Hyperechoic malignancies of the breast: Underlying pathologic features correlating with this unusual appearance on ultrasound

Hyperechogenicity in the breast on ultrasound (US) is usually regarded as a benign feature with only rare hyperechoic malignancies reported to date. In this study, we evaluated the pathologic findings on core needle biopsy of hyperechoic lesions and investigated the histologic features in malignancies that give rise to an echogenic pattern. A total of 163 core needle biopsies (CNB) were performed for “hyperechoic” or “echogenic” lesions between 1/1/05 and 7/31/17. Lesions were classified based on the proportion of hyperechoic areas identified. We found that all lesions with a homogenous hyperechoic pattern (>90% hyperechoic) were benign (n = 17), regardless of the type of margins. Malignancies were found in 21% (7/34, six invasive carcinomas and one lymphoma) of heterogenous lesions with ≥50% hyperechoic areas (all with noncircumscribed margins) and in 31% of lesions with <50% hyperechoic areas (19/61, 14 invasive carcinomas, two lymphomas, and three metastases), including five with circumscribed margins (one invasive carcinoma, one lymphoma, and three metastases). Two major US patterns were identified in malignant lesions, those with a hypoechoic center and hyperechoic rim, corresponding to a central tumor area with dense stroma and tumor cells infiltrating adipose tissue at the periphery (“rim pattern”), and a second “dispersed pattern” with hyperechoic areas distributed throughout the lesion. Hyperechoic malignancies were found to be comprised of a complex intermixture of elements of differing echogenicity including tumor cells, adipose tissue, and fluid (in tubules, stromal clefts, or blood vessels). Our findings support the importance of radiologists specifying the echogenic pattern of hyperechoic lesions, as heterogenous lesions are associated with a higher risk of malignancy and pathologists should be alert to the associated pathologic findings.     

Impact of cleft lip and/or palate on nutritional health and oral-motor development

Infants born with a cleft may require modifications in feeding practices prior to surgical closure of the defect; however, few changes in dietary recommendations are necessary. Often, the delivery method of breast milk or formula can be altered in order to require less effort by the infant and decrease caloric output, thereby increasing the calories ingested to facilitate weight gain and growth. This adaptation may not be necessary when the cleft does not include the palate but can be implemented fairly easily when the baby appears to have difficulty obtaining adequate nutritional intake. Before and after any surgical intervention, the goal remains to continue to supply the infant with sufficient caloric intake to heal and to continue to grow. Although some surgeons may demand modifications in how the baby is fed postoperatively, many advocate cautious reinstitution of normal feeding practices. Early referral for dental care should be encouraged in children born with clefts because these children (even the very young) demonstrate higher dental needs. Education provided to parents regarding causes of and methods to reduce dental disease could help decrease its incidence and help these children require less invasive and difficult rehabilitation therapy.     

Single and combination toxic metal exposures induce apoptosis in cultured murine podocytes exclusively via the extrinsic caspase 8 pathway.

Arsenite, cadmium, and mercury are among the most abundant toxic metals (TM) in the environment. Although the most common renal manifestation of TM toxicity is proximal tubular dysfunction, significant glomerular injury can also occur. We hypothesized that glomerular injury following TM exposure results from TM-induced apoptosis of podocytes. To test this hypothesis we examined the extent of apoptosis and the apoptotic pathways induced in cultured murine podocytes incubated for three days with arsenite, cadmium, or mercury, and with equimolar combinations of all three metals. Apoptosis was detected by DNA laddering, and the number of apoptotic nuclei determined by Tunel assay. Treatment for three days with each TM resulted in DNA laddering and induced a dose-dependent increase in apoptotic nuclei. In contrast, treatment with equimolar combinations of TM induced significantly fewer apoptotic nuclei than individual TM treatments. Apoptosis induced by each TM was associated with a significant (approximately 400%) increase in caspase 8 activity, but no change in caspase 9 activity, and Western analyses revealed a marked up-regulation of Fas (approximately 500%) and FADD (approximately 300%) with no change in expression of Bax, Bcl-2, or Bcl-xL. Similar to the apoptotic response, combinations of TM induced less caspase 8 activity and Fas/FADD expression than individual TM treatments. Collectively, these results demonstrate that (1) TM induced apoptosis in cultured murine podocytes via the extrinsic Fas-FADD caspase 8 pathway, rather than the mitochondrial apoptotic pathway, and (2) combination TM exposure induced less apoptosis than individual TM, indicating an antagonistic rather than an additive or synergistic toxicity.     

Increased [32P]-phosphorylation of tryptic peptides of erythrocyte spectrin in duchenne muscular dystrophy

Increased [³²P]-incorporation in tryptic peptides of the erythrocyte membrane protein spectrin Band 2 in Duchenne muscular dystrophy (DMD) was studied in a consecutive series of 10 matched DMD/control pairs. Spectrin was [³²P]-phosphorylated by cyclic AMP-independent endogenous membrane protein kinase in the presence of [γ-³²P]ATP. [³²P]-labeled spectrin was isolated, purified, and subjected to tryptic cleavage with excess trypsin. The resulting peptides were separated on a high-resolution 5%/15% stacking SDS-polyacrylamide gel electrophoresis system. Liquid scintillation counting was performed on sequential slices of unstained gels. A broad [³²P]-labeled band containing a number of [³²P]-polypeptides was found to be more highly [³²P]-phosphorylated in DMD patients than in their matched controls. This band migrated with an apparent molecular mass of 4.8–5.2 kilodaltons and contained approximately 55% of total [³²P] radioactivity covalently bound to spectrin peptides. These data demonstrated an increased [³²P]-phosphorylation of an identifiable tryptic peptide fraction in DMD that is consistent with previous reports of increased spectrin Band 2 [³²P]-phosphrylation in DMD.