Paraneoplastic Progressive Downbeat Nystagmus, Ataxia and Sensorineural Hearing Loss due to the ANTI-Kelch-11 Protein Antibody.

ABSTRACT: A 45-year-old man with a history of testicular seminoma treated 8 years earlier presented with chronic progressive truncal and limb ataxia, progressive sensorineural hearing loss, and episodic vertigo. Eye movement and neuro-otology examinations showed localizing abnormalities to the bilateral cerebellar flocculus, vermis, and bilateral cerebellar hemispheres. Audiometric testing showed bilateral symmetric sensorineural hearing loss. There was a normal MRI of the brain. Cerebrospinal fluid (CSF) showed modest lymphocytic pleocytosis, and there was an elevated serum choriogonadotrophic hormone. An abdominal CT scan showed a solitary, large retroperitoneal lymph node, and histopathologic examination of the node biopsy showed granulomatous inflammation without microorganisms; eventually, immunohistochemical markers confirmed the diagnosis of metastatic seminoma. Although normal neuroimaging and inflammatory CSF reaction suggested a paraneoplastic etiology, the initial paraneoplastic antibody testing was negative. Subsequent investigation identified a positive kelch-11 protein antibody, thus confirming the paraneoplastic connection between the metastatic seminoma and the subacute neurologic-cochleovestibular syndrome.

Bilateral diffuse uveal melanocytic proliferation with multifocal diffuse integumentary melanocytic proliferation paraneoplastic syndrome: A case report.

Bilateral diffuse uveal melanocytic proliferation (B-DUMP) is a rare paraneoplastic syndrome typically presenting with bilateral visual loss. B-DUMP is associated with extraocular systemic malignancies with the most common being lung cancer in males and uro-gynaecological cancer in females (mainly ovarian cancer). Cutaneous and/or mucosal involvement in patients with B-DUMP has been reported but it is not well characterised. Herein, we present a female in her 70s with diagnosis of stage IV vaginal clear-cell carcinoma and metastatic melanoma of unknown primary that developed progressive bilateral loss of visual acuity compatible with 'B-DUMP'. Simultaneously, she developed multifocal bilateral bluish-greyish patches on the skin that were shown to have a proliferation of dermal melanocytes. We propose that the clinical and histopathologic cutaneous findings seen in patients with B-DUMP be termed 'diffuse integumentary melanocytic proliferation (DIMP)'.

Bilateral Diffuse Uveal Melanocytic Proliferation (BDUMP) associated with B-cell lymphoma: report of a rare case.

BACKGROUND: Bilateral diffuse uveal melanocytic proliferation (BDUMP) is a paraneoplastic ocular syndrome occurring in patients with systemic, often occult but advanced carcinoma and is the hallmark of poor prognosis. Ocular signs precede manifestation of systemic carcinoma by 3-12 months, highlighting the need for appropriate index of suspicion and prompt evaluation. Treatment options for BDUMP are limited. Investigations are aimed at finding the occult primary malignancy, which can be challenging. Modalities for treatment of the ocular findings include corticosteroids, surgery, external beam radiotherapy, and treatment of the underlying malignant neoplasm. However, it is uncertain whether earlier intervention for the systemic malignancy will impact survival, as this paraneoplastic phenomenon is thought to occur in advanced malignancy. CASE PRESENTATION: We report a unique rare atypical case with BDUMP causing visual loss in a 62-year-old female as the presenting sign of central nervous system (CNS) B-cell lymphoma. Multiple grey or grey brown subretinal lesions with pigment clumps were present in both eyes on fundoscopy and multimodal imaging demonstrated multiple discrete lesions at the level of retinal pigment epithelium. Neuroimaging revealed presence of brainstem and cerebellopontine lesions suggestive of CNS lymphoma, which was further confirmed on biopsy. CONCLUSION: In the current atypical case, prompt diagnosis and immediate referral was key, with detailed systemic evaluation by an internist and oncologist. The reported case is distinct for the reason that BDUMP occurred secondary to primary CNS lymphoma, a hitherto unreported association.

Bilateral Diffuse Uveal Melanocytic Proliferation Initially Presented as Glaucoma.

PURPOSE: To report a bilateral diffuse uveal melanocytic proliferation (BDUMP) patient whose initial presentation was glaucoma. METHODS: Clinical review of a BDUMP case. RESULTS: A 65-year-old woman presented with ocular pain of the left eye for 1 day and vision loss of the right eye for 1 week. An ophthalmological examination revealed increased intraocularr pressure in the left eye and shallow anterior chamber in both eyes. BDUMP was diagnosed following a series of auxiliary examinations. After 1.5 years of follow-up, progressive cataracts appeared, and the patient accepted cataract surgery in both eyes. Visual acuity improved from light perception to 20/100 in both eyes 1.5 years after cataract surgery, but declined to light perception again at the last follow-up. CONCLUSION: BDUMP can be initially presented as glaucoma, and cataract surgery can be considered in BDUMP patients in order to improve the patients' quality of life, even if exudative retinal detachment exists.

A slow-release dexamethasone implant for cancer-associated retinopathy.

This case report aims to show the anatomical and functional results of a patient diagnosed as having cancer-associated retinopathy treated with a controlled-release dexamethasone implant (Ozurdex). Anatomical outcomes were assessed using spectral domain optical coherence tomography; and functional outcomes, by measuring visual acuity, microperimetry, and mutifocal electroretinography. The follow-up period was 1 year.

Conjunctival bleeding after ectropion repair due to paraneoplastic primary fibrinolysis.

In addition to predisposing a patient to hypercoaguability and thrombosis, cancers may also cause an antithetical bleeding diathesis through primary fibrinolysis. This paraneoplastic pathology has been documented and studied in prostate cancer patients for nearly a century but is under-recognized as a possible complication of surgery. We report a case of primary fibrinolysis after elective ectropion repair in a patient with prostate cancer. Here paraneoplastic fibrinolysis produced a delayed postoperative hemorrhage requiring specialized therapies, including hospitalization for transfusions of fresh frozen plasma and inhibitors of fibrinolysis. Even in the case of an ambulatory and stable cancer patient, awareness of this complication and its management can help guide surgical decision-making and improve outcomes and follow-up care.

Marked bilateral lower eyelid ectropion in cutis laxa: a paraneoplastic process in multiple myeloma.

PURPOSE: To describe a bilateral involutional lower eyelid ectropion in a patient with cutis laxa, a paraneoplastic process in multiple myeloma. DESIGN: Case report. RESULTS: A 60-year-old male presented with a marked involutional left lower eyelid ectropion. Systemic history included cutis laxa, a paraneoplastic feature of multiple myeloma. After surgical treatment, the ectropion recurred; furthermore, a right lower eyelid ectropion developed. In addition, a distinct dermatochalasis of both upper eyelids was present. CONCLUSIONS: This case is the first description of a marked bilateral involutional ectropion in cutis laxa acquisita.

Neuro-ophthalmic manifestations of cancer: a narrative review.

BACKGROUND AND OBJECTIVE: Neuro-ophthalmic manifestations of cancer are vast and early recognition of a serious ocular condition due to either cancer or its therapy is important for both vision preservation as well as providing valuable treatment and prognostic information regarding the underlying malignancy. This review focuses on direct and indirect effects of cancer on the eye and its adnexa, hematologic malignancy, complications of traditional and novel oncologic therapies, and paraneoplastic syndromes as they relate to the eye as these disorders can lead to potentially devastating or irreversible vision loss. METHODS: PubMed was searched primarily for the following topics: optic nerve infiltration, primary vitreoretinal lymphoma (PVRL), ocular paraneoplastic disorders, and ophthalmic complications of cancer therapeutics. Literature was selected based on historical significance and landmark studies (e.g., Cross et al. series of paraneoplastic optic neuritis patients; Chan's textbook on primary intraocular lymphoma) as well as publications published after 2000. References from select studies were additionally included. Given the sparsity of literature on many subjects, most publications were included during this time frame in our review. KEY CONTENT AND FINDINGS: There are several ophthalmic entities that the oncologist should be aware of including leukemic optic nerve infiltration, PVRL, paraneoplastic syndromes as they related to the eye, and adverse effects of therapeutics. Unfortunately, given the rarity of some of these entities [e.g., paraneoplastic optic neuropathy (PON), cancer-associated retinopathy (CAR)], diagnosis can be difficult and treatment options are often limited. CONCLUSIONS: Oncologists can develop a set of basic ophthalmology examination skills that will help to triage and manage patient eye complaints. In certain instances, oncologists have the potential to avert devastating vision loss with early recognition of neuro-ophthalmic complications.

[A case of cancer-associated retinopathy rapidly leading to blindness with a unique pupillary light reflex].

BACKGROUND: We herein report a case of cancer-associated retinopathy (CAR) associated with malignant lymphoma, beginning with uveitis and rapidly leading to blindness. CASE: A 54-year-old woman presented with a seven-day history of bilateral progressive vision loss. She had no light perception OU. She had keratic precipitates, anterior chamber cells and fine vitreous opacities OU. Fundus examination showed no signs of inflammation, but both a narrowing of the retinal arterioles and non-active diabetic retinopathy were observed. The electroretinogram was extinguished, and optical coherence tomography showed thinning of the outer retinal layer. Systemic examination revealed malignant lymphoma. Anti-recoverin antibody was detected in the patient's serum. Based on these observations, the patient was diagnosed as having CAR. She was treated with steroid pulse therapy, but her visual acuity did not improve. Although she had no light perception, her pupils showed slow and persistent constriction in reaction to strong and long light stimulation during the follow-up period. CONCLUSIONS: In certain circumstances CAR can progress rapidly and lead to blindness within a few days. We observed a delayed, slow, and persistent pupillary light reflex in a CAR patient with no light perception, presumably due to the intrinsic photoactivation of the melanopsin-containing retinal ganglion cells in the uninvolved inner retina.

Lymphoma and unilateral diffuse uveal melanocytic proliferation: when both conditions co-exist in the eye. / Linfoma y proliferación melanocítica uveal difusa unilateral: cuando ambas entidades coexisten en el ojo.

The case is presented of a 60 year-old male with decreased visual acuity in his left eye (LE). In the funduscopic examination, pigmentary alterations associated with sub-retinal orange plaques could be observed that, in autofluorescence, manifested as hypoautofluorescent spots. Subsequently, the patient subsequently developed significant vitritis with large white sub-retinal plaques on the posterior pole of his LE, with no alterations in the right eye. The IL-10/IL-6 coefficient was 0.87, and a lesion suggestive of a lymphoma in the frontal lobe could be seen on brain magnetic resonance scan. The patient was diagnosed with primary lymphoma of the central nervous system with ocular involvement of the LE and associated unilateral diffuse uveal melanocytic proliferation of the same eye. Diffuse uveal melanocytic proliferation is a bilateral para-neoplastic process that occurs as a consequence of carcinomatous tumour processes, although it does not always meet these characteristics.

Paraneoplastic Syndromes in Neuro-ophthalmology.

PURPOSE OF REVIEW: This article discusses the varied types of paraneoplastic syndromes that commonly have neuro-ophthalmologic manifestations. Diagnostic considerations and therapeutic options for individual diseases are also discussed. RECENT FINDINGS: Paraneoplastic syndromes can affect the afferent and efferent visual systems. Paraneoplastic syndromes may result in reduced visual acuity from retinal degeneration, alterations in melanocyte proliferation and uveal thickening, or acquired nystagmus. Ocular motor abnormalities related to paraneoplastic syndromes may present with symptoms from opsoclonus or from neuromuscular junction disease. Diagnosis remains challenging, but serologic identification of some specific antibodies may be helpful or confirmatory. Treatment, in addition to directed therapies against the underlying cancer, often requires systemic corticosteroids, plasma exchange, or immunosuppression, but some specific syndromes improve with use of targeted pharmacologic therapy. SUMMARY: Diagnosis and therapy of paraneoplastic syndromes presenting with neuro-ophthalmic symptoms remain a challenge, but strategies are evolving and new approaches are on the horizon.

Acute bilateral retina hemorrhages beneath internal limiting membrane: An unusual ophthalmological case report of acute leukemia during complete clinical remission.

RATIONALE: Leukemia is a common hematologic disease that causes various systemic complications, such as ophthalmological disorders. The venous congestion is considered to be the main clinical sign that occurs during the initial stage of the disease, whereas white-centered hemorrhages are the most typical manifestations in leukemic retinopathy. These complications usually manifest when the disease presents with clinical and hematological symptoms. In the present study, we report a patient who was diagnosed with leukemic retinopathy. The initial signs of this disease were bilateral hemorrhages that occurred during complete clinical remission. Previous studies regarding this condition are quite rare. PATIENT CONCERNS: We report a 26-year-old man who was diagnosed with leukemic retinopathy and exhibited the initial signs of the disease, namely bilateral hemorrhages with a distinct appearance beneath the internal limiting membrane. In addition, flame-shaped hemorrhages were observed surrounding the optic discs and/or along the vessels in the absence of venous congestion. All these changes were present during complete clinical remission. DIAGNOSES: Bilateral acute leukemic retinopathy, acute lymphoblastic leukemia (pro-B lymphocyte, BCR-ABL chimeric gene-positive). INTERVENTIONS: Clinical remission was achieved following effective systemic chemotherapy that was applied for leukemia in the hematology department. A dynamic observation was applied actively in the absence of surgery and/or medical treatment for ophthalmologic treatment. OUTCOMES: Best corrected visual acuity was 20/40 in the right eye and 20/60 in the left eye, which was considerably better than those noted at the initial visit of the patient (20/250 in the right eye and 20/400 in the left eye). LESSONS: The cautious expectant treatment is safe and helpful for acute leukemic retinopathy. A long-term follow-up is inevitable. Effective systemic chemotherapy that is required for leukemia treatment can achieve clinical remission, which might be helpful in controlling the pathological changes of the eyes.

Thyroid malignancy presenting with visual loss: an unusual case of paraneoplastic retinopathy.

Paraneoplastic retinopathy is a rare cause of painless vision loss, associated with an underlying (and often occult) systemic malignancy. Ocular examination findings are subtle, and the diagnosis is often made on the basis of electrophysiology findings. This report describes the case of a 48-year-old Caucasian man with paraneoplastic retinopathy presenting as visual disturbance, central scotomata and abnormal electrophysiology. He was subsequently diagnosed with papillary thyroid malignancy.

Bilateral diffuse uveal melanocytic proliferation with multiple iris cysts.

IMPORTANCE: Bilateral diffuse uveal melanocytic proliferation (BDUMP) is a rare paraneoplastic syndrome with characteristic findings, including exudative retinal detachment, rapid cataract formation, and uveal melanocytic tumors. We report a case notable for bilateral iris and ciliary body cysts--a rare presentation of the disease. OBSERVATIONS: A woman in her 50s presented with bilateral decreased vision. Her medical history was significant for clear cell adenocarcinoma of the endometrium. Slitlamp examination revealed a contiguous ring of pigmented translucent iris cysts at the pupillary margin of each eye, confirmed with ultrasound biomicroscopy. Ophthalmoscopic examination of the left eye showed a geographic patch of subretinal fluid temporal to the macula that was associated with orange polygonal pigment. The patient underwent periocular injection of triamcinolone acetonide, with resolution of the subretinal fluid. Recurrent fluid was treated successfully with a second injection of triamcinolone. CONCLUSIONS AND RELEVANCE: Our case of BDUMP appears to be the first to demonstrate multiple iris and ciliary body cysts with high-quality color photography and ultrasound biomicroscopy. Involvement of the anterior uveal tract may be more common than reported in the literature because of its occult nature. Ultrasound biomicroscopy and anterior segment optical coherence tomography may be useful in patients with suspected BDUMP to identify anterior uveal tract involvement.

Linfoma y proliferación melanocítica uveal difusa unilateral: cuando ambas entidades coexisten en el ojo / Lymphoma and unilateral diffuse uveal melanocytic proliferation: when both conditions co-exist in the eye

Varón de 60 años que presenta disminución de agudeza visual rápida y progresiva en su ojo izquierdo (OI). En la exploración funduscópica se pueden observar alteraciones pigmentarias asociadas a placas anaranjadas subretinianas que, mediante autofluorescencia, aparecen como múltiples puntos hipoautofluorescentes en el polo posterior. A los 3 meses, el paciente desarrolla una importante vitritis asociada a grandes placas blanco-amarillentas subretinianas en el polo posterior del OI; el ojo derecho no presenta alteraciones. El coeficiente intravítreo IL-10/IL-6 fue de 0,87 y la resonancia nuclear magnética cerebral evidenció una lesión densa en el lóbulo frontal, sugestiva de linfoma. Se diagnosticó al paciente un linfoma primario del sistema nervioso central, con afectación ocular de su OI, que se asoció a una proliferación melanocítica uveal difusa del mismo ojo. La proliferación melanocítica uveal difusa se trata de un proceso paraneoplásico bilateral que ocurre como consecuencia de procesos tumorales carcinomatosos, aunque no siempre cumple estas características

The case is presented of a 60 year-old male with decreased visual acuity in his left eye (LE). In the funduscopic examination, pigmentary alterations associated with sub-retinal orange plaques could be observed that, in autofluorescence, manifested as hypoautofluorescent spots. Subsequently, the patient subsequently developed significant vitritis with large white sub-retinal plaques on the posterior pole of his LE, with no alterations in the right eye. The IL-10/IL-6 coefficient was 0.87, and a lesion suggestive of a lymphoma in the frontal lobe could be seen on brain magnetic resonance scan. The patient was diagnosed with primary lymphoma of the central nervous system with ocular involvement of the LE and associated unilateral diffuse uveal melanocytic proliferation of the same eye. Diffuse uveal melanocytic proliferation is a bilateral para-neoplastic process that occurs as a consequence of carcinomatous tumour processes, although it does not always meet these characteristics