Folliculotropic Mycosis Fungoides with Skewed T-cell Receptor CDR3 Motif: Suggestive of Lipid-antigen Selection?

Folliculotropic mycosis fungoides (FMF), a variant of mycosis fungoides (MF) with distinct clinical features, is characterized by infiltration of malignant T cells in hair follicles. This raises the hypothesis that antigens in the hair follicle may contribute to the pathogenesis of FMF. T-cell receptor ß gene (TRB) sequences as well as dendritic cell subsets in patients with FMF (n = 21) and control patients with MF (n = 20) were studied to explore this hypothesis. A recurrent usage of the TRB junctional genes TRBJ2-1 and TRBJ2-7 was found in patients with FMF compared with those with MF. These genes contribute to an amino acid motif in the complementarity-determining region 3 (CDR3) of the T-cell receptor. This motif was previously found in T cells stimulated by lipids bound to CD1 on antigen-presenting cells. Additional immunohistochemical analysis revealed abundant CD1c- and CD1a- expressing dendritic cells in FMF. The combined findings support a role for lipid-antigen stimulation in FMF.

Multiple distinct T-cell clones in folliculotropic mycosis fungoides.

Multiple distinct T-cell clones have been demonstrated in a subset of mycosis fungoides (MF), but have so far not been documented in folliculotropic MF, a clinical and histological variant of MF. We analyzed T-cell receptor (TCR) gene rearrangements in 8 patients with folliculotropic MF with multiple biopsies (range, 2-5) taken during the course of disease. Two patients had disease stage IA-IIA, 5 stage IIB-IVA, whereas data were not available for 1 patient. TCR ß and γ gene rearrangements were analyzed according to the BIOMED-2 PCR protocol. Multiple clonal TCR gene rearrangements indicating more than 1 T-cell clone were found in 5 patients. Although the number of patients is small, the finding of multiple distinct T-cell clones in 5 out of 8 patients suggests that chronic T-cell stimulation contributes to the development of folliculotropic MF.

Clinical and histopathological features of folliculotropic mycosis fungoides: a Norwegian patient series.

Folliculotropic mycosis fungoides is a variant of cutaneous T-cell lymphoma with distinct clinicopathological features. We describe here the clinical presentation, pathology findings and treatment outcome in 15 Norwegian patients. All patients were diagnosed between 1997 and 2010 at Oslo University Hospital. A spectrum of skin lesions, both typical and atypical, such as leonine facies, acneiform lesions, psoriasiform plaques, purulent ulcerations and cystic milia-like lesions for mycosis fungoides, were seen. Histological examination revealed characteristic infiltration of hair follicles with neoplastic T cells associated with partial destruction of the former. A CD4+ immunophenotype of the neoplastic T cells with loss of one or more T-cell markers was demonstrated. In general, the patients were given more aggressive therapeutic regimens than those with conventional mycosis fungoides, and showed a trend towards more rapid disease progression. In conclusion, this case series confirms the distinct clinical and histological features of folliculotropic mycosis fungoides.

PET with 2-[F-18]-fluoro-2-deoxy-D-glucose (FDG) in patients with cancer of unknown primary (CUP): influence on patients' diagnostic and therapeutic management.

25 patients with cancer of unknown primary (CUP) were studied using PET-FDG. Whole-body-PET scans were performed based on previous morphological information. All patients underwent conventional diagnostic modalities prior to and after the PET-study. True positive results were obtained in 12/25 patients (48%) and the primary identified by PET was confirmed by further procedures. True negative results were obtained in 8/25 patients (32%) and no primary tumor was found by PET or other clinical investigations. False positive results were obtained in 5/25 patients (20%). No false negative results were obtained. In 11 patients having CT compared with PET the primary tumor was exclusively localized by PET in 8 patients (73%) and also by CT in 3 patients (27%); CT was unable to identify the tumor in 8/11 patients detected by PET. PET affected management and directed treatment in 11/25 patients (44%). The sensitivity of PET-FDG was 100%, specificity 61%. These observations demonstrate that PET-FDG is a highly sensitive method to detect CUP. Correctly classified patients in an early stage of disease may lead to benefit from a more targeted therapy with prolonged survival time. In cases of advanced disease PET might not decisively influence survival time.