[Figurated plaque on actinically damaged skin. Actinic O'Brien granuloma].
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Biomedical subjects
Publications and source records attributed to W H Burgdorf.
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The immunomodulatory macrolactams provide an alternative to glucocorticosteroids for the topical treatment of atopic dermatitis and other inflammatory dermatoses. Tacrolimus (FK506), as well as the newer ascomycin derivative ASM 981 (pimecrolimus), penetrate the inflamed epidermis and are suitable for topical therapy. Both substances inhibit the transcription of proinflammatory cytokine genes such as interleukin 2, which are dependent on the nuclear factor NF-AT. They block the catalytic function of calcineurin, which leads to the inhibition of the transport of the cytoplasmic component of NF-AT to the cell nucleus. Multicenter, randomized, double-blind clinical trials with topical formulations have shown the efficacy of both substances in moderate to severe atopic dermatitis. A review is presented of the biochemical and cell biologic properties, mode of action, pharmacokinetic data, side effects, results of the clinical trials, and further indications for tacrolimus and ASM 981, along with an overview of the related substances cyclosporine and sirolimus (rapamycin).
Cowden syndrome is a rare autosomal dominant familial cancer syndrome with a high risk of breast cancer. The most important clinical features include carcinomas of the breast and thyroid, and hamartomatous polyps of the gastrointestinal tract. There are characteristic mucocutaneous features which allow early recognition of the disease and are generally present before internal malignancies develop. We report on a woman in whom the diagnosis of Cowden syndrome was first made after she had been treated for both breast cancer and melanoma.
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BACKGROUND AND OBJECTIVE: Actinic prurigo (AP) is a hereditary photodermatoses with typical symptoms and is quite common in North- and South-America. The key genetic factor appears to be a Native American background. In Europeans this type of AP is extremely rare; some dispute if this disease exists in Caucasians. Some newer publications postulate that these patients share HLA markers with the Native Americans. The most important differential diagnosis for AP is polymorphic light eruption which can be excluded relatively accurately by the clinical picture, typical histology and HLA pattern. PATIENTS/METHODS: The case of a female patient of Mayan ancestry living in Germany is presented. CONCLUSIONS: Since in literature sometimes cases from Europe are diagnosed as AP this is a problem of naming the disease. It would be helpful to integrate the terms hereditary or hereditaria into the name of the disease in indians.
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In 1893, Unna published his theory of Abtropfung in which he suggested that melanocytic nevus cells originate in the epidermis and drop off into the dermis. We studied 3,534 nevi from patients of all ages to reassess this almost sacred concept. If Unna was correct, one would expect that in childhood most nevi would be junctional, while in late adult life almost all nevi would be intradermal. In our series, no child under age 10 had a purely junctional nevus, 52% had compound nevi, and 48% had dermal nevi. In patients older than age 60, 12% had junctional nevi, 23% had compound nevi, and 65% had dermal nevi. Our data fail to support the concept of Abtropfung; they fit better with the contradictory theory of upward migration of nevus cells.
Trichoblastoma and nodular basal cell carcinoma are generally held to be distinctive epithelial neoplasms with some overlapping features. We investigated 30 trichoblastomas in which the basaloid cells expressed cytokeratins (CK) CK5/6, CK14, CK17, CK19, and, in a few cells, vimentin. The cells of the periphery of small and large cysts showed the same profile. Cells lining the lumen of small cysts expressed CK14, CK17, and involucrin, and those in larger cysts showed a positivity for CK1, CK4, CK10, CK14, CK17, and involucrin. The remaining tested antibodies (CK7, CK8, CK13, CK18, CK20, alpha-smooth-muscle actin) were negative in all cases. The cells of the stroma expressed vimentin and in 22 cases, the CD34 antigen. Seventeen nodular basal cell carcinomas showed exactly the same staining pattern. Furthermore, there are striking immunohistochemical similarities between the neoplastic basaloid cells of both neoplasms and the cells of the hair germ. Therefore, trichoblastoma and nodular basal cell carcinoma cannot be distinguished by their pattern of cytokeratin expression in paraffin sections. The virtually identical cytokeratin pattern seen in trichoblastoma, basal cell carcinoma, and the developing fetal hair follicle is compelling evidence for common differentiation pathway.
The expression of cytokeratins (CK), involucrin, vimentin, CD34, and alpha-smooth-muscle actin was studied in fetal and adult hair follicles. The first stage of the developing hair follicle is characterized by palisaded, elongated epithelial cells budding from the epidermal basal layer. These cells express CK5/6, CK14, CK17, CK19, and vimentin. During the following weeks of gestation, different structures in the developing hair follicle can be identified and characterized. The matrical cells display only CK19. The keratinocytes of the outer root sheath express CK5/6, CK14, CK17, CK19, and involucrin; those of the inner root sheath, CK4, CK18, and involucrin; those of the isthmus, the same profile as the ORS. In the infundibulum, the basal-layer keratinocytes express CK5/6, CK14, CK17, and CK19, whereas in the suprabasal layers CK1, CK4, CK10, CK14, and CK17 are seen. The adult hair follicle in anagen fails to express CK19 in the matrical cells and isthmus and both CK17 and CK19 in the infundibulum. These profiles of intermediate filaments and other markers appear to be potentially useful in categorizing neoplasms with apparent follicular differentiation.
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We studied 722 reexcision scars of benign and malignant lesions (except melanocytic lesions) excised over a 24-month period. The formalin-fixed, paraffin-embedded tissue sections were examined histologically and immunohistochemically. The histological features of melanocytic hyperplasia were present in 59 cases (8%), 56 from the sun-exposed skin of the face and neck and three from the trunk [p < 0.00001]. The most common sites were the nose and lower eyelids, but the forehead was also frequently involved. Of the 59 patients, 41 were women (p < 0.0001). Basal cell carcinoma was the most frequent original lesion in both sexes (80%). No melanocytic hyperplasia was found in 663 cases (298 on the trunk and extremities and 365 on the head and neck). We have seen this reaction pattern following reexcision of melanocytic lesions as well. Thus, interpreting reexcision margins when lentigo maligna or similar lesions are reexcised may be fraught with difficulty. It is important for pathologists and dermatopathologists to recognize this phenomenon because histologically the presence of increased numbers of large melanocytes could be misinterpreted as melanoma in situ.
The cutaneous histiocytoses are best divided in the Langerhans' cell histiocytoses and non-Langerhans' cell histiocytoses. In the former group, the cells react with S100 and CD1a antibodies, while in the latter group they express a variety of macrophage markers. Xanthogranuloma is a frequent childhood tumor and the only common non-Langerhans' cell histiocytosis. Xanthogranulomas contain a mixture of several different types of histiocytes that also appear in more pure forms as both solitary tumors and disseminated processes. The varying histiocyte morphology provides a unifying concept for non-Langerhans' cell histiocytoses.
Twelve cases of solitary spindle cell xanthogranuloma, seven of which had originally been misdiagnosed as dermatofibroma/benign fibrous histiocytoma, were clinicopathologically compared with four cases of progressive nodular histiocytosis, a rare generalized non-X histiocytic disorder. Clinically, a single brown-yellowish papule or nodule is characteristic of solitary spindle cell xanthogranuloma, multiple generalized lesions of progressive nodular histiocytosis. Solitary spindle cell xanthogranuloma occurs with decreasing frequency on the head, neck, upper trunk, or occasionally the extremities of young adults (aged 20-40 years), progressive nodular histiocytosis mostly on the trunk of older patients (aged 40-60 years), both without sex predilection. Histologically, both entities are characterized by predominance (> 90%) of spindle-shaped histiocytes arranged in a storiform pattern. Other mononuclear (vacuolated, xanthomatized, scalloped, oncocytic) and multinucleate (Touton) histiocytes are also regularly seen. Immunohistochemically, both entities exhibit a macrophage/dendritic cell lineage positive for KP1/Ki-M1p (CD68), HAM 56 and factor XIIIa as well as for smooth muscle specific actin and HHF35. Ultrastructurally, dense, regularly laminated, myeloid or pleomorphic cytoplasmic inclusions may be found, but no Birbeck granules are present. This study documents that both solitary spindle cell xanthogranuloma and progressive nodular histiocytosis are distinct entities within the spectrum of a xanthogranulomatous reaction characterized by predominance of spindle-shaped histiocytes.
Actinic prurigo (AP) is an idiopathic familial photodermatosis seen in American Indians. We report on 17 patients; 16 had dermatitis and one had actinic cheilitis. Ten patients had acute dermatitis and six had chronic dermatitis. The histologies of acute AP and polymorphous light eruption (PLE; limited concept) are eczematous and indistinguishable. Both show spongiosis, superficial (and sometimes deep) perivascular lymphocytic infiltrates, and papillary dermal edema. Both also show vacuolar degeneration of the basal layer. In contrast, the chronic lichenified AP lesions are associated with marked hyperkeratosis, acanthosis, elongation of the rete ridges, and tissue repair. The large lymphoid germinal centers in the lamina propria are the main features of the lip histology. Seven biopsies were positive in the basal membrane zone on direct immunofluorescent testing, four were negative, and one was inconclusive. IgM was present in six and C3 in two. These immunofluorescent results are probably not significant. Immunofluorescent testing of the lip was negative. Although it is not possible to distinguish acute AP from PLE histologically, it is possible to differentiate the two conditions when chronic AP changes are present.
Papillomatous fleshy facial nevi have a low risk of malignant transformation. In addition, they may undergo ossification in their depths; a nevus with bone is known as a nevus of Nanta. Such a nevus in a 60-year-old female gave rise to a malignant melanoma.
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