Outstanding Response in a Patient With ROS1-Rearranged Inflammatory Myofibroblastic Tumor of Soft Tissues Treated With Crizotinib: Case Report

Abstract

Inflammatory myofibroblastic tumor (IMT) is a very rare subtype of sarcoma, which frequently harbor chromosomal rearrangements, including anaplastic lymphoma kinase (ALK) rearrangements (almost 50% of the IMTs) and other kinase fusions such as ROS1. ROS1 fusions are present in about 10% of IMT, almost half of the ALK-negative IMT patients. Apart from radical surgery for resectable tumors, there is no standard-of-care therapy for advanced IMTs. Nonetheless, the use of tyrosine kinase inhibitors has shown promising efficacy in IMT patients with targetable genomic alterations. We report the case of a 24-year-old patient with chemotherapy-refractory metastatic IMT harboring ROS1 kinase fusion, who experienced a significant clinical and pathological response to crizotinib. This clinical case highlights the need to assess all patients with unresectable IMTs for chromosomal abnormalities and gene mutations and address them to targeted agents as well as clinical trials.

Keywords: ROS1; crizotinib; inflammatory myofibroblastic tumor; inflammatory pseudotumor; retreatment; sarcoma; target therapy.

Figure 1

Timeline of patient’s clinical history.

Figure 2

CT scan 3d-reconstruction of the baseline tumor lesions (A) coronal plane; (B) sagittal plane). L1Vol1 = left thigh mass; L2Vol1 = lesion of the left dorsal muscles next to D11 vertebral body; L3Vol1 = lesion of the left dorsal muscles next to L5 vertebral body; L4Vol1 = lesion of the left gluteus muscles; L5Vol1 = lesion of the left iliopsoas.

Figure 3

CT scan imaging of the tumoral lesions during patient’s treatment history. Evolution during treatment of the tumoral lesions: lesions of the left dorsal muscles next to D11 vertebral body (arrow) and L5 vertebral body (arrowhead), lesion of the left gluteus (circle) and left thigh mass (asterisk). (A) before chemotherapy (March 2019), (B) after second cycle of chemotherapy and before crizotinib (May 2019), (C) after 4 months of crizotinib (September 2019), (D) after 7 months of crizotinib (December 2019).

Figure 4

Clinical presentation of the left thigh mass during patient’s treatment history. (A) before chemotherapy (March 2019), (B) after second cycle of chemotherapy and before crizotinib (April 2019), (C) after 7 days of crizotinib, (D) after 3 months of therapy (August 2019), (E) after 7 months of therapy (December 2019).

Figure 5

IHC analysis of the resected tumor. (A) Hematoxylin and eosin (H&E) stain, original magnification 10×: necrotic area (asterisk) and sclerotic tissue with residual neoplastic spindle cells. (B, C) H&E stain, original magnification 20×: foamy histiocytes (circle) and a vascularized fibrotic area of connective tissue (arrowhead) mark the tumor bed. (D) H&E stain, original magnification 40×: atypical spindled neoplastic cells set in a loose collagenous matrix with a mild inflammatory infiltrate. Neoplastic cells show hyperchromatic and enlarged nuclei (arrows).

Figure 6

Complete regression of multifocal local recurrence in the left thigh. (A) Post-contrast MR T1 fat saturated axial image of upper left thigh shows some irregular enhancing nodules in the anterior compartment (asterisk). (B) The same sequence obtained three months later in the same area reveals complete nodules disappearance.