Malignant melanoma after psoralen and ultraviolet A (PUVA) therapy.
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Biomedical subjects
Publications and source records attributed to H Kerl.
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The object of this study was to evaluate the prognostic impact of a cross-sectional area measured in routinely stained slides of cutaneous melanoma using fully automated image analysis. Hematoxylin-eosin stained slides of 238 specimens of primary cutaneous melanoma with Clark levels III to V were evaluated by digital image analysis using color video images, a scanning stage, and autofocus equipment. The cross-sectional area was significantly related to metastasis-free survival. Lesions with a cross-sectional area < or = 12 mm2 showed a 2-year metastasis-free survival rate of 92+/-2% compared with 41+/-8% in lesions with a cross-sectional area > 12 mm2 (log rank test: z = 71, p < 0.0001). The same was true for overall survival (98+/-1% compared with 82+/-6%; z = 42.12, p < 0.0001). In multivariate analysis, the cross-sectional area seems to provide prognostic information in addition to that provided by Breslow's index. In cases with regression and in small melanomas with vertical growth, however, metastatic spread may occur in lesions with a small cross-sectional area. It was concluded that automated measurement of the cross-sectional area may be helpful in assessing prognosis in cutaneous melanoma.
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The importance of tumor-stroma interaction in many solid tumors of the skin has been demonstrated in recent years. Invasion and metastasis require multiple interactions of the tumor cells with the surrounding stroma. In malignant melanoma most studies concerning tumor-stroma interaction focus on the peritumoral infiltrate, whereas other aspects of tumor-stroma interactions have not been considered. We investigated two morphologic criteria of tumor-stroma interaction in melanocytic skin tumors. Simple infiltration into the surrounding dermis or subcutis without evident stromal reaction (DERMSIMPLE) and the existence of morphologically intact collagen bundles of the reticular dermis within the tumor bulk (PRECOLL) were examined in 373 benign common nevi, 239 dysplastic nevi, 322 Spitz nevi, 368 primary malignant melanomas, and 344 melanoma lesions metastatic to the skin. Our results showed that there is a highly significant difference in the expression of DERMSIMPLE and PRECOLL between benign and malignant melanocytic skin tumors. Concerning DERMSIMPLE, 13.3% of benign skin lesions compared with 28.2% of malignant lesions were positive for this feature; PRECOLL was found in 13.8% benign and 37.1% malignant lesions (chi-squared test; p = 0.0001 for both features). Furthermore, it could be demonstrated that simple infiltration into the surrounding stroma as well as the existence of morphologically intact collagen bundles of the reticular dermis within the tumor bulk increases with tumor progression; between primary malignant melanoma and melanoma metastatic to the skin, for example, there was a highly significant difference for DERMSIMPLE, as well as for PRECOLL (chi-squared test; p = 0.00001). These data indicate that morphologic aspects of tumor-stroma interactions in different benign and malignant melanocytic skin lesions may reflect biological behavior of tumor cells. The analysis of further aspects of tumor-stroma interaction and the relation to the patient's outcome may lead to the development of further prognostic parameters in malignant melanoma.
In a previous qualitative study it has been shown that the incorporation of pre-existing collagen bundles from the reticular dermis into the bulk of melanoma lesions metastatic to the skin indicates rapid systemic spread. In the present study the amount of pre-existing dermal collagen in the bulk of the melanoma lesions in 267 cases of primary melanoma of the skin with a Clark level of at least III was quantitatively assessed using automated image analysis based on RGB (red, green and blue) colour images of sections stained with haematoxylin and eosin. There was a weak correlation between the amount of pre-existing collagen and the Clark level and the Breslow index. With regard to prognosis, a large amount of pre-existing collagen (> 0.13 mm2 per index slide) was significantly associated with a particularly poor outcome (24-month survival rate: 71 +/- 17% compared with 96 +/- 2%; log rank test: P < 0.001). It is clear that a large amount of pre-existing collagen bundles occurring as a particular feature of tumour-stroma interaction indicates high metastatic capacity in primary malignant melanoma.
Sunscreens have been advocated to prevent burning in the hope that this will decrease the chance of developing melanoma. In a single-centre case-control study in Styria, Austria, we examined the risk of cutaneous malignant melanoma in relation to phenotypic markers, sunlight-related factors and sunscreen use. In total, 193 melanoma patients and 319 control subjects answered a comprehensive questionnaire regarding phenotypic markers, a variety of sunlight-related factors and sunscreen use. Risk factors for melanoma were examined through the use of unconditional logistic regression analysis, controlling for age and sex. Screening for confounding factors was done by forward and backward elimination of non-significant variables (P < 0.05). The resulting set of factors were investigated further for effect modification by introducing interactions into the model. The factor most significantly associated with increased melanoma risk was the use of sunscreens. Subjects who often used sunscreens had an increased odds ratio (OR) of 3.47 (95% confidence interval [CI]1.81-6.64) compared with subjects who never used sunscreens (P = 0.001), after adjustment for sex, age and other significant sunlight-related factors. Skin colour and higher numbers of sunbaths were significant protective factors. Subjects with medium skin colour had an adjusted OR of 0.63 (95% CI 0.41-0.99) compared with subjects with light skin colour (P = 0.0022). Subjects who took more than 30 sunbaths per year and subjects who took 20-30 sunbaths per year had, in the absence of sunburn(s), a decreased OR of 0.09 (95% CI 0.02-0.39) and 0.28 (95% CI 0.13-0.64), respectively, compared with subjects who took less than 20 sunbaths per year (P = 0.0002). However, sunbaths had no protective value when they were associated with sunburns. Although we cannot exclude the presence of an unknown confounding factor, our results suggest that the use of sunscreens does not help prevent melanoma.
Accurate clinical diagnosis of malignant melanoma is of great importance for early detection and further treatment. The purpose of this retrospective study was to evaluate the accuracy of clinical diagnosis by using different clinical and histopathological parameters. Calculations are based on a total of 44,258 histopathologically examined skin neoplasms, including 529 melanomas, which were recorded in the histological database of the Department of Dermatology, University of Graz during a 2 year period. The clinical diagnosis of the referring physicians was compared statistically with the final histopathological interpretation. Clinical diagnosis of melanoma showed a sensitivity of 70.1%, a specificity of 99.4%, and a positive predictive value of 60.7%. One hundred and fifty eight melanomas (29.9%) could not be diagnosed clinically. The age-dependent sensitivity was 47.6% in patients <40 years, whereas for patients >80 years the value was 90.2%. Remarkably, the sensitivity in melanomas >4 mm thickness (64.8%) was lower than in 'melanoma in situ' (72.6%). Our findings underline the importance of further development of clinical examination techniques such as dermoscopy and digital epiluminescence microscopy.
Expression of cell surface molecules that mediate cell-matrix and cell-cell interactions largely contributes to the ability of melanoma cells to migrate and spread beyond the primary site of the tumor. CD44, the principal cell-surface receptor for hyaluronate, and its numerous splice variants have been reported to play a crucial role in invasion and the metastatic process of different human neoplasms, including primary malignant melanoma (PMM). The aim of this study was to clarify which isoforms of CD44 (standard CD44 and CD44 variants) are distributed in PMM with a vertical tumor thickness of >1.4 mm. Staining of CD44 standard (CD44s) and splice variants was further examined for diagnostic and prognostic relevance in a panel of melanocytic skin lesions. Ten cases of PMM with Breslow >1.4 mm were analysed by immunohistochemistry using monoclonal antibodies specific for CD44s and the splice variants v3, v5, v6, v7, v7-8, and v10. In addition, using anti-CD44s, v5, and v6 antibodies, 55 melanocytic lesions, including dermal nevi (n=12), Clark nevi (dysplastic nevi) (CN; n=11), melanoma in situ (Mis; n=8), PMM (n=18), and cutaneous metastasis of malignant melanoma (cMMM; n=6) were assessed. Staining intensities were scored visually and evaluated by means of a staining index. In ten cases of PMM with a Breslow index >1.4 mm positive staining was ascertained for CD44s, v5 and for v6 in three cases. No staining was found for v3, v7, v7-8, and v10. Examination of CD44s, v5, and v6 in 55 melanocytic skin lesions revealed a high index for CD44s in all specimens and a weak staining of v5 in Mis; dermal nevi and CN did not stain for v5. However, in PMM and cMMM we found v5 to be strongly positive. The isoform v6 showed a variable index only in PMM, but without connection to established prognostic criteria. We conclude that CD44s and splice variants can not be regarded as indicators for tumor progression in malignant melanomas. However, v5 may potentially serve as a diagnostic marker for melanocytic skin lesions.
PURPOSE: Patients with primary cutaneous melanoma with a Breslow thickness > or = 1.5 mm have only a 30% to 70% probability of survival after surgery, and no adjuvant therapy has so far improved this outcome. Since interferon alfa-2a (IFNalpha2a) exhibits antitumor activity in metastatic melanoma, we investigated whether adjuvant IFNalpha2a diminishes the occurrence of metastases and thus prolongs disease-free survival in melanoma patients after excision of the primary tumor. PATIENTS AND METHODS: In a prospective randomized study, 311 melanoma patients with a Breslow thickness > or = 1.5 mm were assigned to either adjuvant IFNalpha2a treatment (n = 154) or observation (n = 157) after excision of the primary tumor. IFNalpha2a was given daily at a dose of 3 mIU subcutaneously (s.c.) for 3 weeks (induction phase), after which a dose of 3 mIU s.c. three times per week was given over 1 year (maintenance phase). RESULTS: Prolonged disease-free survival was observed in patients treated with IFNalpha2a versus those who underwent surgery alone. This difference was significant (P = .02) for all patients enrolled onto the study (intention-to-treat analysis) at a mean observation time of 41 months. Subgroup analysis showed that Breslow tumor thickness had no influence on treatment results in the groups of patients investigated. CONCLUSION: Adjuvant IFNalpha2a treatment diminishes the occurrence of metastases and thus prolongs disease-free survival in resected primary stage II cutaneous melanoma patients.
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Ancient melanocytic nevus is an example of a simulator of malignant melanoma, designated ancient because it shares numerous features with ancient schwannoma. Knowledge of the histopathologic characteristics of this benign melanocytic neoplasm should enable pathologists to avoid overdiagnosis of it as melanoma arising in the intradermal portion of a nevus. Ancient nevi are found most commonly on the face of older persons. The neoplasm is usually a dome-shaped, skin-colored or reddish brown papule, usually with features of a Miescher's nevus. Histopathologically, ancient nevi are exoendophytic, mostly intradermal proliferations of two populations of melanocytes: one with large pleomorphic nuclei and the other with small monomorphous ones. The large melanocytes may resemble those of the epithelioid type of Spitz's nevus. A few mitotic figures may be present in a particular section. The epidermis usually is uninvolved, but sometimes there may be a junctional component. Other important findings are degenerative changes that include thrombi, zones of hemorrhage, pseudoangiomatous changes, thick rims of sclerosis around dilated venules, fibrosis, and mucin. Ancient nevi frequently are misdiagnosed as melanoma arising in an intradermal nevus.
Early recognition of malignant melanoma is crucial in order to remove lesions at a stage when complete cure can still be achieved. Unfortunately, however, some melanomas defy clinical and/or histopathological recognition, and some benign lesions (melanocytic or non-melanocytic) can present with clinical and/or histopathological aspects simulating malignant melanoma. Awareness of these simulators is important to avoid pointless (and potentially dangerous) aggressive treatments. In this review, we have illustrated the clinicopathological features of the most important benign simulators of malignant melanoma of the skin.
In the present study, we retrospectively evaluated the clinical, laboratory, phototest and phototherapy findings in 133 patients (109 females and 24 males) with polymorphic light eruption (PLE). The median age of the patients at onset of PLE was 26 years (range, 3-62 years). The median duration of PLE at presentation was 6.5 years (range, 1 week to 25 years). Interestingly, we found two peaks in the distribution curve of the individual latent interval, the time between light exposure and the appearance of skin lesions. The first peak occurred at 1-1.5 hr and the second peak at 24 hrs after light exposure. Six of 33 patients tested had antinuclear antibodies (ANA). However, none of these ANA-positive patients had or developed systemic lupus erythematosus during follow-up. Phototesting revealed that minimal erythema doses for UVA and UVB fell within normal limits in 30 patients tested. Provocative phototesting was positive in 17 of 30 (57%) patients tested. The action spectrum fell within the UVA range in 10 (59%), the UVB range in 4 (23%), and both ranges in 3 (18%) of the 17 cases. Ninety-two patients received preventive phototherapy including broad-band UVB, broad-band UVA, or psoralen and ultraviolet A (PUVA). Follow-up information was available for 79 of these patients: the complete protection rate in the first summer season after therapy was 27% for UVB, 0% for UVA, and 53% for PUVA whereas the overall protection rate (including partial and complete responders) was 83% for UVA, 82% for UVB and 65% for PUVA. In contrast, the patients' histories revealed that the use of a sunscreen with a mean sun protection factor (SPF) of 14 did not prevent skin lesions in 88% of PLE patients.
Primary cutaneous lymphomas represent a heterogeneous group of T- and B-cell lymphomas that show considerable variation in histology, phenotype, and prognosis. Recently, the European Organization for Research and Treatment of Cancer (EORTC) Cutaneous Lymphoma Project Group has reached consensus on a new classification for this group of diseases. The EORTC classification for primary cutaneous lymphomas is based on a combination of clinical, histologic, and immunophenotypic criteria, and thus contains well-defined disease entities rather than histologic subgroups. In addition, this new classification contains a number of provisional entities, which may display characteristic histologic features, but are not yet well defined clinically. These provisional entities account for less than 5% of all primary cutaneous lymphomas. In this report the basic principles of this new classification, as well as the characteristic features of the different disease entities, are described. In addition, survival data of 626 patients with primary cutaneous lymphomas derived from the registry of the Dutch Cutaneous Lymphoma Working Group, illustrating the clinical validity of this new classification, are presented.
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We studied the clinical and histopathologic features in five patients with reticulated lentigo. This peculiar pigmented skin lesions has previously been described under the designations "acquired reticulated lentigo", ink spot lentigo, "reticulated melanotic macule" or "reticulated lentigo". Each of the 4 males and 1 females in our study (age range: 16 to 57 years; mean age: 34 years) had a single, 4-6 mm large, black macule with irregular, fingerlike extensions at the periphery. All lesions were situated on the upper back and surrounded by numerous sun-induced freckles. Dermatoscopic examination revealed irregularly formed "meshes" and confirmed the reticulated pattern seen clinically. Reticulated lentigo presented mostly in individuals with skin type 1, red to blond hair, and blue eyes. The clinical diagnosis in 4 out of 5 cases was melanoma in situ. Histopathologically, reticulated lentigo was mainly characterized by a sharply circumscribed hyperpigmentation of the lower epidermis with accentuation at the tips of elongated and clubbed rete ridges. In addition, a normal or slightly increased melanocyte number in the basal layer and an infiltrate of melanophages in the upper dermis was noted. Reticulated lentigo shows histopathologic features similar to those of melanotic macules on volar skin and mucous membranes. Because of its characteristic clinical, dermatoscopic and histopathologic features reticulated lentigo can be regarded as a distinctive clinicopathologic entity.
Two cases of foreign body granulomas developed after correction of face wrinkles with Bioplastique--a new microimplant. The characteristic histopathologic findings of a foreign body granuloma with cystic spaces and bizarre outlined, glassy material led to the correct diagnosis 'Bioplastique-granuloma' in spite of scarce clinical information.
The CHILD syndrome (congenital hemidysplasia with ichthyosiform nevus and limb defects) is usually characterized by lateralization of all associated anomalies. It has been assumed that the event of X-inactivation coincides and interferes with a clone of organizer cells controlling a large developmental field. A 16-year-old girl with bilateral manifestations of CHILD syndrome is described. The inflammatory skin lesions affected the body folds (ptychotropism) in a symmetrical distribution, although only the right side of the neck was involved. In addition, absence of several facial muscles, vertebral defects, and shortening of the leg on the right side were noted, and a ventricular septum defect was present. This unusual case may be explained by the assumption that X-inactivation did not coincide with the origin of inducer cell clones controlling large morphogenetic fields on either side of the body.