Uterine inflammatory myofibroblastic tumor: First report of a ROS1 fusion

Abstract

Inflammatory myofibroblastic tumor (IMT) of the uterus is an uncommon mesenchymal neoplasm that frequently harbors ALK rearrangements. In this report, we describe the first uterine IMT with a FN1-ROS1 fusion, which occurred in a 43-year-old woman who presented with menorrhagia. Morphologically, the well-circumscribed 3 cm tumor was comprised of compact and myxoid foci of relatively bland spindle cells admixed with scattered chronic inflammatory cells limited to the myxoid areas. ROS1 showed moderate cytoplasmic granular staining in < 30% of cells in the myxoid foci, while ALK was negative. RNA sequencing detected a FN1-ROS1 rearrangement that fused FN1 exon 37 to ROS1 exon 34. Although non-ALK-rearranged uterine IMTs are exceedingly rare, this example highlights the importance of performing ROS1 immunohistochemistry and/or molecular analysis in ALK-negative uterine neoplasms morphologically compatible with IMT.

A Novel CASC15-ALK and TFG-ROS1 Fusion Observed in Uterine Inflammatory Myofibroblastic Tumor

“…The ROS1 rearrangement most often occurs in nonfemale reproductive tract IMTs in children (mean: 9 yr) and accounts for ~10% of IMTs (2,20,47). Only 2 cases of ROS1-rearranged uterine IMT have been reported recently, including 1 TIMP3-ROS1 fusion (12), which was associated with pregnancy, and 1 FN1-ROS1 fusion (6). Herein, we describe 1 additional IMT in the female gynecologic tract harboring a TFG-ROS1 fusion.…”

“…Inflammatory myofibroblastic tumor (IMT) of the gynecologic tract is a rare mesenchymal neoplasm of myofibroblastic/fibroblastic origin with varying degrees of myxoid stroma and lymphoplasmacytic inflammation (1)(2)(3). The majority of IMTs in the gynecologic tract are characterized by genetic fusion involving anaplastic lymphoma kinase (ALK) because of chromosome rearrangement (1,(4)(5)(6). The ALK fusion partners identified in IMT of the gynecologic tract include IGFBP5, THBS1, FN1, DES, TIMP3, SEC31A, TPM3, TNC, and TNS1 (3,5,(7)(8)(9)(10)(11).…”

“…The ALK fusion partners identified in IMT of the gynecologic tract include IGFBP5, THBS1, FN1, DES, TIMP3, SEC31A, TPM3, TNC, and TNS1 (3,5,(7)(8)(9)(10)(11). In sporadic cases, genomic fusions involving additional receptor tyrosine kinases, such as ETV6-NTRK3, TIMP3-RET, TIM-P3-ROS1, FN1-ROS1, and SORBS1-RET, and a case with IGFBP5-PDGFRB fusion have been identified in IMT cases lacking ALK genetic rearrangements/fusions (Table 1) (6,(10)(11)(12)14). Herein, we report 1 case of uterine IMT harboring a TFG-ROS1 fusion and 1 case harboring a novel fusion involving ALK, specifically the cancer susceptibility candidate 15-anaplastic lymphoma kinase (CASC15)-ALK.…”

Follicular Dendritic Cell Sarcoma of Uterine Corpus: Report of 2 Cases

“…Neutrophils admixed with lymphocytes have only been reported in one FDCS (vagina) (4) and were not present in our cases. Positivity for ALK (28,29) as well as frequent positivity for smooth muscle markers is typically seen in IMTs which also display ALK gene rearrangements or rarely, alterations in NTRK3, RET, or ROS1 (30)(31)(32).…”

ALK Immunoexpression is Specific for Inflammatory Myofibroblastic Tumor Among Vulvovaginal Mesenchymal Neoplasms

“…Gynecologic tract origin of inflammatory myofibroblastic tumor (IMT), a receptor tyrosine kinase fusion driven mesenchymal tumor that carries malignant potential, is uncommon; most such cases involve the uterine corpus and, more rarely, the cervix or adnexa (1). Nearly all fusion-positive uterine IMTs with a detectable kinase alteration harbor an ALK rearrangement; a rare case involving ROS1 was only recently reported (2)(3)(4)(5)(6)(7). In contrast, IMTs arising outside the gynecologic tract are characterized by a variety of receptor tyrosine kinase gene rearrangements besides ALK, such as ROS1 or NTRK3 (8).…”