Anaplastic lymphoma kinase-negative uterine inflammatory myofibroblastic tumor containing the <i>ETV6-NTRK3</i> fusion gene: a case report

Takahashi, Akimasa; Kurosawa, Manabu; Uemura, Mao; Kitazawa, Jun; Hayashi, Yoshihiko

doi:10.1177/0300060518780873

Cited by 51 publications

(50 citation statements)

References 18 publications

(29 reference statements)

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“…Molecular testing to confirm an ALK or NTRK fusion may be necessary. Recently Takahashi et al 52 reported a ETV6‐NTRK3 fusion in a uterine IMT lacking ALK immunohistochemical expression and ALK fusion. Yamamoto et al 53 reported the utility of pan‐Trk antibody in the detection of NTRK3 ‐rearranged IMT.…”

Section: Ntrk Fusion Uterine Sarcomamentioning

confidence: 99%

NTRK and other recently described kinase fusion positive uterine sarcomas: A review of a group of rare neoplasms

Croce

Hostein

McCluggage

2020

Genes Chromosomes & Cancer

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The landscape of uterine sarcomas has greatly expanded in recent years to include neoplasms with recurrent gene fusions, such as BCOR and YWHAE translocated high‐grade endometrial stromal sarcomas. Sophisticated molecular techniques have also resulted in the description of “new” entities associated with recurrent kinase fusions involving NTRK and RET as well as COL1A1‐PDGFB rearranged uterine sarcomas. These rare neoplasms will be discussed in this review, highlighting that some of the underlying molecular events are clinically actionable and potentially susceptible to targeted therapy. While relatively few of these neoplasms have been described to date, likely being previously lumped under the spectrum of undifferentiated uterine sarcoma, the number of cases will expand in the future given their recognition and the increasing availability of molecular testing. These neoplasms have overlapping morphology (often with a “fibrosarcoma‐like” appearance) and immunohistochemical features, and are characterized by variable clinical outcomes. Although immunohistochemistry may assist in some cases, a definitive subclassification requires confirmatory molecular studies. As these molecular assays may not be routinely available in most laboratories, referral to reference centers may be needed. In order to assist the pathologist, we suggest a diagnostic algorithm for routine practice when dealing with a malignant or potentially malignant uterine spindle cell neoplasm.

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Section: Ntrk Fusion Uterine Sarcomamentioning

confidence: 99%

NTRK and other recently described kinase fusion positive uterine sarcomas: A review of a group of rare neoplasms

Croce

Hostein

McCluggage

2020

Genes Chromosomes & Cancer

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“…A minor subset (approximately 5%) of IMTs harbour an NTRK3 gene rearrangement – in particular, ETV6–NTRK3 gene fusion, which is identical to that in infantile fibrosarcoma . A monoclonal pan‐Trk antibody that reacts with TrkA, TrkB and TrkC was recently developed.…”

Section: Introductionmentioning

confidence: 99%

Diagnostic utility of pan‐Trk immunohistochemistry for inflammatory myofibroblastic tumours

2020

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Aims: Inflammatory myofibroblastic tumour (IMT) is a spindle cell neoplasm of intermediate malignancy, and the diagnosis is often challenging due to the morphological overlap with other spindle cell neoplasms and reactive lesions. More than half of IMTs have the ALK gene rearrangement, and a minor subset have ROS1, NTRK3 or RET gene rearrangements. We sought to determine the potential diagnostic utility of pan-Trk immunohistochemistry for IMTs. Methods and results: We retrospectively examined 40 cases of IMT using immunohistochemistry with a rabbit monoclonal pan-Trk antibody. Gene rearrangement was confirmed by fluorescence in-situ hybridisation and/or reverse transcription-polymerase chain reaction. The IMTs were classified as the ALK (n = 29), ROS1 (n = 2), NTRK3 (n = 2), RET (n = 0) and 'quadruple-negative' (n = 7) genotypes by molecular analyses. Both of the ETV6-NTRK3 fusion-positive cases showed nuclear and cytoplasmic staining for pan-Trk in the majority of tumour cells. None of the ALK, ROS1 or quadruple-negative-type IMTs showed nuclear staining for pan-Trk, but approximately onethird of these IMTs showed focal and weak cytoplasmic staining. One exceptional case of a RANBP2-ALK-positive epithelioid inflammatory myofibroblastic sarcoma (an aggressive variant of IMT) showed moderate cytoplasmic staining for pan-Trk. Conclusions: These results suggest that pan-Trk immunoreactivity with a nuclear and cytoplasmic staining pattern may be useful to identify ETV6-NTRK3-positive IMTs and may be helpful in selecting patients for Trk-targeted therapy.

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“…7 Recent studies have described novel fusions involving ROS1, NTRK, RET, and PDGFRb genes in a subset of ALK-negative cases. [8][9][10] Little is known on the genomic level about potential oncogenic drivers in this subset of IMTs. Given the rarity of IMT, few prospective studies focusing on its targeted therapy are available.…”

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confidence: 99%

Partial Response to Ceritinib in a Patient With Abdominal Inflammatory Myofibroblastic Tumor Carrying a TFG-ROS1 Fusion

Li¹,

Chen²,

Qu³

et al. 2019

Journal of the National Comprehensive Cancer Network

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Inflammatory myofibroblastic tumor (IMT), a rare sarcoma, is primarily treated via resection of the mass. However, there is no standard treatment for recurrence or unresectable tumors. Almost 50% of IMTs carry ALK gene rearrangement that can be treated using ALK inhibitors, but therapeutic options for ALK-negative tumors are limited. This report describes a woman aged 22 years with unresectable ALK-negative IMT. Next-generation sequencing revealed a TFG-ROS1 fusion, and she had a partial response to the ROS1 inhibitor ceritinib. This report provides the first published demonstration of a patient with IMT with ROS1 fusion successfully treated using ceritinib. Our study suggests that targeting ROS1 fusions using the small molecule inhibitor shows promise as an effective therapy in patients with IMT carrying this genetic alteration, but this requires further investigation in large clinical trials.

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Anaplastic lymphoma kinase-negative uterine inflammatory myofibroblastic tumor containing the ETV6-NTRK3 fusion gene: a case report

Cited by 51 publications

References 18 publications

NTRK and other recently described kinase fusion positive uterine sarcomas: A review of a group of rare neoplasms

NTRK and other recently described kinase fusion positive uterine sarcomas: A review of a group of rare neoplasms

Diagnostic utility of pan‐Trk immunohistochemistry for inflammatory myofibroblastic tumours

Partial Response to Ceritinib in a Patient With Abdominal Inflammatory Myofibroblastic Tumor Carrying a TFG-ROS1 Fusion

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