Oman Journal of Ophthalmology

: 2011  |  Volume : 4  |  Issue : 3  |  Page : 125--128

A case series of neuroendocrine (carcinoid) tumor metastasis to the orbit

Kiran Turaka, Arman Mashayekhi, Carol l Shields, Sara E Lally, Brad Kligman, Jerry A Shields 
 Department of Ocular Oncology Service, Wills Eye Institute, Thomas Jefferson University, Philadelphia PA, USA

Correspondence Address:
Kiran Turaka
Ocular Oncology Service, Suite # 1440, Wills Eye Institute, 840 Walnut Street, Philadelphia, PA 19107


Purpose/Background : To report the clinical and radiographic features and treatment outcome of neuroendocrine tumor (carcinoid) metastasis to the orbit. Materials and Methods : Retrospective chart review of four cases. Results : Mean patient age at the time of diagnosis of the primary neuroendocrine tumor and orbital metastasis was 58 and 66 years, respectively, with a mean duration of 8 years between diagnosis of primary tumor and orbital metastasis. Primary neuroendocrine tumor sites were gastrointestinal tract (n = 2), lung (n = 1), and testicle (n = 1). The most common presenting symptom was diplopia (three cases). Magnetic resonance imaging revealed orbital tumor in all cases. Octreotide scan was positive in one case. Treatment was tumor excision in three cases followed by external beam radiotherapy in two cases and one patient was followed without treatment. Tumor cells showed immunoreactivity to chromogranin, synaptophysin, and neuron-specific enolase in all cases. Mean follow-up after orbital tumor diagnosis was 39 months. Three patients had known systemic extraorbital metastasis before orbital involvement (mean interval of 5.9 years) and one case had immediately after development of orbital metastasis. One patient had multiple recurrences of orbital metastasis and eventually underwent exenteration. Two patients died of disseminated metastasis between 2 and 3 years after diagnosis of orbital metastasis. Conclusion : All four patients with orbital metastasis from neuroendocine tumor had evidence of systemic extraorbital metastasis. Aggressive metastatic neuroendocine tumors of orbit can lead to local recurrence even after surgical excision and radiation. Imaging tests were helpful in allowing early diagnosis and for monitoring after treatment.

How to cite this article:
Turaka K, Mashayekhi A, Shields Cl, Lally SE, Kligman B, Shields JA. A case series of neuroendocrine (carcinoid) tumor metastasis to the orbit.Oman J Ophthalmol 2011;4:125-128

How to cite this URL:
Turaka K, Mashayekhi A, Shields Cl, Lally SE, Kligman B, Shields JA. A case series of neuroendocrine (carcinoid) tumor metastasis to the orbit. Oman J Ophthalmol [serial online] 2011 [cited 2020 Sep 22 ];4:125-128
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Full Text


Neuroendocrine (carcinoid) tumors are slow-growing, low-grade neoplasms that usually develop in the gastrointestinal tract and bronchus but can rarely originate in the ovary, thymus, parotid gland, breast, and testis. [1],[2],[3],[4],[5] Although they are thought to be of low malignant potential, they can metastasize to various sites such as liver, lymph nodes, and bone. Neuroendocrine tumor metastasis to the liver can lead to carcinoid syndrome due to release of bioactive amines from the tumor.

Neuroendocrine tumor metastasis to the eye and orbit is rare. [6],[7] Goldberg and associates reported 11 cases of carcinoid tumor metastasis to the orbit out of 245 orbital lesions and discussed the various presenting symptoms and signs and the pathological findings of the lesions. [6] Several authors from various centers reported their cases and discussed about the neuroendocrine tumor metastasis to the orbit. Herein we report four additional cases of neuroendocrine tumor metastatic to the orbit, which will add to the current literature.

Case 1

A 62-year-old man had a neuroendocrine tumor of the rectum treated by colon resection and radiation therapy. Three years later, he experienced diplopia and right periorbital swelling and also was found to have metastasis to the liver, lung, and groin. Indium-111 OctreoScan demonstrated a mass in the right orbit. Visual acuity was no light perception in the right eye (OD) and 20/30 in the left eye (OS). There was right eye proptosis of 10 mm on exophthalmometry and decreased ocular motility in all gazes. Magnetic resonance imaging (MRI) of the orbits revealed a 30-mm well-circumscribed intraconal mass adjacent to the medial rectus muscle displacing the optic nerve medially. The lesion was isointense on T1-weighted images with moderate enhancement after contrast. Enucleation and anterior orbitotomy were performed for the painful blind eye and tumor resection, respectively. Histopathology of the resected lesion showed metastatic neuroendocrine tumor with the tumor cells staining positive for chromogranin, synaptophysin, and neuron specific enolase. At 2 years follow-up, there was no orbital recurrence of the tumor; however, there was progression of the liver, lung, and skin metastases. Despite chemotherapy (carboplatin and TP-16) and external beam radiotherapy (EBRT) of extraorbital tumors, the patient died 3 years after orbital surgery.

Case 2

A 64-year-old woman experiencing diplopia for 6 months was found to have a right orbital tumor on MRI. Three years before onset of eye symptoms, she had a colon carcinoid tumor treated by colectomy. Visual acuity was 20/20 OD and 20/40 OS. Ocular motility of the right eye was slightly limited in up and down gaze. MRI revealed a right orbital mass infiltrating the inferior rectus muscle and the resected lesion showed intermediate to large mononuclear cells with scant cytoplasm, irregular nuclei, and finely granular chromatin on histopathology, with positive staining for chromogranin, synaptophysin, pancytokeratin, and CD10, compatible with diagnosis of neuroendocrine tumor. MRI of the chest and abdomen revealed liver and lung lesions. She died 24 months after initial evaluation due to brain metastasis.

Case 3

A 73-year-old woman presented with drooping of her right upper lid. Twelve years prior she had undergone resection of neuroendocrine tumor in the upper lobe of her right lung and a metastasis to the ninth thoracic vertebra, which was treated with EBRT. Subsequent 5-HIAA study and Indium-111 OctreoScan were within normal limits.

Visual acuity was 20/20 OD and 20/40 OS. There was 1 mm proptosis and 3 mm blepharoptosis on the right side. MRI of the orbit revealed a heterogeneous lesion with contrast enhancement in the superior right orbit measuring 13 × 18 × 14 mm and a smaller lesion adjacent to the lacrimal gland [Figure 1]a. Fine needle aspiration biopsy of the orbital tumor was consistent with neuroendocrine tumor with positive staining for chromogranin, AE1/AE3, synaptophysin, and CD56 but negative staining for CD45 consistent with atypical carcinoid. Excisional biopsy revealed a low-grade non-small cell neuroendocrine tumor. Residual orbital tumor was treated with EBRT. Within the next 2-6 years, she developed recurrent lesions in both lungs and multiple metastatic lesions in the thoracic vertebra, breast, scalp, and cavernous sinus which were treated with a combination of surgical excision, chemotherapy (carboplatin, etoposide, and paclitaxel), and EBRT. Six years after initial presentation, the patient was alive with no orbital tumor recurrence [Figure 1]b.{Figure 1}

Case 4

A 63-year-old man presented with diplopia, redness, and pain of his left eye of 4 weeks duration. He had a history of neuroendocrine tumor of the testicle treated by radical orchiectomy 13 years before presentation followed by metastasis to the ileum, which was treated with bowel resection. Visual acuity was 20/30 OD and 20/25 OS and exophthalmometry revealed 4 mm proptosis of the left eye with mild limitation of ocular motility in lateral gaze. An intraconal, well-circumscribed mass in the left orbit displacing the lateral rectus muscle laterally was noted on MRI [Figure 1]c. Histopathologic evaluation following tumor excision revealed a low-grade atypical neuroendocrine tumor with positive staining for chromogranin, synaptophysin, neuron-specific enolase, and AE1/3 compatible with carcinoid metastasis. Between the next 4.5 years, the patient had three recurrences of the orbital carcinoid which were managed with EBRT, surgical excision, and eventually orbital exenteration after the MRI showed early erosion of orbital bones by the tumor and tumor extension into the maxillary bone [Figure 1]d and e. Histopathology of the exenterated orbital lesion showed multinucleated cells with large hyperchromatic nuclei and seven mitotic figures in 10 high-power fields consistent with aggressive metastatic poorly differentiated neuroendocrine tumor. The patient also developed signs of carcinoid syndrome with carcinoid metastasis to the liver, kidney, and parotid gland. He was alive with systemic metastasis 4 years after initial presentation.

The clinical and pathological features as well as treatment methods and outcomes for each patient are summarized in [Table 1].{Table 1}


Among the ocular structures, the most common site of neuroendocrine tumor metastasis is the uveal tract. [7] Neuroendocrine tumor metastasis to the orbit is not common. [7],[8],[9],[10],[11] The average age of presentation with orbital metastasis of the neuroendocrine tumor was 64 years in the study by Goldberg and associates, [6] 65 years in the study by Mehta and associates, [11] and 66 years in this study.

Diplopia and proptosis are the most common presenting symptoms and signs of orbital metastasis. [6],[10],[11] All patients in our series had diplopia and three out of four had proptosis [Table 1]. Limited ocular motility was noted in 38 (54%) of the 100 patients with metastatic orbital lesions in a study by Shields and associates [12] and three out of four patients in our series (75%) had limited ocular motility.

Metastatic orbital tumors are usually isointense to extraocular muscles (EOM) and hypointense to orbital fat on T1 images and mildly hyperintense to EOM and fat on T2 images with enhancement following contrast administration. [13] In our series, MRI demonstrated a well-circumscribed orbital mass in three cases and one lesion in the inferior rectus muscle. The lesions were heterogeneous on T1- and T2-weighted images in three cases with minimal contrast enhancement in two cases and heterogeneous enhancement in one case. Braffman and coworkers reported the MRI findings in one case of neuroendocrine tumor metastatic to the orbit and noted isointensity to hyperintensity to fat on T1 and hypointensity to the vitreous on T2. [14] Shields and associates [15] evaluated the CT and MRI images in a patient with ileal neuroendocrine tumor metastatic to the orbit and came to the conclusion that MRI provides better resolution than CT. [15] Indium-111 OctreoScan was performed in three out of four of our cases, and only one case (case 4) showed increased radiotracer uptake indicating a somatostatin-rich malignancy such as carcinoid. This patient had a carcinoid syndrome and the high uptake on octreotide scan could correlate with increased tumor activity.

Metastatic neuroendocrine orbital tumors have been reported to have increased Iodine-131-Metaiodobenzylguanidine (MIBG) uptake [16] attributed to the elevated serotonin levels in these tumors. [14] MIBG scan was not performed in any of our cases. Isodori [17] and his team have evaluated the use of 123 I-MIBG and 111 Indium Octreotide scanning in 40 cases of neuroendocrine tumors including six patients (15%) with ocular metastasis (five choroidal lesions and one orbital lesion). None of their patients showed positive uptake with the 123 I-MIBG, but four of the six showed positive uptake with 111 Indium scintigraphy. The authors found the new radiopharmaceutical imaging modalities helpful in staging the disease and diagnosing unsuspected lesions, thereby allowing earlier intervention and more favorable overall survival.

Treatment options for orbital neuroendocrine tumor metastasis include excision, orbital exenteration, radiotherapy, hormonal therapy, and chemotherapy. [17],[18],[19] Three of the cases in our series underwent excision of their orbital lesions and two cases also received supplemental EBRT to the residual lesions. Patient 1 had a painful blind eye and was treated by enucleation and resection of orbital tumor as initial treatment. Patient 4 had multiple recurrences after failed excision and radiotherapy and eventually required exenteration. Three out of four patients had no recurrence of the orbital lesions following their initial treatment. In a review of the literature and 13 cases in their series, Mehta and coworkers [11] found that in general the 5-year survival rate of patients with carcinoid tumors was better for lesions with no atypia (with metastasis 61% and without metastasis 96%) than those with atypia on histological evaluation (with metastasis 24% and without metastasis 75%). The overall survival was 72% at 5 years and 38% at 10 years. They concluded that long-term survival, in addition to tumor histological features, also depended on the presence of other extraorbital systemic metastases and carcinoid syndrome and was improved by new treatment methods such as newer chemotherapy modalities. Histopathology in two of the four cases (cases 3 and 4) showed atypia, both of which had systemic metastasis and both of them were alive at the last follow-up. Overall, of the four patients in our series, two are alive, and two died of widespread systemic metastasis 2 and 3 years after initial evaluation.

In summary, we report four cases of histopathologically proven orbital neuroendocrine tumor (carcinoid) metastasis originating from gastrointestinal tract (colon and rectum) in two cases, lung in one case, and the testicle in another case. The interval between primary carcinoid tumor diagnosis and orbital involvement was a mean of 8 years and three patients had multiple sites of extraorbital metastasis at the time of ocular presentation. Diplopia and proptosis were the most common presenting features. One patient with an aggressive carcinoid tumor developed multiple orbital recurrences and required orbital exenteration, while two other patients died due to extensive systemic metastasis. MRI and octreotide scanning were helpful in allowing early diagnosis and for monitoring after treatment.


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