Imaging of Multiple Myeloma.

Multiple myeloma is the most common bone malignancy. Imaging plays an important role in identifying the extent of the disease, disease process, guiding biopsies, and diagnosing associated spinal and intracranial complications. Multiple myeloma and related plasma cell proliferative disorders have a diverse set of clinicopathologic findings and on neuroimaging present unique and diverse findings from the disease and from complications of the disease and treatment, which are valuable for clinicians and radiologists.

Atypical lobular hyperplasia and lobular carcinoma in situ at core needle biopsy of the breast: An incidental finding or are there characteristic imaging findings?

BACKGROUND: Atypical lobular hyperplasia and classic-type lobular carcinoma in situ, collectively known as lobular neoplasia, are classically described as incidental findings found on breast core-needle biopsy without distinguishing imaging characteristics. OBJECTIVE: The purpose of this study was to investigate concordant imaging findings of lobular neoplasia identified at core-needle biopsy after careful radiologic-pathologic correlation. METHODS: The pathology database was searched from October 1, 2006 to October 1, 2013 for breast biopsies yielding lobular neoplasia not associated with a coexistent malignancy or other high risk lesion in the biopsy specimen. RESULTS: Of the 482 biopsies performed containing lobular neoplasia, 65 cases had lobular neoplasia as the highest risk lesion at core-needle biopsy. Of the 65 total cases in which lobular neoplasia was the highest risk lesion, 18 (28%) cases had concordant imaging correlates. 13 of 18 (72%) cases presented as calcifications on mammography and 5 of 18 (28%) presented on magnetic resonance imaging as a focus (n = 2) or non-mass enhancement (n = 3). CONCLUSION: With careful radiologic-pathologic correlation, mammographically detected calcifications and foci or non-mass enhancement on magnetic resonance imaging can be considered concordant imaging findings of lobular neoplasia after breast core-needle biopsy.

Cisplatin causes over-expression of tachykinin NK(1) receptors and increases ERK1/2- and PKA- phosphorylation during peak immediate- and delayed-phase emesis in the least shrew (Cryptotis parva) brainstem.

Scant information is available regarding the effects of cisplatin on the expression profile of tachykinin NK(1) receptors and downstream signaling during cisplatin-induced emesis. Cisplatin causes peak early- and delayed-phase emesis in the least shrew at 1-2 and 33 h post-injection. To investigate the expression profile of NK(1) receptor during both emetic phases, we cloned the cDNA corresponding to a ~700 base pairs of mRNA flanked by two stretches of nucleotides conserved among different species and demonstrated that the shrew NK(1) receptor nucleotide sequence shares ~90% sequence identity with the human NK(1) receptor. Of the 12 time-points tested, significant increases in expression levels of NK(1) receptor mRNA in the shrew brainstem occurred at 2 and 28 h post-cisplatin injection, whereas intestinal NK(1) receptor mRNA was increased at 28 h. Shrew brainstem and intestinal substance P mRNA levels also tended to increase during the two phases. Furthermore, expression levels of NK(1) receptor protein were significantly increased in the brainstem at 2, 8, and 33 h post-cisplatin. No change in brainstem 5-HT(3) receptor protein expression was observed. The temporal enhancements in NK(1) receptor protein expression were mirrored by significant increases in the phosphorylation status of the brainstem ERK1/2 at 2, 8, and 33 h post-cisplatin. Phosphorylation of PKA significantly increased at 33rd and 40th hour. Our results indicate associations between cisplatin's peak immediate- and delayed-phase vomiting frequency with increased: (1) expression levels of NK(1) receptor mRNA and its protein level, and (2) downstream NK(1) receptor-mediated phosphorylation of ERK1/2 and PKA signaling.

Synergistic antiemetic interactions between serotonergic 5-HT3 and tachykininergic NK1-receptor antagonists in the least shrew (Cryptotis parva).

Significant electrophysiological and biochemical findings suggest that receptor cross-talk occurs between serotonergic 5-HT(3)- and tachykininergic NK(1)-receptors in which co-activation of either receptor by ineffective doses of their corresponding agonists (serotonin (5-HT) or substance P (SP), respectively) potentiates the activity of the other receptor to produce a response. In contrast, selective blockade of any one of these receptors attenuates the increase in abdominal vagal afferent activity caused by either 5-HT or SP. This interaction has important implications in chemotherapy-induced nausea and vomiting (CINV) since 5-HT(3)- and NK(1)-receptor antagonists are the major classes of antiemetics used in cancer patients receiving chemotherapy. The purpose of this study was to demonstrate whether the discussed interaction produces effects at the behavioral level in a vomit-competent species, the least shrew. Our results demonstrate that pretreatment with either a 5-HT(3) (tropisetron)- or an NK(1) (CP99,994)-receptor specific antagonist, attenuates vomiting caused by a selective agonist (2-methyl 5-HT or GR73632, respectively) of both emetic receptors. In addition, relative to each antagonist alone, their combined doses were 4-20 times more potent against vomiting caused by each emetogen. Moreover, combined sub-maximal doses of the agonists 2-methyl 5-HT and GR73632, produced 8-12 times greater number of vomits relative to each emetogen tested alone. However, due to large variability in vomiting caused by the combination doses, the differences failed to attain significance. The antiemetic dose-response curves of tropisetron against both emetogens were U-shaped probably because larger doses of this antagonist behave as a partial agonist. The data demonstrate that 5-HT(3)- and NK(1)-receptors cross-talk to produce vomiting, and that synergistic antiemetic effects occur when both corresponding antagonists are concurrently used against emesis caused by each specific emetogen.