Ocular Manifestations in Neuroendocrine Tumors: A Review Article
DOI:
https://doi.org/10.12775/JEHS.2024.70.55743Keywords
neuroendocrine tumor, ocular, carcinoid, Merkel cell, pheochromocytoma, paragangliomaAbstract
Introduction: Neuroendocrine tumors (NETs) are a diverse group of tumors that arise from neuroendocrine cells and can synthesize and secrete neuropeptides or hormones. Although NETs usually originate from the gastrointestinal tract or bronchopulmonary tree, they can affect various organs, including the eye. The majority of ocular association with neuroendocrine tumors results from metastasis that affects the orbit, however, primary ocular tumors have been reported.
Purpose of the study: The article reviews the presentation of ocular manifestations in neuroendocrine tumors including pheochromocytoma, ocular paraganglioma, gastrointestinal and bronchial NETs, Merkel cell carcinoma and neuroendocrine metastasis.
Materials and methods: In order to summarize the current knowledge on the topic, a literature review of English language papers with a focus on the most current literature was performed. The review was conducted with the PubMed database with 43 works used, accessed before September 2024.
Conclusions: Instances of neuroendocrine tumors leading to ocular manifestations have become increasingly prevalent. These nonspecific symptoms can make it challenging to diagnose ocular NETs. Ocular manifestations are not typically the primary symptom, but patients with tumors located in the eye may experience symptoms such as eye pain, blepharitis or exophthalmos. Ocular motility and vision may also be affected. It is crucial to study the association between those symptoms and NETs, in order to develop a more comprehensive understanding of the matter.
References
Oronsky B, Ma PC, Morgensztern D, Carter CA. Nothing But NET: A Review of Neuroendocrine Tumors and Carcinomas. Neoplasia. 2017;19(12):991-1002. https://doi.org/10.1016/j.neo.2017.09.002
Sandow L, Thawani R, Kim MS, Heinrich MC. Paraganglioma of the Head and Neck: A Review [published correction appears in Endocr Pract. 2024 Aug;30(8):790. doi: 10.1016/j.eprac.2024.06.005]. Endocr Pract. 2023;29(2):141-147. https://doi.org/10.1016/j.eprac.2022.10.002
Lima JV Júnior, Kater CE. The Pheochromocytoma/Paraganglioma syndrome: an overview on mechanisms, diagnosis and management. Int Braz J Urol. 2023;49(3):307-319 https://doi.org/10.1590/S1677-5538.IBJU.2023.0038
Zhu B, Yan J. Orbital Paraganglioma. J Craniofac Surg. 2019;30(6):e503-e506. . https://doi.org/10.1097/SCS.0000000000005408
Huang N, Rayess HM, Svider PF, et al. Orbital Paraganglioma: A Systematic Review. J Neurol Surg B Skull Base. 2018;79(4):407-412. https://doi.org/10.1055/s-0037-1615750
Schueth EA, Martinez DC, Kulwin CG, Bonnin JM, Payner TD, Ting JY. Recurrent Primary Intrasellar Paraganglioma. Case Rep Otolaryngol. 2020;2020:2580160. Published 2020 Jun 26. https://doi.org/10.1155/2020/2580160
Et-Tahir Y, Merzem A, Belgadir H, Amriss O, Moussali N, El Benna N. Salt and pepper appearance: A characteristic feature of paragangliomas. J Clin Neurosci. 2023;114:144-145. https://doi.org/10.1016/j.jocn.2023.06.017
Hill RH 3rd, Platt SM, Bersani TA, Barker-Griffith A, Strumpf KB. Regression of a paraganglioma tumor of the orbit. Orbit. 2015;34(2):99-102. https://doi.org/10.3109/01676830.2014.950290
Farrugia FA, Charalampopoulos A. Pheochromocytoma. Endocr Regul. 2019;53(3):191-212. https://doi.org/10.2478/enr-2019-0020
Khataminia G, Talaiezadeh A, Bagheri A, et al. Ocular muscle metastasis as the initial presentation of a malignant pheochromocytoma: A unique case. Clin Case Rep. 2020;8(9):1689-1692. Published 2020 May 28. https://doi.org/10.1002/ccr3.2990
Rider AJ, Walsh A, Sollenberger EL, et al. Orbital Pheochromocytoma Metastasis in 2 Patients With Known Pheochromocytoma. Ophthalmic Plast Reconstr Surg. 2019;35(6):e131-e134. https://doi.org/10.1097/IOP.0000000000001460
Tayon KG, Kaila V, Sobti D, Vrcek I. Metastatic neuroendocrine carcinoma presenting with left lateral rectus enlargement and orbital cellulitis. Proc (Bayl Univ Med Cent). 2021;34(5):620-622. Published 2021 Jun 15. https://doi.org/10.1080/08998280.2021.1930633
Das S, Pineda G, Goff L, Sobel R, Berlin J, Fisher G. The eye of the beholder: orbital metastases from midgut neuroendocrine tumors, a two institution experience. Cancer Imaging. 2018;18(1):47. Published 2018 Dec 6. https://doi.org/10.1186/s40644-018-0181-5
Mustak H, Liu W, Murta F, et al. Carcinoid Tumors of the Orbit and Ocular Adnexa. Ophthalmic Plast Reconstr Surg. 2021;37(3):217-225. . https://doi.org/10.1097/IOP.0000000000001715
Fanciulli G, Ruggeri RM, Grossrubatscher E, et al. Serotonin pathway in carcinoid syndrome: Clinical, diagnostic, prognostic and therapeutic implications. Rev Endocr Metab Disord. 2020;21(4):599-612. https://doi.org/10.1007/s11154-020-09547-8
Woods MD, Afkhamnejad E, Pakravan M, Charoenkijkajorn C, Lee AG. Optic neuropathy as the presenting manifestation of carcinoid. Can J Ophthalmol. 2023;58(6):e255-e257. https://doi.org/10.1016/j.jcjo.2023.07.014
Hansen BA, Mendoza-Santiesteban CE, Hedges TR 3rd. REVERSIBLE NYCTALOPIA ASSOCIATED WITH VITAMIN A DEFICIENCY AFTER RESECTED MALIGNANT ILEAL CARCINOID AND PANCREATIC ADENOCARCINOMA. Retin Cases Brief Rep. 2018;12(2):127-130. https://doi.org/10.1097/ICB.0000000000000441
Marlow ED, Faia LJ, Wu D, Farley N, Randhawa S. Paraneoplastic ocular sarcoidosis in the setting of recurrent rectal carcinoid tumor diagnosed by F18-fluorodeoxyglucose PET CT. Am J Ophthalmol Case Rep. 2020;20:100887. Published 2020 Aug 20. https://doi.org/10.1016/j.ajoc.2020.100887
Karimi S, Arabi A, Shahraki T. Intravitreal Bevacizumab (Avastin) as an Adjuvant Therapy for Choroidal Carcinoid Metastasis. J Curr Ophthalmol. 2020;32(4):420-422. Published 2020 Dec 12. https://doi.org/10.4103/JOCO.JOCO_54_20
Guo Y, Shao C, Blau T, Tannapfel A, Koch KR, Heindl LM. Ocular Metastasis of Bronchial Typical Carcinoid. J Thorac Oncol. 2018;13(9):1422-1423. https://doi.org/10.1016/j.jtho.2018.04.001
Crespo MA, Villegas VM, Echevarria ME, Gurrea CM, Murray TG, Chevere CM. Adolescent Plaque Brachytherapy for Large Choroidal Metastasis from Lung Carcinoid Tumor. Case Rep Oncol. 2021;14(3):1483-1489. Published 2021 Oct 19. https://doi.org/10.1159/000519045
Wolkow N, Jakobiec FA, Gragoudas ES. LONG-TERM OBSERVATION OF MULTIFOCAL METASTATIC INTRAOCULAR CARCINOID WITH ACQUIRED IRIS HETEROCHROMIA. Retin Cases Brief Rep. 2020;14(3):265-267. https://doi.org/10.1097/ICB.0000000000000690
Zakhartseva LM, Chytaieva HE, Artemov OV. CLINICAL CASE OF NON-TYPICAL METASTASIS OF NEUROENDOCRINE LUNG CARCINOMA TO THE VASCULAR MEMBRANE OF THE EYE. Exp Oncol. 2022;44(2):169-173. https://doi.org/10.32471/exp-oncology.2312-8852.vol-44-no-2.17969
Yagyu K, Ueda T, Miyamoto A, Uenishi R, Matsushita H, Tanaka T. Cancer-associated Retinopathy with Neuroendocrine Combined Large-cell Lung Carcinoma and Adenocarcinoma. Intern Med. 2019;58(22):3289-3294. https://doi.org/10.2169/internalmedicine.2313-18
Carrera W, Tsamis KA, Shah R. A case of cancer-associated retinopathy with chorioretinitis and optic neuritis associated with occult small cell lung cancer. BMC Ophthalmol. 2019;19(1):101. Published 2019 May 2. . https://doi.org/10.1186/s12886-019-1103-4
Chong YJ, Azzopardi M, Ng B, Salvi SM, Sreekantam S. Ocular Metastasis as First Presentation of Large-Cell Neuroendocrine Carcinoma. Case Rep Ophthalmol. 2023;14(1):684-691. Published 2023 Dec 12.. https://doi.org/10.1159/000535233
D'Angelo SP, Bhatia S, Brohl AS, et al. Avelumab in patients with previously treated metastatic Merkel cell carcinoma: long-term data and biomarker analyses from the single-arm phase 2 JAVELIN Merkel 200 trial. J Immunother Cancer. https://doi.org/10.1136/jitc-2020-000674
Tran MN, Ratnayake G, Wong D, McGrath LA. Conjunctival Merkel cell carcinoma: case report and review of the literature. Digit J Ophthalmol. 2022;28(3):64-68. Published 2022 Jul 24. https://doi.org/10.5693/djo.02.2022.02.003
Becker JC, Stang A, DeCaprio JA, et al. Merkel cell carcinoma. Nat Rev Dis Primers. 2017;3:17077. Published 2017 Oct 26.https://doi.org/10.1038/nrdp.2017.77
Sergi MC, Lauricella E, Porta C, Tucci M, Cives M. An update on Merkel cell carcinoma. Biochim Biophys Acta Rev Cancer. 2023;1878(3):188880. https://doi.org/10.1016/j.bbcan.2023.188880
Yamanouchi D, Oshitari T, Nakamura Y, et al. Primary neuroendocrine carcinoma of ocular adnexa. Case Rep Ophthalmol Med. 2013;2013:281351. . https://doi.org/10.1155/2013/281351.
Gess AJ, Silkiss RZ. A merkel cell carcinoma of the lacrimal gland. Ophthalmic Plast Reconstr Surg. 2012;28(1):e11-e13. https://doi.org/10.1097/IOP.0b013e3182127cb5
Kase S, Ishijima K, Ishida S, Rao NA. Merkel cell carcinoma of the conjunctiva. Ophthalmology. 2010;117(3):637.e1-637.e6372. https://doi.org/10.1016/j.ophtha.2009.10.011
Kirwan C, Carney D, O'Keefe M. Merkel cell carcinoma metastasis to the iris in a 23 year old female. Ir Med J. 2009;102(2):53-54.
Cugley DR, Roberts-Thomson SJ, McNab AA, Pick Z. Biopsy-Proven Metastatic Merkel Cell Carcinoma to the Orbit: Case Report and Review of Literature. Ophthalmic Plast Reconstr Surg. 2018;34(3):e86-e88.https://doi.org/10.1097/IOP.0000000000001078
Siegal N, Gutowski M, Akileswaran L, et al. Elevated levels of Merkel cell polyoma virus in the anophthalmic conjunctiva. Sci Rep. 2021;11(1):15366. Published 2021 Jul 28 .https://doi.org/10.1038/s41598-021-92642-w
Bostan C, de Souza MBD, Zoroquiain P, de Souza LAG, Burnier MN Jr. Case series: Merkel cell carcinoma of the eyelid. Can J Ophthalmol. 2017;52(5):e182-e185.https://doi.org/10.1016/j.jcjo.2017.03.009
Furdová A, Michalková M, Javorská L. Merkel cell carcinoma of the eyelid and orbit. Karcinóm z merkelových buniek mihalnice a očnice. Cesk Slov Oftalmol. 2018;74(1):37-43. https://doi.org/10.31348/2018/1/6-1-2018
Valentini R, Grant-Kels JM, Falcone M, Stewart CL. Merkel cell carcinoma and the eye. Clin Dermatol. 2024;42(4):381-389. https://doi.org/10.1016/j.clindermatol.2024.01.010
Shalhout SZ, Emerick KS, Kaufman HL, Miller DM. Immunotherapy for Non-melanoma Skin Cancer. Curr Oncol Rep. 2021;23(11):125. Published 2021 Aug 27. https://doi.org/10.1007/s11912-021-01120-z
Wirth MA, Khan HM, Sabiq F, Agoumi M, Neufeld A. Metastatic neuroendocrine tumor masquerading as orbital cysticercosis. Neuroradiol J. 2023;36(2):229-231. https://doi.org/10.1177/19714009221124305
Togashi K, Nishitsuka K, Hayashi S, et al. Metastatic Orbital Tumor From Breast Ductal Carcinoma With Neuroendocrine Differentiation Initially Presenting as Ocular Symptoms: A Case Report and Literature Review. Front Endocrinol (Lausanne). 2021;12:625663. Published 2021 Feb 22. https://doi.org/10.3389/fendo.2021.625663
Ryan TG, Juniat V, Stewart C, et al. Clinico-radiological findings of neuroendocrine tumour metastases to the orbit. Orbit. 2022;41(1):44-52. https://doi.org/10.1080/01676830.2021.1895845
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