Molecular and clinicopathologic characterization of intravenous leiomyomatosis

Abstract

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 non-neoplastic 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 3 molecular groups: Group 1 (29%) and 2 (18%) with associated del(22q) and group 3 (18%) with del(10q). The remaining IVL had non-specific 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.

Retroperitoneal angioleiomyomatosis

“…Therefore, the diagnosis was made postoperatively by means of histopathology and cell markers examination. As reported in previous studies [1], the tumor was positive for immunomarkers CD31, CD34, D2-40, CD68, Ki-67 (1-2% positive nuclear staining) as well for smooth muscle markers SMA and Desmine.…”

“…Intravenous leiomyomata (IVL) are rare benign vascular neoplasms characterized by intraluminal growth of smooth muscle into either venous or lymphatic vessels outside the limits of myoma. Uterine IVL can extend through the veins, with inferior vena cava extension or pulmonary and heart metastasis, carrying significant morbidity [ 1 – 3 ]. Retroperitoneal development is another unusual growth pattern of uterine leiomyomas and especially of IVL.…”

Correlating genomic copy number alterations with clinicopathologic findings in 75 cases of hepatocellular carcinoma

“…Briefly, differentially labeled test or control DNA and gender-matched normal reference DNA were co-hybridized to a SurePrint G3 Human CGH 8 × 60 K Microarray slide (Agilent Technologies). Post-hybridization image capture, signal feature extraction and copy number analysis were performed using Agilent’s Cytogenomics 2.5 [ 21 , 22 ]. Benign copy number variants recognized in the Database of Genomic Variants ( http://dgv.tcag.ca/dgv/app/home ) were excluded.…”

Correlating genomic copy number alterations with clinicopathologic findings in a case series of hepatocellular carcinoma

“…Brie y, differentially labeled test or control DNA and gender-matched normal reference DNA were co-hybridized to a SurePrint G3 Human CGH 8×60K Microarray slide (Agilent Technologies). Post-hybridization image capture, signal feature extraction and copy number analysis were performed using Agilent's Cytogenomics 2.5 [21,22]. Benign copy number variants recognized in the Database of Genomic Variants (http://dgv.tcag.ca/dgv/app/home) were excluded.…”