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Acridine orange-DNA complex in actinic keratosis.

Electron microscopy processing and staining of nuclei were used to localize reaction products of acridine orange staining in actinic keratosis of human skin. Electron-dense granules about 10-100 nm in diameter were seen exclusively in the euchromatin portion of the nucleus. Almost all tumor cells had granules (mean = 65; SD = 26). These granules were also occasionally observed in the dermal connective tissue cells in the lesion. However, the mean number of 10 granules seen in these cells was definitely less than that of tumor cells. Normal skin controls did not have granules except occasionally in the basal cells of the epidermis.

Acridines↗

Immunohistochemical study on keratin expression in certain cutaneous epithelial neoplasms. Basal cell carcinoma, pilomatricoma, and seborrheic keratosis.

We investigated immunohistochemically 20 basal cell carcinomas (BCC), five pilomatricomas, and nine seborrheic keratoses using anti-BCC keratin monoclonal antibody (BKN-1) and anti-hair keratin monoclonal antibodies (HKN-2, HKN-4- -7). The neoplastic cells in all the cases of BCC were always uniformly stained by BKN-1, HKN-2, and HKN-4, indicating that the BCC cells display a constant antigenicity of keratin, which may be different from that of the normal epidermis. Although no fluorescence by HKN-6 or HKN-7 was seen in any cases of BCC, HKN-5 partially but strongly stained the neoplastic nests in most cases of BCC; BCC may have differentiation toward the lower part of hair follicular epithelium. In pilomatricoma, all the anti-keratin monoclonal antibodies showed a similar staining pattern; the differentiating neoplastic cells undergoing transition from basaloid to eosinophilic were positively stained by each antibody in all the cases. This finding of pilomatricoma corresponds to that of the differentiating cells in the inner hair layers, especially in the hair cortex. In seborrheic keratoses, no fluorescence was recognized with HKN-5- -7, which stain the lower follicular cells in the normal human skin. The staining patterns of seborrheic keratosis by BKN-1, HKN-2, and HKN-4 were similar to those of the normal interfollicular epidermis. These anti-keratin monoclonal antibodies seem to be useful for the investigation of the direction of differentiation of skin adnexal neoplasms.

Antibodies, Monoclonal↗

Solar keratosis can be distinguished from superficial basal cell carcinoma by expression of bcl-2.

Criteria for the histological diagnosis of solar keratosis (SK) and superficial basal cell carcinoma (SBCC) are well defined. On occasion, however, the distinction can be difficult, particularly when evaluating small-punch or superficial shave biopsies in which the overall global architectural pattern of the lesion is not represented. As bcl-2 expression has been established in basal cell carcinoma, this study was undertaken to determine whether it could be employed as a basis for distinguishing SBCC from SK. Ten cases each of typical SBCC and SK were studied. Every example of SBCC showed strong uniform expression of the bcl-2 gene product Bcl-2, whereas all examples of SK were uniformly negative. It is suggested, therefore, that this simple technique is a reliable method for distinguishing these two closely related but disparate lesions.

Antibodies, Monoclonal↗

Pigmented and nested sebomatricoma or seborrheic keratosis with sebaceous differentiation?

Recently, the term sebomatricoma has been proposed as the most appropriate denomination to avoid controversial and confusing terms and to encompass all benign neoplasms with sebaceous differentiation. We report on two specimens that may be interpreted as examples of two new histopathologic patterns in sebomatricoma, namely, pigmented and nested sebomatricoma, or as seborrheic keratosis with sebaceous differentiation. The first case consisted of a neoplasm composed of basaloid immature cells with features of sebaceous differentiation in the form of clusters of sebocytes and sebaceous ducts, in addition to the proliferation of dendritic melanocytes arranged as solitary units scattered through the neoplastic aggregations of immature germinative sebaceous cells. The second case, in addition to the proliferation of single dendritic melanocytes as the first case, showed well-defined nests of basaloid and heavily pigmented germinative sebaceous cells connected to the skin surface and numerous sebaceous ducts. In the first case, the pigmented nature of the lesion was the most striking histopathologic characteristic, whereas the nested pattern was remarkable in the second one. Immunohistochemical investigations demonstrated positivity of cytokeratin MNF116 in neoplastic aggregations of germinative sebaceous cells, whereas the clusters of mature sebocytes and sebaceous ducts expressed epithelial membrane antigen positivity. S-100 protein made evident the scattered dendritic melanocytes, but neoplastic cells resulted negative.

Basal Cell Carcinoma↗

Sebaceoma arising in association with seborrheic keratosis.

We report a case of a 60-year-old woman with a 4-year history of an asymptomatic plaque on her left cheek. The lesion was composed of two distinct adjacent and continuous parts comprising a lateral yellowish flat portion and a medial reddish nodular portion. Histologic examination revealed that the plaque was composed of two different adjacent tumors. The lateral portion of the plaque had the aspect of a seborrheic keratosis (SK) with hyperkeratosis and acanthosis with irregular proliferation of apparently benign basaloid and squamous keratinocytes and small horn pseudocysts. The medial portion showed a dermal tumor made up of differently sized lobules composed of immature sebocytes mixed with single or clustered mature sebaceous cells. Sebaceous ductal differentiation was visible. We made the diagnosis of SK associated with sebaceoma. The association of an SK with a benign neoplasm with sebaceous differentiation is rare. It may only be a coincidence, but a role for the preexisting SK cannot be ruled out.

Female↗

Standardized AgNOR analysis in actinic keratosis.

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 (microm(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 microm(2); SD + 0.332), AK (3.988 microm(2); SD + 0.914), BCC (3.044 microm(2); SD + 0.254), and SCC (5.286 microm(2); SD + 0.920). In AK, a progressive increase of mean NORA values was observed moving from Stage I (3.161 microm(2); SD + 0.600) to Stage II (3.455 microm(2); SD + 0.562), Stage III (4.360 microm(2); SD + 0.295), and Stage IV (5.168 microm(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.

Adult↗

S100A protein expression in the distinction between lentigo maligna and pigmented actinic keratosis.

Lentigo maligna (LM), a type of malignant melanoma in situ, and pigmented actinic keratosis (PAK) may have similar clinical appearances but are different in prognosis and treatment. Diagnosis is established by skin biopsy. In certain cases, microscopic features may be very similar in both entities, making it difficult to determine whether the pigmented atypical cells are keratinocytes or melanocytes. Immunohistochemical markers can be useful for the identification of melanocytes in these cases. There are limitations to the use of some standard immunohistochemistry markers, however. S100 proteins are a varied group of proteins that are of special interest because of their dysregulated expression in neoplastic disorders. Their expression is changed during malignant transformation, progression, and/or metastasis in various cell lines and tumors, including melanomas. Our study analyzed the expression of several of the S100 protein subtypes (S100A2, S100A6, and S100A8/A9 or A12) in 38 LM cases and 44 PAK cases to define their potential value in the distinction between these entities together with their role in the development of early malignant melanoma of the skin. The results showed an upregulation of S100A2 protein in atypical keratinocytes in PAK and in normal keratinocytes adjacent to melanoma cells in LM. There was also an upregulation of S100A8/A9 or A12 protein, as detected by the antibody MAC387, in normal keratinocytes adjacent to both atypical keratinocytes and melanocytes in PAK and LM, respectively. There were statistically significant differences in the level of positive cells and in the pattern of immunoreactivity for anti-S100A2 and MAC387 in each entity, however. Moreover, the findings of our study support the notion that melanocyte-keratinocyte interactions are abnormal in both of these disease entities and may be involved in their progression.

Adult↗

Keratosis lichenoides chronica: proposal of a concept.

It has been a subject of controversy whether keratosis lichenoides chronica (KLC) is a distinctive inflammatory disease of the skin or whether it represents a manifestation of another well-known disease, such as lichen planus, lupus erythematosus, or lichen simplex chronicus. In search of clear criteria for diagnosis of KLC the entire literature pertinent to the subject was studied and findings clinical and histopathologic as they were telegraphed in them were compared with a patient of my own experience. Review of the literature reveals more than 60 patients in whom the diagnosis of KLC was made. Three categories emerge based on whether the findings presented in a particular article (1) do not permit any diagnosis to be rendered; (2) do allow a diagnosis specific to be made, such as of lichen simplex, lichen planus, or lupus erythematosus; or (3) do not correspond to any disease well defined, such as lichen simplex, lichen planus, lupus erythematosus, but seem to show attributes morphologic, clinically and histopathologically, that are repeatable. Patients diagnosed as having KLC obviously represent a potpourri of different diseases, the most common of them being lichen simplex chronicus, lichen planus, and lupus erythematosus. Fewer than 25 patients reported on, however, presented themselves with lesions very similar to one another clinically, namely, an eruption that involved the face in a manner reminiscent of seborrheic dermatitis and with tiny papules on the trunk and extremities, which assumed linear and reticulate shapes by way of confluence of lesions. Individual papules were infundibulocentric and acrosyringocentric. Findings histopathologic were those of a lichenoid interface dermatitis affiliated with numerous necrotic keratocytes and covered by parakeratosis housing neutrophils in staggered fashion. These patients seem to have an authentic and distinctive condition that is exceedingly rare. In conclusion, the diagnosis of KLC should be made only for patients who present themselves with features clinical and findings histopathologic that resemble closely those of what is summarized in this article under category 3.

Dermatitis, Seborrheic↗

Comparison of proteinase activities in squamous cell carcinoma, basal cell epithelioma, and seborrheic keratosis.

The correlation between proteinase activities and invasive and metastatic potentials was investigated by comparing three different kinds of tumors. Extracts from tumor homogenate of 11 squamous cell carcinoma (SCC), 5 basal cell epithelioma (BCE), and 8 seborrheic keratosis (SK) were prepared in order to examine the activity of acid phosphatase and proteinases such as cathepsin B and D, type I and IV collagenase, and plasminogen activator (PA). There was no difference observed between acid phosphatase and cathepsin D activities among the three tumors. Cathepsin B and PA activities were slightly elevated in SCC. Type I collagenase activity of SCC was 9-fold higher than that of SK (p less than 0.01), and type IV collagenase was 3-fold higher per tissue DNA (p less than 0.05). Type I and IV collagenase of BCE were elevated per tissue protein but not elevated per tissue DNA. Correlation was found between the level of cell differentiation in SCC and the activities of cathepsin B, PA, and type I collagenase. Poorly differentiated SCC exhibited a tendency to have higher proteinase activities. Proteinases that showed high activities in malignant tumor homogenate may be related to the degradation of the surrounding cell matrix in addition to intracellular metabolism. Type I and IV collagenase, in cooperation with cathepsin B and PA, might play a major role in invading the dermal stroma and basement membrane.

Basal Cell Carcinoma↗

Lichenoid solar keratosis--prevalence and immunologic findings.

Solar keratoses (SKs) may show basal cell liquefactive degeneration (BLD) and, when extensive, this can result in a superficial resemblance to lichen planus. The frequency of these phenomena and involvement of immune mechanisms in them have been investigated in this study. The prevalence of lichenoid keratosis (LK) was 6.1% in 212 SKs examined retrospectively and 10.7% in 28 examined prospectively. Histologic features were scored on analogue scales and their interrelationships examined. BLD could not be correlated with epidermal atypia, acanthosis, acantholysis, or inflammatory cellular infiltrate; a negative correlation occurred with parakeratosis. Immunoglobulins and/or fibrin and complement were found by immunofluorescence in 78.8% of the 28 specimens examined prospectively. Three LKs showed similar immunofluorescence findings to ordinary SKs. No circulating antibodies to epidermal structures were detected in patients with SKs. It is concluded that (1) no feature of SKs investigated predisposed to lichenoid change, (2) BLD was a frequent feature in SKs whereas full development of LK occurred much less frequently, and (3) immunoprotein deposits were not related to the development of BLD. Clinically, LKs could not be distinguished from ordinary SKs.

Fibrin↗

Correlation between macroscopic fluorescence and protoporphyrin IX content in psoriasis and actinic keratosis following application of aminolevulinic acid.

In fluorescence diagnosis with 5-aminolevulinic acid (ALA)-induced porphyrins (FDAP), protoporphyrin IX (PpIX) accumulation can be macroscopically visualized. Interpretation of these data is still problematic because of the low reproducibility of the procedure and poor understanding of the mechanisms involved in PpIX tumor selectivity. In this study, PpIX accumulation is investigated in patients with psoriasis and actinic keratosis (AK) following FDAP. For this purpose, desquamated lesional and non-lesional skin were incubated with 20% ALA ointment for 3 h, FDAP was performed, and highly fluorescing lesional skin and non-lesional skin were biopsied. In extracts from these biopsies, PpIX, protein, and dsDNA were quantified by spectrofluorometry. Digital images acquired with FDAP were analyzed using image analysis software. PpIX per biopsy in lesional skin in both psoriasis and AK was significantly higher than in non-lesional skin (p < 0.05). When corrected for epidermal involvement, only lesional psoriatic skin showed significantly higher PpIX levels than non-lesional skin. The PpIX-ratio lesional:non-lesional skin (mean(pmol per mL)+/-SEM) was 4.12+/-0.91 in psoriasis and 1.96+/-0.24 in AK. In FDAP, the ratio of lesional:non-lesional skin was 1.77+/-0.06 in psoriasis and 1.37+/-0.07 in AK. Macroscopic fluorescence and PpIX content appeared to be well correlated (r = 0.73), thus making FDAP a good predictor of PpIX content.

Aminolevulinic Acid↗

Infundibular keratosis--report of two cases.

Two cases of infundibular keratosis are presented, characterized histopathologically by funnel-shaped, invaginating, epithelial lobules showing infundibular keratinization and connection with pilosebaceous structures. Lightly-staining, glycogen-laden epithelial cells predominated within the two tumors. Differential diagnoses with other infundibular tumors and relationships to trichilemmoma are discussed.

Aged↗

An unusual mechanical hyperkeratosis of the soles--health sandals keratosis.

A series of 13 patients with hyperkeratosis of both soles of the feet are presented. All patients developed hyperkeratosis after wearing the so-called "health sandals", which have multiple projections on their upper surfaces to stimulate the soles while walking. There was no evidence of hereditary or systemic factors producing the hyperkeratosis and it was concluded to be due to chronic mechanical stimulation of the soles. This side effect of the wearing of "health sandals" (health sandals keratosis) should be noted by dermatologists.

Adult↗

Keratosis lichenoides chronica: a variant of lichen planus.

In order to establish a possible relationship between keratosis lichenoides chronica (KLC) and lichen planus (LP), we performed a comparative study which included routine histologic examination, electron microscopy, and direct immunohistochemical studies from one case of KLC and several patients with LP. Our findings demonstrate that KLC and LP share many similarities; their differences are mostly quantitative. In KLC, the findings are more prominent; we therefore conclude that KLC is at one end of the spectrum of LP.

Chronic Disease↗

A case of seborrheic keratosis distributed along skin cleavage lines.

A 65-year-old woman with seborrheic keratosis following skin cleavage lines is reported. The mostly brownish-yellow lesions were located on the back. The round, oval, spindle, comet, and slightly raised papules varied from 1 mm to 2 cm in diameter. The distribution of lesions was unusual; they tended to follow skin cleavage lines on her lower back and waist. The arrangement of lesions was streamlined. The skin biopsy specimen revealed hyperkeratosis, acanthosis, and papillomatosis. The acanthosis was caused by proliferation of squamous and basaloid cells.

Aged↗

Keratosis lichenoides chronica: marked response to calcipotriol ointment.

Keratosis lichenoides chronica (KCL) is a rare dermatosis characterized by a distinctive seborrheic dermatitis-like facial eruption, together with violaceous, papular, and nodular lesions on the extremities and trunk, typically arranged in a linear and reticulate pattern. KLC is resistant to therapy, although spontaneous remission has been reported. We describe a 35-year-old woman with KLC who had the typical features of widespread violaceous, reticulate, and striae-like eruptions with a prominent keratotic component over a nine-year period and who responded well to treatment with calcipotriol ointment. The immunohistochemical profiles are presented in addition to typical histopathologic features.

Administration, Cutaneous↗