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 Table of Contents  
CASE REPORT
Year : 2021  |  Volume : 1  |  Issue : 2  |  Page : 386-388

Metastatic orbital carcinoid tumors masquerading as “hot” orbit


1 Orbit, Oculoplasty, Reconstructive and Aesthetic Services, Sankara Nethralaya, Medical Research Foundation, Chennai, Tamil Nadu, India
2 Larsen and Toubro Department of Ophthalmic Pathology, Sankara Nethralaya, Medical Research Foundation, Chennai, Tamil Nadu, India

Date of Submission24-Jul-2020
Date of Acceptance27-Nov-2020
Date of Web Publication01-Apr-2021

Correspondence Address:
Dr. Bipasha Mukherjee
Orbit, Oculoplasty, Reconstructive and Aesthetic Services, Sankara Nethralaya, Medical Research Foundation, 18, College Road, Chennai, 600 006 Tamil Nadu
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijo.IJO_2332_20

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  Abstract 


We report two patients presenting with acute orbital inflammation as an unusual manifestation of metastatic carcinoid tumors. Neuroimaging revealed rim enhancing lesions mimicking orbital abscesses in both. Histopathology confirmed the diagnosis of metastatic neuroendocrine tumors with primary in the gastrointestinal tract. Atypical presentation of orbital metastases with inflammatory signs of a “hot” orbit is usually misdiagnosed. The clinical features of inflammation may result from the spontaneous release of inflammatory mediators intrinsic to neuroendocrine tumors. In elderly patients with bilateral, multiple extraocular muscle involvement, or acute-onset proptosis with inflammatory signs should alert the clinician to the rare possibility of metastatic neuroendocrine carcinoma.

Keywords: Carcinoid, neuroendocrine tumors, orbital inflammation, orbital metastasis


How to cite this article:
Mukherjee B, Podury S, Vijay V, Krishnakumar S, Alam MS. Metastatic orbital carcinoid tumors masquerading as “hot” orbit. Indian J Ophthalmol Case Rep 2021;1:386-8

How to cite this URL:
Mukherjee B, Podury S, Vijay V, Krishnakumar S, Alam MS. Metastatic orbital carcinoid tumors masquerading as “hot” orbit. Indian J Ophthalmol Case Rep [serial online] 2021 [cited 2021 Jul 29];1:386-8. Available from: https://www.ijoreports.in/text.asp?2021/1/2/386/312372



Orbital metastasis is a rare neoplastic process with the patients usually presenting with proptosis. Rarely, they can present with inflammatory signs. While lungs and breast carcinomas are the most common primary tumors metastasizing the orbit, virtually any organ of the body can involve the orbit.[1] Carcinoid tumors, though rare, can contribute to 5% of orbital metastasis, and be the initial manifestation of the disease.[1],[2] Orbital metastatic carcinoid tumors presenting as orbital inflammation is rare and can be challenging to the treating ophthalmologists.[2],[3],[4]

We, herewith, present two cases of metastatic carcinoid tumors masquerading as orbital abscesses.


  Case Reports Top


Case 1

A 60-year-old male patient presented with a sudden painful decrease in his right eye vision for the last 1 month along with the prominence of both eyes. He was initially treated with intravenous antibiotics elsewhere for presumed orbital cellulitis. He gave a history of similar symptoms 4 years back. The patient had no systemic complaints. On examination, his best-corrected visual acuity (BCVA) was 3/60; N24 in the right eye and 6/6; N6 in the left. Hertel's exophthalmometry readings were 26 and 24 mm in right and left eye, respectively with restricted elevation in both the eyes. The rest of the examination was within normal limits. Magnetic resonance imaging (MRI) of the orbit showed an ovoid, well-defined enhancing mass involving the right lateral rectus (RLR) muscle belly [Figure 1]a and [Figure 1]b. A ring-enhancing lesion was also noted involving the left inferior rectus (LIR) insertion with infiltration of the adjacent globe [Figure 1]c and [Figure 1]d The patient underwent incision biopsy in both eyes under general anesthesia [Figure 1]e.
Figure 1: (a) T1-weighted MRI axial view showing hyperintense ovoid, well-defined mass involving the right LR muscle belly (white arrow). (b)T2-weighted MRI axial section showing intermediate signal intensity (white arrow). (c)T1-weighted MRI axial section showing hyperintense well-defined ovoid lesion (red arrow) at the insertion of LIR with infiltration of adjacent globe. (d) Peripheral ring enhancement (red arrow). (e)Clinical photograph of patient #1 showing subtle exotropia and hypotropia of the right eye. (f) Gross macroscopic image of the excised masses

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The RLR mass was approached through a lateral orbitotomy. The left inferior orbital mass was approached through a transconjunctival swinging eyelid incision [Figure 1]f. Histopathological examination revealed striated muscle fibers infiltrated with polygonal tumor cells showing a syncytial pattern with minimal atypia and low (2%) Ki-67 proliferative index. The cytoplasm showed eosinophilia and chromatin clumps. The stroma between the tumor lobules was desmoplastic with areas of necrosis [Figure 2]a, [Figure 2]b, [Figure 2]c, [Figure 2]d. Immunohistochemistry revealed positive immunoreactivity to cytokeratin (CK) (AE1/AE3); synaptophysin, chromogranin, and CDX2, suggestive of neuroendocrine neoplasms (NEN) of mid-gut origin [Figure 2]e. The findings were consistent with a well-differentiated Grade I neuroendocrine tumor, probably of gastrointestinal origin. Whole Body 68Ga-DOTANOC positron emission tomography-computed tomography (PET/CT) demonstrated extensive metabolically active disease with primary in the distal jejunal loop. The patient was started on monthly injections of octreotide 20 mg. He is undergoing palliative chemotherapy with the last follow-up 2 years from the initial presentation.
Figure 2: (a) Histopathology showing orbital tissue infiltrated with tumor cells showing organoid/trabecular pattern. (b) The tumor cells are in an organoid pattern with uniform polygonal cells which show a syncytial pattern. The tumor cells show minimal atypia and the cytoplasm shows eosinophilia. (c) The stroma between the tumor lobules is desmoplastic. (d) Areas of necrosis are seen in the tumor lobules. (H and E Stain; 40×). (e) Immunohistochemistry showing positivity for cytokeratin (CK AE1/AE3), synaptophysin (SYN), chromogranin (CHR), and CDX2

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Case 2

A 75-year-old woman presented with sudden onset pain, redness, and swelling of the right eye for 1 day. Examination revealed no perception of light along with relative afferent pupillary defect (RAPD) in the right eye. There was 5 mm of proptosis with a gross limitation of ocular motility in all directions of gazes. [Figure 3]a She was diagnosed with rectal carcinoid 5 years back, which was treated with excision and chemotherapy. An MRI orbit showed a well-circumscribed rim-enhancing intraconal lesion in the right orbit [Figure 3]b and [Figure 3]d An orbital abscess was suspected, which was drained under general anesthesia the same day. The aspirate sent for histopathology was suggestive of metastatic carcinoid tumor cells. This was confirmed on immunohistochemistry which showed positive staining for CK (AE1/AE3); synaptophysin; and chromogranin.
Figure 3: (a) Clinical photograph of patient #2 showing right eye severe proptosis, conjunctival congestion, chemosis. (b)T1-weighted MRI orbit axial view showing a well-circumscribed intraconal lesion in the right orbit, displaying isointense signal with patchy hyperintense rim, optic nerve compressed at the mid-orbit level. (c) T1-weighted contrast-enhanced MRI orbit coronal view showing uniform rim enhancement. (d) Clinical photograph taken 5 years post-surgery showing complete ptosis and total resolution of proptosis

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A diagnosis of metastatic rectal neuroendocrine tumor Grade I was thus made. The patient received 56 Gy of external beam radiotherapy (EBRT) in 28 sittings. A follow-up PET scan revealed the presence of liver metastasis 4 months later for which she was started on oral pazopanib and tegafur/uracil. She is asymptomatic and on palliative treatment at the time of the last follow-up 5 years from initial presentation [Figure 3]c.


  Discussion Top


Carcinoid tumors, or NENs, are a complex group of neoplasms arising from neuroendocrine precursor cells, most commonly in the gastrointestinal tract and bronchial tree.[3] About 12.9% of patients presented with metastatic disease at the time of diagnosis.[1]

There is a predilection for gastrointestinal lesions to metastasize to the orbit.[4] The most frequently reported site of NEN orbital metastases is extraocular muscles.[5] Orbital inflammation can be the initial presentation in any metastatic orbital tumor and is not particularly exclusive to metastatic NENs.[2] However, very few cases of metastatic orbital NENs presenting as orbital inflammation have been reported in the literature till date. NENs metastatic to the orbit may masquerade as orbital cellulitis, Grave's orbitopathy, or inflammatory myositis in 5% of cases.[2],[6],[7],[8],[9] The inflammation seen with these lesions may be due to the spontaneous release of inflammatory mediators intrinsic to the property of the tumor cells. Inflammation secondary to tumor necrosis remains another possibility.[8],[9]

Both our patients presented with the acute inflammatory signs of a “hot” orbit. The initial diagnosis in both patients was orbital cellulitis with abscesses. As per protocol an abscess draining procedure was performed and the aspirate was sent for routine histopathological examination. The results of the histopathological examination along with characteristic immunostaining features pointed towards metastatic NENs of the gastrointestinal (GI) tract.

On MRI, orbital lesions show mild contrast enhancement on CT scan.[10] This is at variance to NENS in other regions where they present as highly vascular tumors. Metastatic orbital NEN presenting as well-circumscribed ring-enhancing intraconal cystic mass typical of an orbital abscess as in our second case has never been reported till date.

Signal intensity on T2-weighted MRI helps distinguish idiopathic orbital inflammatory tumors (low intensity) from metastasis (high intensity).[2] Since neuroendocrine cells express peptide receptors, especially somatostatin receptors, PET/CT with 68Ga-DOTA-peptides present a higher sensitivity for the detection of well- and moderately-differentiated, less aggressive NETs, than conventional CT or scintigraphy.

Further investigations include measurement of urinary levels of 5-hydroxyindoleacetic acid (5-HIAA) which may be raised.[2]

Unlike other metastatic tumors, local excision is recommended for isolated solitary NENs and is associated with an excellent prognosis.[2] For larger lesions excision with external beam, irradiation is advocated. However, multiple recurrences even after excision and EBRT has been reported in aggressive metastatic orbital NENs.[11] Long-acting synthetic somatostatin analogs are used as the first line of treatment in patients with clinically significant tumor burden in low-grade NETs. Since NETs express vascular endothelial growth factor (VEGF) and its receptor (VEGFR); pazopanib, a tyrosine kinase inhibitor, and VEGF inhibitor are used in metastatic NETs.[12]

The increasing number of therapeutic options and diagnostic procedures require a multidisciplinary approach. Follow-up routine examinations every 6–12 months to detect carcinoid-related heart disease are important to adjust therapy as most deaths are related to cardiac toxicity.[2]


  Conclusion Top


Misdiagnosis and delay in instituting proper management are common in metastatic orbital NENs, especially when they present with inflammatory signs. This masquerade should be recognized as metastatic NENs are becoming more common with increased life expectancy.

Acknowledgments

Dr. Veena Noronha, M.D. (Radiology), VRR Scans, Chennai, India.

Dr. Marian Jacob, M.S., F.M.R.F (Ophthalmology), Giridhar Eye Institute, Cochin, India.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Goldberg RA, Rootman J, Cline RA. Tumors metastatic to the orbit: A changing picture. Surv Ophthalmol 1990;35:1-24.  Back to cited text no. 1
    
2.
Modlin IM, Lye KD, Kidd M. A 5-decade analysis of 13,715 carcinoid tumors. Cancer 2003;97:934-59.  Back to cited text no. 2
    
3.
Nagtegaal ID, Odze RD, Klimstra D, Paradis V, Rugge M, Schirmacher P, et al, WHO Classification of Tumours Editorial Board. The 2019 WHO classification of tumours of the digestive system. Histopathology. 2020 Jan;76(2):182-188. doi: 10.1111/his.13975. Epub 2019 Nov 13. PMID: 31433515; PMCID: PMC7003895.  Back to cited text no. 3
    
4.
Mehta JS, Abou-Rayyah Y, Rose GE. Orbital carcinoid metastases. Ophthalmology 2006;113:466-72.  Back to cited text no. 4
    
5.
Kamieniarz L, Armeni E, O'Mahony LF, Leigh C, Miah L, Narayan A, et al. Orbital metastases from neuroendocrine neoplasms: Clinical implications and outcomes. Endocrine 2020;67:485-93.  Back to cited text no. 5
    
6.
Atik A, Krilis M, Shannon K. Small cell neuroendocrine carcinoma masquerading as cellulitis and causing blindness via bilateral orbital involvement. Orbit 2013;32:197-9.  Back to cited text no. 6
    
7.
Sira M, Clauss RP, Maclean C, Rose GE. Orbital metastases from neuroendocrine carcinoma, masquerading as graves orbitopathy. Orbit 2010;29:94-6.  Back to cited text no. 7
    
8.
Meena M, Reddie IC, Kourt G, Martin PA. Unusual presentation of metastatic neuroendocrine (carcinoid) tumor in the orbit. Sudanese J Ophthalmol 2014;6:66-8.  Back to cited text no. 8
  [Full text]  
9.
Knox RJ, Gigantelli JW, Arthurs BP. Recurrent orbital inflammation from metastatic orbital carcinoid tumor. Ophthalmic Plast Reconstr Surg 2001;17:137-9.  Back to cited text no. 9
    
10.
Gupta A, Chazen JL, Phillips CD. Carcinoid tumor metastases to the extraocular muscles: MR imaging and CT findings and review of the literature. Am J Neuroradiol 2011;32:1208-11.  Back to cited text no. 10
    
11.
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;4:125-8.  Back to cited text no. 11
  [Full text]  
12.
Oronsky B, Ma PC, Morgensztern D, Carter CA. Nothing but NET: A review of neuroendocrine tumors and carcinomas. Neoplasia 2017;19:991-1002.  Back to cited text no. 12
    


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  [Figure 1], [Figure 2], [Figure 3]



 

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