## 1 Introduction  
Uveal melanoma accounts for about 3% of all melanomas. Even though uveal melanoma is rather uncommon (incidence of 5.1 cases per million person-years), it represents the most frequent primary intraocular malignancy in the adult population [1; 2]. The neoplasm originates from uveal melanocytes, in descending order of frequency, from the choroid (90%), the ciliary body (6%), or the iris (4%) [2; 3; 4]. Today, three different histologic types of uveal melanoma are recognized: spindle cell, epithelloid cell, and mixed cell type [5; 6; 7]. Various prognostic factors may influence the patient's outcome. In particular, ciliary body involvement, extraocular extension, diffuse growth pattern, some histopathological features (epithelioid cell type), and genetic factors (monosomy 3, 6p gain, or loss of BAP-1 gene) are associated with a more severe prognosis and increased risk of metastases [5]. The diagnosis is essentially entrusted to clinical evaluation and ophthalmological imaging methods; nevertheless, currently, radiological imaging techniques play a critical role in the clinical management of patients with uveal melanoma. In particular, magnetic resonance imaging (MRI) has multifaceted utility for a variety of different purposes: confirmation of clinical diagnosis, assessment of disease extent, evaluation and prediction of tumor response to radiotherapy treatment, follow-up, and detection of local radiotherapy-related complications [8; 9; 10; 11]. Enucleation and, more recently, radiotherapy (plaque brachytherapy and proton beam radiotherapy) represent the two pillars underpinning the local treatment of uveal melanoma. Since the initial observations of [PERSON] et al. [12], different studies and trials have proven no significant difference in terms of mortality between eye-sparing radiation therapies and surgery [13; 14; 15; 16; 17]; therefore, over the last few decades, radiotherapy techniques have gained in importance, and currently represent the most widely used therapeutic option [1]. Enucleation is currently reserved for a few indications: large tumors (basal diameter \(>\)20 mm, thickness \(>\)12 mm), and uveal melanomas with optic nerve or orbital involvement. Enucleation can be divided into the following types: (1) primary, in patients who do not undergo any other type of therapy, and (2) secondary, in patients already treated with eye-conserving radiotherapy. Indications for secondary enucleation include tumor progression after radiotherapy (local recurrence or extrascleral extension) and treatment-related complications (e.g., ocular pain, vision loss, vitreous hemorrhage, neovascular glaucoma, or chronic inflammation) [18; 19; 20]. Over the years, considerable progress has been made in radiotherapy techniques and in the management of radiation-related complications; hence, both primary and secondary enucleation have become less frequent. In different series the rate of secondary enucleation after radiotherapy is up to 12.5% [17; 21]. Although proton beam radiotherapy has been used in the treatment of uveal melanomas since 1975 [22], only a few authors have reported histopathologic findings of irradiated eyes undergoing secondary enucleation; owing to the rarity of neoplasm and of enucleation, the latter becoming increasingly rare, the scientific literature dealing with this topic is scant. The first articles dealing with the histopathologic and ultrastructural features of uveal melanomas enucleated after prior proton beam radiotherapy date back to the 1980s [22; 23; 24; 25]. In these studies, patients underwent enucleation because of treatment failure [23; 25] or clinical treatment-related complications [22; 24; 25]. A- and B-scan ultrasonographies (US) were used as imaging methods to study uveal melanomas before enucleation [22; 23; 24]; nevertheless, a real radiologic-pathologic correlation was not performed. [PERSON] et al.