MVP immunohistochemistry is a useful adjunct in distinguishing leiomyosarcoma from leiomyoma and leiomyoma with bizarre nuclei.

Morphologically, distinguishing between leiomyoma (LM) and leiomyosarcoma (LMS) is not always straightforward, especially with benign variants such as bizarre leiomyoma (BLM). To identify potential markers of malignancy in uterine smooth muscle tumors, proteomic studies were performed followed by assessment of protein expression by immunohistochemistry. Archival formalin-fixed, paraffin-embedded tissues from tumors (n = 23) diagnosed as LM, BLM, and LMS (using published criteria) were selected for the study. Sequential window acquisition of all theoretical fragment ion spectra mass spectrometry was applied to pooled samples of formalin-fixed, paraffin-embedded LM and LMS tumor tissue to assay the relative protein quantities and look for expression patterns differentiating the 2 tumor types. A total of 592 proteins were quantified, and 10 proteins were differentially expressed between LM and LMS. Select proteins were chosen for evaluation by immunohistochemistry (IHC) based on antibody availability and biologic relevance in the literature. IHC was performed on a tissue microarray, and intensity was evaluated using imaging software. Major vault protein (MVP) and catechol O-methyltransferase had 3.05 and 13.94 times higher expression in LMS relative to LM by sequential window acquisition of all theoretical fragment ion spectra mass spectrometry, respectively. By IHC, MVP (clone 1014; Santa Cruz Biotechnology, Dallas, TX) was found to be 50% sensitive and 100% specific when comparing LMS to LM. Catechol O-methyltransferase (clone FL-271; Santa Cruz Biotechnology) had a sensitivity of 38% and a specificity of 88%. Six of 7 BLM had expression of MVP similar to LM. Immunohistochemical staining for MVP is a useful adjunct in distinguishing LMS from LM and BLM in difficult cases.

Use of standard laboratory methods to obviate routine dithiothreitol treatment of blood samples with daratumumab interference.

CONCLUSIONS: Daratumumab is an antibody currently used in the treatment of patients with refractory multiple myeloma. Blood samples from patients being treated with daratumumab may show panreactivity during pre-transfusion testing. To facilitate the provision of blood components for such patients, it is recommended that a baseline phenotype or genotype be established prior to starting treatment with daratumumab. If patient red blood cells (RBCs) require phenotyping after the start of daratumumab treatment, dithiothreitol (DTT) treatment of the patient's RBCs should be performed. The medical charts of four patients treated with daratumumab were reviewed. The individual number of doses ranged from 1 to 14; patient age ranged from 55 to 78 years; two men and two women were included in the review. Type and screen data were obtained from samples collected over 33 encounters with a range of 1 to 13 encounters per patient. All samples were tested initially by automated solid-phase testing. Any reactivity with solid phase led to tube testing with either low-ionic-strength saline, polyethylene glycol, or both. If incubation failed to eliminate the reactivity, the sample was sent to a reference laboratory for DTT treatment and phenotyping. Of the 33 samples tested, 23 (69.7%) samples had reactivity in solid-phase testing. In 8 of the 10 samples that did not react in solid-phase, testing was conducted more than four half-lives after the last dose of daratumumab. Of the 23 that had reactivity in solid-phase, 16 (69.6%) samples demonstrated loss of reactivity using common laboratory methods. For the seven patients whose sample reactivity was not initially eliminated, six were provided with phenotypically matched blood based on prior molecular testing. Only one sample was sent out for DTT treatment. These results suggest that daratumumab interference with pre-transfusion testing can be addressed using common laboratory methods. This finding could save time and money for laboratories that do not have DTT available.