İnflamatuar Miyofibroblastik Tümör
Özet
İnflamatuar miyofibroblastik tümör (İMT), genellikle çocuklarda ve genç erişkinlerde görülen, akciğerler başta olmak üzere vücudun herhangi bir bölgesinde ortaya çıkabilen ve orta biyolojik potansiyele sahip nadir bir mezenkimal neoplazmdır. Hastalar çoğunlukla lokalizasyona bağlı spesifik semptomlar veya ağrısız kitlelerle başvururken, %20'sinde ateş ve kilo kaybı gibi sistemik bulgular gözlenir. Etiyolojisi net olmamakla birlikte, vakaların yaklaşık %80'inde kinaz füzyonları saptanır ve %50'sinde anaplastik lenfoma kinaz (ALK) gen translokasyonu izlenir; bu durum hastalığın onkogen güdümlü doğasını gösterir. Teşhis, iğsi hücre proliferasyonu ve belirgin inflamatuar infiltrat gösteren histolojik inceleme ile konur. Lokalize hastalıkta standart tedavi, sarkom merkezlerinde R0 cerrahi rezeksiyon ile tam eksizyonun sağlanmasıdır. Standart kemoterapilere dirençli olan ilerlemiş veya metastatik İMT olgularında ise tümörün moleküler profili kritik önem taşır. ALK-pozitif ileri evre hastalıklarda ilk basamakta krizotinib kullanımı yüksek objektif yanıt ve uzun süreli sağkalım oranları nedeniyle güçlü bir şekilde önerilmektedir. Krizotinib direnci gelişen olgularda seritinib, alektinib ve lorlatinib gibi yeni nesil ALK inhibitörleri veya NTRK füzyonları varlığında larotrektinib/entrectinib gibi hedefe yönelik tedaviler etkindir. Ayrıca, yüksek PD-L1 ekspresyonu gösteren tümörlerde bağışıklık kontrol noktası inhibitörleri de geleceğe yönelik umut verici alternatif tedavi stratejileri sunmaktadır.
Inflammatory myofibroblastic tumor (IMT) is a rare mesenchymal neoplasm with intermediate biological potential that predominantly affects children and young adults, potentially arising anywhere in the body, most commonly in the lungs. Patients typically present with localized symptoms or painless masses, while approximately 20% experience systemic manifestations like fever and weight loss. Although its etiology remains unclear, kinase fusions are identified in about 80% of IMTs, and approximately 50% harbor anaplastic lymphoma kinase (ALK) gene translocations, demonstrating its oncogene-driven nature. Diagnosis is established via histology, characterized by spindle cell proliferation and prominent inflammatory infiltrate. For localized disease, the standard treatment is complete surgical R0 resection performed at specialized sarcoma centers. Advanced or metastatic IMT cases are typically resistant to standard chemotherapy, making molecular sequencing essential. In ALK-positive advanced disease, frontline treatment with crizotinib is strongly recommended due to its high objective response and prolonged survival rates. In crizotinib-resistant cases, next-generation ALK inhibitors like ceritinib, alectinib, and lorlatinib, or TRK inhibitors like larotrectinib and entrectinib for NTRK fusions, show efficacy. Furthermore, given the frequent expression of PD-L1, immune checkpoint inhibitors represent promising alternative therapies for managing recurrent or refractory IMT.
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