Cognitive decline in an elderly hospitalized patient with primary leptomeningeal melanomatosis.

Abstract: Delirium is one of the most common disorders in hospitalized patients. The authors present the case of an elderly male patient with postoperative cognitive decline that did not resolve with the conventional treatment. The diagnosis was only established on autopsy. A 75-year-old man was evaluated after a fall. Initial evaluation revealed voluntary guarding in the right epigastric region, and free air was detected under the right hemidiaphragm on abdominal radiography. An exploratory laparotomy revealed a perforation that had apparently sealed off. After surgery, he had initial improvement toward baseline; however, after several days, his postoperative course was complicated by a progressive deterioration in mental status, recurrent seizures, and aspiration pneumonia. Computed tomographic scan of the brain showed communicating hydrocephalus. Examination of the cerebrospinal fluid revealed an elevated opening pressure and elevated protein. His mental status continued to deteriorate, and he died. Autopsy revealed the pathologic diagnosis of primary leptomeningeal melanomatosis.

Key Words: altered mental status, primary leptomeningeal melanomatosis

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Delirium is one of the most common disorders encountered in hospitalized patients with medical or surgical illness, particularly among the elderly. It is associated with many complex underlying medical conditions and can be difficult to recognize. The differential diagnosis for postoperative cognitive decline is extensive, with delirium being the most common consideration. Increasing age, duration of anesthesia, repeat operation, infections, and respiratory complications are risk factors for early postoperative cognitive dysfunction. In a patient with a prolonged course of delirium, who does not improve with conventional treatment, and with nondiagnostic clinical assessment and imaging, less common pathologies should be considered. Primary leptomeningeal melanomatosis is a rare variant of malignant melanoma of the central nervous system that arises directly from the melanocytes within the leptomeninges. We report a case of primary leptomeningeal melanomatosis in a 75-year-old male who presented with postoperative cognitive decline. Despite the use of advanced neuroimaging and cerebrospinal fluid cytology, the disease can be difficult to recognize. In this case, the diagnosis was made only at postmortem neuropathologic examination.

Case Report

A 75-year-old male with a history of Alzheimer dementia presented with a decline in mental status after a fall. His history included a seizure disorder. Medications at admission were rivastigmine, valproic acid, olanzapine, and trazodone. On initial evaluation, he was afebrile with stable vital signs, but was noted to be thin and malnourished. There were no pigmented lesions on the skin. Voluntary guarding was elicited in the right epigastric region, and free air was detected under the right hemidiaphragm on abdominal radiography. An exploratory laparotomy revealed significant diverticular disease of the sigmoid colon, and a perforation that had apparently sealed off. After surgery, he had initial improvement toward baseline. However, after several days, his postoperative course was complicated by a progressive deterioration in mental status, recurrent seizures, and aspiration pneumonia. Seizures were controlled with dilantin, and electroencephalography did not reveal any evidence of epileptiform activity. A computed tomographic scan of the brain showed prominence of the ventricular system and cisterns, raising the possibility of communicating hydrocephalus (Fig. 1). Examination of the cerebrospinal fluid (CSF) revealed clear, colorless fluid with an elevated opening pressure of 240 mm Hg and elevated CSF protein of 153 mg/dL (normal, 15 to 45 mg/dL). CSF serology and cultures for viral, bacterial, and fungal infections were negative. He was aggressively treated with antibiotics, with resolution of pneumonia clinically and radiologically. His mental status continued to worsen, and 35 days after his initial admission, he died.

Pathologic Findings

On gross examination of the brain, there was extensive grayish staining over the entire epidural surface (Fig. 2). The arachnoid was milky in appearance. On microscopic examination, all sections of the brain showed infiltration of the arachnoid and many penetrating Virchow-Robin spaces by spindle cells with dark red pigment (Fig. 3). There were no intravascular or intracerebral metastases, but the cranial nerves, cerebellum, and medulla were surrounded by tumor, revealing the pathologic diagnosis of primary leptomeningeal melanomatosis.

Discussion

Pigmented lesions of the leptomeninges includes pigmented meningioma, metastatic malignant melanoma, primary malignant melanoma, meningeal melanocytoma, melanotic schwannoma, and melanoblastosis. (1,2) These are rare lesions arising from normally occurring leptomeningeal constituents. (3) Primary leptomeningeal melanomatosis, a rare variant of primary malignant melanoma, results from the spread of malignant melanocytes into the leptomeninges and Virchow-Robin spaces, with superficial invasion of the brain. The tumor is derived from leptomeningeal melanocytes, which have a neuro-ectodermal origin, as do cutaneous melanocytes. Leptomeningeal melanocytes are normally found in the pia arachnoid, which covers the base of the brain, the caudal medulla, and cervical spinal cord. Clinically, the antemortem diagnosis may be established by means of CSF cytology. Nevertheless, the isolated neoplastic cells in the CSF can easily escape recognition. Primary leptomeningeal melanomatosis may mimic other conditions such as lymphomatous, leukemic, or carcinomatosis meningitis, subacute and chronic meningitis, viral encephalitis, and idiopathic hypertrophic cranial pachymeningitis.

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The clinical presentation in our patient, with cognitive decline and cranial nerve involvement, in retrospect can clearly be attributed to the diffusion of the disease. An increased CSF protein combined with raised intracranial pressure, as in our case, indicates a possible neoplastic process. The raised CSF pressure in this case probably was due to tumor-mediated obstruction of CSF drainage. The increased CSF protein concentration also may have contributed to the high-pressure state and neoplastic infiltration. (4) On radiologic examination, there was communicating hydrocephalus, which was due to the infiltration of the arachnoid villi. Elevated CSF opening pressure, increased protein, and communicating hydrocephalus should arouse the suspicion of a process impairing drainage of CSF. If CSF cytology is negative, then meningeal or brain biopsy is the only definitive test for identification of malignant melanoma cells. Magnetic resonance imaging can show diffuse dural and leptomeningeal contrast enhancement. (5,6)

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On pathologic grounds, the distinction of primary leptomeningeal melanomatosis from diffuse melanosis and melanocytoma must be made on the basis of topographic, gross, and histologic features. By histologic examination, this should be differentiated from metastatic malignant melanoma, which has localized presentation and extracerebral involvement. The diagnosis of primary leptomeningeal melanomatosis depends on the diffuse growth pattern and the absence of malignant melanoma elsewhere.

Conclusion

Postoperative cognitive decline should be extensively evaluated if there is no improvement with the conventional imaging or treatment options. As in the present case, the sequence of clinical, CSF, and radiologic findings should arouse the suspicion of primary malignant leptomeningeal melanomatosis in the differential diagnosis of elderly patients with progressive cognitive decline.

When you gaze long into the abyss, the abyss also gazes into you.
--Friedrich Nietzsche

Accepted April 7, 2004.

References

1. Litofsky NS, Zee CS, Breeze RE, Chandrasoma PT. Meningeal melanocytoma: diagnostic criteria for a rare lesion. Neurosurgery 1992;31:945-947.

2. Tatagiba M, Boker DK, Brandis A, et al. Meningeal melanocytoma of the C8 nerve root: case report. Neurosurgery 1992;31:958-961.

3. Aichner F, Schuler G. Primary leptomeningeal melanoma: diagnosis by ultrastructural cytology or cerebrospinal fluid and cranial computed tomography. Cancer 1982;50:1751-1756.

4. Kobayashi M, Hara K, Nakatsukasa M, et al. Primary spinal leptomeningeal gliomatosis presenting visual disturbance as the initial symptom. Acta Neurochir (Wien) 1996;138:480-481.

5. Pirini MG, Mascalchi M, Salvi F, et al. Primary diffuse meningeal melanomatosis: radiologic-pathologic correlation. AJNR Am J Neuroradiol 2003;24:115-118.

6. Painter TJ, Chaljub G, Sethi R, et al. Intracranial and intraspinal meningeal melanocytosis. AJNR Am J Neuroradiol 2000;21:1349-1353.

RELATED ARTICLE: Key Points

* Prolonged delirium in elderly patients should be evaluated cautiously.

* Malignancy of the structures of the brain can be included in the differential diagnosis.

* Abnormal imaging and cerebrospinal fluid findings should be correlated clinically, and rare pathologies should be considered.

Ravi Bobba, MD, and Edward Arsura, MD, FACP 

From the Department of Internal Medicine, Veterans Affairs Medical Center, University of Virginia, Roanoke-Salem Program, and the University of Virginia School of Medicine, Charlottesville, Salem, VA.

Financial support: None.

Reprint requests to Dr. Edward Arsura, University of Virginia School of Medicine, Veterans Affairs Medical Center, 1970 Roanoke Blvd, Salem, VA 24153. Email: [e-mail]