Photodynamic therapy with 5-aminolevulinic acid: a promising concept for the treatment of cutaneous tumors.
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Biomedical subjects
Publications and source records attributed to H Kerl.
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In neoplastic diseases of the haemopoietic and the lymphatic system, the skin may be infiltrated specifically by neoplastic cells or may display 'nonspecific' cutaneous reactions, frequently associated with a systemic malignancy. Acute febrile neutrophilic dermatosis associated with myeloproliferative disorders and scleromyxedema, lichen myxedematosus, diffuse plane xanthomas and necrobiotic xanthogranuloma associated with paraproteinemia may serve as examples. These conditions as well as several other, often atypical cutaneous manifestations should rise suspicion as to the potential presence of some underlying systemic neoplastic disorder.
BACKGROUND AND DESIGN: Early treatment of erythema migrans is important to prevent late complications. Minocycline possesses several attributes, making it potentially useful in the treatment of borrelial infections. In our study, minocycline was administered to 14 patients with erythema migrans. Punch biopsy specimens were obtained from the (affected) skin of all patients before and after therapy. The formalin-fixed, paraffin-embedded specimens were analyzed by polymerase chain reaction for the presence of Borrelia burgdorferi-specific DNA. RESULTS: Polymerase chain reaction assay succeeded in amplifying B burgdorferi-specific DNA from the first biopsy specimen, obtained from the border of erythema migrans before initiating treatment, in eight (57%) of 14 patients. At the end of minocycline therapy, however, polymerase chain reaction analysis disclosed no B burgdorferi-specific DNA in any of the 14 patients. The good clinical response of our patients with erythema migrans substantiates our molecular findings. CONCLUSIONS: The presented polymerase chain reaction data, together with the clinical outcome, indicate that minocycline may be useful for treatment of early Lyme borreliosis.
A 20-year-old female patient with the typical signs of Wissler's subsepsis allergica (Wissler-Fanconi syndrome) is described. This rare disease is characterized by four typical symptoms: polymorphous exanthemas, recurrent high fever, leucocytosis and arthralgia. In the early stages it is difficult to differentiate from septicaemia. This syndrome has sometimes been considered equivalent to or an initial stage of Still's disease (juvenile rheumatoid arthritis) progressing to degenerative arthritis in many patients, whereas other authors have classified it as a separate entity with good prognosis. The present case demonstrates that Wissler's subsepsis allergica should be considered when ever transient polymorphous exanthema is accompanied by high recurrent fever, leucocytosis and arthralgia.
Late recurrence of malignant melanoma, defined as the occurrence of metastases after a disease-free interval of 10 or more years, is a rare but well-known clinical phenomenon. We report on three female patients who developed in transit metastases 26, 15 and 10 years after excision of the primary tumour. All three patients are disease-free 8 and 9 years after resection of the metastases. Reports in the literature also indicate a favourable prognosis for patients with local recurrence or in transit or regional lymph node metastases. The prognosis for patients with late distant metastases, however, is generally poor. For the first group, an early therapeutic intervention is indicated. This and the occurrence of second and multiple primary melanomas make lifelong aftercare desirable. On the other hand, long-term aftercare of the constantly increasing number of melanoma patients will soon exceed the capacity of existing facilities. A high-risk group for late recurrence that would profit by long-term aftercare cannot be defined at the moment.
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Chemoprevention, the use of drugs to prevent invasive neoplasia, has gained increasing significance in recent years. Especially for the skin, chemoprevention will become of importance, because large areas of the skin are exposed to environmental carcinogenic factors. Furthermore, many skin diseases predispose to the development of multiple skin tumors. One group of chemopreventive agents are the retinoids, which are effective modulators of cell proliferation and differentiation in normal as well as in transformed tissues. Though the mechanism of action of retinoids is not yet fully understood at the molecular level, chemoprevention studies have demonstrated the ability of retinoids to prevent the development of skin cancer, particularly in patients with xeroderma pigmentosum, multiple basal cell carcinoma and oral leukoplakia. A better understanding of the carcinogenic process should improve our ability to develop effective chemoprevention strategies.
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The authors studied five patients with primary cutaneous Hodgkin's disease (PCHD). Each patient presented with skin lesions without evidence of systemic HD. Skin lesions were papules or nodules, many of which regressed spontaneously. Lesions were distinguished from lymphomatoid papulosis (LyP) by the presence of numerous diagnostic Reed-Sternberg (RS) cells that expressed CD30 and CD15 but were negative for CD45R; LyP lesions usually are CD15-, CD45R+. Anaplastic large cell lymphoma (ALCL) was excluded by the polymorphous background of inflammatory cells in PCHD. Three patients with PCHD had a benign course without systemic disease with up to 20 years of follow-up, whereas two other patients developed mixed-cellularity HD in lymph nodes 2 months and 6 years following the onset of PCHD. This study indicates that PCHD does occur as a rare but distinct clinicopathologic entity morphologically and immunophenotypically indistinguishable from nodal HD but with an unexpectedly indolent course in some patients. Patients with PCHD should be observed for development of systemic HD, but unlike patients with LyP or ALCL, an association of PCHD with mycosis fungoides or cutaneous T-cell lymphoma has not yet been observed.
A 31-year-old woman presented with a clinically otherwise unsuspicious area of profuse sweating on her right forearm. Without triggering agents, sweating attacks producing a clear, serous fluid were observed daily. Histopathologic examination of a biopsy specimen showed hyperplastic eccrine glands with pale, stippled cytoplasm characteristic of eccrine hamartoma. No explanation, however, has been given for the fact that several authors observed eccrine hamartomas in the same anatomical location. Adolescent lemurs of the species catta (ringtailed lemur) are equipped with a pair of antebrachial cutaneous glands located on the volar surface of the wrist. They exude a clear secretion enabling them to "brachial branch mark" their territories. Histopathologic findings in the ringtailed lemur's antebrachial organ show characteristics of both apocrine and eccrine glands. In contrast to normal apocrine glands, however, the antebrachial organs of ringtailed lemurs reach the epidermis directly and are not connected to hair follicles. According to the "biogenetic law" of Ernst Haeckel, stating that ontogeny has to be seen as a short and incomplete repetition of phylogeny, a human fetus passes all evolutional stages from a single cell via amphibians and mammals to a human being. Thus, the antebrachial organ of the ringtailed lemur may be the "phylogenetic explanation" for eccrine hamartomas of the forearm in humans. The histopathologic findings of the antebrachial organ and of eccrine hamartomas are in accordance with this hypothesis.
Epidermotropic metastatic malignant melanoma (EMMM) is a well-recognized entity that can simulate primary malignant melanoma, and in the past reports of numerous (> or = 100) such lesions were misconstrued as multiple primary lesions. We present the cases of two patients who had not only numerous epidermotropic metastases that simulated primary melanomas but also 10 lesions that mimicked melanoma in situ. After removal of a primary malignant melanoma, the two patients developed 35 and 22 epidermotropic metastases over a 4-year period before dying with brain and pulmonary metastases, respectively. In these patients, 29 and 22 of the skin lesions were excised, respectively. All had epidermotropic metastases, of which seven and three showed pagetoid melanocytes in a pagetoid pattern exclusively within the epidermis and epithelial structures of adnexa, an "epidermal only" (in situ) pattern. Other lesions showed a continuum of dermal involvement, from the more conventional description of EMMM with the extent of dermal involvement > or = epidermal (n = 2) to epidermal involvement > dermal disease (n = 36). This histologic spectrum of dermal versus epidermal involvement in conjunction with the extremely small size (2.8 mm average histologic diameter), symmetry, large number, and time course of development argues strongly that these lesions represent metastases rather than multiple primary melanomas. The lesions illustrate the diagnostic dilemma posed by EMMM that simulates primary melanoma and further exhibits an "epidermal only" (melanoma in situ) pattern.
The interchromosomal 14;18 translocation occurs in approximately 70-80% of follicular lymphomas and in a lower proportion of high-grade non-Hodgkin lymphomas of the lymph nodes. This translocation results in the fusion of the bcl-2 oncogene on chromosome 18 with immunoglobulin heavy chain genes on chromosome 14, and in the expression of higher amounts of normal bcl-2 protein. We studied bcl-2 expression in biopsies of 108 patients with benign and malignant cutaneous lymphoproliferative diseases (B-cell lymphoma, primary cutaneous, 42; secondary cutaneous, 21; primary cutaneous T-cell lymphoma, 21; B-cell pseudolymphoma, 24), using a monoclonal anti-bcl-2 antibody on paraffin-embedded tissue sections, bcl-2 protein was detected immunohistochemically in 16 of 63 cases of cutaneous B-cell lymphoma, whereas cutaneous T-cell lymphomas and B-cell pseudolymphomas were negative. The proportion of bcl-2 protein expression was significantly higher in secondary (11/21) than in primary cutaneous B-cell lymphomas (5/42; chi 2 test, p < 0.001). Biopsies from 25 of these patients (B-cell lymphoma, 22; B-cell pseudolymphoma, three) were analyzed previously on the molecular level for the t(14;18), using polymerase chain reaction amplification of DNA obtained from paraffin-embedded sections. In four of 11 cases of bcl-2 protein-positive B-cell lymphoma (primary, one; secondary, three) the t(14;18) was detected by polymerase chain reaction. All other cases of B-cell lymphoma, including seven cases where bcl-2 protein was detected by immunohistology, and B-cell pseudolymphoma were negative. These results demonstrate: 1) bcl-2 protein is expressed in a small portion of cutaneous B-cell lymphomas; 2) bcl-2 protein expression is significantly more frequent in secondary than in primary cutaneous B-cell lymphoma; 3) only approximately one-third of cases expressing the bcl-2 protein are characterized also by the t(14;18). bcl-2 protein expression might indicate that the cutaneous manifestation of the lymphoma represents a secondary spread from a node-based lymphoma.
Hyperpigmented macules are a characteristic feature of neurofibromatosis and the McCune-Albright syndrome. Whereas neurofibromatosis 1 has an autosomal dominant mode of inheritance, it has been suggested that McCune-Albright syndrome is the result of a lethal gene surviving by mosaicism. Recent molecular studies have supported this concept by providing evidence of a somatic mutation of the gene encoding the G protein. We report two patients with McCune-Albright syndrome whose melanotic macules show a clear relation to the lines of Blaschko. The lines of Blaschko are thought to represent the dorso-ventral outgrowth of two different cell populations during embryogenesis, thus reflecting genetic mosaicism. A survey of published photographs of patients with McCune-Albright syndrome in the literature revealed additional cases with macules following Blaschko's lines. In other cases, the configuration of the macules was reminiscent of the flag-like rectangular pattern of pigmentation found in human chimaeras. A very early somatic mutation may have similar effects on the pigmentation pattern as a chimaeric state, which is the result of the double fertilization of an ovum. Café-au-lait spots in 10 of our own patients with neurofibromatosis 1 could not be associated with either Blaschko's lines or the rectangular pattern of pigmentation in chimaeras. We conclude that, in contrast with the café-au-lait spots in autosomal dominant neurofibromatosis 1, the configuration pattern of melanotic macules in McCune-Albright syndrome in many cases characteristically reflects the mosaic state of the organism.
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The bcl-2 proto-oncogene encodes a protein that protects cells from programmed cell death (apoptosis). High levels of this protein confer a growth advantage to neoplastic cells even in the absence of a high mitotic rate. This gene is involved in the interchromosomal 14;18 translocation, an abnormality present in more than two-thirds of follicular lymphomas and in about 25% of other non-Hodgkin's lymphomas of the lymph nodes. A recent study also demonstrated the presence of high levels of bcl-2 protein in solid tumors such as squamous cell carcinomas of the lung and related it to a better prognosis. We analyzed bcl-2 protein expression in 20 cases each of basal- and squamous-cell carcinoma and in 5 biopsy specimens of normal skin, using a monoclonal anti-bcl-2 protein antibody with a standard 3-step immunoperoxidase technique on routinely fixed, paraffin-embedded tissue sections. Normal skin showed positive staining of the majority of keratinocytes in the epidermal basal layer. Bcl-2 positivity was also observed within the outer root sheath and the mesenchymal cells of the follicular papillae, the clear cells of the eccrine glands, and in some melanocytes at the dermo-epidermal junction. Neoplastic cells in all cases of basal-cell carcinoma showed a positive cytoplasmic reaction for bcl-2. All biopsy specimens of squamous-cell carcinoma were negative. Expression of bcl-2 protein could also be observed in the majority of peri- and intratumoral lymphocytes in both basal-cell carcinoma and squamous-cell carcinoma.(ABSTRACT TRUNCATED AT 250 WORDS)
Cell motility is a crucial property of tumor cells during invasion and metastasis. In this study we developed a computer assisted system to measure translocation and stationary motility of single cells and used this procedure to evaluate the influence of cytochalasin A (CA) on single-cell motility parameters of K1735-M2 mouse melanoma cells. The cells were seeded at low density into a microincubator. Time lapse microcinematography was performed every 20 seconds from a high power field to assess stationary motility and every 10 minutes with a screening objective to measure translocation. 1 muMol CA was added to the medium 48 hours before measurement. Calculation of stationary motility was performed by subtraction of subsequent images and the resulting image difference was used for quantitative evaluation. Three different measuring windows were drawn to discriminate between membrane ruffling, intracellular organelle transport and overall stationary motility. For each cell we measured change of density (CD), area of change (AC), perimeter of area of change (PC), area of ruffling (AR), number of ruffling sites (NR), change of intracellular organelles (CIO) and number of changing intracellular organelles (NIO). In order to quantify translocation, the center of gravity of each cell was assessed subsequently and the velocity was calculated by connecting the centers of gravity. CA-treated cells showed a significantly lower stationary motility and membrane ruffling compared to the untreated cells (U-test: p < = 0.01), but there was not significant difference concerning the intracellular organelle transport.(ABSTRACT TRUNCATED AT 250 WORDS)
The first case of a solitary dermal Spitz's nevus arising on a nevus spilus is described. The special variant of a combined Spitz's nevus may cause difficulties in differential diagnosis from malignant melanoma in association with a nevus spilus.