No abstract

Higher mIBG scores at diagnosis and occurrence of any residual mIBG-positive metastases after four cycles of chemotherapy predicted unfavorable outcome for patients with stage 4 neuroblastoma. Later clearance of metastases did not improve prognosis. The Curie and the SIOPEN score were equally reliable and predictive.

Punch biopsy was carried out in 32 cases in which thyroid gland changes were sonographically classified as being of homogeneously normal or of homogeneously low echogenicity. Mean follicle lumen size was morphometrically determined from the histological sections. This produced a significant, positive correlation between echogenicity and follicle size. The mean follicle lumen diameter in so-called echonormal structures was 67 microns (SD +/- 23 microns), and 25 microns (SD +/- 8 microns) in low-echogenic lesions. Thus normal echogenicity represented a normofollicular or macrofollicular structure, while a low echogenicity pattern indicated a microfollicular or solid tissue structure. The structure of thyroid carcinomas is not homogeneously normofollicular or macrofollicular; in exceptional cases they are such only focally. Therefore the significance of these findings lies in the exclusion of malignancy in the event of homogeneously normal echogenicity.

Key Points • A carrier of a deleterious splice site mutation in PIGT acquired a second hit in PIGT and developed PNH. To ascertain the genetic basis of a paroxysmal nocturnal hemoglobinuria (PNH) case without somatic mutations in PIGA, we performed deep next-generation sequencing on all exons of known genes of the glycosylphosphatidylinositol (GPI) anchor synthesis pathway. We identified a heterozygous germline splice site mutation in PIGT and a somatic 8-MB deletion in granulocytes affecting the other copy of PIGT. PIGA is essential for GPI anchor synthesis, whereas PIGT is essential for attachment of the preassembled GPI anchor to proteins. Although a single mutation event in the X-chromosomal gene PIGA is known to cause GPI-anchored protein deficiency, 2 such hits are required in the autosomal gene PIGT. Our data indicate that PNH can occur even in the presence of fully assembled GPI if its transfer to proteins is defective in hematopoietic stem cells. (Blood. 2013;122(7):1312-1315)