Jiyun Lee

Leiomyosarcoma of the breast: a pathologic and comparative genomic hybridization study of two cases

Leiomyosarcoma is an extremely rare form of primary breast sarcoma. We present the pathologic and genetic findings of two cases of leiomyosarcoma of the breast. The patients were 44 and 52 years of age and they presented with circumscribed masses of 3.0 and 4.5 cm, (greatest dimension) respectively. Microscopically, the two tumors showed diffuse proliferation of spindle cells with oval and blunt-ended nuclei arranged in short fascicles or bundles. There was moderate cytologic atypia in both cases, and 6 and 12 mitotic figures per 10 high power fields, respectively. No epithelial component was identified. The tumor cells were strongly immunoreactive for markers of smooth-muscle differentiation, including desmin, muscle-specific actin, and smooth-muscle actin. Comparative genomic hybridization analysis showed losses of 10q (two of two cases), 13q (two of two cases), 17p (one of two cases), and gains of 1q (one of two cases) and 17p (one of two cases). The patterns of chromosomal imbalances identified in leiomyosarcoma of the breast are similar to those reported in leiomyosarcoma of soft tissue and uterus and are different from those reported for leiomyoma, indicating that these alterations may be important for development of malignant smooth-muscle tumors regardless of site or organ of origin.

Loss of SDHB and NF1 genes in a malignant phyllodes tumor of the breast as detected by oligo-array comparative genomic hybridization

We report oligo-array comparative genomic hybridization findings in a case of malignant phyllodes tumor of the breast. In addition to gains of 1q and 5p, and losses of 10p and 13q14 approximately q22, this tumor had also losses of two regions to which tumor suppressor genes are mapped: 1p36 (SDHB) and 17q11.2 (NF1). Both genes are associated with hereditary cancer syndromes, including gastrointestinal stromal tumors. Whether these two genes played a role in the development or progression of this phyllodes tumor of the breast with a sarcomatous stromal component warrants further investigation of similar cases.

Ring chromosome 9 [r(9)(p24q34)]: A report of two cases

We report clinical and molecular cytogenetic studies in two patients with ring chromosome 9. Cytogenetics and fluorescent in situ hybridization (FISH) analysis using the p16 gene probe on 9p21, the ABL gene on 9q34, chromosome 9 alpha satellite‐centromeric probes, and TelVision 9p and 9q probes which identify subtelomere‐specific sequences on chromosome 9p and 9q, revealed 46,XX,r(9)(p24q34).ish r(9)(305J7‐T7‐,p16+,ABL+, D9S325−) and 46XY,r(9)(p24q34).ish r(9)(305J7‐T7‐,p16+,ABL+, D9S325−). Based on FISH analysis at least 115 kb was deleted on terminal 9p, and at least 95 kb from terminal 9q. In comparison with other reports of r(9), deletion 9p, and deletion 9q, both patients had clinical characteristics of ring 9 and additional features of deletion 9q or deletion 9p syndrome. The variability between the two cases with r(9) despite similar breakpoints identified by GTG‐banding and FISH may be explained by submicroscopic differences between deletion breakpoints, ring instability, interaction of other genes on the phenotype, and variation in fetal environmental conditions.

De novo three-way chromosome translocation 46,XY,t(4;6;21)(p16;p21.1;q21) in a male with cleidocranial dysplasia.

Cleidocranial dysplasia (CCD) is an autosomal dominant skeletal dysplasia associated with cranial, clavicular, and dental anomalies. It is caused by mutations in the RUNX2 gene, which encodes an osteoblast‐specific transcription factor and maps to chromosome 6p21. We report clinical and molecular cytogenetic studies in a patient with clinical features of CCD including wormian bones, delayed fontanel closure, hypoplastic clavicles and pubic rami, and supernumerary dentition. Additional abnormalities of bone growth and connective tissue, including easy bruisability, scarring, bleeding, joint hypermobility, and developmental delay were also observed. Molecular cytogenetic studies identified a de novo apparently balanced three‐way translocation 46,XY,t(4;6;21)(p16;p21.1;q21). Further mapping revealed the breakpoint on 6p21 to be ∼50 kb upstream of exon 1 of the RUNX2 gene, with RUNX2 being intact on the derivative chromosome 6. We hypothesize that the probands CCD has arisen from disruption of the developmentally regulated gene RUNX2 at the 6p21 breakpoint, due to a position effect mutation which may have altered the expression of the gene. Further studies might unravel a new regulatory element for RUNX2.

Down syndrome with pure partial trisomy 21q22 due to a paternal insertion (4;21) uncovered by uncultured amniotic fluid interphase FISH.

Objective: To emphasize the usefulness and reliability of fluorescence in situ hybridization (FISH) on uncultured amniotic fluid cells in the prenatal diagnosis of common chromosomal aneuploidies. Methods: FISH analyses utilizing centromeric, locus‐specific or whole chromosome paint DNA probes specific for chromosomes X, Y, 13, 18, 21, and 4 were performed on uncultured amniotic fluid cells or the peripheral blood specimen from the father. Routine chromosome analysis was carried out as well. Results: A prenatal case with partial trisomy 21 due to a paternal cryptic insertion (4;21) was ascertained by a rapid overnight FISH on uncultured amniotic fluid cells. The fetus was delivered at term and had classical features of Down syndrome. Conclusion: Our results stress the importance of FISH on uncultured amniotic fluid cells to supplement routine cytogenetics, especially in cases with abnormal ultrasound findings.