Akciğerin rezeke skuamöz hücreli karsinomlarında histopatolojik parametrelerin prognostik önemi
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Dosyalar
Tarih
2019
Yazarlar
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Ege Üniversitesi, Tıp Fakültesi
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Akciğer kanseri, kanser ilişkili ölümlerin başlıca sebepleri arasındadır. Skuamöz hücreleri karsinom (SHK) tüm akciğer karsinomlarının %25-30'unu oluşturmakta olup çoğu hasta ileri evrelerde tanınmaktadır. Rezeksiyon yapılamayan ya da rekürren akciğer karsinomlarında kişiselleştirilmiş tedavi yöntemlerinin kullanımı adenokarsinomlarda (AK), SHK'a göre daha fazla orandadır. SHK grubunda prognozu ön görmede kullanılabilecek, kabul edilmiş histolojik özellikler henüz mevcut değildir. Bu nedenle akciğer SHK incelemesinde, morfolojik prognostik faktörlerin ortaya çıkarılması önem teşkil etmektedir. Bu çalışmada anabilim dalımızda 2000-2016 yılları arasında ameliyat materyallerinde SHK tanısı almış 178 olguya ait hematoksilen&eozin (H&E) boyalı ve arşivimizde mevcut olan immünhistokimyasal (İHK) ki-67 boyalı preparatlar yeniden değerlendirilmiştir. Hastaların klinik özellikleri ile histolojik alt tip, diferansiyasyon, tümör tomurcuklanması, hava boşlukları boyunca yayılım, nükleer boyut, peritümöral stroma ve yangısal hücre infiltrasyonu, mitoz, lenfovasküler invazyon (LVİ), perinöral invazyon (PNİ), nekroz, plevra invazyonu, tümör dışı akciğer parankim özellikleri ve İHK ki-67 proliferasyon indeksi mikroskobik olarak incelenmiş, bu bulguların birbirleriyle ve sağkalımla ilişkisi araştırılmıştır. Çalışmamızda yaş ortalaması 64,3 olup hastaların 160'ı (%89,9) erkek, 18'i (%10,1) kadındır. Tümörlerin 104'ü (%58,4) akciğerin santral, 74'ü (%41,6) periferik lokalizasyonunda bulunmuştur. Ortalama tümör çapı 3,8 cm idir. Hiler lenf nodülü metastazı (LNM) 45 (%30,4) hastada, mediastinal LNM 13 (%9) hastada izlenmiştir. Hastaların patolojik TNM (pTNM) evre guplarına göre, 67'si (%40,9) evre I, 59'u (%36) evre II, 32'si (%19,5) evre III ve 6'sı (%3,7) evre IV hastalardır. Tümörlerin 128'i (%71,9) orta derece diferansiye, 46'sı (%25,8) az diferansiye ve 4'ü (%2,2) iyi diferansiye tümörlerdir. Alt tiplere göre vakaların 90'ında (%50,6) nonkeratinize, 85'inde (%47,8) keratinize, üç olguda (%1,7) bazaloid histoloji görülmüştür. Tümör tomurcuklanması, tümörlerin 67 (%37,6) tanesinde saptanmıştır. Tomurcuklanma derecesine göre derece 1'de 31 hasta (%46,3), derece 2'de 19 hasta (%28,4) ve derece 3'te 17 hasta (%25,4) kaydedilmiştir. Hava boşlukları boyunca yayılım, tümörlerin 79'unda (%44,4) görülmüştür. Nükleus boyutuna göre gruplandırmada tümörlerin 111'inde (%62,4) orta boyutlu, 61'inde (%34,3) büyük boyutlu, 6'sında (%3,4) küçük boyutlu nükleus bulunduğu kaydedilmiştir. Vakaların 76'sında (%42,7) fibröz stroma, 63'ünde (%35,4) orta derecede stroma ve 39'unda (%21,9) ince stroma saptanmıştır. Peritümöral yangısal hücre infiltrasyonu olguların 64'ünde (%36) düşük derecede, 59'unda (%33,1) orta derecede, 55'inde (%30,9) yüksek derecededir. Ortalama mitoz sayısı 10 büyük büyütme alanında (BBA) 21 olarak bulunmuştur. Vakaların 118'i (%66,3) 10 BBA'da 15 ve üzeri mitoz sayısına sahipken, 60 vakada (%33,7) mitoz sayısı 10 BBA'da 15'in altındadır. Arşiv materyallerinin 64'ünde (%36) immünhistokimyasal ki-67 boyalı preperatlar mevcut olup ve ortalama ki-67 proliferasyon indeksi %37,3 bulunmuştur. LVİ olguların 91'inde (%51,1), PNİ 15'inde (%8,4), nekroz 112'sinde (%62,9) ve plevra invazyonu 48'inde (%27) izlenmiştir. Tümöre komşu akciğer parankimi değerlendirmesinde, 48 vakada (%27) spesifik özellik saptanmamıştır. Ortalama sağkalım süresi 101,7 aydır. Tomurcuklanma ile LVİ, PNİ ve peritümöral stroma arasında ve yanı sıra, tomurcuklanmanın derecesiyle nekroz arasında anlamlı ilişki saptanmıştır. Hava boşlukları boyunca yayılım ile LVİ, nekroz ve mitoz sayısıyla ilişkili bulunmuştur. Nükleus boyutu ve peritümöral stroma ile pTNM evresi arasında anlamlı ilişki mevcuttur. Hava boşlukları boyunca yayılım ile mitoz sayısı arasında istatistiksel anlamlı ilişki saptanmıştır. Median tanı yaşı, metastaz durumum ve pTNM evre gruplarıyla median sağkalım arasında anlamlı ilişki bulunmuştur. Akciğer SHK için prognozu ön görmede kullanılabilecek, kabul edilmiş histolojik özellikler hala bulunmamaktadır. SHK ile ilgili histomorfolojik parametrelerin prognostik önemini araştıran çalışma sayısı sınırlı olup henüz güncel ve net prognostik profil gösterilememektedir. Bu nedenle, bu çalışma ile gelecekte tedavi kararını etkileyebilecek morfolojik özellikler ve prognostik faktörlerin belirlenmesine katkıda bulunacağımız görüşündeyiz.
Lung cancer is a major cause of cancer-related deaths. Squamous cell carcinoma (SCC) constitutes 25-30% of all lung carcinomas and most patients are recognized in advanced stages. The use of personalized treatment methods in non-resectable or recurrent lung carcinomas is higher in adenocarcinomas than in SCC. Accepted histological features that can be used to predict prognosis in SCC are not yet available. Therefore, it is important to reveal morphological prognostic factors in lung SCC examination. In this study, we evaluated the haematoxylin&eosin (H&E)-stained and ki-67 immunohistochemical (IHC)-stained slides of 178 cases who were diagnosed SCC in the surgical materials between 2000 and 2016. Clinical features of patients with histological subtype, differentiation, tumor budding, spread through alveolar spaces (STAS), nuclear size, peritumoral stromal content and inflammatory cell infiltration, mitosis, lymphovascular invasion (LVI), perineural invasion (PNI), necrosis, pleural invasion, non-tumoral lung parenchymal characteristics and IHC ki-67 proliferation index were examined microscopically and the relationship of these findings with each other and survival was investigated. The mean age was 64.3 and 160 (89.9%) of the patients were male and 18 (10.1%) were female. 104 (58.4%) of the tumors were found in the central and 74 (41.6%) peripheral locations of the lungs. The mean tumor diameter was 3.8 cm. Hilar lymph node metastasis (LNM) was observed in 45 (30.4%) patients and mediastinal LNM was observed in 13 (9%) patients. According to pathologic TNM (pTNM) stage groups, 67 patients (40.9%) were stage I, 59 (36%) were stage II, 32 (19.5%) were stage III and 6 (3.7%) were stage IV patients. 128 (71.9%) of the tumors were moderately differentiated, 46 (25.8%) poorly differentiated and 4 (2.2%) were well differentiated tumors. According to the subtypes, 90 (50.6%) of the cases had nonkeratinizing, 85 (47.8%) had keratinizing, and three (1.7%) had basaloid histology. Tumor budding was detected in 67 (37.6%) of the tumors. According to the degree of budding, 31 patients (46.3%) in grade 1, 19 patients in grade 2 (28.4%), and 17 patients in grade 3 (25.4%) were recorded. STAS was seen in 79 (44.4%) of the tumors. In the grouping by nuclear size, 111 (62.4%) of the tumors featured medium-sized nuclei, 61 of them (34.3%) were large in size, and 6 (3.4%) of small-size nuclei. In 76 (42.7%) cases, fibrous stroma, 63 (35.4%) intermediate stroma and 39 (21.9%) fine stroma were detected. Peritumoral inflammatory cell infiltration was low in 64 (36%), moderate in 59 (33.1%), and high in 55 (30.9%). The mean number of mitotic count was found to be 21 in 10 high power field (HPF). While 118 (66.3%) of the cases had 10 or more mitosis in 10 HPF, in 60 cases (33.7%) mitotic count was less than 15 in 10 HPF. In 64 (36%) of the archival materials, IHC ki-67 stained slides were present and the mean ki-67 proliferation index was found to be 37.3%. LVI was observed in 91 (51.1%) patients, PNI in 15 (8.4%), necrosis in 112 (62.9%) and pleural invasion in 48 (27%) patients. In the evaluation of lung parenchyma adjacent to the tumor, no specific feature was found in 48 cases (27%). The mean survival time was 101.7 months. A significant relation was found between budding and LVI, PNI and peritumoral stroma, as well as the degree of budding and necrosis. STAS was associated with LVI, necrosis, and mitotic count. There is a significant relationship between nuclear size and peritumoral stroma, and pTNM stage. There was a statistically significant relationship between STAS and mitotic count. A significant relationship was found between median age of diagnosis, metastasis status and median survival with pTNM stage groups. There is still no accepted histologic features that can be used to predict the prognosis of lung SCC. The number of studies investigating the prognostic significance of SCC related histomorphological parameters is limited and yet the current and clear prognostic profile cannot be demonstrated. Therefore, we believe that this study will contribute to the determination of morphological features and prognostic factors that may affect the treatment decision in the future.
Lung cancer is a major cause of cancer-related deaths. Squamous cell carcinoma (SCC) constitutes 25-30% of all lung carcinomas and most patients are recognized in advanced stages. The use of personalized treatment methods in non-resectable or recurrent lung carcinomas is higher in adenocarcinomas than in SCC. Accepted histological features that can be used to predict prognosis in SCC are not yet available. Therefore, it is important to reveal morphological prognostic factors in lung SCC examination. In this study, we evaluated the haematoxylin&eosin (H&E)-stained and ki-67 immunohistochemical (IHC)-stained slides of 178 cases who were diagnosed SCC in the surgical materials between 2000 and 2016. Clinical features of patients with histological subtype, differentiation, tumor budding, spread through alveolar spaces (STAS), nuclear size, peritumoral stromal content and inflammatory cell infiltration, mitosis, lymphovascular invasion (LVI), perineural invasion (PNI), necrosis, pleural invasion, non-tumoral lung parenchymal characteristics and IHC ki-67 proliferation index were examined microscopically and the relationship of these findings with each other and survival was investigated. The mean age was 64.3 and 160 (89.9%) of the patients were male and 18 (10.1%) were female. 104 (58.4%) of the tumors were found in the central and 74 (41.6%) peripheral locations of the lungs. The mean tumor diameter was 3.8 cm. Hilar lymph node metastasis (LNM) was observed in 45 (30.4%) patients and mediastinal LNM was observed in 13 (9%) patients. According to pathologic TNM (pTNM) stage groups, 67 patients (40.9%) were stage I, 59 (36%) were stage II, 32 (19.5%) were stage III and 6 (3.7%) were stage IV patients. 128 (71.9%) of the tumors were moderately differentiated, 46 (25.8%) poorly differentiated and 4 (2.2%) were well differentiated tumors. According to the subtypes, 90 (50.6%) of the cases had nonkeratinizing, 85 (47.8%) had keratinizing, and three (1.7%) had basaloid histology. Tumor budding was detected in 67 (37.6%) of the tumors. According to the degree of budding, 31 patients (46.3%) in grade 1, 19 patients in grade 2 (28.4%), and 17 patients in grade 3 (25.4%) were recorded. STAS was seen in 79 (44.4%) of the tumors. In the grouping by nuclear size, 111 (62.4%) of the tumors featured medium-sized nuclei, 61 of them (34.3%) were large in size, and 6 (3.4%) of small-size nuclei. In 76 (42.7%) cases, fibrous stroma, 63 (35.4%) intermediate stroma and 39 (21.9%) fine stroma were detected. Peritumoral inflammatory cell infiltration was low in 64 (36%), moderate in 59 (33.1%), and high in 55 (30.9%). The mean number of mitotic count was found to be 21 in 10 high power field (HPF). While 118 (66.3%) of the cases had 10 or more mitosis in 10 HPF, in 60 cases (33.7%) mitotic count was less than 15 in 10 HPF. In 64 (36%) of the archival materials, IHC ki-67 stained slides were present and the mean ki-67 proliferation index was found to be 37.3%. LVI was observed in 91 (51.1%) patients, PNI in 15 (8.4%), necrosis in 112 (62.9%) and pleural invasion in 48 (27%) patients. In the evaluation of lung parenchyma adjacent to the tumor, no specific feature was found in 48 cases (27%). The mean survival time was 101.7 months. A significant relation was found between budding and LVI, PNI and peritumoral stroma, as well as the degree of budding and necrosis. STAS was associated with LVI, necrosis, and mitotic count. There is a significant relationship between nuclear size and peritumoral stroma, and pTNM stage. There was a statistically significant relationship between STAS and mitotic count. A significant relationship was found between median age of diagnosis, metastasis status and median survival with pTNM stage groups. There is still no accepted histologic features that can be used to predict the prognosis of lung SCC. The number of studies investigating the prognostic significance of SCC related histomorphological parameters is limited and yet the current and clear prognostic profile cannot be demonstrated. Therefore, we believe that this study will contribute to the determination of morphological features and prognostic factors that may affect the treatment decision in the future.
Açıklama
Anahtar Kelimeler
Akciğer, Skuamöz Hücreli Karsinom, Tomurcuklanma, Hava Boşlukları Boyunca Yayılım, Prognoz, Lung, Squamous Cell Carcinoma, Budding, Spreading Through Air Spaces, Prognosis
