[Dermatoscopy. A new method for the clinical diagnosis of malignant melanoma].
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Dermatology↗
Biomedical subjects
H Kerl
Publications and source records attributed to H Kerl.
[Cutaneous calciphylaxis in chronic renal failure].
A case of a 53-year-old chronically uraemic female patient who suddenly developed widespread cutaneous necrosis on both thighs is presented. On the basis of the typical histopathological features a diagnosis of calciphylaxis was made and supported by elevated serum parathyroid hormone levels. Calciphylaxis is a rare and serious disease, mostly seen in uraemic patients subjected to chronic haemodialysis. Typical features are calcifying panniculitis and thrombosis of small to medium-sized blood vessels followed by necrosis of the skin. The poor prognosis is due to systemic calcifications of visceral organs. When acute cutaneous necrosis of the skin is encountered in patients with chronic uraemia calciphylaxis should always be considered as a possible cause in the differential diagnosis. Determination of the serum parathyroid hormone level is recommended.
Biopsy↗
Pathology of tumor-stroma interaction in melanoma metastatic to the skin.
Tumor invasion and metastasis formation largely depend on tumor-stroma interaction. In the present study morphological correlates of tumor-stroma interaction were examined in 344 melanoma lesions metastatic to the skin. In particular, the presence of simple infiltration into the surrounding dermis or subcutis without evident stromal reaction, the incorporation of pre-existent dermal collagen or subcutaneous fat cells into the tumor bulk, and the formation of a peritumoral capsule or intratumoral fibrous septa were evaluated. Our results showed that simple infiltration into the surrounding tissue as well as the incorporation of pre-existent stroma tissue without destruction is associated with poor outcome, whereas capsule and fibrous septa are favorable prognostic signs, particularly in subcutaneous lesions. Remarkably, simple infiltration is a prognostic indicator independent of the location of the metastasis (locoregional or distant), as shown by multivariate analysis. These data indicate that morphological aspects of tumor-stroma interaction in metastatic skin lesions of melanoma may reflect biological behavior of the tumor cells, may facilitate a pathological subclassification of metastatic melanoma in addition to clinical data, and are directly related to the patient's outcome.
Adult↗
Palmar filiform hyperkeratosis: a new paraneoplastic syndrome?
Filiform hyperkeratosis of the palms and soles is a rare disorder. We describe a 70-year-old man with a 2-year history of multiple, filiform, keratotic projections on the palms and a nodular malignant melanoma on the back. Histopathologic examination of the palmar lesions revealed that each single keratotic projection was composed of a well-defined, compact parakeratotic column. The underlying epidermis showed a thinned granular layer. Five other cases of palmoplantar filiform hyperkeratosis in association with malignant neoplasms have been reported. Filiform hyperkeratosis of the palms and soles may represent a distinct paraneoplastic condition.
Aged↗
bcl-2 protein expression in cutaneous malignant melanoma and benign melanocytic nevi.
bcl-2 is a proto-oncogene belonging to a new category of oncogenes that are not involved in the mechanisms of cell proliferation but instead influence tissue homeostasis regulating cell death. The gene encodes for a protein that preserves cells from death by apoptosis, allowing them to survive in G(o) phase even in the absence of essential growth factors. The expression of bcl-2 protein has been observed in most follicular lymphomas and in approximately 25% of high-grade non-Hodgkin's lymphomas, as well as in solid tumors such as carcinomas of the lung, prostate, and nasopharynx. In this study, we analyzed bcl-2 protein expression in cutaneous malignant melanoma (MM) (29 cases) and benign melanocytic nevi (BMN) (35 cases) using a high specific anti-bcl-2 monoclonal antibody with a standard three-step immunoperoxidase technique on formalin-fixed, paraffin-embedded tissue sections. High levels of bcl-2 protein were observed in 27 of 29 MM (93.1%) and 33 of 35 BMN (94.3%). Our results indicate that bcl-2 protein expression is a common finding in cutaneous melanocytic lesions regardless of their biologic behavior. Expression of the protein in the great majority of MM seems to exclude a prognostic significance of bcl-2 in MM of the skin.
Antibodies, Monoclonal↗
Extramedullary hematopoiesis in pilomatricomas.
We report on seven adult patients with pilomatricomas showing histopathologic findings of extramedullary hematopoiesis. There was no Ovidence of hematological disorders or systemic diseases. Clinically, the lesions appeared to be firm, painless nodules situated on the upper extremities, head, and back. Histopathologically, they represented stereotypical examples of regressive pilomatricomas with relatively small basaloid areas and large masses of cornified eosinophilic material containing shadow cells with variable areas of calcification or ossification. Bone marrow cellular elements, including myeloid and erythroid precursors, and (in two cases) megakaryocytes were present. The finding of extramedullary hematopoiesis in seven (5.8%) of 120 cases of pilomatricomas may suggest that this phenomenon is not uncommon in these neoplasms. Interestingly, hematopoietic infiltrates were histopathologically detected to be contiguous with areas of osseous metaplasia in only two of the seven pilomatricomas in our study. It should further be stressed that extramedullary hematopoiesis in regressive lesions of pilomatricomas is a localized phenomenon and that these findings may not be linked with a systemic hematological disorder. The significance of extramedullary hematopoiesis in pilomatricomas, however, remains to be determined.
Adult↗
Quantitative assessment of fat cells in subcutaneous metastatic melanoma. Correlation with outcome.
The metastatic behavior of tumor cells largely depends on tumor-stroma interactions. In the present study, a particular morphological feature of tumor-stroma interaction was evaluated; hematoxylin-eosin-stained slides of 81 lesions of melanoma metastatic to the skin involving the subcutis were examined by automated image analysis for the presence of preexistent fat cells in the tumor. The area occupied by fat cells, expressed in micrometers squared per slide, was of prognostic significance; lesions with a fat cell area of < 41,000 microns 2 showed a 2-year survival rate of 42%, versus 10% in lesions with a fat cell area of > 41,000 microns 2 (log-rank test, z = 3.24; p < or = 0.01). The adverse effect of fat cell area on prognosis still was seen when age, sex, and site of metastatic spread were concomitantly taken into account in a Cox proportional-hazard model. These data indicate that melanoma deposits involving the subcutis with preservation of preexistent subcutaneous fat cells have high metastatic potential and a high risk for rapid internal dissemination.
Adipose Tissue↗
Correlation of melanoma cell motility and invasion in vitro.
Cell motility and the ability to grow invasively are crucial properties within the metastatic cascade. The relation of cell motility in vitro and metastatic behaviour of tumour cells in animal experiments indicates that they are directly correlated. We undertook this study to see whether a quantitative correlation could be found in complex in vitro systems. Using the assay of directional migration and a newly developed image analysis system to measure cell motility of K1735-M2 mouse melanoma cells and the embryonic chick heart assay of Mareel to follow invasion, we examined the influence of eight compounds on cell motility seven compounds on invasion. For stationary motility we calculated the change of density, area of change, area of ruffling sites (representing only changes at the leading edge and tail of the cell), number of ruffling sites, area of changing intracellular particles and number of intracellular particles. Velocity of single tumour cells and directional migration were also measured. In the invasion assay the parameters STRCSTR and INVASLOG, expressing different forms of stromal (i.e. embryonic chick heart) disintegration and degradation, were calculated. Directional migration and all parameters of stationary motility except number of ruffling sites, changing intracellular particles and number of changing intracellular particles correlated significantly (p < 0.05) with STRCSTR and INVASLOG. For velocity, area of change and area of ruffling we found the most significant correlation with parameters of invasion indicating that both stationary and translocative motility contribute to invasion. Our systems also showed that the compounds tested exerted differential effects on various aspects of motility.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Microsatellite instability and loss of heterozygosity in melanoma.
Alterations in the repeat length of microsatellites have been identified recently in tumors arising in patients with hereditary nonpolyposis colon cancer and in several human sporadic tumors. We examined 40 sporadic melanomas and their corresponding nontumorous skin for microsatellite instability (MSI) and loss of heterozygosity (LOH) at chromosomes 2q, 3p25-26, 5q11.2-13.3, 5q21, 6q27, 9p21, 9p22-pter, 17p12, 17p12-p11.1, and 18q23. Specific loci were amplified by polymerase chain reaction, electrophoresed on polyacrylamide gels, transferred onto nylon membranes, and hybridized with 33P-end-labeled oligonucleotides. MSI was observed in eight of 40 (20%) melanomas at one of 10 loci examined. LOH was found at chromosome region 9p21 in 40%, at 9p22 in 22%, and at 17p in 13% of the informative cases. Comparison between clinicopathologic features of patients with and without MSI revealed no obvious differences. LOH at 9p21 was observed only in lesions greater than 1.5 mm in depth, suggesting that it does not represent an early event in sporadic melanoma. Our results indicate that 1) MSI is a genetic alteration in a proportion of sporadic melanoma, which may reflect a defect in genes involved in DNA replication fidelity; and 2) LOH at chromosome region 9p21 is a significant event in sporadic melanoma. The latter finding further supports the hypothesis that the 9p21 region may contain one or more tumor suppressor genes (e.g., MTS1/CDNK2) involved in the pathogenesis of melanoma.
Adult↗
Computer simulations of histologic patterns in melanoma using a cellular automaton provide correlations with prognosis.
Computer simulations have been used frequently in the life sciences to investigate the mechanisms of morphologic pattern formation. The cellular automaton program SMN5 is designed to simulate tumor growth and to estimate biologic properties by comparing real tumor patterns with computer-simulated reference patterns. This method was applied to 195 cases of primary melanoma of the skin. S-100-stained sections were evaluated by image analysis and compared statistically to a reference set of 4000 simulated patterns. Estimates of tumor cell proliferation, motility, cell loss, cohesion, stroma destruction, and intercellular signals (autocrine and paracrine factors affecting growth, motility, and cell loss) were calculated. Twelve of 18 estimated parameters correlated significantly with tumor progression, as indicated by vertical tumor thickness (linear regression analysis: p < or = 0.05), and 13 of 18 parameters carried prognostic significance (log rank test: p < or = 0.05). Poor prognosis was associated particularly with a pronounced increase in the estimates of proliferation, tumor cell motility, and stromal degradation. Poor prognosis was also associated with a decrease in the estimates of cell loss, tumor cell cohesion, and paracrine growth factor dependence. In multivariate analysis using Cox's proportional hazard model, stromal degradation and motility showed prognostic information in addition to conventional prognostic parameters. The study shows that analytical comparison of real tumors with computer-simulated patterns of a cellular automaton facilitates a functional interpretation of tumor morphology, which carries prognostic significance in cutaneous melanoma.
Computer Simulation↗
Multinucleate cell angiohistiocytoma: treatment with argon laser.
Multinucleate cell angiohistiocytoma mainly affects middle-aged women, and usually presents as grouped reddish-brown papules. Histopathological features include the presence of multinucleate cells in the reticular dermis, and numerous dilated dermal vessels. The lesions are benign, and may persist for years. Treatment is needed for cosmetic reasons. We report the successful use of the argon laser to treat two patients who had multinucleate cell angiohistiocytoma.
Adult↗
An update on pachydermodactyly and a report of three additional cases.
Pachydermodactyly is a benign condition characterized by symmetrical, painless, diffuse swelling of the skin on the lateral aspects of the proximal interphalangeal joints of the fingers. Histopathological examination shows epidermal hyperplasia, an increase of dermal collagen bundles and a slightly increased number of fibroblasts. We report three adolescent males with pachydermodactyly. We also review 20 published cases, and discuss the differential diagnosis, clearly distinguishing pachydermodactyly from 'true' and 'false' knuckle pads.
Adolescent↗
Detection of Epstein-Barr virus in cutaneous and lymph nodal anaplastic large cell lymphomas (Ki-1+).
Epstein-Barr virus (EBV) is a gamma DNA herpes virus which is thought to play a part in the pathogenesis of some non-Hodgkin's lymphomas in individuals with or without immunodeficiency. We investigated 16 lymph nodal and 12 cutaneous anaplastic large cell lymphomas (ALCLs) (Ki-1+), all of which were in patients without immunodeficiency, for the presence of EBV genomes. The highly sensitive polymerase chain reaction (PCR) technique was employed for detection of viral DNA in extracts from formalin-fixed, paraffin-embedded tissue sections. In addition, we performed radioactive and non-radioactive in situ hybridization (ISH) for localization of EBV at the single cell level. EBV-DNA was demonstrated by PCR in five cases of nodal ALCLs (31%). All cutaneous ALCLs were negative. EBV-encoded small nuclear RNAs (EBERs) could be identified by ISH in the tumour cells of one of the five EBV-DNA-positive patients. Our results further support the concept that EBV may be involved in the development of a proportion of nodal ALCLs, but not in cutaneous ALCLs.
DNA, Viral↗
Notalgia paraesthetica and macular amyloidosis.
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Amyloid Neuropathies↗
Cutaneous Hodgkin's disease: an immunohistochemical analysis.
Studies of skin involvement in Hodgkin's disease are infrequent in the literature. In particular, immunophenotypic analyses of specific cutaneous infiltrates have been performed in only a few cases. We analyzed the clinical, histological and immunohistochemical features of specific cutaneous manifestations of Hodgkin's disease comparing histologic and immunophenotypic aspects of skin lesions with those of the nodal counterpart. Seven patients with Hodgkin's disease of the lymph nodes and specific cutaneous lesions, where both nodal and skin biopsies were available for histologic and immunohistochemical analyses, were included in this study. Immunohistochemical stains were performed with a 3-step immunoperoxidase technique on routinely-fixed, paraffin-embedded tissue sections. All 7 patients had nodular sclerosis Hodgkin's disease of the lymph nodes. In the skin, clinical presentations included reddish-brown papules, plaques, nodules and ulcerated tumors. Histologic examination of cutaneous lesions showed features consistent with nodular sclerosis Hodgkin's disease in 6 cases and unclassifiable Hodgkin's disease in one. Reed-Sternberg cells and lacunar cells were present in 4 cases (57.1%). Immunohistochemical analysis of Hodgkin's and Reed-Sternberg cells revealed a constant positivity for CD30 (BerH2) and negativity for CD45 (LCA) in both the lymph nodes and the skin. Staining with CD15 (M1) revealed positivity in 7/7 nodal samples and 5/7 skin biopsies. Cytoplasmic expression of immunoglobulin light chains (both lambda and kappa) was observed in one cutaneous case. The accompanying infiltrate was mostly composed of T-lymphocytes admixed with variable numbers of monocytes/macrophages and eosinophils. Our results indicate that the histology of cutaneous specific manifestations of Hodgkin's disease correlates with that of the nodal counterpart in most cases.(ABSTRACT TRUNCATED AT 250 WORDS)
Hodgkin Disease↗
Confocal laser scanning microscopy: a new optical microscopic technique for applications in pathology and dermatology.
Confocal laser scanning microscopy (CLSM) is a new optical microscopic technique, which offers significant advantages over conventional microscopy. CLSM is microscopy of optical sections. Light, which is emitted from regions other than the focal plane, is cut off by introducing a diaphragm in the beam path. The result is an optical "slice", which shows more details because the blurring from out of focus haze disappears. It has been repeatedly used in experimental, but also in diagnostic dermatopathology. The "in vivo" confocal microscopy, applied directly to the intact skin provides details of living cells in the superficial layers comparable to that of fixed and stained tissue. While the extent of its future applications is hard to predict, its potential for applications in dermatology appears enormous, particularly for studies of fixed or living tissues, where it is desirable to obtain clear images many micrometers below the surface of the tissue under examination.
Animals↗
Immunoreactivity for bcl-2 protein in cutaneous lymphomas and lymphoid hyperplasias.
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Humans↗
Diagnostic reliability of dermoscopic criteria for detecting malignant melanoma.
BACKGROUND: Recently a new standardized terminology in dermoscopy has been provided by a Consensus Meeting held by the Committee on Analytical Morphology of the Arbeitsgemeinschaft Dermatologische Forschung in Hamburg in order to be applied to further studies in this field. OBJECTIVE: In this study on 159 pigmented skin tumors including 65 melanomas, the validity of various dermoscopic criteria proposed by the Consensus Meeting for detecting melanoma was evaluated. METHODS: In each lesion, a detailed clinical and dermoscopic examination, photographic documentation of the clinical and dermoscopic appearance, surgical excision and histopathologic evaluation were performed. Statistical analyses including chi 2 statistics, logistic regression analysis and CART (classification and regression tree) analysis were applied. RESULTS: The diagnosis of melanoma using dermoscopy could be obtained easily, if combinations of the following criteria were observed: whitish veil, pigment network alterations (e.g. irregular pigment network, narrow pigment network, broad pigment network), irregular extensions, black dots and gray-blue areas. Interestingly, however, clinical and dermoscopic examination to detect melanomas yielded the same results, namely a sensitivity of 94%. The combined use of both methods led to an increase in the diagnostic sensitivity of 95%, whereas the combination of clinical and dermoscopic examination with logistic regression analysis of dermoscopic criteria enabled us to detect all 65 melanomas in our data set, thus providing a sensitivity of 100%. Furthermore, an algorithm for the classification of melanoma based on the evaluation of dermoscopic criteria has been constructed by CART analysis showing that the presence of a whitish veil in combination with a pigment network inevitably indicates melanoma. CONCLUSION: The validity of the various dermoscopic criteria set forth by the Consensus Meeting could be demonstrated as some criteria (e.g. whitish veil, irregular pigment network, irregular extensions) were observed with a significant higher frequency in melanomas.
Algorithms↗