Histopathology and Genetic Biomarkers of Choroidal Melanoma

Abstract

Choroidal melanoma (CM), despite its rarity, is the most frequent intraocular malignancy. Over time, several histological variants of CM have been distinguished, including spindle A and B cell, fascicular, epithelioid and necrotic type. However, they have been progressively abandoned as having no prognostic value and currently, the American Joint Committee of Cancer (AJCC) classification identifies three CM cell types: spindle, epithelioid and mixed cell type. Other rare histological variants of CM include: (i) diffuse melanoma; (ii) clear cell; and (iii) balloon cell melanoma. Immunohistochemically, CMs are stained with Human Melanoma Black 45 (HMB45) antigen, S-100 protein, Melan-A (also known as melanoma antigen recognized by T cells 1/MART-1), melanocyte inducing transcription factor (MITF), tyrosinase, vimentin, and Sex determining region Y-Box 10 (SOX10). Several genetic and histopathological prognostic factors of CM have been reported in the literature, including epithelioid cell type, TNM staging, extraocular extension, monosomy 3 and 6p gain and loss of BAP-1 gene. The aim of this review was to summarize the histopathological, immunohistochemical and genetic features of CM, establishing “the state of the art” and providing colleagues with practical tools to promptly deal with patients affected by this rare malignant neoplasm.

MR imaging characteristics of uveal melanoma with histopathological validation

“…It would be desirable to have noninvasive markers that may predict a tumor's response to therapy and provide prognostic information. A biopsy is an invasive procedure and may not always be representative because chromosomal aberrations can be heterogeneous across the tumor [35,36] Both the presence of monosomy 3 [22,37,38] and of extracellular matrix patterns "loops" [39][40][41][42][43][44] are important determinants of poor prognosis and they frequently coexist. All our tumors with loops had monosomy 3 and vice versa, consistent with the literature where monosomy 3 is detected in 67% of tumors with loops [40].…”

“…Both the presence of monosomy 3 [ 22 , 37 , 38 ] and of extracellular matrix patterns “loops” [ 39 – 44 ] are important determinants of poor prognosis and they frequently coexist. All our tumors with loops had monosomy 3 and vice versa, consistent with the literature where monosomy 3 is detected in 67% of tumors with loops [ 40 ].…”

Prognostic Value of the Immunohistochemical Expression of Serine and Arginine-Rich Splicing Factor 1 (SRSF1) in Uveal Melanoma: A Clinico-Pathological and Immunohistochemical Study on a Series of 85 Cases

“…The potential identification of a high-risk group of patients could allow the performance of more frequent controls in order to earlier diagnose cases with liver metastases that could be safely surgically excised [30]. Accordingly, in the last decade our research group reported some novel potential immunohistochemical factors with prognostic impact [5,[31][32][33][34][35], which may be included into the list of the classically reported markers of UM, such as tumor location, tumor size, extraocular invasion, cell type, pathological T stage and immunohistochemical staining with BAP1 [14]. Recently, Luo et al identified a ten-gene signature (SIRT3, HMCES, SLC44A3, TCTN1, STPG1, POMGNT2, RNF208, ANXA2P2, ULBP1 and CA12), able to better stratify the outcome of UM patients [36]; in detail, ANXA2P2, ULBP1, CA12 had a poor prognostic role, while the other genes a positive one.…”

“…UM is a slow-growing tumor with indolent biological behavior but consistently poor prognosis, characterized by the development of liver metastases within 10-15 years after the diagnosis in about 50% of cases [6][7][8][9]. In recent years, the search for genetic and epigenetic prognostic and/or predictive factors of therapeutic response has been one of the most studied topics in cancer research [10,11]; in this regard, loss-of-function mutations of BRCA1 associated protein-1 (BAP1), that have been observed in most metastasizing UM cases and correlated with the immunohistochemical loss of BAP-1 protein, represent one of the most reliable prognostic factors of this tumor [12][13][14]. Serine and arginine-rich splicing factor 1 (SRSF1) is part of the SR protein family, being involved in canonic and alternative pre-mRNA splicing and in the regulation of mRNA transcription [15,16].…”

Histopathologic and MR Imaging Appearance of Spontaneous and Radiation-Induced Necrosis in Uveal Melanomas: Initial Results

“…From a histologic point of view, uveal melanoma can be pigmented, amelanotic or mixed [ 8 , 9 ]; the lesion is generally solid, though necrotic or hemorrhagic areas may occur as well. Necrosis, in particular, may produce cystic spaces or storage of eosinophilic debris within the neoplasm [ 10 ].…”