Acta Neurol Belg DOI 10.1007/s13760-015-0463-7
LETTER TO THE EDITOR
Isolated blepharoptosis may point to HIV-associated Burkitt’s lymphoma Maud Pichon1 • Julien Savatovsky2 • Ce´dric Lamirel3,4 • Ve´ronique Joly1 Antoine Moulignier5
•
Received: 24 December 2014 / Accepted: 20 March 2015 Ó Belgian Neurological Society 2015
Keywords
HIV Burkitt’s lymphoma Ptosis Orbit
Before combined antiretroviral therapy (cART), neuroophthalmologic symptoms were often part of a more prominent neurologic presentation and decisional algorithm relied on brain MRI and lumbar puncture as opportunistic infections and lymphoma were the most frequent etiologies. Introduction of cART has complexified HIVassociated neurological conditions and the need for a multidisciplinary collaboration has never been greater. This case report illustrates how an isolated ptosis with a normal brain MRI was the initial symptoms of a Burkitt’s lymphoma (BL). Diagnosis was delayed until a detailed neuroophthalmic examination localized the lesion in the orbit prompting a dedicated MRI.
& Antoine Moulignier [email protected] 1
Service des Maladies Infectieuses et Tropicales, AP-HP, Hoˆpital Bichat-Claude Bernard, Universite´ Paris 7, 75018 Paris, France
2
Service d’Imagerie Me´dicale, Fondation Adolphe de Rothschild, 75019 Paris, France
3
Service d’Ophtalmologie, AP-HP, Hoˆpital Bichat-Claude Bernard, 75018 Paris, France
4
De´partement d’Ophtalmologie, Fondation Ophtalmologique Adolphe de Rothschild, 75019 Paris, France
5
Service de Neurologie, Fondation Adolphe de Rothschild, 25 rue Manin, 75019 Paris, France
Case report A 25-year-old man, HIV? since 2007, has been treated with cART for 3 months for an HIV-associated spondyloarthropathy. His CD4 T-cell count was 334/mm3 and his plasma viral load (plVL) was 51,100 copies/ml. Three months later, he developed an isolated blepharoptosis affecting the left upper eyelid. His CD4 T-cell count was 453/mm3 and the plVL was \20 copies/ml. The results of brain MRI, ordered by his primary care physician, were normal. Eventually, the patient was referred to a neuroophthalmologist who found a 3-mm left ptosis with decreased levator function, a 3-mm left proptosis, full extraocular motility, normal visual acuity and visual field, and no afferent pupillary defect. This presentation suggested an orbital process. An orbital MRI revealed bilateral heterogeneous infiltration of the extraocular muscles compatible with a lymphoma (Fig. 1). Three weeks after the onset of ptosis, the patient developed a maculopapular skin rash. Because orbital lymphoma was suspected, a pathological examination of the skin lesions was obtained and revealed the presence of numerous monoclonal lymphoid cells. The immunohistochemical staining was positive for CD20 and CD10, negative for CD5 and BCl2, and showed 100 % labeling indices of nuclear staining for Ki 67. cMYC abnormalities were found on the karyotype. In situ hybridization revealed Epstein–Barr-encoded-(early)-RNA. The 18-fluorodeoxyglucose PET scan revealed polyadenopathies with bone marrow, skin, pancreas, heart, and thyroid involvement. The diagnosis of disseminated BL associated with the Epstein–Barr virus was retained and the patient received dose-intensive chemotherapy, including cyclophosphamide, vincristine, prednisolone, and doxorubicine. The discrepancy between full eye movements at the initial neuro-ophthalmic evaluation and the
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Acta Neurol Belg Fig. 1 Coronal T2-weighted images with fat suppression (a), and coronal T1-weighted images after administration of a contrast product and fat suppression (b), showing a bilateral heterogeneous infiltration involving lacrymal glands, extraconal fat on both sides and some of the oculomotor muscles. Axial T1weighted image with fat suppression showing prominent left superior rectus muscle involvement (c), and with restriction on diffusionweighted images b = 1000 (d)
MRI aspect of the muscles could be simply explained by the delay between both exams and the aggressive growth rate of the Burkitt’s lymphoma.
Discussion Neuro-ophthalmic examination suggested an orbital process because of the proptosis and ptosis observed without involvement of the other muscles innervated by the 3rd cranial nerve. Routine brain MRI, which examines thick sections of tissue using no fat suppression, is inadequate for the study of orbital structures. In contrast, dedicated orbital MRI using T2-weighted sequences and post-gadolinium, fat-suppressed, T1-weighted sequences with thin coronal sections is a more sensitive technique, guiding the diagnosis according to the affected structures and the signals recorded. Whereas the enlargement of the superior rectus muscle and the tendons is suggestive of a tumoral process, these structures are spared in thyroid orbitopathy, which is the cause of 95 % of the cases of extraocular muscle enlargement [1]. The definitive diagnosis thus depends solely on the biopsy of the lesion [2]. A thorough workup would be required to determine an extraorbital localization allowing an easier biopsy than that of the orbital structures. Orbital non-Hodgkin lymphoma (NHL) represents 8 % of all extranodal NHL, and accounts for 10 % of all malignant orbital tumors in adults [1]. BL is an NHL, characterized by aggressive growth rates, occurring in three clinical subtypes described as endemic, sporadic, and HIV-associated NHL. Outside Africa BL represents 2 % of all cases of NHL, and up to 20 % of those of HIV-associated NHL [3]. Except for the endemic subtype, which presents in the form of facial or jawbone tumors, often extending to the orbit
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through the nasopharynx, the other subtypes of BL manifest typically as abdominal tumors with bone marrow involvement. The central nervous system is involved in 40 % of the cases of extranodal non-endemic BL, whereas primary orbital involvement has been reported in fewer than 20 cases [3], and in only two cases of HIV infection [4]. The most frequent ocular signs of the disorder are proptosis (81 %), external ophthalmoplegia (56 %), and ptosis (18 %) [3]. The high rate of cell division in BL leads to rapid tumoral growth harmful to orbital tissues. Thus, early diagnosis of the disorder followed by a course of specific chemotherapy would be conducive to a favorable prognosis. Our observation shows that extranodal BL may occur exclusively in the extraocular muscles so that the correct diagnosis may delayed unless the appropriate examinations are promptly scheduled. Thus, in spite of all the sophisticated techniques now available, physical examination skills remain essential for localizing the responsible lesion and ordering the most relevant imaging studies [5]. Acknowledgments The authors are grateful to Kanaya Malkani for a critical reading and comments on the manuscript. Conflict of interest disclose.
None of the authors have competing interest to
Ethical standard This work has been approved by the ethics committee of Fondation Adolphe de Rothschild, France.
References 1. Coupland SE, Hummel M, Stein H (2002) Ocular adnexal lymphomas: five case presentations and a review of the literature. Surv Ophthalmol 47:470–490 2. Kim JW, Lee DK, Fishman M (2010) Orbital smooth muscle tumor associated with Epstein–Barr virus in a human immunodeficiency virus-positive patient. Arch Ophthalmol 128:1084–1085
Acta Neurol Belg 3. Gupta R, Yadav JS, Yadav S, Wadood A (2012) Orbital involvement in nonendemic Burkitt’s lymphoma. Orbit 31:441–445 4. Chin EK, Granier A, Hunter AA, Dwyre DM, Lin LK (2013) Extraocular muscle enlargement leading to the diagnoses of
Burkitt lymphoma and acquired immune deficiency syndrome. Ophthal Plast Reconstr Surg 29:e157–e159 5. Berger JR (2013) Neurologists: the last bedside physician-scientists. JAMA Neurol 70:965–966
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LETTER TO THE EDITOR
Isolated blepharoptosis may point to HIV-associated Burkitt’s lymphoma Maud Pichon1 • Julien Savatovsky2 • Ce´dric Lamirel3,4 • Ve´ronique Joly1 Antoine Moulignier5
•
Received: 24 December 2014 / Accepted: 20 March 2015 Ó Belgian Neurological Society 2015
Keywords
HIV Burkitt’s lymphoma Ptosis Orbit
Before combined antiretroviral therapy (cART), neuroophthalmologic symptoms were often part of a more prominent neurologic presentation and decisional algorithm relied on brain MRI and lumbar puncture as opportunistic infections and lymphoma were the most frequent etiologies. Introduction of cART has complexified HIVassociated neurological conditions and the need for a multidisciplinary collaboration has never been greater. This case report illustrates how an isolated ptosis with a normal brain MRI was the initial symptoms of a Burkitt’s lymphoma (BL). Diagnosis was delayed until a detailed neuroophthalmic examination localized the lesion in the orbit prompting a dedicated MRI.
& Antoine Moulignier [email protected] 1
Service des Maladies Infectieuses et Tropicales, AP-HP, Hoˆpital Bichat-Claude Bernard, Universite´ Paris 7, 75018 Paris, France
2
Service d’Imagerie Me´dicale, Fondation Adolphe de Rothschild, 75019 Paris, France
3
Service d’Ophtalmologie, AP-HP, Hoˆpital Bichat-Claude Bernard, 75018 Paris, France
4
De´partement d’Ophtalmologie, Fondation Ophtalmologique Adolphe de Rothschild, 75019 Paris, France
5
Service de Neurologie, Fondation Adolphe de Rothschild, 25 rue Manin, 75019 Paris, France
Case report A 25-year-old man, HIV? since 2007, has been treated with cART for 3 months for an HIV-associated spondyloarthropathy. His CD4 T-cell count was 334/mm3 and his plasma viral load (plVL) was 51,100 copies/ml. Three months later, he developed an isolated blepharoptosis affecting the left upper eyelid. His CD4 T-cell count was 453/mm3 and the plVL was \20 copies/ml. The results of brain MRI, ordered by his primary care physician, were normal. Eventually, the patient was referred to a neuroophthalmologist who found a 3-mm left ptosis with decreased levator function, a 3-mm left proptosis, full extraocular motility, normal visual acuity and visual field, and no afferent pupillary defect. This presentation suggested an orbital process. An orbital MRI revealed bilateral heterogeneous infiltration of the extraocular muscles compatible with a lymphoma (Fig. 1). Three weeks after the onset of ptosis, the patient developed a maculopapular skin rash. Because orbital lymphoma was suspected, a pathological examination of the skin lesions was obtained and revealed the presence of numerous monoclonal lymphoid cells. The immunohistochemical staining was positive for CD20 and CD10, negative for CD5 and BCl2, and showed 100 % labeling indices of nuclear staining for Ki 67. cMYC abnormalities were found on the karyotype. In situ hybridization revealed Epstein–Barr-encoded-(early)-RNA. The 18-fluorodeoxyglucose PET scan revealed polyadenopathies with bone marrow, skin, pancreas, heart, and thyroid involvement. The diagnosis of disseminated BL associated with the Epstein–Barr virus was retained and the patient received dose-intensive chemotherapy, including cyclophosphamide, vincristine, prednisolone, and doxorubicine. The discrepancy between full eye movements at the initial neuro-ophthalmic evaluation and the
123
Acta Neurol Belg Fig. 1 Coronal T2-weighted images with fat suppression (a), and coronal T1-weighted images after administration of a contrast product and fat suppression (b), showing a bilateral heterogeneous infiltration involving lacrymal glands, extraconal fat on both sides and some of the oculomotor muscles. Axial T1weighted image with fat suppression showing prominent left superior rectus muscle involvement (c), and with restriction on diffusionweighted images b = 1000 (d)
MRI aspect of the muscles could be simply explained by the delay between both exams and the aggressive growth rate of the Burkitt’s lymphoma.
Discussion Neuro-ophthalmic examination suggested an orbital process because of the proptosis and ptosis observed without involvement of the other muscles innervated by the 3rd cranial nerve. Routine brain MRI, which examines thick sections of tissue using no fat suppression, is inadequate for the study of orbital structures. In contrast, dedicated orbital MRI using T2-weighted sequences and post-gadolinium, fat-suppressed, T1-weighted sequences with thin coronal sections is a more sensitive technique, guiding the diagnosis according to the affected structures and the signals recorded. Whereas the enlargement of the superior rectus muscle and the tendons is suggestive of a tumoral process, these structures are spared in thyroid orbitopathy, which is the cause of 95 % of the cases of extraocular muscle enlargement [1]. The definitive diagnosis thus depends solely on the biopsy of the lesion [2]. A thorough workup would be required to determine an extraorbital localization allowing an easier biopsy than that of the orbital structures. Orbital non-Hodgkin lymphoma (NHL) represents 8 % of all extranodal NHL, and accounts for 10 % of all malignant orbital tumors in adults [1]. BL is an NHL, characterized by aggressive growth rates, occurring in three clinical subtypes described as endemic, sporadic, and HIV-associated NHL. Outside Africa BL represents 2 % of all cases of NHL, and up to 20 % of those of HIV-associated NHL [3]. Except for the endemic subtype, which presents in the form of facial or jawbone tumors, often extending to the orbit
123
through the nasopharynx, the other subtypes of BL manifest typically as abdominal tumors with bone marrow involvement. The central nervous system is involved in 40 % of the cases of extranodal non-endemic BL, whereas primary orbital involvement has been reported in fewer than 20 cases [3], and in only two cases of HIV infection [4]. The most frequent ocular signs of the disorder are proptosis (81 %), external ophthalmoplegia (56 %), and ptosis (18 %) [3]. The high rate of cell division in BL leads to rapid tumoral growth harmful to orbital tissues. Thus, early diagnosis of the disorder followed by a course of specific chemotherapy would be conducive to a favorable prognosis. Our observation shows that extranodal BL may occur exclusively in the extraocular muscles so that the correct diagnosis may delayed unless the appropriate examinations are promptly scheduled. Thus, in spite of all the sophisticated techniques now available, physical examination skills remain essential for localizing the responsible lesion and ordering the most relevant imaging studies [5]. Acknowledgments The authors are grateful to Kanaya Malkani for a critical reading and comments on the manuscript. Conflict of interest disclose.
None of the authors have competing interest to
Ethical standard This work has been approved by the ethics committee of Fondation Adolphe de Rothschild, France.
References 1. Coupland SE, Hummel M, Stein H (2002) Ocular adnexal lymphomas: five case presentations and a review of the literature. Surv Ophthalmol 47:470–490 2. Kim JW, Lee DK, Fishman M (2010) Orbital smooth muscle tumor associated with Epstein–Barr virus in a human immunodeficiency virus-positive patient. Arch Ophthalmol 128:1084–1085
Acta Neurol Belg 3. Gupta R, Yadav JS, Yadav S, Wadood A (2012) Orbital involvement in nonendemic Burkitt’s lymphoma. Orbit 31:441–445 4. Chin EK, Granier A, Hunter AA, Dwyre DM, Lin LK (2013) Extraocular muscle enlargement leading to the diagnoses of
Burkitt lymphoma and acquired immune deficiency syndrome. Ophthal Plast Reconstr Surg 29:e157–e159 5. Berger JR (2013) Neurologists: the last bedside physician-scientists. JAMA Neurol 70:965–966
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