in a solution formulation and varying blue light doses to treat multiple AKs on the face and scalp.

Method: This is a multicenter, investigator-blinded, randomized, vehicle-controlled study.

Results: Thirty-six patients with clinically typical AKs were treated with 20% ALA; 14 to 18 hours later, they were irradiated with a nonlaser fluorescent blue light source. With the optimal light dose of 10 J/cm2, 88% of the AKs completely cleared 8 weeks after a single photodynamic treatment, compared with 6% after treatment with vehicle and light.

Conclusion: Topical ALA PDT using a nonlaser, blue light source is an effective treatment for multiple AKs.

Weedon D. Weedon's Skin Pathology. Churchill Livingstone. 1997.

Commonly Used Terms

Dysplasia-Pathologic process with disorderly maturation and development of cells leading to a high potential for progression to cancer.

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Last Updated 10/7/2001

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