DOI: 10.1148/radiol.2473050507
(Radiology 2008;247:905-909.)
© RSNA, 2008
Case 134: Primary Leptomeningeal Melanomatosis1
Mustafa Kemal Demir, MD,
Fugen Vardar Aker, MD,
Okan Akinci, MD and
Asu Özgültekin, MD
1 From the Departments of Radiology (M.K.D., O.A.), Pathology (F.V.A.), and Reanimation (A.O.), Haydarpasa Numune Education and Research Hospital, Istanbul, Turkey. Received March 27, 2005; revision requested May 20; revision received May 29; accepted June 21; final version accepted August 25.
Correspondence: Address correspondence to M.K.D., 11 kisim, Yasemin Apt, D blok, Daire 35 Ataköy, Istanbul, Turkey 34158 (e-mail: demirkemal{at}superonline.com).
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HISTORY
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A 32-year-old man was admitted to the hospital with headache, vomiting, and complex partial seizures. Thirty weeks earlier, he had undergone ventriculoperitoneal (VP) shunt placement to treat hydrocephalus that had been diagnosed with cranial magnetic resonance (MR) imaging. Hydrocephalus was the only abnormality present. During the 30-week interval, two consecutive whole-spine MR examinations were performed 8 weeks apart at different institutions. Neurologic examination revealed mild decreased consciousness, papilledema, and deficits in cranial nerves III, IV, V, and VII. The patient was afebrile, and physical examination revealed no other abnormalities. The findings of laboratory tests, including extensive cerebrospinal fluid studies, were unremarkable. Cranial computed tomography (CT) was performed.
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IMAGING FINDINGS
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Cranial MR imaging performed 30 weeks before this patient was admitted to the hospital revealed hydrocephalus, with dilatation of the third and lateral ventricles. The brain, upper cervical spinal cord, and subarachnoid space were otherwise normal. MR imaging of the whole spine performed 12 weeks after placement of the VP shunt revealed diffuse irregular involvement along the surfaces of the lower brainstem and the spinal cord that obscured the subarachnoid space. The involvement showed punctuate hyperintensities on an unenhanced sagittal T1-weighted fast spin-echo MR image (Fig 1a) and diffuse irregular and intense subarachnoid enhancement on a contrast-enhanced sagittal T1-weighted fast spin-echo MR image (Fig 1b). There were also serpiginous low-signal-intensity areas along the dorsal surface of the spinal cord that were caused by enlargement of the dorsal venous plexus.
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Figure 1a: Midline sagittal (a) unenhanced and (b) contrast material–enhanced (20 mL of gadopentetate dimeglumine [Magnevist; Schering, Berlin, Germany]) T1-weighted fast spin-echo MR images (repetition time msec/echo time msec, 566/10) of the cervical spine obtained 12 weeks after VP shunt placement. In a, punctuate irregular hyperintensities (black arrows) along the surfaces of the lower brainstem and the cervical and upper thoracic spinal cord can be seen. There are also serpiginous low-signal-intensity areas along the dorsal surface of the spinal cord that represent enlargement of the dorsal venous plexus (white arrows). In b, diffuse irregular and intense enhancement (arrowheads) of the subarachnoid space along the surfaces of the lower brainstem and the cervical and upper thoracic spinal cord can be seen. The unenhanced hypointense areas along the dorsal surface of the spinal cord within the dorsal area of the diffuse surface enhancement represent enlargement of the dorsal venous plexus (arrows).
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Figure 1b: Midline sagittal (a) unenhanced and (b) contrast material–enhanced (20 mL of gadopentetate dimeglumine [Magnevist; Schering, Berlin, Germany]) T1-weighted fast spin-echo MR images (repetition time msec/echo time msec, 566/10) of the cervical spine obtained 12 weeks after VP shunt placement. In a, punctuate irregular hyperintensities (black arrows) along the surfaces of the lower brainstem and the cervical and upper thoracic spinal cord can be seen. There are also serpiginous low-signal-intensity areas along the dorsal surface of the spinal cord that represent enlargement of the dorsal venous plexus (white arrows). In b, diffuse irregular and intense enhancement (arrowheads) of the subarachnoid space along the surfaces of the lower brainstem and the cervical and upper thoracic spinal cord can be seen. The unenhanced hypointense areas along the dorsal surface of the spinal cord within the dorsal area of the diffuse surface enhancement represent enlargement of the dorsal venous plexus (arrows).
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Spinal MR images obtained at 20-week follow-up revealed progression of diffuse leptomeningeal involvement with superficial spinal cord invasion (Fig 2). The sagittal T2-weighted MR image obtained at 20-week follow-up showed a diffuse irregular heterogeneous mainly hypointense mass occupying the leptomeninges of the spinal cord (Fig 2c). There was also a high-signal-intensity mass in the cervical spinal cord that possibly indicated edema from spinal cord compression or invasion, disease extending down the central canal, or a combination of these factors (Fig 2c). The flow void areas of venous engorgement adjacent to the high-signal-intensity cerebrospinal fluid along the dorsal surface of the spinal cord also showed signs of progression (Fig 2c).
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Figure 2a: (a, b) Midline sagittal (a) unenhanced and (b) contrast-enhanced T1-weighted fast spin-echo MR images (566/10) of the cervical spine obtained 20 weeks after VP shunt placement. In a, progression of the diffuse irregular and heterogeneous hyperintensities (arrows) along the surfaces of the lower brainstem and the cervical and upper dorsal spinal cord with superficial invasion is visible. The serpiginous low-signal-intensity areas along the dorsal surface of the spinal cord that represent enlargement of the dorsal venous plexus (arrowheads) show progression. In b, progression of the diffuse irregular and intense enhancement of the subarachnoid space with superficial spinal cord invasion (arrows) is visible. The unenhanced hypointense areas caused by venous engorgement (arrowheads) along the dorsal surface of the spinal cord show progression. (c) Midline sagittal T2-weighted fast spin-echo MR image (2600/90) of the cervical vertebrae (C2 through C7 [2–7]) obtained 20 weeks after VP shunt placement shows a diffuse irregular and heterogeneous mainly hypointense mass (arrows) occupying the leptomeninges of the spinal cord. The flow void areas of venous engorgement adjacent to the high-signal-intensity cerebrospinal fluid along the dorsal surface of the spinal cord show progression (white arrowheads). There is also high signal intensity (black arrowheads) in the cervical spinal cord, which probably indicates edema due to spinal cord compression or invasion, disease extending down the central canal, or some combination of these factors.
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Figure 2b: (a, b) Midline sagittal (a) unenhanced and (b) contrast-enhanced T1-weighted fast spin-echo MR images (566/10) of the cervical spine obtained 20 weeks after VP shunt placement. In a, progression of the diffuse irregular and heterogeneous hyperintensities (arrows) along the surfaces of the lower brainstem and the cervical and upper dorsal spinal cord with superficial invasion is visible. The serpiginous low-signal-intensity areas along the dorsal surface of the spinal cord that represent enlargement of the dorsal venous plexus (arrowheads) show progression. In b, progression of the diffuse irregular and intense enhancement of the subarachnoid space with superficial spinal cord invasion (arrows) is visible. The unenhanced hypointense areas caused by venous engorgement (arrowheads) along the dorsal surface of the spinal cord show progression. (c) Midline sagittal T2-weighted fast spin-echo MR image (2600/90) of the cervical vertebrae (C2 through C7 [2–7]) obtained 20 weeks after VP shunt placement shows a diffuse irregular and heterogeneous mainly hypointense mass (arrows) occupying the leptomeninges of the spinal cord. The flow void areas of venous engorgement adjacent to the high-signal-intensity cerebrospinal fluid along the dorsal surface of the spinal cord show progression (white arrowheads). There is also high signal intensity (black arrowheads) in the cervical spinal cord, which probably indicates edema due to spinal cord compression or invasion, disease extending down the central canal, or some combination of these factors.
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Figure 2c: (a, b) Midline sagittal (a) unenhanced and (b) contrast-enhanced T1-weighted fast spin-echo MR images (566/10) of the cervical spine obtained 20 weeks after VP shunt placement. In a, progression of the diffuse irregular and heterogeneous hyperintensities (arrows) along the surfaces of the lower brainstem and the cervical and upper dorsal spinal cord with superficial invasion is visible. The serpiginous low-signal-intensity areas along the dorsal surface of the spinal cord that represent enlargement of the dorsal venous plexus (arrowheads) show progression. In b, progression of the diffuse irregular and intense enhancement of the subarachnoid space with superficial spinal cord invasion (arrows) is visible. The unenhanced hypointense areas caused by venous engorgement (arrowheads) along the dorsal surface of the spinal cord show progression. (c) Midline sagittal T2-weighted fast spin-echo MR image (2600/90) of the cervical vertebrae (C2 through C7 [2–7]) obtained 20 weeks after VP shunt placement shows a diffuse irregular and heterogeneous mainly hypointense mass (arrows) occupying the leptomeninges of the spinal cord. The flow void areas of venous engorgement adjacent to the high-signal-intensity cerebrospinal fluid along the dorsal surface of the spinal cord show progression (white arrowheads). There is also high signal intensity (black arrowheads) in the cervical spinal cord, which probably indicates edema due to spinal cord compression or invasion, disease extending down the central canal, or some combination of these factors.
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Unenhanced CT scans of the brain obtained at admission revealed diffuse meningeal hyperattenuation of cisterns, sylvian fissures, and sulci with basal predominance (Fig 3a). These areas showed intense contrast material enhancement (Fig 3b). No parenchymal lesion was detected.
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Figure 3a: (a) Unenhanced and (b) contrast-enhanced (100 mL iopromide, Ultravist 300; Schering) transverse CT scans obtained at the level of the basal cisterns at admission. In a, diffuse meningeal hyperattenuation of the cisterns (long arrows), sylvian fissures (arrowheads), and sulci (short arrow) is visible. No parenchymal lesion is seen. In b, extensive enhancement of the cisterns (long arrows), sylvian fissures (arrowheads) and sulci (short arrow) is visible. No parenchymal lesion is seen.
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Figure 3b: (a) Unenhanced and (b) contrast-enhanced (100 mL iopromide, Ultravist 300; Schering) transverse CT scans obtained at the level of the basal cisterns at admission. In a, diffuse meningeal hyperattenuation of the cisterns (long arrows), sylvian fissures (arrowheads), and sulci (short arrow) is visible. No parenchymal lesion is seen. In b, extensive enhancement of the cisterns (long arrows), sylvian fissures (arrowheads) and sulci (short arrow) is visible. No parenchymal lesion is seen.
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DISCUSSION
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Included in the differential diagnosis of diffuse involvement of meninges and subarachnoid space are infectious, inflammatory, or neoplastic processes and hemorrhage of various origins. Infectious causes of diffuse involvement of meninges and the subarachnoid space include bacterial, viral, fungal, and parasitic agents. Meningitis secondary to involvement with collagen vascular disease, sarcoidosis, and Wegener granulomatosis is considered an inflammatory process. The diffuse irregular and intense contrast enhancement of the subarachnoid space with basal predominance but without any parenchymal lesion and the irregular and continuous involvement of leptomeninges of the spinal cord make one consider aggressive behavior of a neoplastic condition rather than inflammatory or infectious processes. Although granulomatous diseases—such as tuberculosis, sarcoidosis, or Wegener granulomatosis—may be associated with irregular and intense contrast enhancement of the leptomeninges, including nodularities, they usually have characteristic brain parenchymal involvements, brain systemic involvements, or both, together with certain clinical and laboratory findings (1–3). Moreover, the few punctate high-signal-intensity areas along the ventral upper cervical spinal cord on unenhanced T1-weighted images are indicative of a melanin-containing disease rather than an inflammmatory or infectious process. In this case, these findings constituted the best clues for arriving at a diagnosis (Fig 1a). On unenhanced MR images, T1-weighted hyperintensities in the subarachnoid space together with enhancement rarely occur in patients with proteinaceous diseases. In these patients, neither T1-weighted hyperintensities nor enhancement of the leptomeninges is a prominent finding (4). On the basis of clinical symptoms, laboratory study results, and imaging findings, the diagnosis of any infectious or inflammatory disease is unlikely.
The diffuse enhancement of the subarachnoid space on MR and CT images is used to easily exclude the possibility of an isolated subarachnoid hemorrhage or another hemorrhagic lesion, such as superficial hemosiderosis, which does not fit the profile of the current case.
The marked worsening degree of venous engorgement, which is the important feature seen on this patient's spinal MR images, points to progressing spinal cord compression elsewhere in the spinal column resulting from the extensive leptomeningeal mass lesions; therefore, it is important to examine the entire spine to find the cause. Although dural arteriovenous fistula or any arteriovenous malformation can cause venous engorgement, these entities do not have extensive enhancing spinal cord compression and typically would not result in unenhanced T1-weighted hyperintensity on the spinal cord surface or hydrocephalus and cranial neuropathy at presentation.
Neoplastic processes that involve the leptomeninges are usually malignant, and metastatic leptomeningeal carcinomatosis is considerably more common than primary tumors. Primary sites of solid tumors that frequently spread to the leptomeninges include the breast, lungs, stomach, and genitourinary system, as well as melanomas. Hematologic neoplasms, such as leukemia and lymphoma, are also prone to cerebrospinal fluid dissemination. Central nervous system primary tumors—such as medulloblastoma or primitive neuroectodermal tumor, ependymoma, germ cell tumor, astrocytoma, and glioblastoma—also tend to metastasize to the leptomeninges (5). The radiologic appearance of meningeal carcinomatosis is usually patchy or nodular. In this patient, no primary tumor or hematologic disorder was identified.
Primary leptomeningeal tumors that may contain melanin include pigmented meningioma, melanotic schwannoma, diffuse melanosis, meningeal melanocytoma, and a meningeal variant of primary malignant melanoma, which is also known as primary leptomeningeal melanomatosis (PLM) (6,7). Although pigmented forms of meningiomas and schwannomas are rarely encountered, these well-known entities are not considered in the differential diagnosis of diffuse involvement of the subarachnoid space without a primary localized mass.
Diffuse melanosis or neurocutaneous melanosis is a rare congenital disease characterized by the presence of large or multiple congenital melanocytic nevi and benign or malignant melanocytic tumors of the leptomeninges (8). The MR findings of neurocutaneous melanosis are variable and include hyperintense areas in the temporal lobe on unenhanced T1-weighted images without leptomeningeal enhancement, diffuse leptomeningeal enhancement of the brain and spine, and an extensive mass of malignant melanoma. Within the first 2 years of life, most of these patients develop neurologic manifestations of increased intracranial pressure, seizures, ataxia, and—on occasion—deficits of cranial nerves VI and VII (9,10). The absence of melanocytic nevus and any parenchymal mass in either the brain or the spine militates against the diagnosis of neurocutaneous melanosis.
Meningeal melanocytoma and PLM originate from leptomeningeal melanocytes, which normally are found in the pia arachnoid of the base of the brain, the caudal medulla, or the cervical spinal cord. They actually represent the two ends of the spectrum, ranging from a lesion that is benign in appearance and behavior to one that is malignant in appearance and behavior. However, neither of these entities is associated with pigmented lesions elsewhere, including benign congenital pigmented nevi or frank cutaneous malignant melanoma, as in the current case.
Meningeal melanocytomas may occur at any age. They are usually unilocular, partly encapsulated melanotic tumors, and they appear as nodes attached to the pia mater. They are mainly located in the posterior cranial fossa or the spinal canal (6,11,12). The localized form of this disease may not be distinguished from pigmented meningioma, pigmented schwannoma, or malignant melanoma. Although the clinical features and MR imaging signal intensity characteristics strongly suggest a diagnosis of meningeal melanocytoma, its benign nature and solitary localized form make this diagnosis less likely. The uncommon variant of meningeal melanocytoma with concomitant involvement of the intracranial and intraspinal meninges, also called melanocytosis, must be considered in the differential diagnosis. Unless malignant transformation occurs, the irregular diffuse contrast enhancement pattern with superficial invasion does not make melanocystosis a likely diagnosis (12).
PLM is a rare and highly aggressive neoplasm of the central nervous system, and patients with this disease have a poor prognosis (13,14). This disease is more common in adults than in children. Patients with this disease present with variable symptoms, such as seizures, psychiatric disturbances, cranial nerve palsies, or signs of increased intracranial pressure—including headache, vomiting, papilledema, and deterioration of consciousness (15). Patients with PLM usually have slightly increased signal intensity on T1-weighted images and decreased signal intensity on T2-weighted images, compared with that of the spinal cord. The signal intensity features of melanoma on T1- and T2-weighted images are thought to be caused by the paramagnetic stable free radicals that exist within melanin or the paramagnetic products of hemorrhage (16–18). Although the pigmented tumors may have varied appearances on MR images because of their different degrees of melanin, the identification of T1-weighted shortening on MR images is one of the important imaging clues that leads to the diagnosis of PLM (19). The other important MR imaging finding is the continuous and irregular contrast enhancement pattern with the superficial invasion of parenchyma from the base of the brain to the end of the spinal cord. This feature demonstrates the aggressive behavior of this malignant disease (20). It may involve the spinal cord without any skip area (Fig 4), and it may cause myelopathy due to compression of the spinal cord or involvement of the vessels, as in this patient. In this case, the MR imaging findings and laboratory results combined with the patient's progresive symptoms made PLM the most likely diagnosis.
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Figure 4: Contrast-enhanced sagittal T1-weighted fast spin-echo MR image (566/10) of the thoracic spine obtained through the midline 20 weeks after VP shunt placement shows diffuse irregular and continuous leptomeningeal enhancement, without any skip area down to the level of the conus medullaris. There is superficial invasion (black arrows) of the spinal cord. The flow void areas of venous engorgement along the dorsal surface of the spinal cord are also visible (white arrow).
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This patient's condition worsened progressively, and he died a week after he was admitted to our hospital. Autopsy was performed, and the final diagnosis was PLM. Macroscopic appearances of the tumorlets ranged from dark brown to black. Histopathologic examination revealed that the subarachnoid space was filled with melanoma cells. The superficial cerebral parenchyma was directly infiltrated. Malignant melanoma was not found in other parts of the body.
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FOOTNOTES
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Part one of this case appeared 4 months previously and may contain larger images.
Authors stated no financial relationship to disclose.
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References
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- Sagiuchi T, Ishii K, Utsuki S, et al. Increased uptake of technetium-99m-hexamethylpropyleneamine oxime related to primary leptomeningeal melanoma. AJNR Am J Neuroradiol 2002;23:1404–1406.[Abstract/Free Full Text]
- Yamasaki T, Kikuchi H, Yamashita J, Asato R, Fujita M. Primary spinal intramedullary malignant melanoma: case report. Neurosurgery 1989;25:117–121.[Medline]
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- Farrokh D, Fransen P, Faverly D. MR findings of a primary intramedullary malignant melanoma: case report and literature review. AJNR Am J Neuroradiol 2001;22:1864–1866.[Abstract/Free Full Text]
- Isiklar I, Leeds NE, Fuller GN, Kumar AJ. Intracranial metastatic melanoma: correlation between MR imaging characteristics and melanin content. AJR Am J Roentgenol 1995;165:1503–1512.[Abstract/Free Full Text]
- Rosenthal G, Gomori JM, Tobias S, Diment J, Shoshan Y. Unusual cases involving the CNS and nasal sinuses: case 1—primary leptomeningeal melanoma. J Clin Oncol 2003;21:3875–3877.[Free Full Text]
Congratulations to the nine individuals who submitted the most likely diagnosis (primary leptomeningeal melanomatosis) for Diagnosis Please, Case 134. The names and locations of the individuals, as submitted, are as follows:
- Marc G. De Baets, MD, Collina d'Oro, Switzerland
- Waleed M. Ibrahim, MD, Columbus, Ohio
- Stefanos Lachanis, MD, Athens, Greece
- Manabu Minami, MD, PhD, Yokohama, Japan
- Jose Mondello, MD, Buenos Aires, Argentina
- Ryan P. Rebello, MD, Dundas, Ontario, Canada
- Tsutomu Sakamoto, MD, Tokyo, Japan
- Taro Shimono, MD, Osaka, Sayama, Japan
- Kazuma Terauchi, Fujieda, Shizuoka, Japan
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HISTORY
IMAGING FINDINGS
