EML4-ALK Rearrangement and Its Therapeutic Implications in Inflammatory Myofibroblastic Tumors

Vargas‐Madueno, Fernando; Gould, Edwin W.; Valor, Raul; Ngo, Nhu; Zhang, Linsheng; Villalona‐Calero, Miguel A.

doi:10.1634/theoncologist.2018-0014

Cited by 8 publications

(4 citation statements)

References 25 publications

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“…In this study, both primary and metastatic lesions of the two IMTs were positive for ALK and harbored EML4 (exon 6)-ALK (exon 20) fusion. To date, eighteen EML4-ALK fusion IMTs have been reported (including the present two IMTs) (8,(13)(14)(15)(16)(17)(18)(19)(20) (Supplementary Table 3), eleven of which are located in the lung (11/18, 61.1%). The other cases included two IMTs in the abdominopelvic cavity, two IMTs in the limbs, one IMT in the head, one IMT in the trachea, and one IMT in the hypopharynx.…”

Section: Discussionmentioning

confidence: 85%

“…Thirty-seven patients underwent ALK immunostaining, and 19 patients demonstrated positive results. Gene detection was only performed in 10 patients, and 8 patients had ALK rearrangements, including 3 patients with EML4-ALK fusions (8,(14)(15)(16)(17)(18)(19)(20)(21). Although several studies have demonstrated EML4-ALK fusions in up to 20% of ALK-rearranged IMTs (8), the association between different EML4-ALK fusion variants and IMT disease progression has been insufficiently investigated.…”

Section: Introductionmentioning

confidence: 99%

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Case Report: Early Distant Metastatic Inflammatory Myofibroblastic Tumor Harboring EML4-ALK Fusion Gene: Study of Two Typical Cases and Review of Literature

Han

Qiu

et al. 2022

Front. Med.

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Inflammatory myofibroblastic tumor (IMT) is a distinctive neoplasm that frequently arises in the lung and accounts for ~1% of lung tumors. Distant metastatic IMT is extremely rare and has been poorly investigated. This analysis was specifically performed to explore the clinicopathological and genetic features of early distant metastatic IMT. Two typical patients with distant metastatic IMTs were selected, which accounted for 1.13% of all diagnosed IMTs in the last 5 years. One patient was a 55 year-old male, and the other patient was a 56 year-old female. Both primary tumors arose from the lung, and the initial clinical symptoms of the two patients involved coughing. Both of the imaging examinations showed low-density nodular shadows in the lungs with enhancement around the mass. Microscopically, dense arranged tumor cells, prominent cellular atypia, and high mitotic activity with atypical form were more prominent in the metastatic lesions than in the primary lesions. All of the primary and metastatic tumors in both cases showed positive anaplastic lymphoma kinase (ALK) immunostaining and ALK rearrangement via fluorescence in situ hybridization. The EML4 (exon 6)-ALK (exon 20) fusion variant (v3a/b) was identified by using next-generation sequencing (NGS) and was verified by using reverse transcription polymerase chain reaction (RT-PCR). Furthermore, intronic variants of NOTCH1 and synonymous variants of ARAF were also detected via NGS in one IMT for the first time and were verified in all of the primary and metastatic lesions via PCR. Distant metastasis occurred during a short period of time (1 and 2 months) after the first surgery. One patient presented with multiple metastases to the subcutaneous tissue and bone that responded to ALK inhibitor alectinib therapy, and the tumor was observed to regress 10 months after the initial ALK inhibitor therapy. In contrast, the other patient presented with subcutaneous neck metastasis without ALK inhibitor treatment and succumbed to the disease within 3 months after the surgery. This study demonstrated the possible role of EML4-ALKv3a/b in the malignant progression of IMT and proposed certain therapeutic effects of ALK inhibitors on multiple metastatic IMTs.

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Section: Discussionmentioning

confidence: 85%

Section: Introductionmentioning

confidence: 99%

Case Report: Early Distant Metastatic Inflammatory Myofibroblastic Tumor Harboring EML4-ALK Fusion Gene: Study of Two Typical Cases and Review of Literature

Han

Qiu

et al. 2022

Front. Med.

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“…Apart from its biological characteristics, the discovery that IMT may harbor chromosomal rearrangements at the 2p23 Locus, where the gene site for anaplastic lymphoma kinase (ALK) is, also firmed the borderline neoplasm property of IMT[ 6 - 8 ]. According to several case reports, approximately 30 kinds of genetic rearrangement have been found in IMT, most of which are ALK fusion genes[ 9 - 12 ]. ALK can be detected in about 50% of IMTs[ 13 ].…”

Section: Introductionmentioning

confidence: 99%

Infant biliary cirrhosis secondary to a biliary inflammatory myofibroblastic tumor: A case report and review of literature

Yuan¹,

Shu²,

Zhang³

et al. 2022

WJCC

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BACKGROUND A biliary inflammatory myofibroblastic tumor (IMT) is a rare type of mesenchymoma that, although it has a broad age spectrum, usually occurs in adults. Diagnosis is difficult because biliary IMTs often exhibit nonspecific clinical symptoms and imaging features, resulting in delayed or inappropriate treatment. Although most IMTs are benign, some show malignant properties such as infiltration, recurrence, and metastasis. CASE SUMMARY Here, we retrospectively describe a 10-month-old infant who was admitted to our hospital due to stubborn jaundice. The patient responded poorly to routine medical treatment and his clinical manifestations and laboratory tests lacked specificity, so we turned to repeated ultrasound scans and other imaging examinations. As both hepatosplenic ultrasonography and diffusion-weighted magnetic resonance imaging demonstrated a space-occupying lesion, an exploratory laparotomy was performed. The final diagnosis made over two mo after the disease onset was infant biliary cirrhosis caused by a biliary IMT, which partially infiltrated into the liver. This infant is the youngest case of biliary IMTs that has been reported till now. The patient underwent an incomplete resection of the mass and Kasai Portoenterostomy. However, because of cirrhosis, he also received a paternal liver transplant. Since some IMTs show malignant properties, we proceeded with a three-year of follow-up; however, no recurrence or metastasis has been noted. CONCLUSION Neoplastic disease such as IMTs should be considered when routine medical treatment of obstructive jaundice is not successful. Observation of dynamic imaging changes is helpful for diagnosis. Periodic follow-up is necessary for IMTs.

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“…Most IMTs are associated with ALK rearrangements, but other tyrosine kinase genes, such as ROS1 and RET, rearrangements can be the driver event (3,26). Interestingly, one of the ALK gene fusion partners described in IMT is EML4, and EML4::ALK rearrangements are frequent in non-small cell lung adenocarcinoma (27,28).…”

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confidence: 99%

Uterine Sarcoma With EML4::NTRK3 Fusion: A Spectrum of Mesenchymal Neoplasms Harboring Actionable Gene Fusions

de Castro,

dos Santos,

Mantoan

et al. 2023

International Journal of Gynecological Pathology

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NTRK gene fusions are part of a paradigm shift in oncology, arising as one of the main genomic alterations with actionability in the so-called “agnostic setting.” In gynecologic pathology, the recent description of uterine sarcoma resembling fibrosarcoma and with NTRK rearrangements (NTRK-rearranged uterine sarcoma) highlights the importance of recognizing clinicopathological cues that can lead to genomic profiling. Herein, we report the case of a 43-year-old woman presenting with vaginal bleeding and pelvic mass. Histopathology of the tumor showed moderately atypical spindle cells arranged in long fascicles reminiscent of fibrosarcoma, along with immunohistochemical positivity for S100, CD34, and pan-tropomyosin receptor kinase. This prompted RNA-sequencing and the finding of a rare EML4::NTRK3 fusion. Clinical, histologic, and molecular findings are described, in addition to discussions regarding differential diagnoses and possible implications of the findings in clinical practice.

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EML4-ALK Rearrangement and Its Therapeutic Implications in Inflammatory Myofibroblastic Tumors

Cited by 8 publications

References 25 publications

Case Report: Early Distant Metastatic Inflammatory Myofibroblastic Tumor Harboring EML4-ALK Fusion Gene: Study of Two Typical Cases and Review of Literature

Case Report: Early Distant Metastatic Inflammatory Myofibroblastic Tumor Harboring EML4-ALK Fusion Gene: Study of Two Typical Cases and Review of Literature

Infant biliary cirrhosis secondary to a biliary inflammatory myofibroblastic tumor: A case report and review of literature

Uterine Sarcoma With EML4::NTRK3 Fusion: A Spectrum of Mesenchymal Neoplasms Harboring Actionable Gene Fusions

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