Discussion
PNETs can be clinically divided into functional and non-functional depending on their hormonal activity [10,11]. Non-functional PNETs (NF-PNETs) comprise up to 90% of all PNETs and are often asymptomatic. The lack of hormonal syndromes makes \soutthe clinical symptomatology discrete and non-specific [12]. Clinical features are due to mass effect exerted by a growing tumor and include weight loss, jaundice and abdominal pain [11]. As a result, these tumors are most often diagnosed later during the course of the disease, revealed by signs of local invasion or distant metastasis [10]. In fact, 32 to 73 percent of NF-PNETs are metastatic at the moment of diagnosis [10,13]. Like in the case of our patient who had an unexplained weight loss and in whom malignant pancreatic neuroendocrine carcinoma was diagnosed late in the metastatic stage.
The most commun area of metastasis is the liver [14]. Other sites including bones, spleen, peritoneum and brain have been reported [15,16].
It was long believed that metastatic tumors in uveal tissue were relatively rare but several studies had shown that ocular metastases are reported to be the most common intraocular malignancy, even more frequent than primary uveal melanoma [17,18], occurring through haematogenous spread by carotid and ophthalmic artery [19]. Some reports suggest that the incidence is underestimated. The prevalence of metastases estimated from post-mortem examination ranged from 4 to 10% with a clear predominance of the choroid because of its rich vascular supply [20,21].The most frequently found primitives are lung and breast cancers [22–24]. Uveal metastases from neuroendocrine tumors have only rarely been reported [25], and more rarer from pancreatic ones. In a series of 410 patients with uveal metastases, the primary cancer was a neuroendocrine tumor in only 9 cases (2,2%). The site of the primary neuroendocrine tumor was the bronchial tract in seven patients, the esophagus in one, and the thymus in one [9].
The most common reported complaints are ocular pain, blurred vision and proptosis [26].
Classically, the diagnosis of ocular metastases is evoked in case of a prior history of malignancy. However, these metastases can rarely be diagnosed prior to the detection of the primary tumor. Many patients with a disseminated stage cancer are debilitated and may not complain of visual symptoms, and minor visual problems may be dismissed as trivial or related to treatment these patients take. This may contribute to the higher than expected incidence. In 230 consecutive autopsies of patients who died of cancer of all types, Bloch and Gartner1 found a 12% incidence of ocular involvement.[27] In another small series of 15 cases of ocular carcinoid metastasis, the primary neoplasm was unknown and clinically silent in three cases [28]. In our case, the patient had unilateral eye redness and progressive decrease of visual acuity due to the choroidal metastasis that led to the diagnosis of metastatic pancreatic neuroendocrine carcinoma.
Data regarding survival after the diagnosis of ocular metastases of neuroendocrine tumors are limited. In a series of 13 patients with orbital carcinoid metastases, Mehta et al [29] showed that the overall survival was 72% at 5 years and 38% at 10 years. These findings suggest that patients with neuroendocrine tumors may have prolonged survival despite metastatic dissemination [30]. Early diagnosis and appropriate treatment in order to preserve their vision and quality of life are crucial. Numerous therapeutic modalities are proposed including beam radiotherapy, systemic chemotherapy and surgical excision [31]. External irradiation is an efficient treatment for orbital metastases that improves the visual acuity [32]. It is especially useful for symptomatic patients with single lesions [33]. However, data regarding response of uveal carcinoid metastases after palliative radiation is not available. Chemotherapy has also proven its efficacy in several cases. Fan et al [34] reported a significant regression of both choroidal and visceral metastases after the initiation of cisplatin and etoposide chemotherapy in a 65-year-old woman diagnosed with metastatic bronchial neuroendocrine carcinoma. Authors recommended the use of cisplatin and etoposide in the treatment of aggressive metastatic neuroendocrine carcinoma [35]. Moreover, the combination of chemotherapy and radiotherapy seems to be an efficient therapeutic option. In a series of six patients with ocular metastases from carcinoid tumors, treated with chemotherapy and external radiation, all patients responded well to that treatment and did not require surgical excision [36]. In many studies, chemotherapy has been considered as to be equally as effective as radiation therapy for treatment of ocular metastasis based on clinical lesion regression (decrease in tumor size, elevation, pigment clumping, and fluid resorption) and improved visual acuity. Common practice has been to wait at least 6 weeks to see the effects of systemic therapy on lesion regression. [37]
Concerning the case of our patient, who had an aggressive pancreatic neuroendocrine tumor metastasized to the liver and eye, oncologists opted for cisplatin and etoposide chemotherapy.