Paraneoplastic Amaurosis With Positive Anti-Physician Antibody In A Patient With Breast Cancer: A Case Report.

Introduction: Breast cancer is the most common malignancy in women. However, paraneoplastic neurological syndromes associated with breast cancer are rare and represent a diagnostic and therapeutic challenge. Diagnosing paraneoplastic neurological syndromes is challenging due to the heterogeneity of symptoms, the timing of presentation, and the absence of antibodies. About 80% of patients who develop paraneoplastic neurological syndromes due to breast cancer do not have a cancer diagnosis at the time of presentation. Case presentation: We describe a 51-year-old patient with bilateral amaurosis who, during etiological screening, tested positive for anti-fishing antibodies, which are rare antibodies associated with paraneoplastic syndrome. The final diagnosis confirmed invasive breast carcinoma of the left breast associated with metastases to contralateral axillary lymph nodes (stage IV - T1N0M1), with bilateral amaurosis resulting from a paraneoplastic syndrome. Systemic treatment for breast cancer was initiated with an aromatase inhibitor (anastrozole), cyclin inhibitor (palbociclib), and ovarian suppression (goserelin). The patient maintained bilateral amaurosis during follow-up, and her oncological condition remained stable without signs of disease progression. Conclusion: Paraneoplastic neurological syndromes are rare, and often the diagnosis is delayed, as in this case. Anti-fishing antibodies facilitate the diagnosis of this syndrome, and early-stage treatment can provide a good prognosis.


Objective
To report a rare and atypical presentation of breast cancer, diagnosed due to a paraneoplastic syndrome, highlighting the impact of the disease on the patient's quality of life and the importance of suspicion and early diagnosis.
Indeed, here's a translation and some improvements to the writing quality:

Case Report
A 51-year-old premenopausal Caucasian woman with a medical history of hypertension and hypertriglyceridemia presented with severe bilateral optic neuropathy.She had experienced bilateral blurred vision and painless, progressive worsening of visual acuity over a year, which had left her dependent on others for daily activities.Ophthalmologic examination revealed photoreactive isochoric pupils, relative afferent pupillary defect on the left, and bilateral optic disc atrophy, worse on the right.Her visual acuity was 20/70, but her ability to perceive light and colors was better in the left eye.Confrontation, and visual field testing, showed a total scotoma for near objects and a tubular field for distant objects.
Neurological examination was routine, as were breast examinations.
Brain magnetic resonance imaging (MRI) revealed signal changes in the right hippocampus, reduced brain volume, and microangiopathic glucose in the white matter of both cerebral hemispheres (Figure 1).Optical coherence tomography showed ganglion cell loss in the macula, sparing the fovea, and more significant temporal nerve fiber layer loss in the right eye.Orbital MRI showed signal changes in the left intraorbital optic nerve pathway without contrast enhancement, which could be related to optic neuritis without signs of inflammatory activity (Figure 2).In investigating the primary site of neoplasia, computed tomography of the chest, abdomen, and pelvis, thyroid ultrasound, transvaginal ultrasound, and cervical-vaginal cytology showed no abnormalities.Mammography showed two oval-shaped nodules in the left breast, with partially defined margins: one measuring 1.3 cm in the middle third of the inferomedial quadrant and the other measuring 0.9 cm in the posterior third, at the junction of the medial quadrants (Figure 3).Breast ultrasound revealed a hypoechoic oval nodule with lobulated contours, located in the superomedial quadrant of the left breast at 11 o'clock, measuring 0.9 x 0.7 x 0.5 cm (Figure 4).This was associated with a prominent right axillary lymph node with regular and defined contours Breast cancer is the most common cancer in women, accounting for 10.4 % of all cancers among women worldwide.The mortality rate has decreased by 34 % over the last 30 years, indicating significant improvements in diagnosis and treatment [1,2].However, paraneoplastic neurological syndromes (PNS) present a diagnostic and therapeutic challenge in managing breast cancer.Paraneoplastic syndromes are rare systemic manifestations in approximately 0.01 % to 1 % of cancer patients.PNSs occur in patients with malignancies through an autoimmune mechanism, and these manifestations are not explained by local tumor invasion or metastases.They can present with cerebellar symptoms such as ataxia, nystagmus, and dysarthria, as well as peripheral neuropathies, stiff-person syndrome, encephalomyelitis (including limbic encephalopathy), and paraneoplastic retinopathy.Breast cancers associated with paraneoplastic syndromes are more aggressive and have poor prognoses [3].Diagnosing paraneoplastic syndromes is difficult due to the heterogeneity of symptoms, the time of presentation, and the absence of antibodies, and it usually occurs before the diagnosis of breast cancer in 80% of patients who develop PNSs [4].The pathophysiology of paraneoplastic syndromes is a consequence of the natural immune response against neoplastic antigens.Ophthalmic involvement is mainly related to anti-Hu, We describe a 51-year-old woman with bilateral amaurosis resulting from severe bilateral optic neuritis, which was subsequently diagnosed with breast cancer with metastasis to the contralateral axilla and the presence of anti-amphiphysin antibodies.This case report was approved on February 1, 2023, by the Research Ethics Committee, under CAAE number 64675822.5.0000.5463.

Figure 1 :
Figure 1: Cranial magnetic resonance imaging showing right hippocampus signal alteration, brain volume reduction, and microangiopathic glucose in the white matter of both cerebral hemispheres.

Figure 2 :
Figure 2: Orbital magnetic resonance imaging: signal alteration in the left intraorbital optic nerve pathway, without contrast enhancement, which may be related to optic neuritis without signs of inflammatory activity.
measuring 3.1 x 2.6 x 1.3 cm, with signs of cortical thickening and tapering of the central echogenic hilum.A biopsy of the breast nodule revealed invasive breast carcinoma of the non-special type in the left breast, with immunohistochemical evaluation consistent with luminal A tumor (ER+/PR+/Ki67 5%/Her2 negative).A right axillary lymph node biopsy confirmed carcinoma infiltration with the primary site in the breast.PET-CT revealed indeterminate lymphadenopathy in the right axilla, with no other suspected neoplastic sites.The final diagnosis confirmed invasive breast carcinoma of the left breast, luminal A subtype, with metastasis to the contralateral axilla, stage IV (T1N0M1), associated with the paraneoplastic syndrome of bilateral amaurosis due to severe bilateral optic neuropathy.Systemic treatment for breast cancer was initiated with an aromatase inhibitor (Anastrozole), a cyclin inhibitor (Palbociclib), and ovarian suppression (Goserelin), as the patient was in the premenopausal period.Throughout follow-up, the patient maintained the stability of the oncologic condition, without signs of disease progression, but did not improve her ophthalmologic symptoms, maintaining bilateral amaurosis.

Figure 3 :
Figure 3: Mammography: 2 oval-shaped nodules with partially defined margins in the left breast: one in the middle third of the inferomedial quadrant, measuring 1.3 cm, and another in the posterior third, at the junction of the medial quadrants, measuring 0.9 cm.