Uterine inflammatory myofibroblastic tumors in pregnant women with and without involvement of the placenta: a study of 6 cases with identification of a novel TIMP3-RET fusion

E. Heidi Cheek, Numrah Fadra, Rory A. Jackson, Jaime I. Davila, William R. Sukov, Mary T. Uckerman, Amy Clayton, Gary L. Keeney, Kevin Carl Halling, Jorge Torres-Mora, J. Kenneth Schoolmeester

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Uterine inflammatory myofibroblastic tumors (IMTs) have been reported in association with pregnancy and, in some instances, secondarily involve the placenta. The clinicopathological spectrum of these tumors in the setting of pregnancy is not well defined. We investigated the clinical, morphologic, immunohistochemical, molecular cytogenetic, and genetic features of 6 uterine IMTs occurring in pregnant women. Each tumor was discovered at parturition, and none was identified by prenatal ultrasound. Patient age ranged from 25 to 41 years (mean 31.5). Tumor size ranged from 1.5 to 9 cm (mean 4.7). Four of 6 had usual IMT features, with at least focal deciduoid change in 3. Necrosis was identified in 3 tumors; and multinucleated cells, in 3 tumors. Sex hormone receptor expression was consistent with estrogen receptor negative or focally weakly positive and progesterone receptor diffusely moderately or moderately to strongly positive in all 6 tumors. ALK immunohistochemistry was strongly positive in 5 tumors, and all of these had an ALK rearrangement detected by break-apart fluorescence in situ hybridization. Subsequent RNA sequencing of these 5 tumors identified a TIMP3-ALK fusion in 4 and a THBS1-ALK in 1. In the ALK-negative tumor, RNA sequencing detected a novel TIMP3-RET fusion that was confirmed by RET break-apart fluorescence in situ hybridization. Follow-up was available for 2 of 6 patients 5 and 19 months after diagnosis. Neither patient developed recurrence. ALK immunohistochemistry will distinguish most uterine IMTs, but if ALK expression and gene studies are negative, in the appropriate morphologic context, evaluation of other tyrosine kinase genes known to be more commonly altered in extrauterine IMTs such as ROS1, NTRK3, PDGFRβ, and RET may be necessary for diagnostic confirmation.

Original languageEnglish (US)
Pages (from-to)29-39
Number of pages11
JournalHuman Pathology
Volume97
DOIs
StatePublished - Mar 2020

Keywords

  • ALK
  • Inflammatory myofibroblastic tumor
  • Placenta
  • Pregnancy
  • RET
  • Uterus

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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