Inflammatory Myofibroblastic Tumour: State of the Art

Abstract

An inflammatory myofibroblastic tumor (IMT) is a neoplasm composed of myofibroblastic and fibroblastic spindle cells accompanied by inflammatory cells, including lymphocytes and eosinophils. It is an ultra-rare tumor, the optimal management of which remains to be defined. Surgery is the treatment of choice for localized tumors. The treatment of advanced disease is not precisely defined. Chemotherapy regimens result in an overall response rate of approximately 50% based on retrospective data. The latest pathophysiological data highlight the role played by tyrosine kinase fusion genes in IMT proliferation. Anaplast lymphoma kinase (ALK) oncogenic activation mechanisms have been characterized in approximately 80% of IMTs. In this context, data regarding targeted therapies are most important. The aims of this article are to review the latest published data on the use of systematic therapy, particularly the use of molecular targeted therapy, and to publish an additional case of an IMT with Ran-binding protein 2 (RANPB2)-ALK fusion showing a long response to a tyrosine kinase inhibitor.

Epithelioid inflammatory myofibroblastic sarcoma of the lung ALK+/ NTRK+/ PD-L1+

“…To the best of our knowledge, about 60 cases of EIMS have been described and this case represents the fifth primitive pulmonary one [1,3]. Its topographic location, epithelioid microscopic morphology, immunophenotypic ALK expression, and aggressive features appear overall consistent with those already reported in the literature.…”

“…These findings, which have been described in rare case reports, have already been the subject of studies about a) the possible interaction between PD-L1 expression and some rare tumor subtypes with rich inflammatory stroma [4]; b) the correlation between ALK molecular pathways and the PD-1/ /PD-L1 immune checkpoints [2]; c) the involvement of pathways related to rearrangements of tyrosine kinase receptors [1].…”

“…The one described case was a localized disease, and even microscopically, the surgical margins (both pulmonary and pleural) were free from neoplastic infiltration (staging: R0). In such cases, scarce literature data suggest surgery as the treatment of choice [1]. Therefore, the clinical-oncological decision was made to wait and see, with close follow-up.…”

“…In the case of a recurrence, which is reported in about one-quarter of these surgically treated tumors [1], the question will arise whether to treat with new surgery or with oncological therapy. In this context, since chemotherapy appears to have no effect on the progression of EIMS [1], two microscopical findings in our case appear noteworthy: 1) the clear overexpression of PD-L1 in areas with epithelioid morphology (EIMS) compared to those with spindle cells (IMT), and 2) the nuclear expression of NTRK.…”

“…EIMS, as well as IMT, harbor anaplastic lymphoma kinase (ALK) gene fusions; however, recent publications have described different ALK fusion genes involved in EIMS, with particular reference to Ran-binding protein 2 (RANBP2)-ALK fusion. Unlike other neoplasms such as non-small cell lung carcinomas, very little is known about neurotrophic tyrosine receptor kinase (NTRK) and/or PD1/PD-L1 immune checkpoints alterations in such tumors and their value as targets for tailored molecular therapies [1,2].…”