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AFIP ARCHIVES

1503

From the Archives of the AFIP
Pigmented Lesions of the Central
Nervous System: Radiologic-Pathologic
Correlation1
CME FEATURE
See accompanying
test at http://
www.rsna.org
/education
/rg_cme.html

LEARNING
OBJECTIVES
FOR TEST 6
After reading this
article and taking
the test, the reader
will be able to:
■■Describe

the clinical and pathologic
features of pigmented lesions of the
central nervous system (CNS).
■■Identify

the imaging characteristics of
pigmented lesions of
the CNS.
■■Discuss

the differential diagnosis of
pigmented lesions
of the CNS.

TEACHING
POINTS
See last page

Alice Boyd Smith, Lt Col, USAF MC • Elisabeth J. Rushing, COL, MC,
USA • James G. Smirniotopoulos, MD
Pigmented lesions of the central nervous system (CNS) are a diverse
group of entities that run the gamut from benign to malignant. These
lesions may be well circumscribed or diffuse, and their imaging appearances are influenced by the degree of melanin content as well as
the presence or absence of hemorrhage. Pigmented lesions include
primary melanocytic lesions of the CNS and metastatic melanoma,
as well as other CNS neoplasms that may undergo melanization, including schwannoma, medulloblastoma, and some gliomas. Primary
melanocytic lesions of the CNS arise from melanocytes located within
the leptomeninges, and this group includes diffuse melanocytosis and
meningeal melanomatosis (seen in neurocutaneous melanosis), melanocytoma, and malignant melanoma. Primary melanin-containing
lesions of the CNS must be differentiated from metastatic melanoma
because these lesions require different patient workup and therapy.
Absence of a known primary malignant melanoma helps in the differential diagnosis, but an occult primary lesion outside the CNS must
be sought and excluded. Pigmented lesions of the CNS are uncommon, and knowledge of their imaging characteristics and pathologic
features is essential for their identification.

radiographics.rsna.org

Abbreviations: CNS = central nervous system, CSF = cerebrospinal fluid
RadioGraphics 2009; 29:1503–1524 • Published online 10.1148/rg.295095109 • Content Code:
From the Departments of Radiologic Pathology (A.B.S.) and Neuropathology (E.J.R.), Armed Forces Institute of Pathology, Washington, DC; and
Department of Radiology and Radiological Sciences, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Rd, Bethesda, MD
20814 (A.B.S., J.G.S.). Received May 6, 2009; revision requested June 2 and received June 9; accepted June 9. All authors have no financial relationships to disclose. Address correspondence to A.B.S. (e-mail: ).
1

The opinions or assertions contained herein are the private views of the authors and are not to be construed as official nor as reflecting the views of
the Departments of the Army, Navy, or Defense.


1504  September-October 2009

Introduction

Teaching
Point

Teaching
Point

Melanocytes occur normally within the leptomeninges and are more concentrated at the base of
the brain and on the ventral surface of the cervical spinal cord. In these locations, pigmented
leptomeninges may be visible macroscopically at
surgery or autopsy. The number of these melanocytes is generally comparable to that found
in cutaneous pigmentation (1). Leptomeningeal
melanocytes, like their cutaneous counterparts,
are of neuroectodermal (neural crest) origin.

At magnetic resonance (MR) imaging, these
pigmented foci frequently demonstrate T1 and
T2 shortening, which is believed to be related to
the presence of melanin; if hemorrhage is present, it may also contribute to this finding. The
imaging characteristics of melanin are thought to
be caused by the presence of paramagnetic free
radicals (indole semiquinones and semiquinones)
(2,3). Interaction of the unpaired electrons in
melanin with water protons results in dipoledipole interactions, which lead to the T1 and T2
shortening (4). Gebarski and Blaivas (1) demonstrated radiologic-pathologic correlation of leptomeningeal melanocytes by showing that these
normal deposits of melanosomic melanin can
occasionally be seen as areas of T2 hypointensity
along the ventral aspect of the medulla oblongata where they tend to be most concentrated.
Occasionally, they noted that faint, spotty areas
of T1-weighted hyperintensity were observed on
normal images, but this finding did not correlate
well with the pigmentation seen at pathologic
evaluation (1). Infrequently, melanocytic lesions
may arise from these normal melanocytes.
Melanocytic neoplasms of the central nervous
system (CNS) are rare, and most frequently they
are metastatic in origin. Primary melanocytic lesions of the CNS may occur as discrete masses or
diffuse proliferations and include neurocutaneous
melanosis, meningeal melanocytoma, primary
leptomeningeal melanomatosis, and melanoma. It
is important to differentiate primary melanincontaining lesions of the CNS from metastatic
melanoma, because these lesions require a different patient workup and alternate therapeutic options. The absence of a known primary malignant
melanoma helps in the differential diagnosis; however, an occult primary lesion outside the CNS
must be sought and excluded. Other pigmented


radiographics.rsna.org

CNS lesions include neoplasms that may undergo
melanization, such as schwannoma, medulloblastoma, and glioma, as well as melanocytic neuroectodermal tumor of infancy, a rare pigmented
neoplasm that occurs in the first 2 years of life. In
this article, we review the clinical, imaging, and
pathologic findings of these rare lesions.

Neurocutaneous Melanosis

Neurocutaneous melanosis is a rare congenital
disorder characterized by the presence of large or
multiple congenital melanocytic cutaneous nevi
associated with intracranial leptomeningeal melanocytosis (5). It was first described in 1861 by
Rokitansky, who reported a case of a 14-year-old
girl with a congenital nevus and mental retardation who developed hydrocephalus (6). Since that
time, approximately 100 cases of neurocutaneous
melanosis have been reported in the literature
(6). Most cases are sporadic; the disorder typically occurs in Caucasians, and there is an equal
gender predilection (7,8). Deregulation of hepatocyte growth factor/scatter factor, a cytokine
that stimulates the proliferation, migration, and
morphogenesis of cultured epithelial cells, has
been implicated in the pathogenesis of the disorder because of its role in the distribution and
proliferation of melanocytes (6,9).
Current evidence indicates that neurocutaneous melanosis is a phakomatosis that results from
congenital dysplasia of the neuroectodermal melanocyte precursor cells, leading to proliferation of
melanin-producing cells in the skin and leptomeninges (10). Neurocutaneous melanosis has been
reported to be associated with other neurocutaneous syndromes such as Sturge-Weber syndrome
(11,12). An association with Dandy-Walker malformation (hypoplasia or absence of the cerebellar
vermis, hypoplasia of cerebellar hemispheres, large

fourth ventricle, and large posterior fossa) has
been reported in 8%–10% of children with neurocutaneous melanosis (13). The exact pathogenesis
for this association is unknown, but some suggest
that obstruction of the fourth ventricle by melanocytes may play a role, or that associated leptomeningeal anomalies affect the development of the cerebellum and fourth ventricle (14). However, the
most widely accepted hypothesis is that leptomeningeal melanosis interferes with the inductive
effects of primitive meningeal cells on deposition
of extracellular matrix, neuronal migration, and
formation of the normal basal cerebrospinal fluid
(CSF) resorption pathways (15,16). The prognosis


RG  ■  Volume 29  •  Number 5

Figure 1.  Photograph shows a newborn infant
with a giant congenital nevus that involves the
back, with multiple smaller satellite nevi.

for patients with Dandy-Walker malformation and
neurocutaneous melanosis is extremely poor, with
all reported patients dying by 4 years of age from
malignant transformation of the melanosis (15).
The leptomeningeal involvement in neurocutaneous melanosis differs from that seen in primary
melanoma of the meninges, which results in focal
pigmented lesions of the leptomeninges. The dura
mater is not typically affected, but involvement
of the cerebral parenchyma, choroid plexus, and
ventricular ependyma has been reported (17).
Parenchymal melanin deposits most likely represent melanocytes tracking along the perivascular
spaces. The anterior temporal lobe, particularly in
the region of the amygdala, is the most frequent

location for parenchymal melanocytic accumulation. Other sites include the cerebellum, thalami,
and base of the frontal lobe (5,17).
Patients with neurocutaneous melanosis have
multiple (more than three) pigmented nevi on
the head, neck, or dorsal spine, and two-thirds
of patients have a giant congenital “bathing
trunk” melanocytic nevus that typically affects
the lumbosacral region (Fig 1) (18). Giant congenital nevi occur in approximately one in 20,000
newborns and are defined as those that are ex-

Smith et al  1505

pected to grow to a diameter of at least 20 cm in
adulthood (19). Six percent to 11% of patients
with giant congenital nevi develop symptomatic
neurocutaneous melanosis, and those with nevi
involving the head, posterior neck, or paravertebral area are at the greatest risk (20,21). These
patients are also at risk for developing leptomeningeal melanoma and cutaneous melanoma (22).
Fox (23) proposed the original diagnostic
criteria for neurocutaneous melanosis in 1972.
Kadonaga and Frieden (24) revised the criteria,
which are as follows: large (currently or estimated to become no less than 20 cm in diameter
in adults or 6–9 cm in infants) or multiple (≥
three) congenital nevi associated with meningeal
melanosis or CNS melanoma; no evidence of
cutaneous melanoma; and no evidence of meningeal melanoma except in patients whose skin
examination reveals no malignant lesions.
In the first 2 years of life, patients with neurocutaneous melanosis typically develop neurologic
manifestations related to increased intracranial
pressure or seizures. In rare cases, symptoms

begin in adulthood, and some patients remain
asymptomatic (19,25,26). Hydrocephalus occurs
in the majority of patients and is related to either
meningeal thickening or CSF outflow obstruction
or decreased CSF reabsorption (7,17). Other
reported complications include subdural or parenchymal hemorrhage, syringomyelia, and spinal
arachnoiditis (7). Approximately 20% of patients
have spinal involvement and develop symptoms
of myelopathy, radiculopathy, or bowel or bladder
dysfunction (6). A second, smaller peak of symptom development occurs during puberty or the
young adult years (6). Patients who present later
in life may manifest with neuropsychiatric symptoms, including depression and psychosis (14).
The development of benign melanocytic proliferation of the leptomeninges has a poor prognosis,
and neither radiation therapy nor chemotherapy
improves the patient outcome (16). Patients with
neurocutaneous melanosis are reported to develop
malignant melanoma in approximately 40%–60%
of cases (23).) Faillace et al (27) have suggested
that malignant transformation is heralded by development of intraparenchymal invasion or intracranial or intraspinal masses. The majority of patients die within 3 years from benign overgrowth
of melanocytic cells or development of malignant
melanoma (6).


radiographics.rsna.org

1506  September-October 2009

Figure 2.  Neurocutaneous melanosis. (a) Photograph of the whole brain and upper spinal cord shows diffuse
brown pigmentation. (b) Photomicrograph (original magnification, ×120; hematoxylin-eosin stain) reveals that
the leptomeninges are populated by a neoplastic spindle cell proliferation containing melanin (arrows).


Figure 3.  Neurocutaneous melanosis
in a 2-year-old boy
with a history of seizure disorder. (a) Precontrast axial CT image demonstrates an
area of mild hyperattenuation along the
left Sylvian fissure
(arrow). The patient
also had hydrocephalus and a ventriculoperitoneal shunt was
recently placed (airfluid level in ventricle). (b) Postcontrast
axial CT image reveals leptomeningeal
enhancement.

Pathologic and Histologic Features
Gross examination of the brain reveals dense
black-brown discoloration overlying the affected
surfaces (Fig 2a), and areas of localized lesions
may demonstrate nodularity. At histologic examination, neurocutaneous melanosis resembles
cutaneous nevi, with polygonal cells with prominent nucleoli and cytoplasmic melanin (Fig 2b).
Invasion of the Virchow-Robin spaces is noted
(23). Results of immunohistochemical staining are also similar to those for cutaneous melanocytic lesions: negative for keratins or other
epithelial or glial markers and positive for S-100

protein (the marker for melanocytic and neuroepithelial differentiation) and HMB-45 (the
marker for melanocytic differentiation).

Imaging Appearance
Computed tomography (CT) is not optimal,
compared with MR imaging, for demonstrating
neurocutaneous melanosis. The foci of melanincontaining cells may appear only as subtle areas
of high attenuation. They are difficult to visualize

on CT images unless conversion to melanoma has
occurred (Fig 3a). Hydrocephalus may be present
and is thought to occur when extensive melanosis
is present. Leptomeningeal enhancement may be
seen on postcontrast CT images (ie, obtained after
administration of contrast material) (6) (Fig 3b).


RG  ■  Volume 29  •  Number 5

Smith et al  1507

Figure 4.  Neurocutaneous melanosis in a 14-year-old boy with transient palsies of the
seventh and eighth cranial nerves. (a) Axial T1-weighted image demonstrates T1 shortening (arrows) in both medial temporal lobes. (b) Postcontrast axial T1-weighted image
shows linear enhancement of the leptomeninges that is best seen along the midbrain. (c) Coronal fluid-attenuated inversion recovery (FLAIR) image demonstrates high signal intensity in
the sulci (arrowheads) and in the bilateral amygdalae (arrows). (d) Sagittal T2-weighted
image of the cervical and thoracic spine demonstrates an arachnoid cyst (arrow) at the
level of the midthoracic spine.

MR imaging findings of neurocutaneous melanosis include foci (typically 3 cm or less in size)
of T1 shortening within the brain parenchyma
and meninges. These foci are most commonly
found in the anterior temporal lobe (especially in
the region of the amygdala), cerebellar white matter, cerebellar nuclei, and the brainstem (Fig 4a).

Leptomeningeal enhancement has been reported
in cases of neurocutaneous melanosis (Fig 4b) and,
when associated with hydrocephalus, may suggest
diffuse leptomeningeal spread (5,17,28,29). The
presence of leptomeningeal or intraparenchymal



1508  September-October 2009

radiographics.rsna.org

Figure 5.  Neurocutaneous melanosis
in a 14-month-old boy with a history of
congenital hairy nevus (same patient as
in Fig 1) and Dandy-Walker syndrome.
Postcontrast sagittal T1-weighted image
demonstrates extensive leptomeningeal
enhancement and an enhancing mass
(*) in the posterior fossa, findings consistent with degeneration to malignant
melanoma. Note that the brainstem is
compressed against the clivus (arrow)
because of the posterior fossa cyst and
the enhancing mass.

Figure 6.  Melanocytoma in a 37-year-old man with headaches. (a, b) Axial T1-weighted (a)
and axial T2-weighted (b) images demonstrate a solitary mass lesion that involves the posterior
fossa and Meckle cave; the mass exhibits T1 and T2 shortening. (c) Postcontrast T1-weighted
image shows avid enhancement of the lesion. (d) Intraoperative photograph reveals the darkly
pigmented lesion.


RG  ■  Volume 29  •  Number 5

Smith et al  1509


Figure 7.  Intramedullary melanocytoma in a 59-year-old man with numbness in his right arm for 5 months.
(a) Sagittal T2-weighted image demonstrates an intramedullary lesion with T2 shortening at the level of C2-3,
with surrounding edema and hydrosyringomyelia. (b) Sagittal T1-weighted image without contrast material enhancement shows T1 shortening within the lesion. (c) Intraoperative photograph shows the darkly pigmented,
intramedullary lesion.

Teaching
Point

lesion enhancement has been thought to correlate
with malignant degeneration; however, at least one
report has contradicted this hypothesis, and some
authors have suggested that focal nodular or thick
plaquelike enhancement may be more indicative
of malignant degeneration (15,28). If malignant
melanoma develops, a mass lesion may be seen.
Hayashi et al (30) reported a case in which leptomeningeal hyperintensity was seen on the T2
FLAIR images; the authors speculated that either
the high protein concentration within the CSF or
the T1 shortening effect of malignant melanoma
may contribute to the observed hyperintensity. The
parenchymal foci may also appear hyperintense on
T2 FLAIR images (Fig 4c) (30). Hypoplasia of the
cerebellum and pons may be seen and is usually
associated with melanosis in these locations (5,31).
Associated spinal and intracranial arachnoid cysts
and spinal lipomas have been described (Fig 4d)
(32,33). Degeneration into malignant melanoma
is indicated by progressive growth, surrounding
vasogenic edema or mass effect, or development of
central necrosis (Fig 5) (5).


Meningeal Melanocytoma

Meningeal melanocytomas are rare, pigmented,
slow-growing, and typically benign neoplasms
that arise from the normal melanocytic cells of
the leptomeninges; however, malignant behavior
of these tumors has been reported (34). Limas

and Tio (35) first described these lesions in 1972;
before this, they were referred to as melanotic
meningioma. Approximately 110 cases of meningeal melanocytoma have been reported (34,36).
The annual incidence of meningeal melanocytoma is estimated to be one case per 10 million
population, and females are affected more often
than males (37). Meningeal melanocytomas may
manifest at any age, but most patients are in the
5th decade of life.
The clinical signs and symptoms associated
with these lesions depend on their location and include myelopathy, radiculopathy, cranial nerve deficits, seizures, and hydrocephalus (34). Meningeal
melanocytomas are predominantly located in the
posterior cranial fossa, Meckle cave, or cervical
and thoracic spinal canal, probably because of the
normally higher density of melanocytes in these
locations (Fig 6). These tumors are usually solitary
(38). In rare cases, spinal intramedullary tumors
are observed (Fig 7). Supratentorial lesions also
are rare, with approximately 25 cases reported in
the literature (39). A thorough physical examination of the patient is required to rule out a primary
cutaneous, ocular, or mucosal melanoma, especially because the histologic characteristics of melanocytoma and melanoma overlap.



1510  September-October 2009

Figure 8.  Melanocytoma in a 64-yearold woman with a
2-week history of
right-sided headaches.
(a) Photograph of
a gross specimen
demonstrates a
well-circumscribed,
reddish-brown lesion with a dural
attachment (arrow).
(b) Photomicrograph
(original magnification, ×200; hematoxylin-eosin stain)
shows a cellular neoplasm with the cells
arranged in “nests”
(arrows). Mitotic figures are absent, and
no pigmentation is
seen. (c) Axial nonenhanced CT image
reveals an extraaxial lesion of iso- to
slightly hyperattenuation relative to gray
matter. The lesion
contains a focal area
of low attenuation, a
finding suggestive of
cystic degeneration.
(d) Axial T2-weighted
image shows the
heterogeneous extraaxial mass with
a large focus of T2

prolongation, suggestive of cystic degeneration. (e) Coronal
T1-weighted image
demonstrates the cystic region with a focus
of T1 shortening medial to it, an appearance that most likely
represents melanin.
(f) Postcontrast T1weighted image shows
avid enhancement of
the solid portion of
the mass.

radiographics.rsna.org


RG  ■  Volume 29  •  Number 5

Complete surgical resection may be curative,
but in up to 22% of cases lesions recur within
3 years after surgery, even if complete resection
is achieved (40). Without complete resection,
the recurrence rate is even higher: up to 50% of
cases (40). Radiation therapy is reserved for cases
in which complete resection is not possible or
in which there is a recurrence (40). There have
been reports of melanocytomas transforming
into malignant melanoma, spreading along the
leptomeninges, and even demonstrating distant
metastasis (34,41–43).

Pathologic and Histologic Features
At gross examination, most meningeal melanocytomas appear black, but red, white, tan,

brown, and blue lesions have been observed (44).
Melanocytomas tend to compress rather than
infiltrate the adjacent tissues; however, parenchymal invasion has been reported in cases of intermediate malignancy (45).
Because these lesions are based on the meninges, meningeal melanocytomas may be
mistaken for meningioma at gross inspection.
At microscopic examination, they may demonstrate tight cellular nests or whorls (Fig 8a,
8b), similar to those seen in meningiomas; in
fact, in the past, these lesions were referred to
as melanotic meningioma (45). Use of electron
microscopy and immunoperoxidase staining is
helpful in differentiating between melanocytoma
and meningioma (46). Electron microscopy, although not routinely used for tumor diagnosis,
demonstrates the absence of desmosomes and
interdigitating cellular processes that are found
in meningiomas; it can also reveal the presence
of melanosomes. Immunohistochemical analysis demonstrates the expression of melanocytic
marker proteins (such as S-100, melan A, and
HMB-45) but an absence of meningothelial cell
markers (such as EMA) (47).
Meningeal melanocytomas are histologically
characterized as cellular lesions, and the cytoplasm contains variable amounts of melanin pig-

Smith et al  1511

ment in intracellular granules. Amelanotic examples are reported. The important histologic differential diagnoses of meningeal melanocytoma
are melanotic schwannoma and malignant melanoma. The differentiation of melanocytoma from
melanoma can be difficult. The lack of mitotic
activity, nuclear pleomorphism, and hyperchromaticity, as well as an indolent growth pattern
spanning more than 4 years, are all characteristics
that indicate a melanocytoma rather than a melanoma (10). However, a small subset of meningeal

melanocytic tumors may be difficult to classify as
either a melanocytoma or a malignant melanoma
because they demonstrate intermediate histologic
features (45). In such cases, a designation such as
“melanocytic neoplasm of indeterminate biologic
potential” is sometimes applied.

Imaging Appearance
At CT, meningeal melanocytoma manifests as
an extraaxial iso- to hyperattenuating lesion that
enhances after administration of contrast material, an imaging appearance similar to that of
meningiomas. Unlike meningioma, however,
meningeal melancytoma rarely manifests with tumor calcification and hyperostosis of the adjacent
bone (38). At MR imaging, these lesions typically
demonstrate isointensity to hyperintensity with
T1-weighted pulse sequences and hypointensity
or isointensity with T2-weighted pulse sequences,
and they enhance homogeneously after administration of gadolinium (44,48,49) (Figs 8, 9).
The variable signal intensity most likely is related
to the varying amounts of melanin within lesions, but it may also be caused by intratumoral
hemorrhages (46). MR imaging does not allow
melanocytomas to be reliably distinguished from
other extraaxial neoplasms, such as meningiomas,
schwannomas, and malignant melanoma, which
occur in similar locations (Fig 9).

Teaching
Point



1512  September-October 2009

Figure 9.  Melanocytoma in a 23-yearold woman with headaches. (a) Axial T1weighted image demonstrates a lesion in
the middle cranial fossa, with mass effect on
the midbrain and intrinsic T1 shortening
involving the lateral portion of the lesion.
The medial portion is isointense relative to
gray matter. (b) On the axial T2-weighted
image, the lesion is slightly iso- to hypointense and has a mild degree of surrounding
edema within the adjacent temporal lobe.
(c) Postcontrast T1-weighted image demonstrates relatively avid enhancement of the
mass and a dural tail (arrow).

Figure 10.  Primary leptomeningeal melanomatosis in a 32-year-old man
with a 1-week history of nausea, vomiting, and headaches. (a) Photograph
of the cauda equina demonstrates diffuse black staining of the leptomeninges. (b) Photograph of a cross section of the cauda equina demonstrates
cells with brown pigmentation surrounding the nerve roots (*). (c) Sagittal
postcontrast T1-weighted image of the spine shows diffuse enhancement
along the cauda equina (arrows).

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RG  ■  Volume 29  •  Number 5

Primary Leptomeningeal Melanomatosis

Primary leptomeningeal melanomatosis is a rare,
aggressive neoplasm of the CNS that arises from
melanocytes within the leptomeninges and carries a poor prognosis. It is also referred to as a

meningeal variant of primary malignant melanoma. The malignant melanocytes spread in the
leptomeninges, into the Virchow-Robin spaces,
and superficially within the brain substance. The
first case of diffuse leptomeningeal melanomatosis was described by Virchow in 1859 (50).
Primary leptomeningeal melanomatosis is more
common in adults (peak prevalence, 4th decade
of life) than in children, and patients present with
variable signs and symptoms including seizures,
signs of increased intracranial pressure, psychiatric disturbances, cranial nerve palsies, and spinal
cord compression (50,51). The ante mortem
diagnosis of primary leptomeningeal melanomatosis can be challenging, because it may be difficult to recognize on radiologic images, and the
isolated tumor cells within the CSF may be hard
to recognize at cytologic analysis (52,53).

Smith et al  1513

weighted images. Intense enhancement is seen on
the postcontrast images (Fig 10c). The differential diagnosis for these imaging findings includes
meningeal carcinomatosis, meningitis, and idiopathic hypertrophic pachymeningitis.

Primary Malignant
Melanoma of the CNS

At examination of the gross specimen, diffuse
darkening and thickening of the leptomeninges is
noted (Fig 10a). Primary leptomeningeal melanomatosis can histologically mimic a variety of
other lesions, including brain metastasis from a
malignant melanoma elsewhere in the body (54).
Polygonal neoplastic cells with cytoplasmic pigment and nuclei containing prominent nucleoli
are noted (Fig 10b). The diffuse growth pattern

of this neoplasm, as opposed to the localized lesions found in metastatic melanoma, and the
absence of malignant melanoma elsewhere in the
body assist in making the diagnosis.

Primary malignant melanoma of the CNS accounts for approximately 1% of all melanoma
cases (55). The lesion occurs most frequently
in adults (mean age, 50 years), particularly
men (56). Primary malignant melanoma most
often develops within the leptomeninges, a site
that reflects the common neural crest origin of
both melanocytes and meningothelial cells (57).
Primary malignant melanoma arising within the
ventricles has been reported; the atypical site
may be due to arrested migration of melanocytic
cells whereby they are deposited within the pia
mater. From their location within the pia mater,
melanocytes may be incorporated into the choroid plexus (4). Spinal melanoma is extremely
rare, and most cases are intradural or have both
intra- and extradural components (3,58). The
diagnosis of a primary CNS melanoma is based
on the absence of any other melanoma, both
outside the CNS and in other CNS sites (55).
The prognosis for patients with primary malignant melanoma of the CNS is better than that
for those with metastatic melanoma, with reports
of survival up to 12 years after presentation; however, the prognosis worsens with the presence of
leptomeningeal spread (44,59,60). Recurrence
after surgery tends to be localized and distant
metastases are rare (44,59). The usefulness of
chemotherapy, radiation therapy, and immunotherapy in the treatment of these lesions has not
been clearly established (59).


Imaging Appearance

Pathologic and Histologic Features

CT and MR imaging reveal diffuse thickening of
the leptomeninges, with abnormal enhancement
on the postcontrast images. On T1-weighted images, the regions of melanocytosis may be isointense or hyperintense from T1 shortening due
to the paramagnetic properties of the melanin,
and they are correspondingly hypointense on T2-

Primary malignant melanoma is typically a darkly
pigmented neoplasm (Fig 11a). Histologic evaluation reveals a highly cellular tumor with the cells

Pathologic and Histologic Features


1514  September-October 2009

radiographics.rsna.org

Figure 11.  Primary meningeal melanoma in a 34-yearold woman with headaches
and right-sided neck pain.
(a) Photograph of the gross
specimen demonstrates a predominantly darkly pigmented
lesion with a central area that
is unpigmented. (b) Photomicrograph (original magnification, ×200; hematoxylineosin stain) reveals that the
tumor is composed of sheets
of pleomorphic cells with
prominent nucleoli. Some of

the neoplastic cells contain
melanin pigment (arrow).
(c) Sagittal T1-weighted image shows a lesion centered
in the region of the foramen
magnum that has scattered areas of T1 shortening (arrows).
(d) On the postcontrast image, the lesion is enhanced.

arranged in sheets. Pleomorphic cells with abundant cytoplasm and dark pigmentation are noted,
although amelanotic examples have been observed
(Fig 11b). Nuclear pleomorphism, mitoses, and
prominent nucleoli are also seen.

Imaging Appearance
As with melanocytic lesions elsewhere, primary
malignant melanoma varies in its imaging features, based on the degree of melanocytic content
(61) and the presence or absence of hemorrhage.
Typically, these lesions demonstrate some degree
of both T1 and T2 shortening and enhancement
on postcontrast images (Fig 11c, 11d). The enhancement pattern is typically homogeneous, but
it may be inhomogeneous, peripheral, or nodular
(58). Unfortunately, there are no distinguishing
imaging characteristics to separate primary malignant melanoma from other melanocytic lesions of
the CNS (3). The imaging findings of primary malignant melanoma of the CNS are similar to those
of metastatic melanoma; therefore, careful examination of the patient for the presence of melanoma

involving the skin, eyes, and mucosal surfaces is
necessary to exclude a primary lesion (61).

Melanotic Schwannoma


Melanotic schwannomas are rare lesions, with
only about 80 cases reported in the literature
(62,63). They have been described as neoplasms
with features intermediate between those of
schwannoma and malignant melanoma (64). Both
melanocytes and Schwann cells are derived from
neuroectoderm. Several theories for the etiology
of melanotic schwannomas have been proposed,
including the melanomatous transformation of
neoplastic Schwann cells, phagocytosis of melanin
by Schwann cells, and the simultaneous presence of two distinct neoplastic populations of
proliferating melanocytes and Schwann cells
(65,66). Two forms of melanotic schwannoma
are described: sporadic and psammomatous (67).
Psammomatous melanotic schwannoma is associated with Carney complex, which consists of
myxomas (of the heart, breast, and skin), spotty
pigmentation, and endocrinopathy (Cushing syndrome, precocious puberty, and acromegaly) (68).


RG  ■  Volume 29  •  Number 5

Smith et al  1515

Figure 12.  Metastatic melanotic schwannoma in a 69-year-old man with palsies of
the right fifth, sixth, and seventh cranial
nerves. (a) Postcontrast CT image reveals
an enhancing lesion in the right aspect of
the pons. Enhancement extends anteriorly
along the second division of the trigeminal
nerve into the cavernous sinus and infraorbital foramen (arrows). (b) Photograph of

the gross specimen demonstrates a darkly
pigmented lesion involving the right aspect
of the pons. (c) Photomicrograph (original
magnification, ×120; hematoxylin-eosin
stain) shows that the spindle cell neoplasm
contains numerous pigment-laden cells
(arrows). The patient also had metastatic lesions involving the lungs and mandible.

Melanotic schwannomas typically occur in
patients a decade younger than those with other
types of schwannomas, with peak prevalence in
the 4th decade of life (age range, 10–92 years).
Patients usually present with symptoms of nerve
compression (63). These lesions are more typically intracranial, but they also occur within the
spinal canal (69). When they develop within the
spine, the tumors most often arise in the thoracic
region and they may be intramedullary (70).
Twenty percent of patients will have multiple
melanotic schwannomas.
The behavior of these tumors is typically benign, but 10% of melanotic schwannomas will
undergo malignant degeneration (63). Metastasis
and meningeal seeding have been reported but
are exceedingly rare (Fig 12) (64). Treatment
consists of surgical resection, and the prognosis is typically excellent if complete resection is
achieved (69). In a review by Killen et al (71),
24% of all melanotic schwannomas were noted to
recur, and patients with tumors associated with
the cranial nerves had the worst prognosis.

Pathologic and Histologic Features

At gross examination, the melanin content of the
melanotic schwannoma imparts a dark blue, purple, or black appearance. These tumors are usually well circumscribed and may contain areas of
hemorrhage. Results from immunohistochemical
staining help secure the diagnosis. Histologic examination reveals spindle-shaped Schwann cells in
combination with melanosomes of various stages
of maturation (63). Psammoma bodies, melanin,
and fat can be seen in the psammomatous form
of melanotic schwannoma (72). These lesions
stain positive for S-100 protein and vimentin, and
they stain variably with glial fibrillary acid protein,
HMB-45, and other melanocytic markers.

Imaging Appearance
At CT, melanotic schwannoma manifests as a
hyperattenuating lesion, which may have areas of
calcification (Fig 13a). At MR imaging, melanotic schwannomas, unlike other pigmented lesions,


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1516  September-October 2009

Figure 13.  Melanotic schwannoma in a
24-year-old woman with Carney complex
and complaints of low back pain. (a) Nonenhanced CT image demonstrates a hyperattenuating lesion that expands the right sacral
foramina. Focal areas of calcification are present (arrow). (b) Axial T1-weighted image
shows that the mass is isointense relative to
muscle. No T1 shortening is present. (c) Axial
T2-weighted image demonstrates variable signal intensity within the lesion, which contains
areas of hyperintensity.


are hypointense to isointense with T1-weighted
pulse sequences and isointense to slightly hyperintense with T2-weighted pulse sequences (Fig
13b, 13c). However, their signal characteristics
vary, and areas of T1 and T2 prolongation may be
seen (Fig 14) (73). On postcontrast images, the
enhancement pattern of the lesions varies.

Other CNS
Lesions with Pigmentation

Several other CNS tumors may demonstrate
melanocytic differentiation in rare cases. Medulloblastomas are among the more common of
these lesions, and a melanocytic variant was
included in the 2007 World Health Organization
report (74). Melanocytic differentiation of lowgrade glial neoplasms has been reported, as
well as one case report of a gliosarcoma with
melanocytic differentiation (75). In rare cases,
craniopharyngiomas may contain melanin
(76). Metastasis of melanoma to a preexisting
intracranial neoplasm is exceedingly rare, with
only two cases reported in the literature (34).
Melanocytes in pigmented neoplasms, such as
teratoma, tend to be more dispersed, whereas
pigmentation secondary to a metastatic melanoma is more likely to be focal (Fig 15).

Melanoma Metastases

The CNS is a common site of metastases from
malignant melanoma, which is the third most

common neoplasm (after lung and breast cancers) to metastasize to the brain (78). In patients
with metastatic melanoma, 39% have brain
metastases, as reported at autopsy (79). The
majority of patients have multiple lesions, and
the cerebrum is a more common location than
the cerebellum (79). In some cases, the primary
tumor remains undetectable, and thus the CNS
metastases are difficult to differentiate from primary CNS melanoma, but the primary form is
much less common that the metastatic form (4).
Patients with melanoma metastatic to the CNS
have a poor prognosis, with a median survival of
113 days after discovery (80).

Pathologic and Histologic Features
Metastatic melanoma displays a spectrum of
morphologic features, ranging from spindled to
epithelioid cells, and may show variable pigmentation (Fig 16). Melanomas that lack pigmentation at light microscopic examination may pose


RG  ■  Volume 29  •  Number 5

Smith et al  1517

Figure 14.  Melanotic schwannoma
in a 53-year-old
woman with headaches. (a) Sagittal
T1-weighted image demonstrates a
hyperintense lesion
anterior to the medulla. (b) Axial T2weighted image reveals heterogeneous
signal within the lesion (arrow). The T2

prolongation in the
left cerebellar hemisphere is the result of
a previous unrelated
surgery.

Figure 15.  Teratoma in a 19-month-old boy
with a history of multiple generalized seizures.
(a) Axial T1-weighted image demonstrates a lesion that originates from the pineal region and
that contains scattered areas of T1 prolongation
(arrow). Hydrocephalus is present. (b) On the
T2-weighted image, the lesion appears heterogeneous. (c) Photograph of the gross specimen reveals scattered areas of pigmentation throughout
the lesion (arrows).


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1518  September-October 2009

Figure 16.  Metastatic melanoma in a 58-year-old man with seizures. (a) Photograph of
a gross specimen reveals numerous darkly pigmented lesions located predominantly at the
gray-white matter junction. (b) Photomicrograph (original magnification, ×200; hematoxylin-eosin stain) reveals nests of tumor cells with areas of melanin pigment (arrows).

Figure 17.  Metastatic melanoma in a
63-year-old man with a 3-week history of
ataxia and memory loss. Postcontrast CT
image reveals several enhancing lesions with
surrounding vasogenic edema at the graywhite matter junction; one in the right frontal lobe shows hemorrhage (arrow).

a particular diagnostic challenge. Cytologic
features are sometimes helpful in alerting the

pathologist to consider this entity. The neoplastic
cells often possess prominent nucleoli, a finding
that should prompt immunohistologic study to
confirm the diagnosis. Marked cellular and nuclear atypia, a high mitotic activity, and necrosis
are seen. These lesions are likely to hemorrhage.

Figure 18.  Metastatic melanoma in a
17-year-old boy with a history of melanoma involving the anterior chest wall.
Postcontrast CT image demonstrates numerous enhancing subependymal lesions
(arrows).

Imaging Appearance
Similar to other metastases, multiple foci of
metastatic melanoma are predominantly located
at the gray-white matter junction and have surrounding vasogenic edema. Enhancement is
seen on postcontrast images. The tendency of
metastatic melanoma to hemorrhage also affects imaging characteristics (Fig 17). The differential diagnosis for hemorrhagic metastatic
lesions in the CNS includes breast cancer,
lung cancer, choriocarcinoma, thyroid cancer,


RG  ■  Volume 29  •  Number 5

Smith et al  1519

Figure 19.  Metastatic melanoma in a 32year-old woman with headaches. (a) Coronal
T1-weighted image demonstrates a hyperintense sellar mass that superiorly displaces
the optic chiasm (arrow). (b) Coronal T2weighted image reveals the hypointense lesion
(arrow). (c) Photomicrograph (original magnification, ×200; hematoxylin-eosin stain) of
a sectioned specimen demonstrates melanincontaining cells.


and renal cell cancer (81). At CT, in the absence of hemorrhage, the lesions may be iso- to
hyperattenuating.
Attempts have been made to characterize the
MR imaging patterns of metastatic melanoma
as melanotic or amelanotic. For melanotic melanoma, the expected pattern is hyperintensity
relative to cortex on T1-weighted images and
hypointensity relative to cortex on T2-weighted
images. The pattern for amelanotic melanoma
is similar to that of other brain neoplasms, with
hypo- to isointensity on T1-weighted images
and iso- to hyperintensity relative to cortex on
T2-weighted images. However, this pattern approach is an oversimplification, and the amount
of melanin-containing cells in metastases is
extremely variable. It has been postulated that
intralesional hemorrhage plays a greater role in
influencing the imaging appearance of melanoma than does the melanin content (2). Isiklar
et al (78) found that 24% (ten) of 42 lesions
had the typical melanotic imaging pattern, and
all ten contained melanin. They noted that tumors with more than 10% melanin-containing
cells revealed the melanotic MR imaging pattern. They postulated that blood products could
have attributed to the melanotic imaging pattern; however, they did not believe that blood
products were the dominant influence on signal
characteristics in all cases. In evaluating the

amelanotic lesions, Isiklar et al (78) found that
over half of the tumors (10 of 16) that appeared
“amelanotic” at imaging actually contained
melanin (as confirmed with histologic analysis), although nine of the 10 had less than 10%
melanin-containing cells. A review of studies

in which imaging appearances of melanoma
Teaching
were evaluated provides no clear consensus as
Point
to whether the imaging findings are more influenced by paramagnetic effects of melanin or
by blood products or by a combination of both
(2,78,82). In addition, melanoma may manifest
imaging characteristics that do not follow either
the melanotic or amelanotic patterns. In a study
of metastatic melanoma in the cerebellopontine
angle and internal auditory canals (a rare location, with less than 10 reported cases), Arriaga
et al (83) found that these lesions were isointense on T1-weighted images and hyperintense
on T2-weighted images, in which case the differential diagnosis included meningioma (83).
The imaging patterns of metastatic melanoma
may also vary depending on anatomic location.
Most patients have multiple lesions, with the cerebral hemispheres being the most common site
(79). A miliary pattern of brain metastasis has
been reported, and subependymal spread may be
seen as well (84,85) (Fig 18). In rare cases, metastases of melanoma can also occur in the choroid plexus and pituitary gland (79) (Fig 19). In


1520  September-October 2009

Figure 20.  Melanotic neuroectodermal tumor of infancy
in a 14-month-old
girl with new onset
of a seizure disorder.
(a) Photograph of a
cross-sectioned gross
specimen reveals areas containing melanin (arrow). (b) Photomicrograph (original magnification,

×120; hematoxylineosin stain) of a
sectioned specimen
shows tumor cells
with abundant eosinophilic cytoplasm,
some of which contain melanin (arrows).
(c) Axial nonenhanced CT image
(produced with bone
algorithm) demonstrates marked hyperostosis in the left parietal region. (d) Axial nonenhanced
CT image shows
a hyperattenuating mass adjacent
to the hyperostosis
(arrows). (e) Axial
T2-weighted image
demonstrates the hyperostosis as well as
the soft-tissue mass,
which is slightly hyperintense relative
to gray matter. Mild
intraparenchymal
edema is seen adjacent to the lesion.
(f) Postcontrast T1weighted image demonstrates enhancement of the softtissue component.

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RG  ■  Volume 29  •  Number 5

a study of 105 patients with stage III melanoma,
Das Gupta and Brasfield (79) described only one
patient with a metastasis to the choroid plexus.


Melanotic Neuroectodermal Tumor of Infancy

Melanocytic neuroectodermal tumor of infancy is a rare condition that affects newborns
and infants. The neoplasm was first described
in 1918 by Krompecker, who described it as a
melanocarcinoma (86). Its histogenesis is uncertain, but melanocytic neuroectodermal tumor is
thought to have a neural crest origin (87). These
lesions are believed to represent a dysembryogenic neoplasm that arises from the neural crest
cells, based on findings from ultrastructural, immunohistochemical, electron microscopic, and
molecular genetic studies (88,89). The neural
crest origin of this tumor is further supported
by its secretion of vanillylmandelic acid or other
catecholamines. This finding is also observed in
other neoplasms of neural crest origin such as
pheochromocytomas, ganglioneuroblastoma, and
neuroblastoma (89,90).
Melanocytic neuroectodermal tumors are reported to be more common in boys than in girls,
and greater than 90% occur in children less than
1 year old (91–93). Most frequently, melanocytic neuroectodermal tumor arises in the anterior
aspect of the maxilla (60% of cases), but it can
involve the skull (10.8% of cases, usually in the
region of the anterior fontanelle), dura mater,
and brain (4.3%) (94,95). It has also been observed within the epididymis, femur, mediastinum, and ovary (87).
The majority of these neoplasms are slowgrowing, benign tumors that have a 2% chance of
malignant degeneration. Even though it is a benign
neoplasm, melanocytic neuroectodermal tumor is
frequently worrisome clinically because of its rapid
onset and growth rate. Most patients with melanocytic neuroectodermal tumor are cured with complete resection of the mass, but local recurrence
rates of 15%–45% have been reported (96).


Pathologic and Histologic Features
At gross inspection, melanocytic neuroectodermal
tumors appear well circumscribed but not encapsulated (Fig 20a). Histopathologic examination
demonstrates a unique biphasic pattern with
larger pigmented melanocyte-like cells and smaller
nonpigmented neuroblast-like cells arranged in a
background of fibrous connective tissue stroma
(Fig 20b). At immunohistochemical analysis, specimens stain positive for cytokeratin, synaptophysin,
glial fibrillary acidic protein, and Leu-7. They are
usually negative for S-100 protein (97).

Smith et al  1521

Imaging Appearance
Imaging of melanocytic neuroectodermal tumor of infancy when it involves the brain, skull,
or dura mater may reveal tumoral calcification
and calvarial hyperostosis, which is best visualized with CT (Fig 20c, 20d). At MR imaging,
the lesions tend to be isointense relative to brain
with T1-weighted pulse sequences and isointense to hyperintense with T2-weighted pulse
sequences (Fig 20e); however, they may demonstrate areas of T1 and T2 shortening, findings
that may reflect the intratumoral melanin (96).
Enhancement occurs on postcontrast images and
is typically marked (Fig 20f).

Conclusions

Pigmented lesions of the CNS are rare entities that may appear similar to other CNS neoplasms at both imaging and histologic evaluation.
Metastatic melanoma should be ruled out when
many of these lesions are encountered, since the
prognosis and therapeutic options for pigmented

lesions differ substantially from what is expected
for melanoma. Knowledge of the clinical and
pathologic spectrum of these lesions aids in the
differentiation of these neoplasms from other
more common entities that may have overlapping
imaging features.

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This article meets the criteria for 1.0 credit hour in category 1 of the AMA Physician’s Recognition Award. To obtain
credit, see accompanying test at />

RG

Volume 29

Number 5

September-October 2009

Smith et al

From the Archives of the AFIP: Pigmented Lesions of the Central
Nervous System: Radiologic-Pathologic Correlation
Alice Boyd Smith, Lt Col, USAF MC, et al
RadioGraphics 2009; 29:1503–1524 • Published online 10.1148/rg.295095109 • Content Code:

Page 1504
Melanocytes occur normally within the leptomeninges and are more concentrated at the base of the
brain and on the ventral surface of the cervical spinal cord.

Page 1504
It is important to differentiate primary melanin-containing lesions of the CNS from metastatic
melanoma, because these lesions require a different patient workup and alternate therapeutic options.
The absence of a known primary malignant melanoma helps in the differential diagnosis; however, an
occult primary lesion outside the CNS must be sought and excluded.
Page 1509
Degeneration into malignant melanoma is indicated by progressive growth, surrounding vasogenic
edema or mass effect, or development of central necrosis.
Page 1511
The lack of mitotic activity, nuclear pleomorphism, and hyperchromaticity, as well as an indolent
growth pattern spanning more than 4 years, are all characteristics that indicate a melanocytoma rather
than a melanoma
Page 1519
A review of studies in which imaging appearances of melanoma were evaluated provides no clear
consensus as to whether the imaging findings are more influenced by the paramagnetic effects of
melanin or by blood products or by a combination of both.


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