Melanoma of unknown primary (MUP) is a type of metastatic melanoma with no evidence of a primary tumor. Recent evidence suggested better survival in MUP as compared to melanoma with a known primary ...site (MKP). However, prognostic markers that reliably predict overall survival in MUP are lacking. The primary objective of this study was to analyze the mutational status of the BRAF, NRAS, and KIT oncogenes and to investigate if the genotype or other clinical parameters were associated with overall survival. We retrospectively analyzed the genotype and the clinical course of 40 patients with MUP. Mutations of BRAF and NRAS were determined with pyrosequencing. Mutations of KIT were investigated with a nested PCR approach followed by Sanger sequencing. Survival fractions were calculated applying the Kaplan-Meier model. Mutations in the BRAF (50.0%), NRAS (17.5%), and KIT genes (5.0%) were found frequently, but had no major impact on overall survival (p=0.62). The AJCC stage was a strong prognostic factor with a hazard ratio for death of 0.17 (stage III vs. IV; p=0.04). All patients diagnosed with stage III disease survived the median follow-up period of 23 months (p=0.03). The survival rates of patients with stage IV were significantly associated with rapid disease progression but not with metastatic tumor load at primary diagnosis (p=0.01). Altogether, AJCC stage and time to disease progression were important prognostic parameters. We propose that the kinetics of the disease but not the initial metastatic burden nor the mutational status is relevant for survival in advanced MUP.
Several groups confirmed Merkel cell polyomavirus (MCPyV) as the likely causative agent of Merkel cell carcinoma. Hematolymphoid disorders are known to be a substantial risk factor for Merkel cell ...carcinoma, and vice versa. The association between MCPyV and hematologic neoplasms is poorly analyzed, as well as the speculation that lymphocytes may serve as reservoir for MCPyV. Therefore, we investigated the prevalence of MCPyV DNA in primary cutaneous T- and B-cell lymphomas, pseudolymphomas (PLs), and inflammatory skin diseases with dominant lymphocytic infiltrate. We performed a molecular pathology study in 22 tissue samples and 1 blood sample of different cutaneous lymphomas from 19 patients (17 mature T-cell neoplasms, 5 mature B-cell neoplasms, and 1 immature hematopoietic malignancy), 13 PLs from 12 patients, and 25 various inflammatory skin diseases from 23 patients. All tumors were analyzed for the presence of MCPyV DNA by polymerase chain reaction, confirmed by Southern blot hybridization of polymerase chain reaction products. We detected MCPyV DNA in 4 of 23 (17.4%) cutaneous lymphoma tissue samples (3 of 17 mature T-cell neoplasms and 1 of 5 mature B-cell neoplasms), in 2 of 13 (15.4%) PL tissue samples, and 2 of 25 (8%) inflammatory skin conditions (1 drug reaction and 1 erythema multiforme). We conclude that MCPyV DNA is infrequently, but consistently present in lesional tissue from patients with primary cutaneous lymphomas, PLs, and inflammatory skin diseases; prevalence is in the range of 8%-17%. Our results suggest that MCPyV does not play a significant role in the pathogenesis of cutaneous lymphoproliferative disorders.
Angiolymphoid hyperplasia with eosinophilia (ALHE) is commonly regarded an angioproliferative process characterized by the presence of prominent, bizarrely shaped blood vessels. These vessels are ...accompanied by an inflammatory infiltrate that is thought to be a reactive component. Both the cell of origin and the pathogenesis of ALHE remain controversial. To define the histogenesis of this disorder, we analyzed the phenotypic and genotypic profile of the inflammatory infiltrate in ALHE by immunohistochemistry and T-cell receptor gene rearrangement by polymerase chain reaction (PCR) and denaturing gradient gel electrophoresis, as well as automated high-resolution PCR fragment analysis. Five of 7 ALHE patients displayed a clonal T-cell population and proliferative T-cell activity in lesional tissue. Most of these cases followed a protracted and therapy-reluctant course with recurrences. These data suggest that ALHE or a subset of ALHE cases harboring a clonal T-cell population may represent a T-cell lymphoproliferative disorder of a benign or low-grade malignant nature. HUM PATHOL 33:1023-1029. Copyright 2002, Elsevier Science (USA). All rights reserved.
Molecular diagnostics in cutaneous lymphomas Möbs, Markus; Cerroni, Lorenzo; Flaig, Michael J. ...
Journal der Deutschen Dermatologischen Gesellschaft,
05/2013, Letnik:
11, Številka:
s4
Journal Article
The prevalence of infections by nontuberculous mycobacteria (NTM) has steadily increased over the past decades, especially in immunocompromised patients.
We present a patient with IgA-deficiency and ...mixed cutaneous infection by two slowly growing mycobacteria, Mycobacterium (M.) haemophilum and M. kansasii.
Cutaneous M. haemophilum infections most often result from HIV or transplantation-associated immunosuppression. Rarely, M. haemophilum may also infect healthy patients or iatrogenically immunosuppressed patients without transplantation. M. kansasii is one of the most frequent NTM and large awareness exists about its involvement in human diseases. Mycobacterial diagnosis of cutaneous infections should be considered in long-lasting skin lesions.
Proteomic analysis of human prostate cancer Ahram, Mamoun; Best, Carolyn J. M.; Flaig, Michael J. ...
Molecular carcinogenesis,
01/2002, Letnik:
33, Številka:
1
Journal Article
Recenzirano
Proteomics is a promising approach in the identification of proteins and biochemical pathways involved in tumorigenesis. In an effort to discover such proteins and pathways that are deregulated in ...prostate tumorigenesis, cellular proteomes of matched normal prostate epithelial cells and high‐grade prostate cancer cells were analyzed by tissue microdissection, two‐dimensional electrophoresis, and mass spectrometry. Forty protein alterations were detected in the tumors; however, the majority of these changes were not shared among the 12 neoplasms. In contrast, parallel cDNA microarray analysis identified a number of common gene expression changes. The marked heterogeneity of the observed protein alterations may have significance with regard to tumor biology and research strategies for molecular profiling analyses of human prostate cancer. Published 2002 Wiley‐Liss, Inc.
Background: The spectrum of mycosis fungoides is exceedingly broad. Many different variants have been described, based on both clinical appearance and histological pattern. A rare form which shows ...preferential infiltration of hair follicles by malignant lymphocytes is follicular mycosis fungoides.
Methods: We reviewed our experience with nine cases of follicular mycosis fungoides.
Results: The unifying feature was infiltration of the hair follicle epithelium by atypical lymphocytes causing varying degrees of damage to the hair follicles. In some specimens the lymphocytes displayed only minor atypia leading to a misinterpretation as pseudolymphoma. Gene rearrangement studies were particularly helpful for establishing a diagnosis of malignant lymphoma. Additionally, epidermotropism of lymphocytes, eosinophils and mucin deposition were present to varying degrees. Mucin makes the distinction from mycosis fungoides‐associated follicular mucinosis difficult. We found both dermal mucin and a follicular mucinosis pattern present at different stages of disease in the same patient.
Conclusions: We suggest the term mycosis fungoides‐associated follicular mucinosis should be replaced by follicular mycosis fungoides in future lymphoma classification schemes.
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