A marker chromosome in post-transplant bone marrow.

Detection of small supernumerary marker chromosomes in karyotype analysis represents a diagnostic challenge. While such markers are usually detected during cytogenetic studies of constitutional chromosome abnormalities, they have also been found in specimens submitted from patients with acquired malignancies. We report here the detection of a marker chromosome in a bone marrow specimen from a patient who received a bone marrow transplantation. We discuss the importance of proper characterization and interpretation of marker chromosomes in clinical practice.

Smooth muscle and adenoma-like renal tumor: a previously unreported variant of mixed epithelial stromal tumor or a distinctive renal neoplasm?

We describe 6 cases of a biphasic renal neoplasm, which we designate smooth muscle and adenoma-like renal tumor, which do not cleanly fit any category as currently defined. There were 4 females and 2 males (age, 27-70 years); neither male had a history of hormone exposure. All 5 neoplasms with available history were discovered incidentally on imaging studies with sizes ranging from 4 to 20 cm. The stroma was composed of smooth muscle fascicles alternating with looser, edematous areas; none of the cases contained ovarian-like stroma. The complex but cytologically benign epithelial component consisted of tubulopapillary nodules, branching tubules, clefts, and large cysts. The stroma of all of the cases labeled diffusely for desmin. Estrogen receptor labeling was absent in 4 cases with only minimal (<10%) weak labeling in the remaining 2. The epithelial component of each case labeled diffusely for cytokeratin 7 and was patchy for α-methyl-CoA racemase (P504S). Carbonic anhydrase IX, HMB45, WT-1, and inhibin were negative. None of the 5 cases tested demonstrated trisomies of chromosome 7 or 17 by fluorescence in situ hybridization. Two patients with significant follow-up are disease free at 18.5 and 2.5 years. Smooth muscle and adenoma-like renal tumor could potentially represent a variant of mixed epithelial stromal tumor, which would expand its reported spectrum. However, the absence of clinical history of hormone exposure, predominance of smooth muscle with lack of ovarian-like stroma, prominence of epithelial nodules, and typical absence of estrogen receptor labeling suggest that it may represent a distinct entity.

Chromosomal defects track tumor subpopulations and change in progression in oligodendroglioma.

To assess karyotypic changes and tumor subpopulations in progression of oligodendroglioma (ODG) we analyzed histologically diagnosed 1p/19q codeleted cases using single nucleotide polymorphism (SNP) microarray data. We separated cases according to grade, which was assigned blind to karyotype information beyond 1p/19q status. The 51 WHO grade II (O2) and 18 WHO grade III (O3) specimens showed frequent chromosomal locations and patterns of change including loss of heterozygosity (LOH), often copy-neutral, on 9p and LOH on 4p and 4q together. Analysis of co-occurrence indicated that most defects were independent but also suggested increased likelihood of defects on 11q, 13q, and 14q in the presence of defects on 18, 4, and 9, respectively. We used the relative degree of change in B-allele frequency as an indicator of an abnormality's extent, and we present simulated data to clarify how information on subpopulations was thus inferred. Among 9p defects, 89.3% involved the whole tumor, whereas only 47.6% of 4q defects did so. We modeled extent through the tumor as due to a karyotypic change's likelihood of occurring and the fitness it confers on its subpopulation, and used group data to estimate these values. To assess progression directly, we evaluated specimens from six patients who underwent multiple resections since 1996. Four of these patients had received no chemotherapy or radiation, permitting assessment of the natural history of the tumor karyotype in situ. Defects present throughout a tumor at first resection remained so, whereas among subpopulations, some expanded, some remained constant, and some disappeared. The rate of expansion among subpopulations that did so was not uniform, and estimates of fitness predicted subpopulation composition at recurrence. These results extend prior studies of increased karyotypic abnormality in progression of oligodendroglioma and reveal the complex dynamics of subpopulations in the tumor over time.