Monitoring malignant T-cell clones by direct TCR expression assay in patients with leukemic cutaneous T-cell lymphoma during extracorporeal photopheresis.

BACKGROUND/PURPOSE: Accurate assessment of malignant T-cell clones in patients with leukemic cutaneous T-cell lymphoma (L-CTCL) is crucial for diagnosis, treatment, and monitoring disease. Although multiple approaches to quantitate malignant T-cell clones have been reported, a cost-effective assay with broad coverage is not available. We report a NanoString-nCounter-Technology-based direct TCR expression assay (DTEA) that was previously developed to quantify both TCR-Vα and TCR-Vß usages after adoptive immunotherapy. This study was performed to test the effectiveness of DTEA in assessing malignant T-cell clones in L-CTCL patients. METHODS: Total RNAs extracted from peripheral blood mononuclear cells of patients before starting extracorporeal photopheresis (ECP) (n = 15) and during therapy at 3 months and 6 months (n = 12) were used for DTEA, with customized probes for 45 TCR-Vα and 46 TCR-Vß family members. RESULTS: At baseline, DTEA detected TCR-Vß clones in all 15 patients (100%) compared to flow cytometry that detected TCR-Vß clones in 9 of 13 patients (69.2%). In addition to predominant TCR-Vß clones, DTEA also detected additional TCR-Vß clones in 8 of 15 patients (53.3%). Furthermore, DTEA simultaneously identified clonal TCR-Vα usages, which allowed us to pair TCR-Vα and TCRVß usages by malignant T-cells and identify diversified clonotypes. Changes in the relative frequencies of clonal TCR-Vß and TCRVα usages over therapy were consistent with patients' clinical responses. CONCLUSIONS: Our results indicate that DTEA can effectively assess malignant T-cell clones by detecting clonal TCR-Vα and TCR-Vß usages. By providing a global view of TCR repertoires, DTEA may also help us understand the origin(s) of malignant T-cells and pathogenesis of CTCL.

Tumefactive Demyelinating Lesions in Children: A Rare Case of Conus Medullaris Involvement and Systematic Review of the Literature.

Tumefactive demyelinating lesions are an uncommon manifestation of demyelinating disease that mimic primary central nervous system neoplasms and can pose a diagnostic challenge in patients without a pre-existing diagnosis of multiple sclerosis. Although a biopsy may be required to distinguish TDL from neoplasms or infection, certain ancillary and radiographic findings may preclude the need for invasive diagnostic procedures. We describe the case of a 15-year-old boy with a tumefactive demyelinating lesion involving the conus medullaris. An exhaustive systematic literature search of pediatric cases of TDL yielded an additional 78 cases. This review summarizes the current knowledge and recommendations for the diagnosis and management of this condition, highlighting the clinical, demographic, and radiologic features of 79 reported cases, including our own. Furthermore, it underscores areas of the literature where evidence is still lacking. Further research is needed to optimize clinical detection and medical management of this condition.