Molecular and clinicopathologic characterization of intravenous leiomyomatosis

• DOI: 10.1038/s41379-020-0546-8
• Publication Date: 2020-04-27T10:03:17Z
• Authors: Zehra Ordulu; Hongyan Chai; Gang Peng; Anna G. McDonald; Michele De Nictolis; Eugenia Garcia-Fe...; David Hardisson; Jaime Prat; Peining Li; Pei Hui; Esther Oliva; Natalia Buza
• Keywords: Adult; 0301 basic medicine; 13q; HMGA2; 8p; 8q; Microarray; Hyaline; Article; Intravenous leiomyomatosis; 03 medical and health sciences; 0302 clinical medicine; Vascular; Angioleiomyoma; Leiomyomatosis; Genetics; SOX10; Humans; Cyclin D1; Phosphorylation; Acgh; Cyclin-Dependent Kinase Inhibitor p16; Aged; Aged, 80 and over; 14q; Phosphorylated Rb; Comparative Genomic Hybridization; Uterus; CAIX; Molecular; P16; Der(14); Middle Aged; 1q; 22q; SDHB; 1p; 10q; 3. Good health; IVL; Uterine Neoplasms; Female; Cellular; RB

Intravenous leiomyomatosis (IVL) is an unusual uterine smooth muscle proliferation that can be associated with aggressive clinical behavior despite a histologically benign appearance. It has some overlapping molecular characteristics with both uterine leiomyoma and leiomyosarcoma based on limited genetic data. In this study, we assessed the clinical and morphological characteristics of 28 IVL and their correlation with molecular features and protein expression, using array comparative genomic hybridization (aCGH) and Cyclin D1, p16, phosphorylated-Rb, SMARCB1, SOX10, CAIX, SDHB and FH immunohistochemistry. The most common morphologies were cellular (n = 15), usual (n = 11), and vascular (n = 5; including 3 cellular IVL showing both vascular and cellular features). Among the immunohistochemical findings, the most striking was that all IVL showed differential expression of either p16 or Cyclin D1 in comparison to surrounding nonneoplastic tissue. Cytoplasmic phosphorylated-Rb was present in all but one IVL with hyalinization. SMARCB1, FH, and SDHB were retained; S0X10 and CAIX were not expressed. The most common genetic alterations involved 1p (39%), 22q (36%), 2q (29%), 1q (25%), 13q (21%), and 14q (21%). Hierarchical clustering analysis of recurrent aberrations revealed three molecular groups: Groups 1 (29%) and 2 (18%) with associated del(22q), and Group 3 (18%) with del(10q). The remaining IVL had nonspecific or no alterations by aCGH. Genomic index scores were calculated for all cases and showed no significant difference between the 14 IVL associated with aggressive clinical behavior (extrauterine extension or recurrence) and those without (median scores 5.15 vs 3.5). Among the 5 IVL associated with recurrence, 4 had a vascular morphology and 3 had alterations of 8q. Recurrent chromosome alterations detected herein overlap with those observed in the spectrum of uterine smooth muscle tumors and involve genes implicated in mesenchymal tumors at different sites with distinct morphological features.