İnvaziv malign melanomun klinikopatolojik kriterleri ile genel sağkalım ilişkisi ve 2018 Dünya Sağlık Örgütü melanom sınıflamasına göre yeniden değerlendirilmesi
The relationship between invasive malignant melanoma and its clinicopathological features and the reassessment of melanoma according to the 2018 World Health Organization
- Tez No: 658291
- Danışmanlar: DOÇ. DR. FERİHA PINAR UYAR GÖÇÜN
- Tez Türü: Tıpta Uzmanlık
- Konular: Patoloji, Pathology
- Anahtar Kelimeler: Belirtilmemiş.
- Yıl: 2021
- Dil: Türkçe
- Üniversite: Gazi Üniversitesi
- Enstitü: Tıp Fakültesi
- Ana Bilim Dalı: Tıbbi Patoloji Ana Bilim Dalı
- Bilim Dalı: Belirtilmemiş.
- Sayfa Sayısı: 357
Özet
Melanom, pigment oluşturan hücreler ve baskın olarak deride bulunan melanositlerin malignitesidir. Deri dışında, göz (iris), kulak (koklea), gastrointestinal sistem, leptomeninksler, oral ve genital mukozal membranlarda da görülür. Malign melanom, kadınlarda ve erkeklerde 5. en sık görülen malignitedir. Amerika'da, tüm deri kanserlerinin %4'ünü oluşturmasına rağmen, deri kanserlerine bağlı mortalitenin %75'inden sorumludur. DSÖ 2018 Melanom sınıflaması, farklı histopatolojik, klinik ve genomik veriler doğrultusunda melanom gelişiminin farklı yolaklar üzerinden gerçekleştiğini ortaya koymuştur. Çalışmamızda Gazi Üniversitesi Tıp Fakültesi Tıbbi Patoloji Anabilim Dalı'nda tanı almış, primer deri melanomu, mukozal melanomu, konjonktival melanomu ve uveal melanomu olan toplam 304 hasta (166 erkek ve 138 kadın) Dünya Sağlık Örgütü sınıflamasına tabi tutulmuştur. Ortalama tanı yaşı 58,09 ± 16,97 y (aralık 1- 95, ortanca 60,5) olarak saptanmıştır. On dokuz (%6,25) hasta herhangi bir sınıfta yer almazken, 96 (%31,58) hasta düşük kümülatif güneş hasarı ilişkili melanom, 45 (%14,80) hasta yüksek kümülatif güneş hasarı ilişkili melanom, 6 (%1,97) hasta dezmoplastik melanom, 7 (%2,30) hasta Spitz melanom, 48 (%15,79) hasta akral melanom, 40 (%13,16) hasta mukozal melanom, 17 (%5,59) hasta konjenital nevüsten gelişen melanom, 7 (%2,30) hasta mavi nevüsten gelişen melanom ve 19 (%6,25) hasta uveal melanom olarak sınıflandırılmıştır. Mukozal melanom vakalarında sağkalım süresi diğer tüm sınıflardan daha kısa olarak saptanmıştır (p
Özet (Çeviri)
Melanoma is a malignancy of pigment-producing cells and melanocytes which are prominently located in the skin. In addition to the primary skin melanoma, melanoma is also seen in the uvea, cochlea, gastrointestinal tract, leptomeninges, ocular, oral, and genital mucosal membranes. Melanoma is the fifth most common malignancy in females and males. Even though melanoma constitutes 4% of all skin malignancies, it is responsible for 75% of skin cancer-related mortality. In the 2018 WHO Classification of Skin Tumours book, a new multidimensional pathway classification for melanocytic lesions has been proposed. This new classification is based on the role of ultraviolet radiation, the cell (or tissue) of origin, and characteristic recurrent genomic alterations. In our study, 304 melanoma patients (138 females and 166 males), who were diagnosed in the Gazi University Hospital, Pathology Department, has been included. These cases were classified according to the new multidimensional pathway system depending on the clinicopathological features. The mean patient age at diagnosis was 58,09 ± 16,97 yrs (range, 1- 95, median 60,5). According to the new classification, the cases were classified as low cumulative sun damage (CSD) melanoma/superficial spreading melanoma (SSM) in 96 (31,58%), high-CSD melanoma /LMM in 45 (14,80%) of cases, desmoplastic melanoma in 6 (1,97%), Spitz melanoma in 7 (2,3%), acral melanoma in 48 (15,79%), mucosal melanoma in 40 (13,16%), melanoma in congenital nevus in 17 (5,59%), melanoma in blue nevus in 7 (2,3%), uveal melanoma in 19 (6,25%). Finally, nineteen (6,25%) of the cases could not be included in any pathway. Overall survival of mucosal melanoma cases was statistically significantly lower than the other melanoma classes (p1/1 mm², diagnosis at the pT3 were significantly associated with shorter overall survival. In uveal melanoma cases, conjunctiva and lens involvement was an unfavorable effect on overall survival, whereas the cases with the largest tumor diameter of 9,1-15 mm had shorter overall survival than the cases with the largest tumor diameter of >15 mm. In metastatic melanoma cases, the diagnosis age of >60 yrs had a shorter overall survival when compared with the patients with the diagnosis age of 31-60 yrs. Lung and central nervous system localization for metastatic melanoma had a worse overall survival than lymph node, skin, and subcutaneous soft tissue whereas liver, bone marrow, paranasal sinus metastasis had shorter overall survival than lymph node metastasis. Cytoplasmic features of metastatic melanoma cases have been found also important for overall survival. Pale eosinophilic cytoplasm and eosinophilic-clear cytoplasm had shorter overall survival than pale eosinophilic-clear cytoplasm. Neuroendocrine-like nuclear features were also associated with worse overall survival than vesicular nuclei. Perivascular pseudorosette formation reduced the overall survival of metastatic melanoma patients. The same appearance has been described for primary melanoma as a case report in the literature. It has been reported that angiotropism is seen more frequently in metastatic melanoma cases than melanoma cases without metastasis. This difference leads to an argument that melanoma metastasis pathways could be diverse and include other options besides lymphovascular invasion. Perivascular pseudorosette has not the same appearance as angiotropism. However, the definition of angiotropism also covers the perivascular pseudorosette formation. Extravascular migratory metastasis in melanoma was firstly described approximately 20 years ago as an alternative metastatic pathway characterized by angiotropism. This idea has been endorsed by different studies related to melanoma metastasis pathways. Conclusively, in our study, the overall survival was found to be associated with the new WHO melanoma classification that depends on clinicopathologic features. In WHO classification, solar damage is one of the primary criteria used for the classification of melanoma according to multidimensional pathways. Melanomas with no solar elastosis or without related to solar damage were found out with shorter overall survival than melanomas with histologic evidence of solar elastosis. In primary skin melanoma with clinicopathologic evidence for precursor lesion had longer overall survival than without precursor lesion. Identification of precursor lesion as a prognostic parameter was thought to be valuable and could deserve further study to describe developmental pathways in melanoma. In this study, regression was found to be positively effective on overall survival as opposed to the conflicting ideas in the literature. TILs in both primary skin and conjunctival melanoma were associated with longer overall survival. The importance of early recognition and diagnosis of melanoma for improving patient outcomes was supported by the higher mortality rates of metastatic melanoma than primary ones. Finally, in metastatic melanoma patients, the significant negative impact of perivascular pseudorosette formation on overall survival might be supportive for the idea of melanoma extravascular metastasis pathway in which melanocytes have a perivascular arrangement and show angiotropism.
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