Overexpression of p27KIP1 in seborrheic keratosis.

BACKGROUND: The pathogenesis of seborrheic keratosis (SK) is not well understood. SKs are slow growing, but the details of cell cycle control in these lesions are not known. We hypothesized that cyclin-dependent kinase inhibitors would be strongly expressed in SKs and that the proliferation rate would be low. OBJECTIVES: To quantify the expression of Ki67, p16(INK4a), p21(WAF1), and p27(KIP1 )in SK. METHODS: We assessed acanthotic SKs (n=10) and irritated SKs (n=10) for Ki67, p16(INK4a), p21(WAF1), and p27(KIP1 )expression using immunohistochemistry. RESULTS: For nonirritated acanthotic pattern SKs, the Ki67 index was 3.4% (range 0.6-6.5%), confirming a low proliferation rate. The p16(INK4A) index was 6.0% (range 0-16%), and the p21(WAF1) index was 4.8% (range 0-25%). p27(KIP1) was strongly and diffusely expressed in all SKs, with a labeling index of 78% (range 75-85%). The labeling indices were similar in irritated SK lesions with a slightly increased proliferation rate and corresponding decrease in p27(KIP1) expression. CONCLUSIONS: We conclude that in SKs, strong expression of the cyclin-dependent kinase inhibitor p27(KIP1) appears to be a major mechanism controlling keratinocyte proliferation.

Histologic spectrum of melanocytic nevi removed from patients > 60 years of age.

BACKGROUND: The histology of melanocytic nevi removed from older patients often differs from that of nevi from younger adults. According to the literature, the most common nevus in older individuals is the intradermal nevus, and purely junctional nevi are rare and should alert the pathologist to a possible melanoma precursor. OBJECTIVE: To evaluate the histologic features of melanocytic nevi removed from patients > 60 year of age. METHODS: Biopsies of nevi (N=215) from 172 patients > 60 years (mean age 69+/-7 years) were examined retrospectively by three dermatopathologists, a consensus diagnosis was rendered, and the spectrum of histologic features was documented. RESULTS: Junctional melanocytic nevi were frequently diagnosed in older patients (21% of cases) and a lentiginous, often heavily pigmented growth pattern was common (12% of nevi). Severely atypical (dysplastic) changes were found in 6% of nevi removed from older patients. CONCLUSIONS: We conclude that benign junctional nevi are relatively common in older patients and that a lentiginous, heavily pigmented growth pattern, traditionally associated with younger individuals, is often seen in both junctional and compound nevi in this older age group. This pattern must be differentiated from dysplastic nevus and melanoma in situ, which they may clinically resemble.

Prospective step sections for small skin biopsies.

CONTEXT: In our laboratory, for small skin biopsies or curetted specimens, 3 slides are prepared before the case is reviewed by the dermatopathologist. OBJECTIVE: To examine the utility of these "prospective" step sections in improving diagnostic accuracy and turnaround time. DESIGN: Five hundred consecutive cases, in which step sections had been cut prior to slide review, were studied. For each specimen, 3 slides, each consisting of 1 ribbon of tissue containing 4 to 6 sections, were obtained at 50-microm intervals from the paraffin block. RESULTS: Fifty-eight biopsies (12%) were nondiagnostic using slide 1 alone. Step sections provided a diagnosis in 19 of 58 cases. In an additional 15 cases (3%) in which a diagnosis was possible using slide 1, deeper levels resulted in a change in diagnosis. Thus, in 34 (7%) of 500 biopsies, deeper levels resulted in improved diagnostic accuracy. In addition, the pathologist would have ordered step sections in a further 117 cases (23%) to clarify the diagnosis rendered on level 1 or to exclude other lesions. Thus, 30% of small skin biopsies would have required deeper levels if step sections had not been obtained prior to slide review. CONCLUSIONS: In our laboratory, the use of prospective step sections is essentially cost-neutral and case turnaround time is improved by 9% to 45%. Step sections result in a changed diagnosis in 7% of small skin biopsy specimens.

Interpretation of skin biopsies by general pathologists: diagnostic discrepancy rate measured by blinded review.

CONTEXT: Slide review has been advocated as a means to reduce diagnostic error in surgical pathology and is considered an important component of a total quality assurance program. Blinded review is an unbiased method of error detection, and this approach may be used to determine the diagnostic discrepancy rates in surgical pathology. OBJECTIVE: To determine the diagnostic discrepancy rate for skin biopsies reported by general pathologists. DESIGN: Five hundred eighty-nine biopsies from 500 consecutive cases submitted by primary care physicians and reported by general pathologists were examined by rapid-screen, blinded review by 2 dermatopathologists, and the original diagnosis was compared with the review interpretation. RESULTS: Agreement was observed in 551 (93.5%) of 589 biopsies. Blinded review of these skin biopsies by experienced dermatopathologists had a sensitivity of 100% (all lesions originally reported were detected during review). False-negative errors were the most common discrepancy, but false positives, threshold discrepancies, and differences in type or grade were also observed. Only 1.4% of biopsies had discrepancies that were of potential clinical importance. CONCLUSIONS: Blinded review demonstrates that general pathologists reporting skin biopsies submitted by primary care physicians have a low diagnostic error rate. The method detects both false-negative and false-positive cases and identifies problematic areas that may be targeted in continuing education activities. Blinded review is a useful component of a dermatopathology quality improvement program.

Atypical fibroxanthoma with prominent sclerosis.

BACKGROUND: Malignant cutaneous spindle cell lesions with marked sclerosis are uncommon. Only a few cases of cutaneous leiomyosarcoma and dermatofibrosarcoma protuberans with sclerosis have been published. METHODS: We report a case of atypical fibroxanthoma (AFX) with prominent sclerosis and hyalinization occurring on the scalp of an 81-year-old male. RESULTS: Histopathologic examination revealed an exophytic, well-delineated, focally ulcerated tumor arising in sun-damaged skin. The lesion was composed of atypical spindle cells arranged in a fascicled and vaguely storiform pattern. Occasional multinucleated giant cells were present. The tumor cells were strongly positive for CD99 (O13), vimentin, and smooth muscle actin, and focally positive for CD68. There was striking sclerosis with hyalinization throughout the lesion. CONCLUSIONS: Rarely, AFX may exhibit marked sclerosis with areas of complete replacement of tumor by hyalinized collagen. In a small biopsy, such hyalinization may be a diagnostic pitfall leading to an erroneous diagnosis.

Expression of desmin and smooth muscle myosin heavy chain in dermatofibromas.

BACKGROUND: The histopathologic features of dermatofibroma vary remarkably, and this diversity may occasionally cause problems in differentiating between benign and malignant mesenchymal lesions, including smooth muscle neoplasms. Immunohistochemical stains are sometimes necessary to clarify the histogenesis of a lesion. OBJECTIVE: To evaluate dermatofibromas for expression of desmin and smooth muscle myosin heavy chain (SM-MHC) antigens, which are commonly used as evidence of smooth muscle differentiation. METHODS: We studied 100 consecutive cases of dermatofibroma using hematoxylin-eosin-stained sections and immunoperoxidase staining with antibodies against desmin, SM-MHC, and smooth muscle actin. RESULTS: We found focal positivity for desmin in 9 cases, and in 2 of these cases, at least 10% of lesional cells showed strong expression. We found focal staining for SM-MHC in 10 cases, and in 2 of these cases, at least 10% of the lesional cells were positive. Regions positive for desmin and/or SM-MHC did not show definite histologic features of myogenous differentiation on hematoxylin-eosin-stained sections. All dermatofibromas expressing desmin and SM-MHC were also strongly positive for smooth muscle actin. CONCLUSIONS: About 10% of dermatofibromas show focal expression of desmin and SM-MHC, and this expression may be present in up to 10% to 15% of lesional cells. Thus, in dermal spindle cell lesions, focal expression of these muscle antigens, like that of smooth muscle actin, is not diagnostic of a smooth muscle tumor.