Inflammatory Myofibroblastic Tumors of the Female Genital Tract Are Under-recognized

Abstract

Inflammatory myofibroblastic tumor (IMT) of the female genital tract is under-recognized. We investigated the prevalence of ALK-positive IMT in lesions previously diagnosed as gynecologic smooth muscle tumors. Immunohistochemistry (IHC) for ALK was performed on tissue microarrays of unselected tumors resected from 2009 to 2013. Three of 1176 (0.26%) “leiomyomas” and 1 of 44 (2.3%) “leiomyosarcomas” were ALK IHC positive, confirmed translocated by fluorescence in situ hybridization (FISH) and therefore more appropriately classified as IMT. On review significant areas of all 4 tumors closely mimicked smooth muscle tumors morphologically, but all showed at least subtle/focal features suggesting IMT. Recognizing that the distinction between IMT and leiomyoma/leiomyosarcoma can be subtle, we then reviewed 1 hematoxylin and eosin slide from each patient undergoing surgery for “leiomyoma” from 2014 to 2017 and selected cases for ALK IHC with a low threshold. Of these, 30 of 571 (5.3%) underwent IHC. Two were confirmed to be IHC positive and FISH rearranged. Of the 6 IMTs, only 1 tumor with a previous diagnosis of leiomyosarcoma, an infiltrative margin and equivocal necrosis, metastasized. Of note it demonstrated a less aggressive clinical course compared with most metastatic leiomyosarcomas (alive with disease at 6 y). The patient was subsequently offered crizotinib to which she responded rapidly. In conclusion, IMTs may closely mimic gynecologic smooth muscle tumors. IMTs account for at least 5 of 1747 (0.3%) tumors previously diagnosed as leiomyoma and 1 of 44 (2.3%) as leiomyosarcoma. These tumors may be recognized prospectively with awareness of subtle/focal histologic clues, coupled with a low threshold for ALK IHC.

Inflammatory myofibroblastic tumor of the uterus that might STUMP you: Report of a case with clinicopathological and immunohistochemical findings

“…Inflammatory myofibroblastic tumor (IMT) of the female genital tract is rare neoplasm with less than 75 cases reported in the literature [1][2][3][4]. The distinction between IMTs and other mesenchymal uterine tumors, especially those with myxoid changes can be subtle.…”

Uterine inflammatory myofibroblastic tumour: A case report

“…Inflammatory myofibroblastic tumour (IMT) is a mesenchymal neoplasm with intermediate biological potential, which may be under-recognised in the uterus. [1][2][3] Morphological and immunophenotypic overlap exists between uterine IMT and some other uterine mesenchymal neoplasms, including smooth muscle tumours. 2 Morphological features suggestive of IMT may be subtle or focal and include myxoid change, tapered nuclei, and a lymphoplasmacytic infiltrate.…”

“…2 Morphological features suggestive of IMT may be subtle or focal and include myxoid change, tapered nuclei, and a lymphoplasmacytic infiltrate. 1 Chromosomal rearrangements involving the anaplastic lymphoma kinase (ALK) gene appear to be frequent in uterine IMT, [1][2][3] and absent in other uterine mesenchymal neoplasms. 2 Therefore, ALK immunohistochemistry (IHC) and ALK florescent in situ hybridisation (FISH) appear to be useful tools to confirm the diagnosis of uterine IMT.…”

“…3 Although most uterine IMTs follow a benign clinical course, local recurrence and metastases have been observed in a small subset. 1 Correct diagnosis is important to ensure accurate prognosis and optimal management, which may include a tyrosine kinase inhibitor. We present a case of uterine IMT with morphology and IHC suggestive of a leiomyosarcoma with myxoid change.…”

Are ALK rearrangements found in smooth muscle tumours of the gastrointestinal tract?

“…and Pickett et al . identified a subset of uterine smooth muscle tumours, which were initially diagnosed as leiomyomas or smooth muscle tumours of uncertain malignant potential, that harboured ALK fusions and were immunohistochemically positive for ALK . These tumours closely mimicked smooth muscle tumours, but showed focal, myxoid change, tapered nuclei, and lymphoplasmacytic infiltrate, which are features suggestive of inflammatory myofibroblastic tumours.…”