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Biomedical subjects

E Rieger

Publications and source records attributed to E Rieger.

At least 37 records · Page 2Linked to original sources

[Late metastasis of malignant cutaneous melanoma].

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.

Adult↗

bcl-2 protein expression and correlation with the interchromosomal 14;18 translocation in cutaneous lymphomas and pseudolymphomas.

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.

Blotting, Southern↗

Expression of the homeobox gene HOXC4 in keratinocytes of normal skin and epithelial skin tumors is correlated with differentiation.

Homeobox (HOX) genes share a highly conserved 183-bp sequence. The encoded proteins are capable of binding to specific DNA sequences and functioning as transcription factors. HOX genes play a critical role in the temporal and spatial differentiation of cells during embryogenesis. In several adult tissues, HOX genes are expressed in a constant, tissue-specific pattern, whereas in malignant tumors of these tissues an altered expression pattern was found. We investigated the expression of HOXC4 in adult normal skin by reverse-transcription polymerase chain reaction and non-radioactive RNA in situ hybridization. Moreover, HOXC4 expression was studied in various epidermal neoplasms (solar keratosis, six specimens; Bowen's disease, four; squamous cell carcinoma, nine; basal cell carcinoma, three) by RNA in situ hybridization. HOXC4 was found to be expressed in the suprabasal layers of the epidermis in normal skin specimens and the adjacent non-lesional epidermis of all other specimens. Atypical keratinocytes of solar keratoses and Bowen's disease as well as basaloid cells of basal cell carcinomas were negative. In squamous cell carcinoma, well differentiated areas with keratinization showed HOXC4 expression, whereas poorly differentiated areas were negative. Immunostaining with an antibody against cytokeratin 10, a marker of epidermal differentiation, was performed. A good correlation between the distribution pattern of HOXC4 and cytokeratin 10 in the lesions examined was found. These results suggest that HOXC4 is expressed mainly in differentiated keratinocytes. Lack of differentiation (as in neoplastic cells) is accompanied by downregulation of HOXC4 expression.

Aged↗

Melanotic macules following Blaschko's lines in McCune-Albright syndrome.

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.

Child, Preschool↗

Two computer programs using logit transformation for the analysis of S-shaped curves.

Two BASIC computer programs using logit transformation for the analysis of S-shaped curves are presented. The first program estimates the median effective dose (ED50) of drugs. A maximum likelihood method similar to Finney's algorithm of probit analysis is applied. The second fits S-shaped curves to empirical data which cannot be transformed easily to proportions. Logit transformation proves to be a simple and accurate alternative to probit transformation when computing memory is limited or calculation speed is critical.

Algorithms↗

Topical photodynamic therapy with endogenous porphyrins after application of 5-aminolevulinic acid. An alternative treatment modality for solar keratoses, superficial squamous cell carcinomas, and basal cell carcinomas?

BACKGROUND: Topical photodynamic therapy with endogenous porphyrins consists of irradiation of a tumor with visible light after the application of exogenous 5-aminolevulinic acid. OBJECTIVE: To assess the effectiveness of this modality, patients with precancerous conditions and various skin cancers were treated. METHODS: Thirteen patients with 70 skin lesions were enrolled. Standard treatment involved the topical application of 20% 5-aminolevulinic acid in an oil-in-water emulsion. The emulsion was applied under an occlusive dressing for 4 to 8 hours before exposure to photoactivating light. RESULTS: We observed a complete response after a single treatment for all 9 solar keratoses, 5 of 6 early invasive squamous cell carcinomas, and 36 of 37 superficial basal cell carcinomas. Only 1 of 10 nodulo-ulcerative basal cell carcinomas completely resolved. Eight cutaneous metastases of malignant melanoma were therapeutic failures. CONCLUSION: Topical photodynamic therapy with endogenous porphyrins is effective for superficial epithelial skin tumors.

Administration, Cutaneous↗

Granulomatous panniculitis caused by Candida albicans: a case presenting with multiple leg ulcers.

A 61-year-old woman had rapidly enlarging ulcers on both legs and three draining subcutaneous nodules on the left thigh. Findings of skin biopsy specimens revealed granulomatous panniculitis with a large number of blastospores and pseudohyphae. Candida albicans was cultured from the ulcers, the nodules, the mouth, the esophagus and gastric juice, feces, and urine. The ulcers healed after 5 months of therapy with itraconazole. Predisposing factors were diabetes mellitus, dysfunction of the hypothalamic-pituitary system, hypochromic anemia, and prior treatment with a broad-spectrum antibiotic. In contrast to three other reported cases of Candida panniculitis, our patient had not undergone immunosuppressive therapy.

Candidiasis, Cutaneous↗

Proliferative activity in Spitz's naevi compared with other melanocytic skin lesions.

Proliferative activity has been shown to correlate with the degree of malignancy in various human neoplasms. Immunostaining with the monoclonal antibody PC10 binding to proliferating cell nuclear antigen (PCNA) facilitates the assessment of proliferation in routinely fixed, paraffin-embedded tissue sections. In this study we investigated the expression of PCNA in 29 Spitz's naevi in comparison with 43 primary malignant melanomas (MM), 18 cutaneous metastases of malignant melanoma (MMM) and 16 benign melanocytic naevi (BMN). After selection of the microscopic field with the highest number of PCNA-positive nuclei, the nuclear density (NDmax) of PCNA-stained nuclei in this field was assessed using interactive image analysis. The mean value of NDmax (given as 1000 nuclei/mm3 tissue) of SN was 27.9 (+/- 16.7) and differed significantly from that of MM (48.1 +/- 40.5; U-test: p < 0.05) and that of MMM (114.4 +/- 56.3; p < 0.01). Comparing NDmax of the subgroups of MM according to their maximal vertical tumour thickness with NDmax of SN we found significant differences only between SN and MM > 1.5 mm thick (n = 14; NDmax = 67.8 +/- 36.1) but not between SN and MM < or = 1.5 mm thick (n = 29; NDmax = 38.8 +/- 39.3). PCNA expression in SN did not differ from that of BMN (NDmax 23.8 +/- 28.5). Proliferative activity as assessed by measurement of PCNA expression therefore showed significant differences between BMN, SN and thin primary melanomas on one hand and thick primary melanomas and cutaneous metastases of malignant melanomas on the other hand.

Antigens, Neoplasm↗

Cutaneous immunocytomas: a clinicopathologic study of 26 cases.

The clinical and histological features of 16 patients with a primary cutaneous immunocytoma and 10 patients with a secondary cutaneous immunocytoma are reported. In all cases the diagnosis was based on the presence of monotypic plasma cells or lymphoplasmacytoid cells. Our data show that primary cutaneous immunocytomas are a distinct type of cutaneous lymphoma, characterized by (a) the presence of solitary or localized skin lesions (13 of 16 cases); (b) preferential localization on arms and legs (15 of 16 cases); (c) excellent response to local treatment (15 of 16 cases) and (d) a favourable prognosis. Histologically, these primary cutaneous immunocytomas are characterized by the presence of nodular or diffuse infiltrates with monotypic lymphoplasmacytoid/plasma cells located at the periphery of the infiltrates. Important clinical and histological differences were noted between primary and secondary immunocytomas. In the latter group more widespread skin disease was seen, often in the presence of paraproteins and/or autoimmune diseases. In contrast with the peripheral localization of the monotypic cells in primary cutaneous immunocytomas the monotypic lymphoplasmacytoid/plasma cells in secondary immunocytomas formed diffuse infiltrates or these cells were found dispersed throughout the infiltrate. There were no differences in clinical presentation or course between the different subtypes of cutaneous immunocytomas (lymphoplasmacytic, lymphoplasmacytoid and polymorphic immunocytomas). The differential diagnosis between primary cutaneous immunocytomas and cutaneous plasmacytomas, primary follicular centre cell lymphomas and cutaneous 'pseudolymphomas' is discussed.

Adult↗

Comparison of proliferative activity as assessed by proliferating cell nuclear antigen (PCNA) and Ki-67 monoclonal antibodies in melanocytic skin lesions. A quantitative immunohistochemical study.

Immunostaining with the monoclonal antibodies PCNA and Ki-67 provides a simple method for the assessment of growth fractions of tumors. Contrary to Ki-67, PCNA antibody can be applied on aldehyde- or alcohol-fixed and paraffin-embedded tissues, thus allowing studies on archival material. For 77 melanocytic skin lesions, we compared PCNA immunostaining on formalin-fixed tissue with Ki-67 immunostaining on frozen material of the same lesion. 16 benign melanocytic nevi (BMN, from 16 patients), 43 primary malignant melanomas (PMM, 42 patients), and 18 skin metastases of malignant melanoma (MMM, 12 patients) were included in the study. Maximum nuclear density (NDmax) of PCNA- and Ki-67-positive nuclei was assessed using interactive image analysis. NDmax values for both PCNA and Ki-67 differed significantly between the three diagnostic groups (Kruskal-Wallis H-test: p << 0.001). Mean values (given as 1000 nuclei/mm3 tissue) increased considerably from benign to malignant lesions (PCNA: BMN: 23.8 +/- 28.4 [mean +/- standard deviation], PMM: 48.1 +/- 41.0, MMM: 117.0 +/- 64.6; Ki-67: BMN: 6.4 +/- 3.3, PMM 25.0 +/- 31.1, MMM: 95.2 +/- 47.2). Correlation between NDmax values of PCNA- and Ki-67-positive nuclei was significant (Linear regression analysis: r = 0.51, p << 0.001). Furthermore, for PMM a significant correlation between histologic parameters related to prognosis (Breslow index and mitotic rate) and PCNA as well as Ki-67 expression was found (PCNA-Breslow index: r = 0.42, p < 0.01; Ki-67-Breslow index: r = 0.60, p << 0.001; PCNA-mitotic rate: r = 0.40, p < 0.01; Ki-67-mitotic rate: r = 0.50, p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗

Systemic and local toxicity in the rat of methyl tert-butyl ether: a gallstone dissolution agent.

Methyl tert-butyl ether (MTBE) is an organic solvent that has been used to dissolve gallstones via a percutaneous transhepatic catheter into the gallbladder. To test whether MTBE might cause serious tissue injury if accidentally infused outside the gallbladder, the effect of MTBE (0.2 ml/kg) injected into the hepatic parenchyma, or administered intravenously or intraperitoneally, was examined in the rat. The toxicity of isopropyl acetate (IPA), an organic solvent with a similar chemical structure, was examined similarly. Intracaval injection of MTBE caused the highest mortality (100%). Mortality was less (59%) after intrahepatic injection and still less (17%) after peripheral vein injection. Most animals died instantaneously from cardiorespiratory arrest. Almost all animals that were injected with MTBE intrahepatically or intravenously showed localized areas of congestion, hemorrhage, and interstitial edema in the lungs. These changes were more severe in rats which survived for 24 hr than in those which died sooner. In those rats receiving intrahepatic injections, most rats which survived for 24 hr had liver necrosis at the site of injection. Intraperitoneal injection of MTBE produced 100% survival with only 1/5 rats showing a mild pulmonary injury at autopsy. IPA had toxic effects similar to those evoked by MTBE. To test whether tumor necrosis factor was involved in organ injury, serum levels were measured; they remained unchanged. These experiments indicate that two organic solvents, MTBE and IPA, are cytotoxic to local tissues and cause severe, and often fatal, lung damage when infused into a central vein. Less toxicity occurred if solvents were given into a peripheral or portal vein or intraperitoneally.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetates↗

Clinicopathologic and immunologic features associated with transformation of mycosis fungoides to large-cell lymphoma.

Mycosis fungoides (MF) can progress to a large-cell malignant lymphoma (LCL). This transformation is associated with a more aggressive biologic behavior and course. We reviewed cutaneous tumors of 36 MF patients and divided them into two groups, one showing histologic evidence of transformation into LCL, another characterized by infiltrates of small- to medium-sized cerebriform cells (nontransformed cases). Biopsies of patches or plaques from early MF stages were available from 34 patients. Twenty of the 36 cases (55.6%) showed transformation to a large-cell variant: nine tumor-stage (T) medium-sized and large-cell pleomorphic, five T immunoblastic, two T large-cell anaplastic, and four unclassified T LCL. Sixteen cases represented nontransformed tumor stage MF. In 23 cases, including both nontransformed (n = 6) and LCL (n = 17) groups, immunohistochemical investigations revealed aberrant patterns of antigen expression (partial loss of one or more T cell-associated antigens) and the presence of activation- and proliferation-associated antigens. Clusters of B-lymphocytes formed a distinctive component of the infiltrate in two nontransformed and nine LCL biopsies. Although survival rates after tumor onset did not significantly differ between the two groups (5-year survival rate 23% for nontransformed patients, 11.1% for LCL patients, p greater than 0.05), overall survival from first biopsy diagnostic of MF showed a statistically significant difference between patients with nontransformed tumor stage MF compared with LCL patients (10-year survival rate 46.6% and 11.2%, respectively, p less than 0.02). The recognition of transformation to LCL in MF should provide a better assessment of future therapeutic approaches.

Adult↗

Analysis of the 14;18 translocation in cutaneous lymphomas using the polymerase chain reaction.

A series of 25 cutaneous B-cell lymphoid proliferations was analyzed for the presence of the (14; 18) translocation using the polymerase chain reaction. Junctional sequences of rearranged chromosomes 14 and 18 were amplified in vitro, and t (14; 18) specific sequences were detected in 1 of 14 primary cutaneous B-cell lymphomas, in 3 of 8 primary nodal B-cell lymphomas and in none of 3 B-cell pseudolymphomas. These results indicate that the t (14; 18) may occur in a small subset of primary cutaneous lymphoma. However, the difference in incidence of the t (14; 18) between primary nodal and primary cutaneous lymphomas suggests that different molecular mechanisms are involved in the pathogenesis of these lymphomas.

Base Sequence↗

Cutaneous myxoid fibroblastoma. A histological, immunohistochemical, and ultrastructural study.

A fibroblastic skin tumor with a myxoid matrix is reported that cannot be easily classified as one of the well-known entities of fibrous/fibrohistiocytic and myxoid skin tumors. A 27-year-old white woman presented with a reddish, dome-shaped cutaneous nodule 8 mm in diameter on the left popliteal fossa that had developed spontaneously within the preceding 2 years. There was no sign of recurrence 30 months after excision. Light microscopic examination showed a well-circumscribed tumor confined to the upper dermis and consisting of stellate and spindle-shaped cells arranged loosely in a fascicular pattern resembling tissue cultures of fibroblasts. There were almost no collagen bundles between tumor cells, and Mowry's staining showed large amounts of glycosaminoglycans. Immunohistochemical studies of the tumor cells showed reactivity only to vimentin, whereas markers of histiocytes, dermal dendrocytes, and neurogenic and myogenic differentiation were negative. By electron microscopy, the majority of tumor cells contained elliptical nuclei, but some tumor cells had conspicuous multisegmented nuclei with several large and small nuclear segments connected by thin nuclear bridges (labyrinth nuclei). Single fibrils were found within the interstitium; collagen fibers were rare. Histological and ultrastructural examinations identified tumor cells as fibroblasts. High cellularity distinguishes this tumor from cutaneous myxoma. We conclude that this lesion represents a newly recognized tumor of fibroblastic origin. The name cutaneous myxoid fibroblastoma is proposed.

Adult↗

[The clinical spectrum of organ manifestations of tuberous sclerosis].

Since the first description of the classic triad of adenoma sebaceum, epilepsy and mental retardation by Vogt, various manifestations have been added to the clinical picture of Bourneville-Pringle disease or tuberous sclerosis. Diagnosis, therapy and potential complications of the more frequent manifestations are summarized. Since even oligosymptomatic patients may develop dangerous complications, the importance of thorough examination is emphasized.

Adenoma↗

Expression of cytoskeletal components in melanocytic skin lesions. An immunohistochemical study.

The cytoskeleton is considered to be important for maintaining cell shape and facilitating cell movement. In the present study, the expression of cytoskeletal components is examined in benign and malignant melanocytic skin tumors. Paraffin sections of 75 cases (25 each of nevocellular nevus, primary malignant melanoma, and cutaneous metastases of malignant melanoma) were stained with antibodies to tubulin, myosin, actin, and vimentin using a three-step immunoperoxidase method. The staining results were assessed independently for tumor cells and stroma cells in comparison to inbuilt reference structures. Vimentin is found in all melanocytic lesions in the tumor as well as in the stroma cells. In malignant lesions, the tumor cell staining intensity varies between neighboring regions; particularly in malignant melanoma the staining is pronounced in the tumor periphery (chi 2 test: p less than 0.05). Actin is only weakly positive in nevus cells and primary melanoma tumor cells, but strongly expressed in metastatic tumor cells (p less than 0.001). Nevus fibroblasts are only weakly positive, whereas the stroma fibroblasts in the malignant lesions are strongly positive (p less than 0.001). The same is true for myosin and tubulin expression in dermal fibroblasts (p less than 0.001), whereas the tumor cells are equally (weakly) positive in all melanocytic lesions. Our study shows that there are significant differences in the immunohistochemical expression of cytoskeletal components in various melanocytic tumors. There is an elevated expression of vimentin and actin in the tumor cells, particularly of metastatic lesions. However, the most pronounced differences are found in the dermal fibroblasts.(ABSTRACT TRUNCATED AT 250 WORDS)

Actins↗

[Oligosymptomatic Bourneville-Pringle tuberous sclerosis of the brain with giant cell astrocytoma].

We report on a 9-year-old boy who developed subependymal giant-cell astrocytoma associated with tuberous sclerosis. Apart from a few hypopigmented skin patches, the boy's clinical picture was completely unremarkable until the onset of diplopia and vertigo reflecting increased intracranial pressure. Magnetic resonance imaging of the brain revealed subcortical hamartomas in addition to the intraventricular tumour. Seizures and mental retardation were absent. The boy's mother had suffered from seizures during childhood and presented with typical skin lesions. The importance of thorough examination and regular follow-up even in patients with oligosymptomatic variants of tuberous sclerosis is emphasized.

Adult↗