Mikozis fungoides hastalarında PD-1 belirtecinin tanısal algoritmadaki rolü
Küçük Resim Yok
Dosyalar
Tarih
2021
Yazarlar
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Ege Üniversitesi, Tıp Fakültesi
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Amaç: Mikozis fungoides (MF) en sık görülen kutanöz T hücreli lenfomadır. Ortalama tanı yaşı altıncı dekad içinde olmakla birlikte çocuklarda ve daha ileri yaşlarda da görülebilir. Klinik olarak hastalığın evresine göre yama, plak ve tümoral lezyonlarla seyretmektedir. Erken dönemde tipik olarak gluteal alan ve gövde gibi güneş görmeyen bölgelere sınırlı, değişken boyutlarda eritemli, ince skuamlı yama tarzı lezyonlar ya da ince plaklarla karakterizedir. Erken evre MF, dermatit, psoriasis vulgaris ve liken planus gibi inflamatuvar dermatozlar ile parapsoriasis grubu hastalıkları taklit edebilir ve bu dönemde alınan biyopsiler tanı koydurucu niteliklere sahip olmayabilir. MF’de deri lezyonlarının başlangıcı ile klinik ve histopatolojik olarak kesin tanının konulması arasında geçen ortalama süre 4-6 yılı bulabilir. MF’de erken tanı, hastaların prognozunu iyi yönde etkileyeceği gibi ileri evrelerde ihtiyaç duyulan tedavilere bağlı yan etkilerin önlenmesini de sağlayacaktır. Programmed Death-1 (PD-1) immünglobulin süperailesinden transmembran bir glikoprotein olup PDL-1 ve PDL-2 ligandlarına bağlanıp CD28-CD80 yolağını baskılayarak T hücre reseptör sinyal iletimini azaltır. T hücre fonksiyonlarında meydana gelen bu azalmanın, neoplastik hücrelerin immün sistemden kaçmasına neden olduğu düşünülmektedir. Bu çalıĢmada PD-1’in MF tanısında ve MF’in inflamatuvar dermatozlardan ayırımında potansiyel bir belirteç olarak değerlendirilmesi ve MF hastalarında anlamlı pozitiflik saptanırsa PD-1 pozitifliği ile klinik ve TNMB evreleri, histolojik alt tip ilişkilerinin sorgulanması amaçlanmıştır. Gereç ve yöntemler: Birinci grupta klinik ve histopatolojik olarak mikozis fungoides tanısı almış 44; ikinci grupta psoriasis vulgaris, dermatit ve liken planus gibi inflamatuvar dermatoz tanısı almış 30 ve üçüncü grupta (ara grup) parapsoriasis, pitriyazis likenoides gibi klonal dermatit grubundan 21 ve klinik değerlendirmede ayırıcı tanıda MF düşünülen ancak histopatolojik olarak yeterli MF bulgusu saptanmayan 9 MF şüpheli hasta olmak üzere toplam 30 hasta yer almıştır. Her gruptaki biyopsilerde immünhistokimyasal yöntemle PD-1 ekspresyonu araştırıldı. Semikantitatif değerlendirmeyle boyanma göstermeyen olgular negatif (0), hücrelerin %10’undan az boyanma fokal pozitif (1+), hücrelerde %11-50 boyanma multifokal pozitif (2+), %50 hücreden fazla boyanma diffüz boyanma (3+) olarak kabul edildi. Bulgular: MF grubunda hem pozitiflik oranı hem de boyanan hücre yüzdesine göre boyanma derecesi inflamatuvar grup ve ara gruba göre istatistiki olarak anlamlı derecede yüksek bulunmuĢtur (p: <0,001 ve p:0,001). MF hastalarının 16’sı lezyon kliniğine göre yama, 18’i plak ve 10’u tümör evresindeydi. Yama evresinde %25’lik pozitiflik, plak evrede %55 ve tümöral evrede %80 pozitiflik saptandı. Bu farklılıklar istatistiksel açıdan anlamlı bulunmuştur (p:0,2). Ayrıca plak ve tümöral evrede, yama evresine göre 2+ ve 3+ boyanma oranı anlamlı derecede daha yüksek saptandı (p:0,011). TNMB evrelemesine göre MF hastaları erken ve ileri evre olarak sınıflandırıldığında PD-1 pozitiflik ve PD-1 ile 2+ veya 3+ boyanma yüzdesi oranı, ileri evrede erken evreye göre anlamlı derecede daha yüksek saptandı (p:0,008 ve p:0,007). Sonuç: PD-1 ile pozitifliği ile MF’in klinik, TNMB evreleri ve histolojik tipi arasında ilişki saptandı. Evre IA ve IB PD-1 pozitif MF hastalarının çoğunda biyopsinin alındığı anda yaygın yama/plak lezyonların olması, tedavi sonrası MF nüksü, büyük hücre dönüşümü ve progresif folikütropik tip gibi negatif prognostik özellikler mevcuttu. Bu nedenle PD-1 pozitifliğinin saptandığı erken evre MF hastalarının daha yakından takip edilmesi ve deriye yönelik tedavilere dirençli olgularda sistemik tedaviye daha erken başlanması düşünülebilir.
Aim: Mycosis fungoides (MF) is the most prevalent cutaneous T cell lymphoma. Average age of diagnosis is in sixth decade but it can be seen also in children and old patients. Clinically it follows patch, plaque and tumoral stages. In its first phase, it is localized to sun-protected sites such as gluteal area, trunk and characterized by erythematous patch lesions with fine scale or thin plaques. Early stage MF can mimic inflammatory dermatoses such as psoriasis vulgaris, lichen planus, dermatitis and parapsoriasis group diseases. Early stage biopsies may not be diagnostic. Time elapsed between the first appearence of skin lesions and definite clinical and histopathologic diagnosis may reach 4-6 years. Early diagnosis of MF can both improve prognosis and prevent the morbidities associated with treatments in advanced stage. Programmed Death-(PD-1) is an immunoglobulin superfamily transmembrane glycoprotein and after binding to its ligands PDL-1 and PDL-2, it diminishes T cell receptor signaling by inhibiting CD28-CD80 pathway. It is thought that this repression of T cell functions may play a role in the escape of neoplastic cells from immune system. In this study, it was aimed to evaluate value of PD-1 in MF diagnosis and in discriminating MF from inflammatory dermatoses. Also, if statistically meaningful positivity found to be present in MF group compared to other groups, this positivity was aimed to be compared within clinical, TNMB stages and histopathologic subtypes in MF group. Materials and methods: There were 44 MF patients in the first group; 30 inflammatory dermatosis patients in the second group with diagnoses such as psoriasis vulgaris, lichen planus and dermatitis and 30 patients in the third group consisting of 21 parapsoriasis, pityriasis lichenoides chronica group patients and 9 patients who did not have histopathological MF diagnosis but still had suspicious clinical MF findings. Biopsies for each group were examined for PD-1 expression by immunohistochemistry. Cases that did not show staining were accepted as negative (0); with less than 10% of cells staining as focal positive (1+); with 11-50 % of cells staining as multifocal positive (2+); and with more than 50% of cells staining as diffuse positive (3+) according to semi-quantitative evaluation. Results: Both positive staining rate and degree of statining positivity were stastically higher in MF group compared to inflammatory group and third group (p: <0,001 and p:0,001 respectively). There were 16 patch, 18 plaque and 10 tumour stage patients in MF group. Positivity rate in patch, plaque and tumoral stages were 25%, 55% and 80% respectively. Both positivity rate and 2+ (++) or 3+ (+++) staining rates were higher in plaque and tumoral stages compared to patch stage (p:0,2 and p:0,011 respectively). When MF patients were classified as early and advanced stage according to TNMB staging, both positivity and 2+ (++) or 3+ (+++) staining rates were higher in advanced stage compared to early stage (p:0,008 and p:0,007 respectively). Conclusion: There was correlation between PD-1 positivity and clinical, TNMB stages and histologic subtype of mycosis fungoides. There were negative prognostic factors such as relapse, large cell transformation, foliculotropic subtype in most of stage IA and IB PD-1 positive MF patients. So PD-1 positive early MF patients may need to be monitored more closely and systemic therapies may be considered earlier in patients refractory to skin-based treatments.
Aim: Mycosis fungoides (MF) is the most prevalent cutaneous T cell lymphoma. Average age of diagnosis is in sixth decade but it can be seen also in children and old patients. Clinically it follows patch, plaque and tumoral stages. In its first phase, it is localized to sun-protected sites such as gluteal area, trunk and characterized by erythematous patch lesions with fine scale or thin plaques. Early stage MF can mimic inflammatory dermatoses such as psoriasis vulgaris, lichen planus, dermatitis and parapsoriasis group diseases. Early stage biopsies may not be diagnostic. Time elapsed between the first appearence of skin lesions and definite clinical and histopathologic diagnosis may reach 4-6 years. Early diagnosis of MF can both improve prognosis and prevent the morbidities associated with treatments in advanced stage. Programmed Death-(PD-1) is an immunoglobulin superfamily transmembrane glycoprotein and after binding to its ligands PDL-1 and PDL-2, it diminishes T cell receptor signaling by inhibiting CD28-CD80 pathway. It is thought that this repression of T cell functions may play a role in the escape of neoplastic cells from immune system. In this study, it was aimed to evaluate value of PD-1 in MF diagnosis and in discriminating MF from inflammatory dermatoses. Also, if statistically meaningful positivity found to be present in MF group compared to other groups, this positivity was aimed to be compared within clinical, TNMB stages and histopathologic subtypes in MF group. Materials and methods: There were 44 MF patients in the first group; 30 inflammatory dermatosis patients in the second group with diagnoses such as psoriasis vulgaris, lichen planus and dermatitis and 30 patients in the third group consisting of 21 parapsoriasis, pityriasis lichenoides chronica group patients and 9 patients who did not have histopathological MF diagnosis but still had suspicious clinical MF findings. Biopsies for each group were examined for PD-1 expression by immunohistochemistry. Cases that did not show staining were accepted as negative (0); with less than 10% of cells staining as focal positive (1+); with 11-50 % of cells staining as multifocal positive (2+); and with more than 50% of cells staining as diffuse positive (3+) according to semi-quantitative evaluation. Results: Both positive staining rate and degree of statining positivity were stastically higher in MF group compared to inflammatory group and third group (p: <0,001 and p:0,001 respectively). There were 16 patch, 18 plaque and 10 tumour stage patients in MF group. Positivity rate in patch, plaque and tumoral stages were 25%, 55% and 80% respectively. Both positivity rate and 2+ (++) or 3+ (+++) staining rates were higher in plaque and tumoral stages compared to patch stage (p:0,2 and p:0,011 respectively). When MF patients were classified as early and advanced stage according to TNMB staging, both positivity and 2+ (++) or 3+ (+++) staining rates were higher in advanced stage compared to early stage (p:0,008 and p:0,007 respectively). Conclusion: There was correlation between PD-1 positivity and clinical, TNMB stages and histologic subtype of mycosis fungoides. There were negative prognostic factors such as relapse, large cell transformation, foliculotropic subtype in most of stage IA and IB PD-1 positive MF patients. So PD-1 positive early MF patients may need to be monitored more closely and systemic therapies may be considered earlier in patients refractory to skin-based treatments.
Açıklama
Anahtar Kelimeler
PD-1, Mikozis Fungoides, İnflamatuvar Dermatoz, PD-1, Mycosis Fungoides, Inflammatory Dermatoses
