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.