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Ocular symptoms secondary to meningeal carcinomatosis in a patient with lung adenocarcinoma: a case report
© Sabater et al.; licensee BioMed Central Ltd. 2012
Received: 24 July 2012
Accepted: 12 December 2012
Published: 18 December 2012
Meningeal carcinomatosis (MC) is a rare complication associated with hematologic and solid tumors. MC develops when malignant cells gain access to the leptomeningeal space, producing several clinical symptoms. Loss of vision and ocular motility deficit are the most frequent ocular symptoms reported. Fundus examination usually appears normal, although optic nerve alterations like optic atrophy or papilledema have been described. MC diagnosis is usually completed by magnetic resonance imaging (MRI) and cerebrospinal fluid (CSF) analysis. Indicated treatment for MC usually involves intrathecal chemotherapy combined with radiotherapy, although survival rate is extremely low.
A 66-year old man with stage IV metastatic lung adenocarcinoma, presented to the Ophthalmology Department with a two-month history of double vision, soft headaches and dizziness episodes. The patient presented a best visual corrected acuity of 0.7 in his right eye and 0.8 in his left eye. Diplopia was corrected with 6-prism diopters base-out prism in right eye. Funduscopy showed a bilateral papilledema, juxtapapillary exudates and splinter hemorrhages. Brain MRI showed a diffuse leptomeningeal enhancement in cortical sulcus. Lumbar puncture was performed and cerebrospinal fluid (CSF) cytology revealed malignant cells compatible with a diagnosis of MC. Intrathecal chemotherapy was administered.
MC is a serious complication of systemic cancer patients, involving a poor prognosis. Early diagnosis is extremely important, although treatment is frequently aimed to reduce the symptoms and extend survival. Eye symptoms may be the chief complaint, so MC should be considered in any patient with vision loss or diplopia accompanied by neurologic symptoms and in the absence of an intraocular cause, especially in the context of systemic cancer.
Meningeal carcinomatosis (MC) is a rare and severe complication of a number of neoplastic processes. Hematologic tumors are the most frequent cause of MC, particularly acute lymphoblastic leukemia and non-Hodking lymphoma. Among solid tumors, the most frequent causes of MC are breast and lung adenocarcinoma as well as melanoma. The incidence of this complication is around 3% in breast cancer, 7% in lung cancer and 1.5% in melanoma . MC is the first manifestation of systemic cancer in only 5-10% of patients, although it is frequently seen in patients with disseminated systemic disease [2, 3].
MC occurs when tumor cells reach the leptomeningeal space either through the blood, the cerebrospinal fluid (CSF) or by growing along nerve and vascular sheaths. As a consequence, most patients present with different multifocal neurological symptoms that may involve the cranial nerves (oculomotor, facial, cochlear and optic), the spine and the cerebrum [3, 4]. Ocular symptoms were first reported by Katz, being diplopia and vision loss the most frequent ocular complaints [1, 5].
Early diagnosis and treatment are usually very complicated. Magnetic resonance imaging (MRI) is more sensitive than computed tomography (CT) scan in detecting brain meningeal dissemination, although the spine should also be assessed by MRI or CT myelography . MRI may show focal or diffuse leptomeningeal enhancement as well as tumoral lesions . However, these findings are non-specific, and should be evaluated in the particular clinical context. On the other hand, CSF analysis should be performed in all patients with suspected MC. Malignant cells are detected in the CSF in only 50% of patients with MC in the first lumbar puncture . Therefore, repeated CSF sampling is usually needed. Finally, the CSF protein concentration (50 mg/dl) and the opening CSF pressure (>25 cm H2O) are frequently elevated, whereas the glucose concentration (<60 mg/dl) is usually decreased.
Differential diagnosis should include inflammatory processes (rheumatoid arthritis, eosinophilic granuloma), infections, granulomatous infiltrations (sarcoid, tubercular), previous administration of chemotherapy, venous thrombosis, subarachnoid haemorrhage, trauma and previous intracranial surgeries .
MC is associated with a bad prognosis with a mean survival rate of 3–6 months . Treatment aims to extend survival and stabilize or improve neurological symptoms . Surgical treatment includes the placement of a ventriculoperitoneal shunt in patients with symptomatic hydrocephalus, although these patients have very poor prognosis [11, 12]. Involved-field radiotherapy may also be applied to patients with MC, although it does not commonly achieve a prolonged survival . On the other hand, intrathecal or ventricular administered chemotherapy is a more selective and less toxic treatment for patients with MC . Methotrexate, cytosine arabinoside and thiotepa are the most frequent drugs, although other substances have been tested in several clinical trials .
A 66-year old white man with a history of benign prostatic hyperplasia and tuberculosis, presented to the Ophthalmology Department complaining of double vision, non-intense headaches and dizziness episodes from two months ago. The patient was diagnosed fours month ago of stage IV lung adenocarcinoma with pericardial and bone metastases, in treatment with Alimta plus Carboplatin and Zoledronic Acid. Brain MRI performed four days ago showed no brain lesions.
MC is becoming a relatively frequent complication secondary to systemic cancer patients, as a consequence of better survival rates . MC occurs when tumor cells disseminate and grow in the leptomeningeal space and/or the cerebrospinal fluid (CSF). Consequently, these patients may present with different multifocal neurological symptoms. As demonstrated in this case, our patient complained of double vision as well as headaches and dizziness episodes. Furthermore, funduscopy revealed an evident bilateral papilledema that in association with a metastatic lung adenocarcinoma clearly orientated the diagnosis towards a neurologic process. In these cases, early diagnosis is important, although treatment is intended to reduce the symptoms and at best extend survival, especially when neurologic symptoms are already present .
Currently, diagnostic approach to ascertain MC requires performing cranial and spinal MRI, CSF cytology, CSF flow analysis and CSF glucose and protein concentration . In first place, a CT scan was performed and it showed no brain lesions. In contrast, brain MRI, which is more sensitive that CT for detecting brain meningeal dissemination, showed a diffuse leptomeningeal enhancement, which was compatible with the diagnosis of MC. On the other hand, spinal MRI was completely normal. In second place, CSF cytology showed several malignant aggregated cells in the sample. However, in some other cases where there is a clinically suspected MC and negative CSF cytology, different tumour-specific markers may be evaluated . Finally, CSF flow analysis revealed an elevated intracranial pressure, a high protein concentration and a low glucose concentration. Accordingly, diagnosis of MC was made based on the clinical symptoms and the test results.
The patient received treatment for MC with intrathecal methotrexate, which was further administered on a weekly basis until CSF cytology became negative after five weeks. Then, treatment was administered every three weeks. Although systemic chemotherapy at high doses could be useful in this case, intrathecal chemotherapy allows a better distribution throughout the subarachnoid space with less systemic toxicity . After 1.5 months of treatment, the patient referred stabilization of the neurological symptoms, including diplopia. Intrathecal methotrexate acts by inhibiting the metabolism of folic acid. Therefore, inhibits the synthesis of DNA, RNA, thymidylates, and proteins, having a greater toxic effect on rapidly dividing cells. Thus, methotrexate was effective in this case by reducing the uncontrolled local growth of tumoral cells that were responsible for diplopia and other neurological symptoms.
In conclusion, ocular symptom(s) may be the chief complaint of MC. For that reason, leptomeningeal carcinomatosis should be considered in any patient with ocular symptoms in the absence of an intraocular cause, particularly in the setting of disseminated cancer.
Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.
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