# Histopathology and Genetic Biomarkers of Choroidal Melanoma
## 6 Prognostic Factors  
The pathology report must classically contain some useful information to guide the oncologist on the patient's outcome. The exact location of the tumor must be indicated considering that melanomas confined to the choroid tend to have a more favorable prognosis than melanomas extending into the ciliary body [39]. The possible evidence of extraocular extension with particular attention to infiltration of the sclera along emissary vessels and nerves. In order to identify this kind of infiltration serial sections may be required. It is also advisable to measure the diameter of the extraocular extension with an ocular micrometer because the microscopic extraocular extension has no negative prognostic impact [40]. Further classical morphologic features with an impact on patient outcomes, such as cell type, specific growth pattern (diffuse CMs tend to be associated with a less favorable prognosis [41]), greatest thickness and largest basal diameter of the tumor (on which the 8 th edition of Tumor, node, metastasis-TNM-staging depends [42]) and proliferative activity, both as a mitotic index (number of mitoses/mm\({}^{2}\)) and Kio7 proliferation rate [43], must be reported by the pathologist. In recent years the evidence of inflammatory anti-tumor response has become increasingly important, hence pathology reports should also contain the potential presence of prominent tumor-infiltrating lymphocytes (>100 lymphocytes per 20 (40\(\times\)) high power fields) and tumor-associated macrophages, that seem to be associated with an increased likelihood of metastasis [13]. The pathologic finding of closed loops of PAS-positive material encircling packets of tumor cells or at least three back-to-back loops has a strong independent association with tumor-related mortality. These loops stain for laminin and fibronectin and have been shown to conduct plasma cells and red blood cells and are formed by highly invasive tumor cells through a process known as vasculogenic mimicry [14]. In addition to the abovementioned prognostic factors, our group recently reported some new immunohistochemical markers with prognostic value in predicting the risk of distant metastases [44; 45; 46; 47; 48; 49]. CM pathologic prognostic factors are summarized in Table 2.  
\begin{table}
\begin{tabular}{l l} \hline \hline
**Gene Symbol** & **Gene Name** \\ \hline LTA4H & Leukotriene A4 hydrolase \\ \hline MTUS1 & Microtubule-associated tumor suppressor 1 \\ \hline ROBO1 & Roundabout, axon guidance receptor, 1 \\ \hline SATB1 & SATB homeobox 1 \\ \hline
**Control Genes** \\ \hline MRPS21 & Mitochondrial ribosomal protein S21 \\ \hline RBM23 & RNA-binding motif protein 23 \\ \hline SAP130 & Sin3A-associated protein, 130 kDa \\ \hline \hline \end{tabular}
\end{table}
Table 1: _Cont._  
\begin{table}
\begin{tabular}{l} \hline \hline
**Pathologic Prognostic Factors of Choroidal Melanoma** \\ \hline Cell type (epithelial, spindle, mixed cell type) \\ \hline Tumor location \\ \hline TNM staging (T-stage based on largest tumor basal diameter and thickness) \\ \hline Extraocular invasion \\ \hline Mitotic index \\ \hline Ki67 proliferation rate \\ \hline Intratumoral inflammatory infiltrates (tumor-infiltrating lymphocytes and tumor-associated macrophages) \\ \hline PAS-positive peritumoral loops \\ \hline \hline \end{tabular}
\end{table}
Table 2: Main histologic findings with prognostic value in choroidal melanoma.