Metastatic Breast Cancer Presenting as Progressive Ophthalmoplegia 30 Years After Initial Cancer Diagnosis

A 60 year-old woman presented with painless progressive ophthalmoplegia of the right eye. She had a history of left-sided breast carcinoma 30 years ago that was managed with mastectomy only, with appropriate serial follow-up investigations. On examination, her visual acuity was 20/400 in the right eye and 20/20 in the left. She had a right relative afferent pupillary defect. Ocular examination was significant for 2 mm of ptosis, complete ophthalmoplegia, and 2+ chemosis in the right eye. The left eye was normal. MRI of the brain and orbits showed bilateral retrobulbar infiltrative disease in the right eye greater than that in the left eye. Right orbitotomy and biopsy confirmed an infiltrative signet ring cell/histiocytoid carcinoma consistent with metastatic lobular breast carcinoma. Given that recurrence of breast cancer is most common during the second year after the initial disease and rarely reported beyond 20 years after the initial diagnosis, our patient's delayed recurrence 30 years after the treatment of initial disease is unusual and rare. However, it highlights the importance of including metastatic cancer in the differential diagnosis for ophthalmoplegia.

Photo and Video Essay Section Editors: Melissa W. Ko, MD Dean M. Cestari, MD Peter Quiros, MD Metastatic Breast Cancer Presenting as Progressive Ophthalmoplegia 30 Years After Initial Cancer Diagnosis Sam Karimaghaei, BS, Subahari Raviskanthan, MBBS, Peter W. Mortensen, MD, Amina I. Malik, MD, Andrew G. Lee, MD FIG. 1. Fat-suppressed T1 axial (A) and coronal (B) MRI of brain and orbits showing enhancement throughout the right intra and extraconal regions including the muscles. There is encasement of the optic nerve. Abstract: A 60 year-old woman presented with painless progressive ophthalmoplegia of the right eye. She had a history of left-sided breast carcinoma 30 years ago that was managed with mastectomy only, with appropriate serial follow-up investigations. On examination, her visual acuity was 20/400 in the right eye and 20/20 in the left. She had a right relative afferent pupillary defect. Ocular examination was significant for 2 mm of ptosis, complete ophthalmoplegia, and 2+ chemosis in the right eye. The left eye was normal. MRI of the brain and orbits showed bilateral retrobulbar infiltrative disease in the right eye greater than that in the left eye. Right orbitotomy and biopsy confirmed an infilMcGovern Medical School (SK), the University of Texas Health Science Center at Houston, Houston, Texas; Department of Ophthalmology (SR, PWM, AM, AGL), Blanton Eye Institute, Houston Methodist Hospital, Houston, Texas; Departments of Ophthalmology, Neurology, and Neurosurgery (AGL), Weill Cornell Medicine, New York, New York; Department of Ophthalmology (AGL), University of Texas Medical Branch, Galveston, Texas; University of Texas MD Anderson Cancer Center (AGL), Houston, Texas; Texas A and M College of Medicine (AGL), Bryan, Texas; and Department of Ophthalmology (AGL), the University of Iowa Hospitals and Clinics, Iowa City, Iowa. The authors report no conflicts of interest. Address correspondence to Andrew G. Lee, MD, Department of Ophthalmology, Blanton Eye Institute, Houston Methodist Hospital, 6560 Fannin Street 450, Houston, TX 77030; E-mail: aglee@ houstonmethodist.org e446 trative signet ring cell/histiocytoid carcinoma consistent with metastatic lobular breast carcinoma. Given that recurrence of breast cancer is most common during the second year after the initial disease and rarely reported beyond 20 years after the initial diagnosis, our patient’s delayed recurrence 30 years after the treatment of initial disease is unusual and rare. However, it highlights the importance of including metastatic cancer in the differential diagnosis for ophthalmoplegia. Journal of Neuro-Ophthalmology 2022;42:e446–e447 doi: 10.1097/WNO.0000000000001385 © 2021 by North American Neuro-Ophthalmology Society A 60-year-old woman presented with painless progressive ophthalmoplegia of the right eye. She had left-sided breast carcinoma diagnosed 30 years before presentation, status post mastectomy without adjuvant chemotherapy or radiation therapy. Her last routine mammogram was 2 years before presentation, without any evidence of tumor recurrence. Surgical, family, ocular, and medication histories were noncontributory. On examination, her visual acuity was 20/ 400 in the right eye and 20/20 in the left eye. Her pupils were isocoric with a right relative afferent pupillary defect. She had 2-mm ptosis of the right upper lid with complete Karimaghaei et al: J Neuro-Ophthalmol 2022; 42: e446-e447 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Photo and Video Essay ophthalmoplegia. Mild proptosis was noted at the bedside, but no Hertel exophthalmometry was performed. Slit-lamp biomicroscopy showed mild chemosis right eye. The left eye was normal. Intraocular pressure measurements were 21 mm Hg in the right eye and 20 mm Hg in the left eye. MRI of the brain and orbits in September 2020 showed bilateral retrobulbar infiltrative disease right eye . left eye (Fig. 1). Computed tomography scans of the chest, abdomen, and pelvis revealed ascites, retroperitoneal infiltrate, and extensive osteoblastic lesions. A right orbitotomy via superomedial lid crease approach was performed for tissue diagnosis, and biopsy confirmed an infiltrative signet ring cell/histiocytoid carcinoma consistent with metastatic lobular breast carcinoma. Immunohistochemistry showed estrogen receptor positive, progesterone receptor negative, and HER2/neu negative status. Her initial breast cancer pathology specimen was unavailable for comparative genotyping. Most cases of breast cancer recurrence occur during the second year after the treatment of initial disease (1). Recurrence beyond 20 years has been rarely reported in the past several decades (2). In one 2013 review listing 6 cases of delayed recurrence, the earliest relapse occurred 13 years after treatment in the chest wall and the latest 32 years after treatment in the cervical lymph nodes (1). Another report in 2016 noted a case of breast cancer relapse 24 years after mastectomy (2). Up to 30% of patients with metastatic breast cancer may have involvement of the eye and visual pathways (3). The uvea, particularly the choroid, is the most common site of ocular metastatic breast cancer due to its high vascularity. Common manifestations of ocular metastatic disease include ocular pain, blurred vision, visual field deficits, metamorphopsia, floaters, and photopsia. Orbital breast cancer metastasis most commonly affects the extraocular muscles, often presenting with pain, proptosis, and diplopia. Exophthalmos may result from mass effect in the orbit, whereas desmoplastic fibrosis and tumor infiltration of normal orbital soft tissue is the presumed mechanism for the enophthalmos in metastatic scirrhous breast carcinoma (4,5). While the orbital and ocular lesions in our patient are a common manifestation of metastatic breast cancer, her delayed recurrence 30 years post mastectomy is unusual and rare. The initial histopathology was unavailable to us for comparative genotyping, which makes it possible that she had multiple primary malignant neoplasms (MPMN) of the breast, rather than recurrence of the same malignancy. A retrospective study of patients with breast cancer found that 3.6% (8/223), when they were specifically assessed, had a Karimaghaei et al: J Neuro-Ophthalmol 2022; 42: e446-e447 second primary malignant breast neoplasm, over a 4 year period of analysis (6). MPMN is also more common in patients with BRCA1 or BRCA2 gene mutations, and our patient was lost to follow-up, so her BRCA status remains unknown. However, there are also no other case reports of such delayed metachronous MPMN of the breast. This case stresses the importance of including malignancy in the differential of any patient with any degree of ophthalmoplegia. The patient must be asked about any history of cancer. If medical history is positive for treated breast cancer, even decades of disease-free survival should not exclude recurrence with metastatic disease as a possible etiology. STATEMENT OF AUTHORSHIP Category 1: a. Conception and design: S. Karimaghaei, S. Raviskanthan, P. W. Mortensen, A. Malik, and A. G. Lee; b. Acquisition of data: S. Karimaghaei, S. Raviskanthan, P. W. Mortensen, A. Malik, and A. G. Lee; c. Analysis and interpretation of data: S. Karimaghaei, S. Raviskanthan, P. W. Mortensen, A. Malik, and A. G. Lee. Category 2: a. Drafting the manuscript: S. Karimaghaei, S. Raviskanthan, P. W. Mortensen, A. Malik, and A. G. Lee; b. Revising it for intellectual content: S. Karimaghaei, S. Raviskanthan, P. W. Mortensen, A. Malik, and A. G. Lee. Category 3: a. Final approval of the completed manuscript: S. Karimaghaei, S. Raviskanthan, P. W. Mortensen, A. Malik, and A. G. Lee. REFERENCES 1. Omidvari S, Hamedi SH, Mohammadianpanah M, Nasrolahi H, Mosalaei A, Talei A, Ahmadloo N, Ansari M. Very late relapse in breast cancer survivors: a report of 6 cases. Iran J Cancer Prev. 2013;6:113–117. 2. Xiao L, Hu X, Wang S, Yong-Sheng G, Yu Q, Gao S, Zhang H, Wei Y, Zhao Q, Yuan SH. A case report of local recurrence developing 24 years after mastectomy for breast cancer recurrence from breast cancer after 24 years. Medicine (Baltimore). 2016;95:e3807. 3. Wickremasinghe S, Dansingani KK, Tranos P, Liyanage S, Jones A, Davey C. Ocular presentations of breast cancer. Acta Opthalmologica Scand. 2006;85:133–142. 4. 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