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Biomedical subjects

R Fink-Puches

Publications and source records attributed to R Fink-Puches.

At least 19 recordsLinked to original sources

Clinical aspects and pathology of primary cutaneous B-cell lymphomas.

Primary cutaneous B-cell lymphomas (pCBCL) occur more frequently than generally believed. The most important subtypes are: marginal zone B-cell lymphoma/immunocytoma, follicle center-cell lymphoma and large B-cell lymphoma of the leg. A correct diagnosis can be rendered only in the context of knowledge of the clinical findings. Progress in terms of classification and biology is associated with the application of modern techniques including immunohistology and laser beam microdissection followed by molecular analysis. Future definitions of pCBCL will be based on their molecular abnormalities and their etiology and pathogenesis. Awareness of the special clinical behavior of pCBCL should prevent unnecessarily aggressive treatment.

Humans↗

Diagnostic criteria of primary cutaneous B-cell lymphomas and pseudolymphomas.

Primary B-cell lymphomas of the skin are defined as malignant B-cell proliferations presenting with cutaneous involvement alone and no evidence of extracutaneous manifestations over a period of at least six months when complete staging has been performed. The major subtypes are follicle center-cell lymphoma, marginal zone lymphoma and large B-cell lymphoma of the leg (EORTC classification 1997). Primary B-cell lymphomas of the skin differ significantly from nodal lymphomas especially with respect to their clinical behavior. Pseudolymphomas of the skin are inflammatory diseases that simulate malignant lymphomas either clinically, histopathologically, or both. Particular pseudolymphomas may mimic cutaneous B-cell lymphomas. The most important examples are: lymphomatoid drug reactions, lymphocytoma (borrelia burgdorferi as causative agent), arthropod reactions, pseudolymphomas associated with vaccinations or tattoos and inflammatory pseudotumors. In recent years, new immunohistological and molecular techniques have added important criteria for the differentiation of cutaneous lymphomas from pseudolymphomas.

Diagnosis, Differential↗

[Therapy of primary cutaneous B-cell lymphomas].

BACKGROUND AND OBJECTIVE: Primary cutaneous B-cell lymphomas (PCBCL) represent a unique type of extranodal B-cell lymphomas. Recently, the "European Organization for Research and Treatment of Cancer (EORTC)-Cutaneous Lymphoma Study Group" classified PCBCL into two major groups: one with low-grade malignancy and excellent prognosis (follicle center cell lymphoma, immunocytoma/marginal zone B-cell lymphoma) and the other with intermediate malignancy and worse prognosis (large B-cell lymphoma of the leg). The clinical course and the prognosis of both groups clearly distinguish them from nodal lymphomas with similar morphological aspects, thus underlying the need for different treatment modalities. PATIENTS/METHODS: We investigated retrospectively the therapeutic data from 51 patients with PCBCL (40 low grade lymphomas, 11 large B-cell lymphomas). Several treatment modalities were used: total excision, radiotherapy, polychemotherapy, systemic corticosteroids, systemic antibiotics, as well as a variety of combination treatments. RESULTS: Recurrence, dissemination and/or death of the patients were not significantly related to any single treatment modality. CONCLUSIONS: In our opinion, the choice of treatment for PCBCL depends on the histologic classification, the number, spread and localization of the infiltrates, and on the general condition of the patient.

Adult↗

[Cutaneous angiosarcoma].

BACKGROUND AND OBJECTIVES: Angiosarcomas of the skin arise almost exclusively in the following clinical settings: 1. the face and scalp, usually in elderly individuals, 2. lymphedematous regions (lymphedema-associated angiosarcomas), and 3. skin that has been previously irradiated (post-radiation angiosarcomas). Clinical and histopathologic diagnosis of angiosarcoma is difficult often resulting in great delay that obviates against early and possibly successful treatment of these very aggressive neoplasms. Diagnostic problems are described, and prognostic factors as well as the effect of different forms of treatment on the outcome are discussed. PATIENTS/METHODS: Retrospective study of 11 patients with cutaneous angiosarcomas. Clinical presentation, histopathology, therapy and survival time are analysed. RESULTS: Only 1 of 11 cases cutaneous angiosarcoma was clinically identified. Survival time was 1-24 months. Three patients who received radical surgery have not developed metastases and are still alive. CONCLUSIONS: Clinical and histopathologic diagnosis of cutaneous angiosarcomas is often very difficult. Prognosis is very bad; radical surgery seems to be the best therapeutical option.

Adult↗

Cutaneous spindle-cell B-cell lymphoma: a morphologic variant of cutaneous large B-cell lymphoma.

The morphologic spectrum of large B-cell lymphoma is broad. Several unusual variants have been described such as lymphoma with myxoid stroma, sclerosing B-cell lymphoma, signet ring-cell lymphoma, and multilobated B-cell lymphoma among others. We report on five cases of cutaneous large B-cell lymphoma in which the neoplastic cells were spindle-shaped. In two cases, the clinical features fulfilled those of a primary cutaneous lymphoma; in the three other cases, the lymphoma most likely arose primarily in the skin, but incomplete clinical workups precluded definite categorization. The patients ranged in age from 30 to 89 years and presented with solitary lesions on the trunk or head. Histopathologic examination revealed nodular or dense diffuse infiltrates involving the entire dermis as well as the subcutaneous fat in some cases. Thickened collagen bundles between the spindled cells were present in one case. Cytomorphologic analysis showed the presence of round or oval medium-sized and large-sized lymphocytes with features of centrocytes and centroblasts in some foci, with others dominated by cells with spindle-shaped, elongated, twisted nuclei with dispersed chromatin and scant cytoplasm. Immunohistologic analysis revealed that both round or oval and spindled cells were positive for CD20 in all cases; in all cases tested, these cells were also positive for MIB-1 and were negative for CD3, CD5, CD43, CD45RO, CD21, CD30, CD68, S-100, HMB-45, actin, smooth-muscle actin, and cytokeratin. Bcl-2 was expressed in one of three cases tested. Analysis of the rearrangement of the J(H) gene by polymerase chain reaction performed in one case showed a monoclonal pattern. Spindle-cell large B-cell lymphoma represents a distinctive rare subtype of the cutaneous large B-cell lymphoma and can arise primarily in the skin in some cases. Recognition of this variant is necessary to avoid misdiagnosis of other cutaneous malignant spindle-cell tumors.

Adult↗

Surgical treatment of CHILD nevus.

We report a young girl with an unusual manifestation of CHILD syndrome in whom skin lesions showed involvement of the right side of her neck as well as symmetrically distributed ptychotropic involvement of the large body folds. Excision resulted in improvement and finally healing of skin lesions within the submammary folds, where breast reduction was also performed, whereas excision of axillary lesions and subsequent grafting with split skin turned out to be unsuccessful.

Adolescent↗

Solitary skin lesions with histopathologic features of early mycosis fungoides.

Mycosis fungoides (MF) is a cutaneous T-cell lymphoma that usually begins with cutaneous patches that evolve into plaques and tumors. A few recent reports describe a solitary variant of MF distinct from localized pagetoid reticulosis, a disease in which solitary verrucous lesions occur on acral skin. Solitary skin lesions with some of the histopathologic features of MF rarely occur during treatment with several drugs, especially antidepressants or antihistamines. We analyzed the clinicopathologic features of 20 patients with solitary skin lesions showing histopathologic features of patch- or early plaque-stage MF. Eight men and 12 women (mean age 50.6, range 23-82, median 49) had solitary, small erythematous patches or plaques located on the trunk (16 cases, 6 of them on the breast), upper extremities (3 cases), and inguinal region (1 case). Ten patients were treated with one or more drugs; only two of them received antidepressants or antihistamines. Histopathologic examination revealed in all cases a band-like infiltrate in the upper dermis, frequently with epidermotropism of solitary lymphocytes. Atypical lymphocytes were present in a minority of cases. Immunohistology showed a predominance of CD3+ T lymphocytes, in most cases admixed with clusters of CD20+ B-cells. Only a small proportion of the infiltrate was CD8+. Molecular analysis of the rearrangement of the T-cell receptor genes was performed in 16 cases using the polymerase chain reaction (PCR) technique and revealed a monoclonal band in 8 of them. After surgical excision, 2/14 patients had a recurrence near the surgical scar. In 18 patients with complete follow-up data, no evidence of "classic" MF could be observed after a mean follow-up of 31.9 months. Solitary skin lesions with the histopathologic features of MF can be considered as a distinct clinicopathologic entity, probably representing a solitary variant of mycosis fungoides.

Adult↗

Cutaneous involvement in lymphoblastic lymphoma.

Lymphoblastic leukemia/lymphoma (LBL) is a malignant neoplasm of precursor lymphocytes of B- or T-cell phenotype. Involvement of the skin is relatively uncommon. We examined retrospectively the clinicopathologic, immunophenotypic, and molecular genetic features of six patients with cutaneous involvement of LBL (B-LBL=5; T-LBL=1). Patients presented clinically with solitary, large tumors located on the head (3 cases) or the back (1 case), or with generalized tumors (2 cases). Ulceration was uncommon. In two patients the onset of skin lesions was concomitant to the diagnosis of lymphoblastic leukemia. Histopathologic examination showed in all cases a dense, diffuse, monomorphous infiltrate located in the entire dennis and subcutaneous fat. A typical "starry sky" pattern was observed in the majority of the lesions. In some areas neoplastic cells were aligned in a "mosaic-like" fashion. Cytomorphologically, medium sized lymphoid cells with round or convoluted nuclei, inconspicuous nucleoli and scant cytoplasm predominated. There were no significant differences in the histopathologic features of skin lesions in T- and B-LBL. In B-LBL, CD79a was more useful than CD20 in determining the phenotype of neoplastic cells (4/5 cases positive for CD79a as compared to 2/5 cases positive for CD20). TdT, CD10 and CD43 were positive in 4 cases, CD34 in 2. The case of T-LBL revealed positivity for CD1a, CD3, CD43 and TdT, and negativity for CD34 and for B-cell markers. All neoplasms were positive for CD99 and bcl-2, and showed a high proliferation rate. Molecular genetic analysis of J(H) and T-cell receptor (TCR) genes performed using a polymerase chain reaction technique revealed a monoclonal rearrangement of J(H) genes in all five B-LBLs. One of these cases showed also a concomitant TCR-gamma gene rearrangement. A monoclonal rearrangement of the TCR-gamma gene was detected in the case of T-LBL. Our study shows that skin lesions of LBL present characteristic clinicopathologic and molecular features allowing the differentiation from other cutaneous lymphomas, even in cases without clinical history of previous precursor lymphoblastic leukemia/lymphoma.

Adult↗

Long-term follow-up and histological changes of superficial nonmelanoma skin cancers treated with topical delta-aminolevulinic acid photodynamic therapy.

OBJECTIVE: To investigate the immediate and long-term effects of photodynamic therapy with delta-aminolevulinic acid (ALA-PDT) on superficial basal cell carcinomas (BCC) and superficial squamous cell carcinomas (SCC). DESIGN: Retrospective study with 60 months of maximal follow-up. SETTING: University-based hospital in Graz, Austria. PATIENTS: Forty-seven subjects with a total of 95 superficial BCC and 35 superficial SCC. INTERVENTIONS: A compound of 20% delta-aminolevulinic acid was topically applied under an occlusive and light-shielding dressing before exposure to either UV-A or different wave bands of polychromatic visible light (full-spectrum visible light, >515, >570, or >610 nm). MAIN OUTCOME MEASURES: Primary tumor responses and recurrence rates in the long-term follow-up, as well as histological changes associated with ALA-PDT, were studied. RESULTS: The complete primary response rate for all wave bands of light was 86% (82/95) for superficial BCC and 54% (19/35) for superficial SCC. There was no statistically significant difference among the response rates to the different wave bands of light. After a median follow-up of 19 months (range, 3-60 months) for BCC and 8 months (range, 3-47 months) for SCC, the overall recurrence rate was 44% (36/81) and 69% (11/16), respectively. At 36 months after therapy, the projected disease-free rate was 50% (95% confidence interval, 43%-57%) for BCC vs 8% (95% confidence interval, 7%-9%) for SCC (P<.001, log-rank test). Histopathologic studies revealed a significant increase of fibrosis in the dermis after ALA-PDT and appearance of a sharp border between fibrotic and nonfibrotic tissue. In 15 of 16 BCC examined, the border between fibrotic and nonfibrotic tissue was deeper in the dermis than the maximum tumor thickness before therapy (P<.001, Wilcoxon signed rank test). Similar histopathologic observations were made in SCC. CONCLUSIONS: Our study revealed poor long-term cure rates for superficial BCC and SCC treated with topical ALA-PDT and visible light. The histopathologic observations showing remarkable fibrosis in the dermis indicated that the effect of ALA-PDT reached deeper than the initial depth of invasiveness of the neoplastic tissue, suggesting in turn that the poor long-term results of ALA-PDT cannot be explained by insufficient penetration of the therapy effect.

Administration, Topical↗

Comparison of phototherapy with near vs. far erythemogenic doses of narrow-band ultraviolet B in patients with psoriasis.

The therapeutic effectiveness of radiation from a 311 nm ultraviolet B (UVB) lamp (Philips TL-01) in a near vs. far erythemogenic therapy regimen was investigated in 13 patients with widespread, symmetrically distributed psoriasis. The patients received UV therapy starting with 70% of the 311 nm minimal erythema dose (MED) on one randomly chosen half of the body and 35% of the 311 nm MED on the other half. Therapy was given three to five times a week, and the UVB dose in both regimens was increased simultaneously in the same relation. For the 11 patients completing the study, the mean psoriasis area and severity index (PASI) score for the near vs. far erythemogenic treatment side was 21.2 vs. 18.5 before therapy (Wilcoxon's test, not significant), 11.8 vs. 14.4 at week 1 (P = 0.003), 8.2 vs. 12.0 at week 2 (P = 0.004), and 6.6 vs. 15.6 at week 3 (P = 0.005). After 3 weeks, a satisfactory response (i.e. improvement of the initial PASI score by more than 75%) was observed in six of 11 patients on the near erythemogenic treatment side vs. three of 11 patients on the far erythemogenic side. However, the definitive median total number of treatments needed to achieve a satisfactory therapy response on the near vs. far erythemogenic sides was 12 vs. 16 (P = 0.022), whereas the definitive median cumulative UV dose was 14.0 vs. 9.1 J/cm2 (P = 0.088), respectively. These results suggest that near erythemogenic 311 nm UVB therapy may clear psoriasis faster than far erythemogenic therapy but that the latter regimen may be equally effective as it requires slightly more treatment sessions at a lower (and possibly less carcinogenic) cumulative UV dose.

Adult↗

Automated measurement of melanoma cross-sectional area.

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.

Adolescent↗

Expression of two morphologic parameters concerning tumor-stroma interaction in benign and malignant melanocytic skin lesions.

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.

Collagen↗

Incorporation of pre-existing collagen bundles in primary cutaneous 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.

Adolescent↗

Systematized inflammatory epidermal nevus with symmetrical involvement: an unusual case of CHILD syndrome?

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.

Abnormalities, Multiple↗

Primary clinical response and long-term follow-up of solar keratoses treated with topically applied 5-aminolevulinic acid and irradiation by different wave bands of light.

Photodynamic therapy with 5-aminolevulinic acid (ALA-PDT) is based on photosensitization by endogenous synthesis of protoporphyrin IX and its transient accumulation especially in malignant epithelially derived tissues. Recent studies have indicated that ALA-PDT is effective for the treatment of solar keratoses (SK), but there has been a lack of long-term clinical follow-up. The goal of the present study was to investigate the immediate and long-term effect of ALA-PDT on SK. Twenty-eight patients with a total of 251 SK were enrolled in the study. Standard treatment involved the topical application of 20% ALA, under occlusive and light-shielding dressing for 4 hours before exposure to UVA and/or different wave bands or wave band combinations of polychromatic visible light (full-spectrum visible light, and/or different wave bands of filtered visible light > 515, > 530, > 570, or > 610 nm) in one or two treatment sessions. The primary complete response rate of SK to ALA-PDT was 64% after one treatment, but 85% when the responses to a second treatment were included. Taken all treatments together, the complete response rate for lesions on face, scalp and neck was 93% for full-spectrum visible light, 96% for the combination of full-spectrum visible light and filtered light, 91% for different wave bands of filtered visible light, and 100% for the combination of long wave UVA and full-spectrum visible light, respectively. The complete response rate for lesions on forearms and hands was 51% for full-spectrum visible light and 33% for the combination of full-spectrum visible light and filtered light. The greater response rate for SK on the face, scalp, and neck was associated with a higher surface fluorescence and immediate response rate after ALA photosensitization at these sites (chi 2; p = 0.0001). However, due to the treatment protocol the mean light dose applied to lesions on the face, scalp and neck (50 J cm-2) was substantially higher than that for lesions on forearms and hands (35 J cm-2). In the long term follow-up of SK on face scalp and neck, the projected disease-free rate at 36 months after therapy was 71% for lesions treated with full-spectrum visible light versus 23% for lesions treated with different wave bands of filtered light (Log rank-Mantel Cox; p = 0.0001). These results indicate that treatment with full-spectrum visible light at higher light doses may be the most effective and promising form of light exposure in ALA-PDT of SK.

Administration, Topical↗

Cytoplasmic microtubules in two different mouse melanoma cell lines: a qualitative and quantitative analysis using confocal laser scanning microscopy and computer-assisted image analysis.

The microtubular system as one part of the cellular cytoskeleton is not only necessary for mitotic activity of malignant cells but also for invading neighboring tissues and for the formation of distant metastases. In the present study, the amount and distribution of tubulin in two murine melanoma cell lines (K1735-M2: high metastatic clone; K1735-c116: low metastatic clone) were determined quantitatively using an indirect immunofluorescence technique, confocal laser scanning microscopy (CLSM) and computer-assisted image analysis. Additionally, qualitative and quantitative changes after application of the microtubule-inhibitor nocodazole were investigated. Quantitative analysis showed a significant difference between the high and low metastatic cell line for the parameter TEXTURE, indicating a finer structured network within the high metastatic cells. After treatment with nocodazole the parameters TEXTURE and DENSITY were reduced, suggesting a decrease of assembled tubulin and a less delicate structure of the remaining microtubules. Our study shows that CLSM combined with computer-assisted image analysis provides a new method to examine quantitative variations of the cytoskeleton possibly related to cell function.

Animals↗