CT-guided biopsy of focal lesions in patients with multiple myeloma may reveal new and more aggressive cytogenetic abnormalities.

BACKGROUND AND PURPOSE: Cytogenetic abnormalities, especially chromosome 13 deletion, are high-risk factors for multiple myeloma. Attaining the highest detection rates of cytogenetic abnormalities is important to provide accurate prognostic information to the referring oncologist. The purpose of this study was to use CT-guided percutaneous fine-needle aspiration bone biopsy (CT-guided FNA) of MR-detected focal lesions in patients with multiple myeloma to increase identification of abnormal cytogenetics. METHODS: Patients enrolled in two clinical trials for myeloma therapy underwent MR imaging of the entire spine and pelvis. CT-guided FNA biopsy samples obtained from MR-detected focal lesions in these patients were sent for cytogenetic analysis. FNA results were then compared with random bone marrow sampling of the iliac crest done at or near the same time as the FNA to provide the data revealed in this study. RESULTS: Forty-one patients (47 lesions) in one of the trials and 37 patients (38 lesions) in the other trial had biopsies performed. CT-guided FNA revealed cytogenetic abnormalities in 21% of the total patient population and new information in nearly 10% of the patients in one trial and in 20% of those in the other trial. CONCLUSION: CT-guided biopsy of MR-detected focal lesions is a safe technique that can provide important cytogenetic information in a significant number of patients with multiple myeloma not identified during random marrow sampling.

Use of power Doppler in pediatric neurosonography: a pictorial essay.

In pediatric neurosonography, conventional color Doppler imaging has been the primary adjunct to routine gray-scale imaging. Power Doppler sonography is a relatively recent development that does not have the limitations of conventional color Doppler ultrasound. The power Doppler technique measures the energy of moving red blood cells instead of the velocity and direction of flow. Advantages of this technique include increased sensitivity for identifying flow in slow-flow states, more complete evaluation of a vessel, and more accurate evaluation of the course of the vessel. Power Doppler sonography is helpful in evaluation of the neonatal brain in a variety of clinical situations: identifying the exact locations of extraaxial fluid collections, differentiating intraventricular clot from normal choroid plexus, detecting intraventricular hemorrhage, and demonstrating asymmetries in cerebral perfusion. However, in certain difficult cases, use of both conventional color Doppler sonography and power Doppler sonography produces increased diagnostic accuracy because these techniques furnish complementary information.

In vivo and in vitro formation and dissociation of HLA-DR complexes with invariant chain-derived peptides.

HLA-DR molecules associated with class II-associated invariant chain peptides (CLIP) are generated in vivo as an intermediate in class II maturation. Such complexes can be produced in vitro by proteolytic digestion of DR alpha beta I complexes, suggesting that CLIP is a residual fragment that remains associated with class II molecules following I chain degradation. In vitro, CLIP dissociation from DR alpha beta dimers occurs at different rates depending on the allele, and is facilitated by low pH and by detergents containing 8-10 carbon unbranched hydrocarbons, or by primary aliphatic amines or carboxylic acids. The accumulation of DR alpha beta CLIP complexes in HLA-DM-negative antigen-processing mutant cells argues that a functionally similar mechanism, dependent on HLA-DM expression, catalyzes in vivo CLIP dissociation and generation of normal class II-peptide complexes.

Transport and intracellular distribution of MHC class II molecules and associated invariant chain in normal and antigen-processing mutant cell lines.

We have compared the intracellular transport and subcellular distribution of MHC class II-invariant chain complexes in a wild-type HLA-DR3 homozygous cell line and a mutant cell line, T2.DR3. The latter has a defect in antigen processing and accumulates HLA-DR3 molecules associated with an invariant chain-derived peptide (CLIP) rather than the normal complement of peptides derived from endocytosed proteins. We find that in the wild-type cells, CLIP is transiently associated with HLA-DR3 molecules, suggesting that the peptide is a normal class II-associated intermediate generated during proteolysis of the invariant chain. In the mutant cell line proteolysis of the invariant chain is less efficient, and HLA-DR3/CLIP complexes are generated much more slowly. Examination of the mutant cell line by immunoelectronmicroscopy shows that class II-invariant chain complexes accumulate intracellularly in large acidic vesicles which contain lysosomal markers, including beta-hexosaminidase, cathepsin D, and the lysosomal membrane protein CD63. The markers in these vesicles are identical to those seen in the class II-containing vesicles (MIICs) seen in the wild-type cells but the morphology is drastically different. The vesicles in the mutant cells are endocytic, as measured by the internalization of BSA-gold conjugates. The implication of these findings for antigen processing in general and the nature of the mutation in particular are discussed.

Intracellular transport and peptide binding properties of HLA class II glycoproteins.

Protein antigens internalized by an antigen presenting cell are degraded into peptides, a subset of which binds to the class II glycoproteins encoded by the major histocompatibility complex to form epitopes recognized by specific T cells. Current evidence suggests that the immunogenic peptides are generated in an endosomal, acidic compartment containing internalized antigen, proteinases, and exocytic class II molecules. These exocytic class II glycoproteins are associated during transport from the endoplasmic reticulum to the endosomal compartment with an additional glycoprotein, the invariant chain. Proteolytic degradation of the invariant chain in the endosomal compartment dissociates it from the class II glycoproteins, which only then acquire the capacity to bind peptides. After peptide binding occurs, the class II-peptide complexes are transported to the antigen-presenting cell surface for recognition by T cells.